Dr. Alaa Mosbah, MD OBS & GYN: Fertilization

Sunday, January 20, 2008

Fertilization

2 comments:

Mohamed said...: hello dr.
thx for the CS video , it's now on the : www.mansmed.com
it's uploaded there and i have downloaded it today.; 25 January, 2008 07:02
mido said...: thanksssssssssssssssssssssssssssssssssssssssss; 21 February, 2008 15:56

Radiation exposure during pregnancy

The 5 types of radiation include:
(1) Ionizing rays (x-rays),
(2) Cosmic rays,
(3) Microwaves,
(4) Ultrasound, and
(5) Electromagnetic fields.
1- Ionizing rays
X-rays are the most frequent iatrogenic exposure besides prescription medications. During their careers, all obstetricians and gynecologists are asked about the effects of radiation exposure on a pregnancy, and they are expected to be able to judge the need for diagnostic or therapeutic radiation. The effects of radiation are well studied, but as cohort age and long-term effects become clear, information continues to evolve in this ever-changing field. Knowledge about exposures also changes rapidly.
The primary exposures are diagnostic x-rays, radio-pharmaceuticals, workplace exposures, and environmental exposures such as those that occurred after the Three Mile Island and Chernobyl nuclear reactor accidents, and in Iraq following the Gulf War II. Documented effects include (1) intrauterine lethality, (2)organ malformation, (3)mental impairment, and later-onset (4) leukemia and solid tumors.

X-rays are measured in several types of units, the most important of which are the radiation absorbed dose (rad), which is the measure in the United States, and the gray (Gy), which is an international measure. Both rads and grays typically refer to single-time exposures (eg, diagnostic procedures). The roentgen equivalent man (rem) unit of measure and sievert (Sv) unit are used to quantify radiation exposure over time (eg, environmental releases). Conversion factors for these measurements are 1 Gy equals 100 rad and 1 Sv equals 100 rem.

X-rays have both immediate effects and delayed effects:

A].Immediate effects:

Immediate (deterministic) effects are usually intrauterine, often post-conceptual, effects involving damage to growing and pattern-forming cell populations. If the exposure occurs when cell numbers are few, such as during the blastocyst or pre-implantation stage, very early abortion or implantation failure occurs. These effects demonstrate both a dose-response curve and a threshold below which no effects are observed.
As with other teratogens, the embryonic stage is crucial because windows exist for the appearance of effects. The fetal dose is also critical, and a simple application of a maternal calculated dose should not be substituted.

The damage threshold begins at 0.1-0.15 Gy, which causes abortion at pre-implantation, and extends to 1 Gy, which is associated with fetal death in utero at term. Organogenesis represents a window of sensitivity for the fetus during gestational weeks 3-7. The threshold is thought to be 0.05-0.5 Gy.

Skeletal defects have been noted in humans, most particularly reduced head circumference. Animal data point to more frequent defects of the genitourinary system and eye in addition to skeletal effects. Severe mental retardation is another human effect noted at this threshold (0.05-0.5 Gy). The window for these effects is gestational weeks 8-25. Mental retardation has been noted at maternal doses of 1.5 Gy. Fetuses exposed during weeks 8-25 also demonstrate an onset of effects secondary to radiation. These effects include mental retardation, a downward shift in intelligence quotient (IQ) of 30 IQ units/Gy, lower school performance, and unprovoked seizure. All effects are more severe if the exposure occurs during gestational weeks 8-15. Importantly, note that while infants of normal intelligence remain within 1 standard deviation of normal following exposure, borderline infants are rendered mentally retarded at relatively low exposures.

B].Delayed effects:
These effects do not show a threshold, and they occur in the later years of the exposed individual’s life. Fetal x-ray exposures are associated with later-onset childhood leukemia and solid tumors. The demonstrated relative risk in multiple case-control studies is 1.39 (95% confidence interval: 1.3-1.49). This increased risk was documented by the very large Oxford Survey of Childhood Cancers, and the finding was confirmed by multiple US and European studies. The increased risk is thought to occur following an exposure of 0.05 Gy.

Thyroid cancer in childhood is a special concern. Multiple studies have shown that direct external exposure of children’s thyroids results in an increased frequency of cancer. Such exposures occurred following the Chernobyl accident and during medical procedures. The lag time until detection of cancer is 5 years after exposure. In contrast, in utero exposure during the second and third trimester of pregnancy (eg, Chernobyl, maternal thyroid ablation) is associated with an onset of childhood thyroid cancer before the 5-year lag time; these cancers are associated with increased morbidity and aggressiveness.
Radiation is a dose-dependent teratogen. Below a certain threshold, radiation levels are similar in exposed populations and control populations who have received only background radiation.1 A fetus is most vulnerable to radiation-induced central nervous system damage 8 to 15 weeks after conception . Radiation from x-ray and CT scans is measured in rad, rem, gray, and sievert (1 rad = 1 rem = 0.01 Gy = 0.01 Sv).
The United States Centers for Disease Control and Prevention’s Radiation Safety Committee recommends that fetuses of laboratory workers not receive more than a cumulative dose of 500 mrad during the entire gestation period. This occupational exposure guideline is one-tenth of the safe dose and should not be confused with the teratogenic-threshold dose. Pregnant women exposed to <5000 mrad have similar pregnancy outcomes to controls who have received only background radiation.
Most radiodiagnostic examinations expose fetuses to less than 5000 mrad of radiation .X-ray examination of the abdomen is associated with 250 mrad, and an abdominal CT scan with 3000 mrad. There is no significant increase in major malformations in pregnant women inadvertently exposed to these radiation doses. These women should be reassured and counseled appropriately.

Estimated fetal radiation doses during some common radiodiagnostic procedures
FETAL DOSE (MRAD)
X-RAY

Upper gastrointestinal series
100
Cholecystography
100
Lumbar spine radiography
400
Pelvic radiography
200
Hip and femur radiography
300
Retrograde pyelography
600
Abdominal (kidneys, uterus, bladder) radiography
250
Lumbar spine,

• Anteroposterior
750
• Lateral
91
• Oblique
100
Barium enema
1000
Intravenous pyelogram
480
COMPUTED TOMOGRAPHY

Head
0
Chest
16
Abdomen
3000
Intervention;

Clearly, preventing exposure during the first trimester is advisable. Clear counseling is needed for patients with conditions that require uptake scans or radio-nuclide therapy. Patients should be advised that no known safe dose exists in regard to later-onset childhood cancers. The balancing of risk to both patients (fetus and mother) must take into account the value that any given diagnostic test will have for decision-making. For occupational exposures, the limit is 1 mSv after pregnancy notification.
2- Cosmic rays:
Cosmic radiation is ionizing radiation by heavy particles, such as protons and helium nuclei that originate outside the earth. This form of ionizing radiation is most evident at very high altitudes. Primary exposure requires many in-air hours; therefore, airplane crewmembers and pilots, rather than passengers, are typically at risk.
Relatively few studies have been performed on human exposure to cosmic radiation. Risks are real, but the medical community and the general public have little awareness of them.

Two organizations, the US National Council on Radiation Protection and Measurement (NCRP) and the International Commission on Radiologic Protection (ICRP), provide the following recommendations on permissible doses:
General public - 1 mSv
Aircrews - 20 mSv/y averaged over 5 years (maximum 50 mSv/year)
Fetuses - 2 mSv (not to exceed 0.5 mSv/month)
Notably, aviators generally have a lower overall incidence of cancer compared to the general population. The risks of all other forms of transportation outweigh those of flight, although an association exists between frequent flying and certain specific cancers, most notably brain, colon, and hematopoietic cancers.
Also, ionizing radiation has the previously noted fetal effects of decreased head circumference, mental retardation, and childhood cancer.
Aviation workers can easily exceed the NCRP and ICRP limit recommendations. Charter jet crews and passengers fly at higher altitudes with more consequent exposure. Changes in intensity occur with changes in solar flare activity on the sun, and the intensity may exceed 10 mSv/h at 42,000 ft. The US Federal Aviation Administration and the US Occupational Safety and Health Administration recognize flight crews as individuals exposed to radiation. Computer systems are available to calculate exposures, but these systems are not mandatory.

Intervention;
Health care providers should obtain complete occupational histories and discuss risk of exposure with pregnant patients. Given the variability of exposure and that no easy monitoring is possible, any mandatory cut-off or exclusion of pregnant workers from their jobs would be potentially discriminatory and may lead to risks to the child due to altered socioeconomic status.

3- Microwaves:
Microwaves are a form of electromagnetic radiation with particularly long wavelengths. In contrast to ionizing radiation, which travels in extremely short, high-energy waves, energy in microwave radiation affects objects and cells by thermal action only. Microwaves raise the temperature within cells and are cytotoxic to individual cells only at high exposures. No specific DNA-damaging mechanism exists, and no stochastic effects are observed in exposed populations.

4- Ultrasound:Ultrasound involves the creation of very high-frequency sound, emission of this sound, and analysis of how the sound alters upon encountering objects of different densities when reflected back to the emitter. Physical effects, such as well-contained thermal effects, occur when the vibration at these very high speeds is used (e.g. between the paddles of a harmonic scalpel).The energy of ultrasound is carried by the physical particles of the media and objects affected. The energy does not reach an ionizing level, and no DNA-specific effects are observed.
5- Electromagnetic fields:
Despite multiple studies, including some very large studies, the low-energy electromagnetic fields generated by power lines, video displays, and other electric and electronic devices have no demonstrable effects. Some of these studies have been conducted in response to clusters of events, such as increased spontaneous abortion rates in a specific area.

Infertility evaluation & treatment

This guidance is based on the National Institute for Clinical Excellence (NICE) guideline (February 2004).
Definition :
Infertility is the inability to conceive, but a couple are regarded as infertile if after regular sexual intercourse they have not conceived in 2 years [National Collaborating Centre for Women's and Children's Health, 2004].
Classification :
Infertility is classed as primary in couples who have never conceived and secondary in couples who have previously conceived [National Collaborating Centre for Women's and Children's Health, 2004].
Infertility may be categorized into unexplained (30%), or secondary to ovulatory failure (27%), male factors (19%), tubal factors (14%), or endometriosis (5%) [NHS CRD, 1992; De Kretser, 1997; Templeton, 2000]. The presence of disorders in both the man and the woman has been reported to occur in about 39% of cases [Thonneau et al, 1991; National Collaborating Centre for Women's and Children's Health, 2004].

The prevalence of infertility is around 14% in European countries, affecting one in seven couples [National Collaborating Centre for Women's and Children's Health, 2004].
Of all couples attempting to conceive, 16% are unsuccessful after 1 year. This reduces to 8% after 2 years and 7% after 3 years [National Collaborating Centre for Women's and Children's Health, 2004].
Infertility is more common with increasing age: female fertility declines with age although the effect on male fertility is less clear. With regular sexual intercourse only 6% women aged 35 years and 23% of those aged 38 years will have failed to conceive after 3 years [National Collaborating Centre for Women's and Children's Health, 2004].
The number of couples seeking help has increased although it is not thought that there has been a major increase in the prevalence of infertility. Theories such as a decline in sperm count due to environmental factors are controversial. Behavioural factors such as a tendency to delay childbearing may play a role [Himmel et al, 1997; Templeton, 2000].
Causes of infertility in women
1.Disorders of ovulation
2.Premature ovarian failure
3.Polycystic ovarian syndrome: often associated with 4.hirsutism, obesity, acne, and menstrual irregularity.
5.Hypothalamic-pituitary causes:
6.Anterior pituitary macro or microadenoma may alter 7.prolactin secretion and lead to amenorrhoea and anovulation. Although stress may cause a transient rise in prolactin, levels higher than 1000 ml/litre suggest an adenoma.
8.Hypogonadotrophic hypogonadism: the commonest cause is excessive exercising, being underweight or both. People with anorexia nervosa are normally amenorrhoeic.
9.Sheehan's syndrome (panhypopituitarism most often following massive postpartum haemorrhage or trauma) is now very rare.
10.Kallmann's syndrome (amenorrhoea and anosmia due to congenital lack of hypothalamic production of gonadotrophin-releasing hormone) is rare.
11.Thyroid: hyperthyroidism and hypothyroidism may lead to menstrual disorders and ovulatory dysfunction.
12.Adrenal: Cushing's syndrome and congenital adrenal hyperplasia may cause anovulation.
13.Tubal, uterine and cervical factors
14.Genital tract infection causing tubal damage: chlamydial infection is a major risk factor [Land and Evers, 2002].
15.Previous pelvic surgery causing tubal damage or adhesions, or previous cervical surgery causing scarring or shortening of cervix and, rarely, cervical stenosis.
16.Submucosal fibroids may distort the uterine cavity and impair implantation [Campbell and Monga, 2000].
17.Previous sterilization
18.Cervical mucus defect or dysfunction
19.Endometriosis: tubal distortion and limitation of fimbrial motility due to pelvic adhesions.
20.Drugs :
Nonsteroidal anti-inflammatory drugs, in particular indometacin, can inhibit ovulation.
Chemotherapy with cytotoxic drugs can induce ovarian failure, which may be permanent.
Recreational drugs, such as marijuana and cocaine, have also been associated with impaired ovulatory and tubal function.
[Dukes, 1996; Janssen and Genta, 2000; National Collaborating Centre for Women's and Children's Health, 2004]
21.Other factors
Occupational/environmental factors which may affect fertility include shift work, intense physical workload, pesticides, solvents and formaldehyde [National Collaborating Centre for Women's and Children's Health, 2004].
Psychogenic factors may affect fertility but studies have not consistently shown this [Himmel et al, 1997].
Significant systemic illness e.g. thyroid problems
[Cooke, 1996; Hargreave and Mills, 1998; Chen and Brzyski, 1999; Chambers, 1999; Campbell and Monga, 2000; Hamilton-Fairley and Taylor, 2003; National Collaborating Centre for Women's and Children's Health, 2004; Symonds and Symonds, 2004; HFEA, 2004b]
Causes of infertility in men :
1.Defective spermatogenesis
2.Commonest cause of male subfertility: reduced count of mainly dysfunctional spermatozoa (oligoasthenoteratozoospermia) of unknown cause
3.Congenital, e.g. Klinefelter's syndrome (karyotype 47 XXY, small testes and sterility)
4.Hypogonadotrophic hypogonadism, e.g. Kallmann's syndrome
5.Pituitary causes, e.g. hyperprolactinaemia from a pituitary adenoma
6.Genital tract abnormalities
7.Previous vasectomy
8.Past history of infection, e.g. mumps orchitis; epididymitis and prostatovesiculitis may also lead to infertility
9.Congenital absence of vas deferens: 1-2% of infertile men
10.Testicular tumour: may be palpable on examination
11.Maldescended testes: absence of testes on examination
12.Varicocele: present in up to approximately 25%-40% of subfertile men, although its association with infertility is not clear [Wong et al, 2000]
13. Drugs :
Sulfasalazine, neuroleptics, and nitrofurantoin can affect semen quality and cause oligospermia. The effect is usually reversible on withdrawal of medication [Dukes, 1996; National Collaborating Centre for Women's and Children's Health, 2004].
Chemotherapy with cyotoxic drugs can induce permanent azoospermia [National Collaborating Centre for Women's and Children's Health, 2004].
Beta-blockers, cimetidine, psychotrophic drugs, and spironolactone can cause impotence or ejaculatory dysfunction [National Collaborating Centre for Women's and Children's Health, 2004].
The use of drugs such as anabolic steroids and cocaine can adversely affect the quality of semen.
[Dukes, 1996; National Collaborating Centre for Women's and Children's Health, 2004]
14.Other factors :
Ejaculation disorders, e.g. retrograde ejaculation, impotence
Environmental factors which may affect fertility include agricultural chemicals, X-ray exposure, solvents, and heavy metals [National Collaborating Centre for Women's and Children's Health, 2004].
Antibodies against spermatozoa, e.g. post vasectomy
Exposure of testes to heat
Psychogenic stress and its association with infertility in men is not clear. A higher incidence of male sexual disturbances has been observed in couples undergoing fertility investigation and treatment [Saleh et al, 2003; National Collaborating Centre for Women's and Children's Health, 2004].
Significant systemic illness, e.g. cardiac failure, chronic renal failure, neoplasia, uncontrolled diabetes, liver cirrhosis, thyrotoxicosis.
[Wu, 1996; De Kretser, 1997; Himmel et al, 1997; Hargreave and Mills, 1998; Chambers, 1999; Hirsh, 2003]
Likely outcomes of infertility :
Without treatment
For couples who have been trying for less than a year, the conception rate is between 80% and 90%.
For couples who have been trying to conceive for up to 3 years, the conception rate is about 40% in a 1-year period (equivalent to a monthly fecundity rate of 4-5%) if the woman is aged about 30 years.
For couples who have been trying for more than 3 years, the conception rate is still up to 25% in a 1-year period.
If a male or female subfertility factor has been identified, there is still a likelihood of spontaneous conception, although the success rates may be lower.
[NHS CRD, 1992; Himmel et al, 1997; Hargreave and Mills, 1998; Te Velde and Cohlen, 1999].
With treatment
In vitro fertilization (IVF): the overall live birth rate per treatment cycle is 21.8% (25.1% for women aged less than 38 years). If frozen embryos are used the success rate is about 12% per treatment cycle. After five attempts, just over half of women aged under 34 years will have conceived [HFEA, 2004a; HFEA, 2004b]. One in 20 pregnancies that result in a live birth will be a multiple pregnancy. Twins are much are more common than triplets (ratio of 15:1) [National Collaborating Centre for Women's and Children's Health, 2004].
Intracytoplasmic sperm injection (ICSI): the overall live birth rate per embryo transfer is 28.7% (25.7% for women over 38 years) .
Intrauterine insemination (IUI) has a pregnancy rate of 9% per treatment cycle using ovulation stimulation in couples with unexplained infertility [National Collaborating Centre for Women's and Children's Health, 2004].
Donor insemination (DI) has a live birth rate of about 10-12% with each attempt in women under 30 years, and 9% in women aged 35-39 years [HFEA, 2004b].
Oocyte donation has a live birth rate of 25-40% with each attempt (eggs donated by women under 36 years)[HFEA, 2004b].
Embryo donation has a live birth rate of 16.8% using frozen embryos and 27.3% using fresh embryos [Lee and Yap, 2003].
Gamete intrafallopian transfer (GIFT) has a pregnancy rate of 25-30% in any one treatment cycle [HFEA, 2004b].
Tubal surgery: reported pregnancy rates range between 5% and 50%, with the severity of tubal damage being closely linked to outcome [National Collaborating Centre for Women's and Children's Health, 2004].
Reversal of sterilization: pregnancy rates of up to 85.7% have been reported, although rates depend on the type of previous surgery and age. A successful outcome is more likely in younger women [Cohen et al, 1999; Yoon et al, 1999; Tourgeman et al, 2001; Hanafi, 2003].
Reversal of vasectomy results in subsequent pregnancy rates ranging between 35% and 71% [Himmel et al, 1997].
Medical treatment for male factor infertility is effective only if the cause is hypogonadotrophic hypogonadism, where 80% of men have achieved a positive sperm count [National Collaborating Centre for Women's and Children's Health, 2004].
Medical treatments for ovulatory dysfunction caused by hyperprolactinaemia results in an ovulation rate of 70-80% [Hamilton-Fairley and Taylor, 2003].
Pulsatile gonadotrophin-releasing hormone for hypothalamic amenorrhoea results in conception rates of 80-90% after 12 months' use [Hamilton-Fairley and Taylor, 2003].
Management Issues :
General issues
Assessment and investigations for infertility are not generally advised until the couple have been unable to achieve a pregnancy after a year of unprotected intercourse. Some people who present with concerns about their fertility need only simple reassurance that the chance of conception is 84% in the first year if they do not use contraception and have regular sexual intercourse. About half of couples who do not conceive in the first year will conceive in the second year (a cumulative pregnancy rate of 92%) [National Collaborating Centre for Women's and Children's Health, 2004].
Regular sexual intercourse (two or three times a week) throughout the cycle should ensure that intercourse falls within the fertile period. Timing of intercourse using temperature charts and luteinizing hormone detection methods causes stress and has not been shown to improve conception rates. They are therefore not recommended [Hargreave and Mills, 1998; National Collaborating Centre for Women's and Children's Health, 2004].
Folic acid supplements should be taken whilst trying to conceive and for the first 12 weeks of pregnancy in order to reduce the risk of neural tube defects. Most women should take 400 micrograms daily. A higher dose of 5 mg daily is recommended for women who either have a family history of neural tube defect, who have had a baby with a neural tube defect, who are taking antiepileptic medication, or who have coeliac disease [Wald, 1991; Lumley et al, 2003; National Collaborating Centre for Women's and Children's Health, 2004].
Rubella status should be checked. If seronegative, rubella vaccination is indicated and the woman should be advised not to become pregnant within 1 month of the vaccination. Note: the Department of Health has advised that seronegative women should be vaccinated using MMR (measles, mumps, and rubella) since the Department is no longer able to secure supplies of licensed rubella vaccine [CMO, 2003].
Cervical screening should be offered in accordance with the national cervical screening programme guidance [National Collaborating Centre for Women's and Children's Health, 2004].
For further information see the PRODIGY Preconceptual counselling guidance.
Assessment of the infertile couple in primary care
When should I assess?
Couples who are concerned about their fertility should be offered an initial assessment (history and examination) in primary care. Specifically enquire about lifestyle and sexual history to identify couples who may be less likely to conceive [National Collaborating Centre for Women's and Children's Health, 2004].
Couples who have not conceived after 1 year of regular unprotected sexual intercourse, or have been identified as less likely to conceive, should also be offered initial investigations, e.g. semen analysis, assessment of ovulation, or both [National Collaborating Centre for Women's and Children's Health, 2004].
How should I assess the woman?
History
A full medical, sexual, and social history should include:
Maternal age (fertility decreases with age)
Previous children born to the woman, previous pregnancies and miscarriages (with same or different partner)
Length of time trying to conceive, and frequency and difficulties of sexual intercourse
Length of time since stopping contraception and type of contraception
Menstrual cycle details: including length of cycle and symptoms and signs of ovulation, e.g. ovulatory discomfort, changes in cervical mucus
Cervical smear history and previous pelvic surgery, e.g. appendicitis
Symptoms of pelvic inflammatory disease or endometriosis, e.g. dyspareunia and dysmenorrhoea
Past history of sexually transmitted diseases or pelvic inflammatory disease [World Health Organization Task Force on the Prevention and Management of Infertility, 1995]
Systemic or debilitating diseases including thyroid dysfunction, diabetes, inflammatory bowel disease, and anorexia nervosa
Drug history
Details of occupation for possible exposure to hazards that can reduce fertility, e.g. pesticides, nitrous oxide, formaldehyde and solvents [National Collaborating Centre for Women's and Children's Health, 2004].
Lifestyle factors that may affect fertility, e.g. smoking, alcohol intake, excessive exercise, stress. Excessive travelling that limits optimal coital timing may indirectly affect fertility.
[Chambers, 1999; Symonds and Symonds, 2004]
Examination :
Pelvic examination may identify factors causing infertility, such as vaginal infection or tenderness indicating endometriosis or pelvic inflammatory disease. Bimanual examination may reveal fibroids or an ovarian cyst [Hargreave and Mills, 1998; Chambers, 1999].
Also look for obesity (associated with lower fertility), hirsutism, acne, or both (associated with polycystic ovary syndrome), and galactorrhoea (suggestive of hyperprolactinaemia) [Chambers, 1999].
Initial investigations
Mid-luteal phase progesterone levels should be checked in all women to confirm ovulation. The sample should be taken 7 days before the expected period (day 21 in a 28‑day cycle) [National Collaborating Centre for Women's and Children's Health, 2004].
In women with prolonged irregular menstrual cycles, depending on the timing of menstrual periods, serum progesterone may need to be taken later in the cycle, and repeated weekly thereafter until the next menstrual cycle starts [National Collaborating Centre for Women's and Children's Health, 2004].
Serum gonadotrophins (follicle-stimulating hormone and luteinizing hormone) should be measured in all women with irregular menstrual cycles. Women with high levels of gonadotrophins are likely to have reduced fertility [National Collaborating Centre for Women's and Children's Health, 2004].
Thyroid function tests should only be undertaken in women with symptoms of thyroid disease. Women with possible fertility problems are no more likely than the general population to have thyroid disease [National Collaborating Centre for Women's and Children's Health, 2004].
Prolactin estimation should be reserved for women with an ovulatory disorder, galactorrhoea or a suspected pituitary tumour [National Collaborating Centre for Women's and Children's Health, 2004].
Chlamydia screening. NICE recommends that all women who will be undergoing uterine instrumentation should be tested for chlamydia, as infertility investigations may result in iatrogenic pelvic inflammatory disease. Although the prevalence of Chlamydia trachomatis is only 1.9% in subfertile women, the number of people diagnosed with uncomplicated chlamydia infection has risen steadily since 1993 particularly in the 16-19‑year-old age group. We would therefore recommend that chlamydia screening should be part of the assessment of all women presenting with infertility. If the test is positive, women and their partners should be referred for appropriate management and contact tracing [PHLS et al, 2000; National Collaborating Centre for Women's and Children's Health, 2004].
How should I assess the man?
History
A full medical, sexual, and social history should include:
Previous children born to the man (with same or different partner)
Length of time trying to conceive, and frequency and difficulties of sexual intercourse
Past history of mumps, sexually transmitted diseases, or testicular trauma [World Health Organization Task Force on the Prevention and Management of Infertility, 1995; Kennedy, personal communication, 2004]
Previous surgery e.g. herniorrhaphy
Previous urogenital pathology and treatment, e.g. undescended testis or orchidopexy
Systemic or debilitating diseases, e.g. cardiac failure, chronic renal failure, neoplasia, uncontrolled diabetes liver cirrhosis, thyrotoxicosis [Wu, 1996]
Drug history
Details of occupation for possible exposure to pesticides, X-rays, solvents, paints, chemicals from smelting or welding [National Collaborating Centre for Women's and Children's Health, 2004].
Lifestyle factors that may affect fertility, e.g. smoking, alcohol intake, excessive travelling that limits optimal coital timing, excess exercise, stress, social or occupational situations that may cause testicular hyperthermia.
[Chambers, 1999; Symonds and Symonds, 2004]
Examination
Scrotal examination may reveal lumps (cancer, varicocele, or hernia), small, soft testes, or undescended testes in some cases.
The penis should be examined, including a check of the position of the urethral meatus, for structural abnormalities and signs of infection.
Assess secondary sexual characteristics.
Look for gynaecomastia.
[Cooke, 1996; Hargreave and Mills, 1998; Chambers, 1999]
Initial investigations
One fresh semen specimen should be taken during the initial investigation. The specimen should be produced after 2-3 days abstinence from sex. The specimen should be sent to the laboratory as quickly as possible as analysis should be carried out preferably within 1 hour of production [Chambers, 1999; National Collaborating Centre for Women's and Children's Health, 2004].
Interpret using the World Health Organization (WHO) normal values:
Volume 2 ml or more
Liquefaction time within 60 minutes
pH 7.2 or more
Sperm concentration greater than 20 million/ml
Motility: 50% or more motile (grades a and b) or 25% or more with progressive motility (grade a) within 60 minutes of ejaculation. (Grade a is rapid progressive motility, with sperm moving swiftly, usually in a straight line; grade b is slow or sluggish progressive motility and sperm may be less linear in their progression.)
Vitality: 75% or more live
White blood cells: fewer than 1 million per ml
Morphology >30% normal forms (or >15% based on strict morphological criteria)
If the result of the first semen sample is normal, a repeat confirmatory test should ideally be taken 3 months after the initial test as this allows time for the cycle of spermatozoa to be completed.
If the result of the first semen sample is abnormal then a repeat test should be done. If there is a gross spermatozoa deficiency (azoospermia or severe oligospermia) then the repeat test should be done as soon as possible.
[National Collaborating Centre for Women's and Children's Health, 2004]
Which investigations are not generally recommended?
Basal body temperature charts do not reliably predict ovulation and are not recommended [Guermandi et al, 2001; National Collaborating Centre for Women's and Children's Health, 2004].
Ovulation predictor kits are widely available but there is no evidence that attempts to time intercourse to the menstrual cycle will result in improved conception rates and they are not recommended [Hargreave and Mills, 1998; Chambers, 1999].
The routine use of postcoital testing has no predictive value for pregnancy rates [National Collaborating Centre for Women's and Children's Health, 2004].
Screening for antisperm antibodies should not be offered, as there is no evidence of effective treatment to improve fertility [National Collaborating Centre for Women's and Children's Health, 2004].
Lifestyle advice ;
Smoking
Smoking cessation is advisable for both men and women. Smoking, including passive smoking has been shown to be detrimental to fertility in women [Hughes and Brennan, 1996; Augood et al, 1998; Hull et al, 2000; BMA, 2004]. In men, although there is no clear evidence that smoking delays conception or affects fertility, it may affect sperm quality and general health [BMA, 2004].
Alcohol limitation
Women should be advised to limit alcohol to 1 to 2 units once or twice a week. The evidence for a link between alcohol and female infertility is conflicting, and the limits for safe consumption are not known, but until more is known, low consumption of alcohol when trying to become pregnant and during pregnancy is advisable [DH, 2003; National Collaborating Centre for Women's and Children's Health, 2004].
Men should be informed that alcohol consumption within the Department of Health's recommendations of 3 to 4 units a day is unlikely to affect their fertility. Excessive alcohol consumption can be detrimental to semen quality [National Collaborating Centre for Women's and Children's Health, 2004].
Weight
Weight loss should be encouraged in women with a body mass index (BMI) greater than 29, as this is likely to increase their chance of ovulation and therefore conception. There is no proven association between male obesity and infertility, although obesity is associated with poorer general health, a reduction in sperm motility and increased DNA fragmentation [Rich-Edwards et al, 2002; Kort et al, 2003a; Kort et al, 2003b; National Collaborating Centre for Women's and Children's Health, 2004].
Women who have a body mass index of less than 19 and either amenorrhoea or irregular menstruation should be advised that gaining weight is likely to increase their chance of conception [National Collaborating Centre for Women's and Children's Health, 2004].
Nutrition
A well-balanced diet will contribute to general good health for both partners. Although there is little research on nutritional factors in infertility, there have been studies suggesting that nutritional deficiencies may play a role; e.g. vitamins C, D, E, selenium, zinc, and folate deficiencies may affect sperm quality [Wong et al, 2000].
There is no consistent evidence to link consumption of caffeinated beverages (tea, coffee, and cola) and infertility [National Collaborating Centre for Women's and Children's Health, 2004].
Clothing
Men should be informed that although there is an association between an elevated scrotal temperature and reduced semen quality, it is uncertain whether wearing loose-fitting underwear improves semen quality [Tiemessen et al, 1996; Munkelwitz and Gilbert, 1998; National Collaborating Centre for Women's and Children's Health, 2004].
Secondary and tertiary care management
General issues
Specialist infertility clinics are the referral centres of choice. While many secondary care centres carry out a range of infertility treatments, in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and donor insemination (DI) are usually only offered in tertiary care.
General practitioners may find that because of the strict confidentiality of the Human Fertilisation and Embryology Act, that they may not be sent information about their patient's assisted conception treatment. Sometimes letters will be set from the unit to the patient for them to release to their doctor as they see fit [Braude and Muhammed, 2003].
National recommendations
The Department of Health recommends that each primary care trust offer:
All women aged 23-39 who meet the NICE clinical criteria (see below) a minimum of one full cycle of IVF from April 2005. In the longer term it is expected that primary care trusts will progress towards fully implementing NICE guidance.
Priority to couples who do not already have a child living with them.
NICE recommend that all couples where the woman is aged 23-39 years at the time of treatment and who have an identified cause for their fertility problems (such as azoospermia or bilateral tubal occlusion) or who have infertility for at least 3 years' duration should be offered up to three stimulated cycles of in vitro fertilization treatment [National Collaborating Centre for Women's and Children's Health, 2004].
Assessment in secondary care
Investigations in women normally include tubal patency tests. Women who are not known to have comorbidities (e.g. pelvic inflammatory disease, endometriosis, or previous ectopic pregnancy) should be offered a hysterosalpingogram or hysterosalpingo-contrast-ultrasonography. Women thought to have comorbidities should be offered diagnostic laparoscopy and dye so that tubal and other pelvic pathologies can be assessed at the same time [National Collaborating Centre for Women's and Children's Health, 2004].
Investigations in men include an assessment of the sperm, starting with a review of results obtained from primary care investigations. In men with abnormal sperm, a more detailed examination is carried out which may include microbiological tests, sperm culture, endocrine tests, imaging of the urogenital tract, and testicular biopsy.
Types of fertility treatment
Medical treatment
Ovulation induction with clomifene: clomifene is an effective treatment for anovulation, and may be used in selected women [Hughes et al, 2004]. The following needs to be noted:
The Committee on Safety of Medicines (CSM) recommend that no more than six cycles are given. Long-term cyclical therapy is also not recommended [CSM, 1995; ABPI Medicines Compendium, 2002].
NICE recommends treatment for up to 12 cycles. Use beyond this has been associated with an increased risk of ovarian cancer [Rossing et al, 1994; National Collaborating Centre for Women's and Children's Health, 2004].
Ovarian ultrasound monitoring of at least the first cycle where clomifene is prescribed is important, to titrate the drug to an appropriate dose and reduce the likelihood of multiple pregnancy [National Collaborating Centre for Women's and Children's Health, 2004].
Counselling, with regard to the risks of multiple pregnancy, ovarian hyperstimulation, foetal reduction, and possible risk of ovarian cancer, should be given.
Metformin or laparoscopic ovarian drilling may be offered to women with polycystic ovary syndrome who have not responded to clomifene [National Collaborating Centre for Women's and Children's Health, 2004].
Gonadotrophins may be offered to women with clomiphene-resistant anovulatory infertility, but carry a significant risk of multiple pregnancy. Careful monitoring with ultrasound is needed [Kennedy, personal communication, 2004].
Pulsatile gonadotrophin-releasing hormone and dopamine agonists are other treatments for the induction of ovulation.
Drug-induced ovarian suppression is no longer recommended for women with endometriosis because it does not improve pregnancy rates [Duckitt, 2003; National Collaborating Centre for Women's and Children's Health, 2004].
Dopamine agonists should be offered to women with ovulatory disorders secondary to hyperprolactinaemia. Investigations should be done to exclude a pituitary adenoma or extrapituitary tumour before proceeding with infertility treatment [Hamilton-Fairley and Taylor, 2003; National Collaborating Centre for Women's and Children's Health, 2004].
Gonadotrophin drugs are effective in improving fertility in men with hypogonadotrophic hypogonadism [National Collaborating Centre for Women's and Children's Health, 2004].
Surgical treatment :
Tubal surgery may be effective in women with mild tubal disease. Tubal catheterization or cannulation improves the chance of pregnancy in women with proximal tubal obstruction [National Collaborating Centre for Women's and Children's Health, 2004].
Laparoscopic surgery appears to improve the chance of pregnancy in women with all grades of endometriosis [National Collaborating Centre for Women's and Children's Health, 2004], although the evidence from some of the studies is conflicting [Duckitt, 2003].
Surgery for fibroids should be considered if there is no other explanation for infertility. It is essential for intracavity fibroids [Hart, 2003] and should be considered for intramural fibroids >5 cm in diameter, particularly when they are encroaching on the cavity [Kennedy, personal communication, 2004].
Surgery for varicoceles should not be offered, as it does not improve pregnancy rates [National Collaborating Centre for Women's and Children's Health, 2004].
Surgical correction of epididymal blockage in men with obstructive azoospermia is likely to restore fertility [National Collaborating Centre for Women's and Children's Health, 2004].
Assisted conception
Intrauterine insemination (IUI) is the process, timed to coincide with ovulation, by which sperm is placed in the woman's uterus using a fine plastic tube. Low doses of ovary-stimulating hormones are usually also given, to maximize pregnancy rates. If IUI does not work, people move on to try IVF, or ICSI. Ovarian stimulation combined with IUI increases pregnancy rates in subfertile women with mild endometriosis [National Collaborating Centre for Women's and Children's Health, 2004].
Donor insemination (DI) is the insemination of sperm from a donor into a woman, via her vagina into the cervical canal or into the uterus itself (IUI). Sometimes low doses of ovary-stimulating hormones are used in conjunction with DI, with the aim of increasing pregnancy rates. DI should be considered as an option when the man has no or very few sperm on testicular biopsy or surgical extraction; has had a vasectomy, and reversal has failed or not been tried; or has an infectious disease such as HIV, or where there is a high risk of transmitting a genetic disorder to the offspring [National Collaborating Centre for Women's and Children's Health, 2004].
In vitro fertilization (IVF) involves retrieval of the egg(s), which is mixed with sperm and incubated for 2-3 days; the resultant embryo(s) is then injected into the uterus via the cervix. The Human Fertilisation and Embryology Authority recommends that only two embryos be implanted, to reduce the risk of multiple pregnancy [Braude and Rowell, 2003a; National Collaborating Centre for Women's and Children's Health, 2004].
Intracytoplasmic sperm injection (ICSI) involves an individual sperm being injected directly into the egg, to bypass natural barriers that prevent fertilization. ICSI is used for couples who have failed to achieve successful fertilization through conventional IVF, or where the quality or numbers of sperm is too low for normal IVF to be likely to succeed. ISCI is now the treatment of choice in severe male factor infertility [Kennedy, personal communication, 2004]. It may be worth re-referring to specialist clinics men with very low sperm counts who have been told in the past they cannot be helped [Chambers, 1999; Braude and Rowell, 2003a].
Oocyte donation involves stimulation of the donor's ovaries and collection of eggs, which are then fertilized by the recipient's husband's sperm. After 2-3 days the embryos are transferred to the uterus of the recipient via the cervix, following hormonal preparation of the endometrium. This method is suitable for women who have ovarian failure (either premature, or following radiotherapy or chemotherapy); who have had bilateral oophorectomy; where there is gonadal dysgenesis, including Turner's syndrome, or where there is a high risk of transmitting a genetic disorder. It is also used in certain cases of IVF failure [National Collaborating Centre for Women's and Children's Health, 2004].
Embryo donation. Couples who have had successful IVF or ICSI treatment may decide to donate their spare embryos to help other infertile couples [HFEA, 2004b].
Gamete intrafallopian transfer (GIFT) involves egg retrieval, mixing the eggs with the prepared sperm, and then injecting the eggs (maximum of three) with the sperm into the fallopian tube [Chambers, 1999; HFEA, 2004b]. There is insufficient evidence to recommend its use in preference to IVF in couples with unexplained infertility problems or male factor fertility problems [National Collaborating Centre for Women's and Children's Health, 2004].
[DH, 2004b]
Problems with assisted conception :
Ovulation hyperstimulation syndrome
Ovarian hyperstimulation syndrome (OHSS) generally develops if a woman has had an excessive response to gonadotrophins and has produced a large number of follicles (over 20). It is particularly severe in people with polycystic ovary syndrome who have been treated with human gonadotrophin-releasing hormone analogues. It can follow the use of clomifene in sensitive people, e.g. those with polycystic ovarian syndrome.
OHSS presents:
Early: within 1-5 days of human gonadotrophin injection, soon after egg collection and embryo transfer
Late: 7-14 days after embryo transfer when endogenous human chorionic gonadotrophin (HCG) rises after successful implantation
Symptoms and signs include:
Feeling unwell, nausea, vomiting
Abdominal pain, distension, or both caused by enlarged ovaries and acute ascites
Bowel disturbance--constipation or diarrhoea
Dark concentrated urine due to reduced renal perfusion and low urine output
Dyspnoea due to splinting of the diaphragm secondary to ascites or pleural effusion
Leg and vulval oedema
Seek urgent advice from a specialist unit if OHSS is suspected.
Ectopic pregnancy
Ectopic pregnancy occurs in about 4% of pregnancies that occur after assisted conception. Heterotopic (one embryo in the uterus and one in the tube) pregnancy is extremely rare naturally (one in 30,000 pregnancies) but the rate may be as high as one in 100 pregnancies in women who have had assisted conception [Tal et al, 1996].
[Braude and Rowell, 2003b]
Counselling and information on infertility
It is important to involve both partners in all aspects of management. Discussion of wishes, plans, beliefs, and motives are important [Himmel et al, 1997].
Counselling should be made available to all infertile couples, and may cover these different aspects:
Implications of investigations and treatments
Emotional support for social and psychological issues such as stress
Help with ethical and legal issues, especially for assisted conception
Therapeutic counselling to help people accommodate the feelings they have about their infertility.
Information on infertility is often available locally and should be provided to the couple. National sources of up-to-date information include the Human Fertilisation and Embryology Authority (http://www.hfea.gov.uk/) and the patient organizations CHILD (http://www.child.org.uk/), ISSUE (http://www.issue.co.uk/) and BICA (http://www.bica.net/).
Anonymity of donors
Children born as a result of sperm, eggs, or embryos donated after 1 April 2005 will be able to access the identity of their donor when they reach the age of 18 years. This change in the regulation will not be retrospective. Anybody donating before April 2005 will remain anonymous.
Under existing regulations, when they reach the age of 18 years, people may ask the HFEA to confirm whether they were born as a result of donated sperm, eggs or embryos. Those intending to marry, including those who plan to do so before they reach the age of 18 years, may also ask whether the HFEA register shows that they are related to the person they intend to marry.

High-risk pregnancy

Definition :
High-risk pregnancy is broadly defined as one in which the mother, fetus, or newborn is at or may possibly be at increased risk of morbidity or mortality before, during, or after delivery. Many factors are involved, including maternal health, obstetric history, and fetal disease.

PRECONCEPTIONAL EVALUATION
Preconceptional evaluation and counseling of women of reproductive age has gained increasing acceptance as an important component of women's health.

MATERNAL ASSESSMENT FOR POTENTIAL FETAL OR PERINATAL RISK

INITIAL SCREENING :

History

A. MATERNAL AGE
Extremes of maternal age increase risks of maternal or fetal morbidity and mortality. Adolescents are at increased risk for preeclampsia-eclampsia, intrauterine growth restriction (IUGR), and maternal malnutrition.
Women 35 years of age or older at the time of delivery are at higher risk of pregnancy-induced hypertension, diabetes, and obesity as well as other medical conditions. Chromosomal abnormalities are also more common in infants born to older women, as will be discussed in detail later. An increased risk of cesarean section, preeclampsia, and placenta previa is noted in women with advanced maternal age.
B. MODALITY OF CONCEPTION
It is important to differentiate spontaneous pregnancy from that resulting from assisted reproductive technologies (ART). Use of ART increases the risks of multiple gestation, pregnancy-induced hypertension, and preterm delivery.
C. PAST MEDICAL HISTORY
Specific disease states may adversely affect the outcome of pregnancy for the mother or infant. Pregnancy itself may aggravate certain medical disorders and alleviate others.
D. FAMILY HISTORY
A detailed family history is helpful in determining any increased risk of heritable disease states (eg, Tay-Sachs, cystic fibrosis, sickle cell disease) which may affect the mother or fetus during the pregnancy or the fetus following delivery.
E. ETHNIC BACKGROUND
Population screening for certain inheritable genetic diseases is not cost effective due to the relative rarity of the gene in the general population. However, many genetic diseases affect certain ethnicities in disproportionate amounts, allowing those groups to be screened in a cost-effective way.
F. PAST OBSTETRIC HISTORY
1. Habitual abortion
A diagnosis of habitual abortion can be made after 3 or more consecutive spontaneous losses of a previable fetus. Habitual abortion is best investigated before another pregnancy occurs. If the patient is currently pregnant, as much of the work-up as possible should be performed.
Karyotype of abortus specimen
Parental karyotype
Survey for cervical and uterine anomalies
Connective tissue disease work-up
Screening for hormonal abnormalities (ie, hypothyroidism)
Acquired and inherited thrombophilias
Infectious disease evaluation of the genital tract
2. Previous stillbirth or neonatal death
A history of previous stillbirth or neonatal death should trigger an immediate investigation as to the conditions or circumstances surrounding the event. If the demise was the result of a nonrecurring event such as cord prolapse or traumatic injury, then the present pregnancy has a risk approaching a background risk. However, stillbirth or neonatal death may also suggest a cytogenetic abnormality, structural malformation syndrome, fetomaternal hemorrhage or thrombophilia (fetal or maternal), requiring a similar investigation as above.
3. Previous preterm delivery
The greater the number of preterm deliveries, as well as the degree of prematurity, the higher the risk at present for preterm delivery in the index pregnancy. Despite intense investigation, the incidence of preterm delivery has remained unchanged. Two-thirds of preterm deliveries occur near term (34 to 37 weeks), and these carry minimal fetal or neonatal morbidity. The remaining one-third of preterm deliveries accounts for nearly all of the perinatal morbidity and mortality. Approximately 50% of newborns born under 1000 grams suffer from intracranial hemorrhage, retinopathy of prematurity, or bronchopulmonary dysplasia, all of which carry significant long-term consequences. Approximately 40% of preterm delivery is due to spontaneous preterm delivery, another 40% is due to preterm rupture of membranes, and the remaining 20% is due to iatrogenic preterm delivery (eg, delivery due to preeclampsia or deteriorating fetal status). Spontaneous preterm labor is a complex process, but discrete pathophysiological processes have been identified (but may coexist): maternal and/or fetal stress, ascending genital tract infection, abruption (decidual hemorrhage), and uterine distension. Risk factors for preterm labor include prior history of preterm labor, multifetal pregnancy, vaginal bleeding in more than one trimester, in utero exposure to diethylstilbestrol (DES), uterine anomalies, incompetent cervix, and preterm labor in the index pregnancy. Screening for preterm labor in high-risk patients may include cervical length measurements by transvaginal sonography, fetal fibronectin of cervicovaginal secretions, and salivary estriol.
4. Rh isoimmunization or ABO incompatibility
Blood typing of both parents and maternal antibody screening should be performed at the initial prenatal visit. Women at risk for Rh(D) isoimmunization should be screened for anti-Rh(D) antibody at presentation, at 28 weeks gestation, and at delivery.
5. Previous preeclampsia-eclampsia
Previous preeclampsia-eclampsia increases the risk for hypertension in the current pregnancy, especially if there is underlying chronic hypertension or renal disease.
6. Previous infant with genetic disorder or congenital anomaly
A woman with a previously affected infant should be offered genetic counseling. Screening or testing is available for some defects using maternal blood samples (eg, alpha-fetoprotein; AFP), ultrasonography, amniocentesis, chorionic villus sampling, and DNA analysis.
7. Teratogen exposure
A teratogen is any substance, agent, or environmental factor that has an adverse affect on the developing fetus. Whereas malformations caused by teratogen exposure are relatively rare, knowledge of exposure can aid in the diagnosis and management.
a. Drugs
Alcohol, anti-seizure medications (pheny-toin, valproic acid, etc), lithium, mercury, thalidomide, diethylstilbestrol (DES), coumadin, isotretinoin, etc.
b. Infectious agents
CMV, Listeria, rubella, toxo-plasmosis, varicella, Mycoplasma, etc.
c. Radiation
It is commonly believed that medical diagnostic radiation delivering less than 0.05 Gy to the fetus has no teratogenic risk.

ANTEPARTUM COURSE

Uniform Perinatal Record

A consistent method of recordkeeping which is easily understandable from doctor to doctor and location to location is ideal to manage the high-risk patient. In the event of a transfer of care during a pregnancy, or a review of a previous pregnancy, having a coherent, accessible prenatal record helps avoid duplication of tests and helps to expedite diagnostic confirmation and the onset of treatment. Preprinted records such as American College of Obstetricians and Gynecologists (ACOG) forms provide uniform data for each patient and are helpful in diagnosis as well as in management decision making.
Prenatal Visits

Every prenatal visit is an opportunity to not only screen for problems that may complicate the course of the pregnancy but also to anticipate any problems before they develop. Several factors should be evaluated at each visit.

A. VITAL SIGNS
Fever (> 100.4° F), even without other subjective complaints may be due to a wide source of infectious etiologies. Urinary, pulmonary, and hematological sources of the fever should be considered. Signs or symptoms of chorioamnionitis should be assessed, and if chorioamnionitis is suspected, amniocentesis for microscopy and culture should be considered. Depending on clinical correlation, delivery may be necessary. Very high fevers (> 103° F) may trigger preterm labor and may also have an adverse effect on the early development of the fetal central nervous system. Antipyretics may be necessary to lower the temperature.

B. PULSE
Maternal tachycardia can be a sign of infection, anemia, or both. Isolated mild tachycardia (> 100 beats per minute [bpm]) should be evaluated and followed up. Moderate to severe tachycardia (> 120 bpm) needs immediate evaluation, including but not limited to a hemogram and an ECG.

C. BLOOD PRESSURE

The normal pattern of maternal blood pressure readings is for a decrease from baseline during the first trimester, reaching its nadir in the second trimester, and slightly rising in the third trimester, although not as high as the baseline levels. Repeated blood pressure readings of 140/90 mm Hg 6 hours apart or a rise of 30 mm Hg systolic pressure or 15 mm Hg diastolic pressure should be considered evidence of pregnancy-induced hypertension. Consideration of the patient's medical history, prepregnancy blood pressure, and gestational age should all be considered in forming a diagnosis and management strategy.
D. URINALYSIS

At the first prenatal visit, a clean-catch urine culture and sensitivity should be performed. Any growth should be treated with the appropriate antibiotics. At all subsequent visits, urine dipstick testing to screen for protein, glucose, leukocyte esterase, blood, or any combination of markers is useful in identifying patients with a change in their baseline urinary composition.

Screening Tests :
Screening tests are performed at the appropriate time during the pregnancy.
A. FASTER (FIRST AND SECOND TRIMESTER EVALUATION OF RISK FOR ANEUPLOIDY) TRIAL
Transvaginal sonography between 103/7 weeks and 136/7 weeks to visualize and measure nuchal translucency, along with serum measurements of PAPP-A and free β-hCG is currently being studied in several institutions throughout the United States as a screen for Down syndrome, as well as other aneuploidies and malformations.
B. MATERNAL SERUM ANALYTE TESTING
Frequently known as the “triple screen,” this test includes maternal serum alpha-fetoprotein (msAFP), β-hCG, and estriol. In some institutions, only the msAFP is used, while in other institutions a fourth test, inhibin, is included, making it a “quad test.” The usefulness of this screen is its ability to identify pregnancies at an increased risk for open neural tube defects, as well as for certain chromosomal abnormalities, especially trisomy 21 (75% sensitivity for Down syndrome detection). This test is effective at 15–19 weeks' gestation and can therefore identify an at-risk pregnancy in time to pursue more definitive diagnosis, if desired. It is important to note, however, that the triple screen is not a definitive test and that many positive screens have yielded normal fetuses and many abnormal fetuses have had normal screens.
C. DIABETES SCREEN
Routine screening consists of performing a glucose challenge test between 24 and 28 weeks. The test consists of a 50-g oral glucose load with a plasma glucose level drawn exactly 1 hour after. If the value is over 140 mg/dL, a more specific glucose tolerance test (GTT) should be performed. The GTT involves obtaining a fasting plasma glucose level, giving a 100-g oral glucose load, then drawing plasma levels at 1 hour, 2 hours, and 3 hours after the glucose load. A test is considered positive for gestational diabetes if two out of the four values are elevated.
D. ISOIMMUNIZATION
A patient who is Rh-negative with a pregnancy fathered by an Rh-positive man should be screened for antibodies at the first prenatal visit and again at 24–28 weeks. If there continues to be no antibodies, Rhogam should be administered at 28 weeks to prevent sensitization of the mother during the last trimester and delivery. In the event of a previously isoimmunized patient, the typing and screening performed at the initial visit would detect antibodies, which are reported as a numerical titer. These titers should be followed every 4 weeks to assess for worsening isoimmunization. In the presence of worsening titers, follow-up with amniocentesis may be appropriate. Peak systolic velocity of the fetal middle cerebral artery as determined by sonographic Doppler evaluation has been demonstrated to correlate with degree of fetal anemia, allowing for noninterventional diagnosis and management of fetal isoimmunization; however, the definitive treatment is intrauterine fetal transfusion.
E. BETA HEMOLYTIC STREPTOCOCCUS
This is also known as the group B Streptococcus (GBS) test, and between 10% and 30% of pregnant women are colonized with GBS in the vaginal or rectal areas. Whereas they are usually asymptomatic colonizations, perinatal transmission can result in a severe and potentially fatal neonatal infection. Any documented GBS bacteriuria needs to be treated at the time of diagnosis, as well as intrapartum. Intrapartum antibiotic prophylaxis has been shown to decrease the risk of perinatal GBS transmission. There are two approaches to screening: Screen patients at 35–37 weeks' gestation and treat positive cultures with intrapartum antibiotics, or treat patients based on risk factors with intrapartum antibiotic prophylaxis.

Fetal Assessment

Comprehensive fetal assessment begins in the first trimester with nuchal translucency and continues throughout the pregnancy into labor and delivery. Conceptually, antepartum testing in pregnancies at risk falls into one of two categories: assessment of prenatal diagnosis and assessment of fetal well-being.

A. ASSESSMENT OF PRENATAL DIAGNOSIS
Performed during all trimesters, the techniques used are diverse, and the information obtained varies according to the quality of imaging, depth of investigation, and gestational age of pregnancy.
1. Ultrasound
Ultrasound has had a continuous evolution over the last 20 years, with better equipment being produced each year. Real-time sonography allows a 2-D image to demonstrate fetal anatomy, as well as characteristics such as fetal weight, movement, volume of amniotic fluid, and structural anomalies such as myomas or placenta previa which may affect the pregnancy. 3-D sonography allows volume to be ascertained, creating a three-dimensional appearing image on the 2-D screen, which assists in identifying certain anatomical anomalies. Most recently, 4-D machines have been developed, which produce a 3-D image in real time. As the machines become more technically advanced and the computers that run them become faster, the images obtained will continue to improve and push the boundaries of sonographic prenatal diagnosis.
Diagnostic ultrasonography is widely used in the assessment of the pregnancy and the fetus. It is not, however, the standard of care, nor is it recommended by ACOG for every pregnancy. The indications for ultrasonography are multiple and diverse, and the type and timing of the examination varies depending on the information being sought.
A basic ultrasound examination should provide such information as fetal number, presentation, documentation of fetal viability, placental location, and assessment of gestational age. A limited ultrasound examination is a goal-directed search for a suspected problem or finding. A limited ultrasound may be used for guidance during procedures such as amniocentesis or external cephalic version, assessment of fetal well being, or documentation of presentation or placental location intrapartum. A comprehensive ultrasound examination provides information on fetal anatomy, growth, anomalies, and physiologic complications.
Ultrasound evaluation of fetal anatomy may detect some major structural anomalies. Gross malformations such as anencephaly and hydrocephaly are more commonly diagnosed and rarely missed; however, more subtle anomalies such as facial clefts, diaphragmatic hernias, and neural tube defects are more commonly reported to have been missed by ultrasound. The basic fetal anatomy survey should include visualization of the cerebral ventricles, four-chamber view of the heart, and examination of the spine, stomach, urinary bladder, umbilical cord insertion site, and renal region. Any indication of an anomaly should be followed by a more comprehensive sonogram. Typically, the fetal anatomic survey is performed at 17–20 weeks; however, there is controversy surrounding the potential benefits of an earlier sonogram at 14–16 weeks using the transvaginal probe. The earlier scan allows earlier detection of anomalies that are almost always present by the second trimester, as well as allowing greater detailed viewing of the fetal anatomy by using the higher-resolution vaginal transducers.
2. Aneuploidy screening
Multiple sonographic markers for aneuploidy have been identified. The presence of single or multiple markers adjusts the patient's age-related risk of aneuploidy based on the particular markers present. Such sonographic findings include, but are not limited to:
Echogenic intracardiac focus
Choroid plexus cysts
Pyelectasis
Echogenic bowel
Short femur
Hypomineralization of the fifth digit of the fetal hand
3. Amniocentesis
Amniocentesis is frequently performed under the guidance of ultrasonography. A needle is inserted transcutaneously through the abdominal wall into the amniotic cavity, and fluid is removed. There are many uses for this amniotic fluid, including cytology for detection of infection, alpha-fetoprotein evaluation for neural tube defect assessment, assessment of fetal lung maturity (which will be discussed later in the chapter), and the most common indication of cytogenetic analysis. In this case, amniocentesis is often performed between 15 and 20 weeks' gestation and fetal cells from the amniotic fluid are obtained. Risks associated with the procedure are considered to be very low, with the risk of abortion as a result of amniocentesis considered to be between 1 in 200 to 1 in 450 amniocenteses.
4. Chorionic villus sampling
Chorionic villus sampling (CVS) is an alternative to amniocentesis. It is performed between 10 and 12 weeks' gestation, and can be performed either transcervically or transabdominally. CVS is also performed under sonographic guidance, with the passing of a sterile catheter or needle into the placental site. Chorionic villi are aspirated and undergo cytogenetic analysis. The benefit of CVS over amniocentesis is its availability earlier in pregnancy; however, the rate of abortion is higher—as high as 1%. One disadvantage
of CVS is that unlike amniocentesis, it does not allow diagnosis of neural tube defects.
5. Fetal blood sampling
Also referred to as cordocentesis or percutaneous umbilical blood sampling (PUBS), this is an option for chromosomal or metabolic analysis of the fetus. Benefits of the procedure include a rapid result turnaround rate and the ability to perform the procedure in the second and third trimester. Intravascular access to the fetus is useful for the assessment and treatment of certain fetal conditions such as Rh sensitization and alloimmune thrombocytopenia. There is a higher risk of fetal death, however, when compared to the other methods. Fetal loss rates are approximately 2%, but can vary depending on the fetal condition involved.

B. ASSESSMENT OF FETAL WELL-BEING
1. Fetal monitoring techniques
Assessment of fetal status can be performed using a wide variety of techniques.
a. External fetal monitoring
The external measurement of the fetal heart rate is done by using a continuous beam of ultrasound waves focused on the fetal heart. This ultrasound monitor utilizes Doppler effects to sample the frequency of moving fetal heart valves and the atrial and the ventricular systole. The complex received signal wave is then peak detected and entered into the heart rate monitor. The computer averages several consecutive frequencies, which helps minimize artifact, before the signal is displayed and printed. This process of averaging is called autocorrelation, and produces a fetal heart rate pattern which closely resembles that derived from a fetal ECG, although there is more baseline variability inherent in this method.
b. Internal fetal monitoring
The internal measurement of the fetal heart rate is an invasive procedure, utilizing an electrode attached to the fetal scalp. A bipolar spiral electrode is placed transcervically and penetrates the fetal scalp. A reference electrode is placed on the maternal thigh to eliminate electrical interference. The fetal ECG is detected, and the R wave is the signal used for peak detection and for counting. This signal is very clear, and allows accurate beat-to-beat and baseline variability to be measured. Artifact is kept to a minimum, and there is little need for autocorrelation.
c. Sonographic fetal monitoring
There have been reports of a number of sonographically related surveillance techniques for fetal status published in the literature. Such testing techniques as biophysical profile and Doppler velocimetry have been extensively studied and widely used for antepartum evaluation. Doppler velocimetry is a noninvasive technique based on vascular impedance. Most often, the umbilical artery is utilized for this purpose. Both the peak values as well as the actual waveform can be utilized to identify abnormally growing fetuses, or fetuses at risk of cardiac failure or other adverse outcome. Most of the benefit is seen in growth-restricted pregnancies, and use for generalized surveillance is not recommended. Biophysical profile consists of fetal heart rate evaluation combined with sonographically assessed parameters of fetal well being, including fetal breathing movements, fine motor movement, gross fetal tone, and amniotic fluid volume.
2. Fetal heart rate interpretation
a. Antepartum fetal surveillance
In determining which patients should have antepartum fetal surveillance, a major factor to consider is the lack of evidence that any routine surveillance method results in a decreased risk of fetal death. Therefore, we generally begin monitoring in pregnancies in which the risks of fetal demise are known to be increased. These can include maternal conditions such as antiphospholipid syndrome, lupus, diabetes, or other maternal medical problems. They can also include pregnancy-related conditions such as preeclampsia, IUGR, multiple gestation, poor obstetrical history, or postterm pregnancy.
Antepartum surveillance should include a nonstress test (NST) as a minimum. The addition of sonographic monitoring is common, most often as some variant of the biophysical profile. The criteria for the NST are: baseline between 120 and 160 bpm, the presence of periodic accelerations (ie, two accelerations in 20 minutes) of fetal heart rate of 15 bpm over baseline for 15 seconds, the absence of decelerations of the fetal heart rate, and the subjective assessment of variability of the fetal heart rate. In the case of a nonreassuring NST, further evaluation or delivery depend on the clinical context. In a patient at term, delivery is warranted. Near term, determination of fetal lung maturity can be considered. Remote from term poses a more challenging dilemma to the clinician. If resuscitative efforts are not successful in restoring reactivity to the NST, ancillary tests or testing techniques may prove useful in avoiding a premature iatrogenic delivery for nonreassuring fetal heart rate patterns, since the false-positive rate may be as high as 50–60%.
C. ANCILLARY TESTS
1. Vibroacoustic stimulation
An auditory source, often an artificial larynx, is placed on the maternal abdomen. A short burst of sound is delivered to the fetus. This has proven successful in shortening the duration needed for the test to show reactivity, without compromising the predictive value of the absence of acidosis with a reactive NST.
2. Fetal scalp stimulation
The presence of an acceleration after a vaginal exam where the examiner stimulates
the fetal vertex with the examining finger confirms the absence of acidosis (pH > 7.2).
3. Oxytocin challenge test
This may be used to elicit a confirmatory abnormal fetal heart rate response, with one report showing a better correlation with adverse outcome than the NST alone. Other studies, however, have demonstrated no improvement in predicting morbidity over an NST. This is performed by intravenous infusion of dilute oxytocin until three contractions occur in 10 minutes. A positive test indicates decreased fetal reserve, with a 20–40% incidence of abnormal fetal heart rate (FHR) patterns in labor. A positive test is the presence of a late deceleration after each of the three contractions, a negative test shows no decelerations, and anything else is equivocal. Repetitive variable decelerations are termed “suspicious” and are associated with abnormal FHR patterns in labor, particularly in postterm gestations.
Fetal Maturity Tests
Indications for assessing fetal lung maturity—The American College of Obstetricians and Gynecologists has recommended that fetal pulmonary maturity should be confirmed before elective delivery at less than 39 weeks' gestation unless fetal maturity can be inferred from any of these criteria: Fetal heart tones have been documented for 20 weeks by nonelectronic fetoscope or for 30 weeks by Doppler; and 36 weeks have elapsed since a serum or urine hCG-based pregnancy test was reported to be positive.
A. LECITHIN:SPHINGOMYELIN RATIO
The lecithin:sphingomyelin (L:S) ratio for assessment of fetal pulmonary maturity was first introduced by Gluck and colleagues in 1971. The test depends upon outward flow of pulmonary secretions from the lungs into the amniotic fluid, thereby changing the phospholipid composition of the latter and permitting measurement of the ratio of lecithin to sphingomyelin in a sample of amniotic fluid. The concentrations of these two substances are approximately equal until 32–33 weeks of gestation, at which time the concentration of lecithin begins to increase significantly while the sphingomyelin concentration remains about the same. The measurement of sphingomyelin serves as a constant comparison for control of the relative increases in lecithin because the volume of amniotic fluid cannot be accurately measured clinically. Determination of the L:S ratio involves thin-layer chromatography after organic solvent extraction. It is a difficult test to perform and interpret; care at each step of sample handling is critical for consistent results. The sample should be kept on ice or refrigerated if transport to a laboratory is required. Improper storage conditions can change the L:S ratio since amniotic fluid contains enzymes that can be affected by temperature. The amniotic fluid samples must be mixed well. The presence of blood or meconium can interfere with test interpretation. Bloody samples give false information due to the presence of sphingomyelin in blood and decreased extraction of lecithin by cold acetone techniques in the presence of red blood cells. Therefore, if blood or other particulate matter is present in the amniotic fluid sample, a low-speed, short centrifugation can be used to remove the cellular component.
Interpretation of the results should be carried out with consideration of the individual clinical circumstances. For example, some physicians require a higher L:S ratio for confirmation of fetal pulmonary maturity in pregnancies complicated by isoimmunization or diabetes mellitus.
A threshold value for prediction of lung maturity should be calculated in individual centers by correlation with clinical outcome, because the variation within and between laboratories can be considerable. Empirically, the risk of respiratory distress syndrome (RDS) is exceedingly low when the L:S ratio is greater than 2.0.
B. PHOSPHATIDYLGLYCEROL
Phosphatidylglycerol (PG) is a minor constituent of surfactant. It begins to increase appreciably in amniotic fluid several weeks after the rise in lecithin. Its presence is more indicative of fetal lung maturity as PG enhances the spread of phospholipids on the alveoli; thus, its presence indicates a more advanced state of fetal lung development and function.
PG determination is not generally affected by blood, meconium, or other contaminants; its ability to predict pulmonary maturity is the same whether or not contam-ination is present. This is an advantage for assessing fetal lung maturity status since these substances are commonly found in amniotic fluid.
PG testing is performed by thin-layer chromatography (as for the L:S measurement), so it may be determined alone or in conjunction with L:S testing. It can be reported qualitatively as positive or negative, where positive represents an exceedingly low risk of RDS, or in a quantitative fashion, in which a value ≥ 0.3 is associated with a minimal rate of respiratory distress.
C. FOAM STABILITY INDEX
The foam stability index (FSI) is a rapid predictor of fetal lung maturity and is based upon the ability of surfactant to generate stable foam in the presence of ethanol. Ethanol is added to a sample of amniotic fluid to eliminate the effects of nonsurfactant factors on foam formation. The mixture is shaken and will demonstrate generation of a stable ring of foam if surfactant is present in the amniotic fluid. The FSI is calculated

by utilizing serial dilutions of ethanol to quantitate the amount of surfactant present.
Amniotic fluid samples should not be collected in silicone tubes when this test is planned, as the silicone will produce “false foam.” The discriminating value indicative of lung maturity is usually set at ≥ 47. A positive result virtually excludes the risk of RDS; however, a negative test often occurs in the presence of mature lungs. The presence of blood or meconium interferes with results of the FSI.
D. FLUORESCENCE POLARIZATION
The fluorescence polarization test uses polarized light to quantitate the competitive binding of a probe to both albumin and surfactant in amniotic fluid; thus, it is a true direct measurement of surfactant concentration. It reflects the ratio of surfactant to albumin and is measured by an automatic analyzer, such as the TDx-FLM. An elevated ratio has been correlated with the presence of fetal lung maturity; the threshold for maturity is 55 mg of surfactant per gram of albumin.
Evaluation of the accuracy of TDx measurements has also been studied, specifically in diabetic patients. Despite initial evidence that higher cutoffs were required for diabetics, it is currently believed that the same cutoff for lung maturity can be used for both nondiabetic and diabetic patients.
The accuracy of this test compares favorably with the well-established L:S and PG tests. Blood and meconium contamination interfere with interpretation, although the degree or direction of the interference is unclear. There is insufficient evidence regarding the accuracy of this test for determination of fetal lung maturity in vaginally-collected specimens.
A disadvantage to the TDx-FLM method is the large quantification scale. Values greater than 55 are regarded as mature; however, values of 35–55 are considered borderline. In addition, there is controversy as to whether gestational age should be used in interpreting the TDx for determining the likelihood of RDS. In one report, higher threshold values were needed at earlier gestational ages to determine lung maturity and lower thresholds were required at later gestational ages.
Intrapartum Fetal Surveillance
Assessment of the fetus in labor is a challenging task. Certain techniques that were useful in the antepartum period are no longer accurate, and certain new techniques have become available. With the presence of contractions, fetal heart rate monitoring is no longer a nonstress test. Fetal heart rate assessment is still the initial test of choice. Continuous fetal monitoring and intermittent auscultation have been extensively reviewed, and the evidence does not support one over the other for routine obstetric care. Several reports suggest that continuous monitoring results in higher operative delivery rates without an associated neonatal benefit. For the present, the controversy over routine FHR monitoring remains, but the clinical practice is nearly universal for continuous electronic monitoring of the FHR in hospitals and many birthing centers.
In the intrapartum period, access to the fetus allows for further evaluation in the face of a nonreassuring FHR tracing. Direct measurement of the physiologic status of the fetus is possible after adequate cervical dilation and rupture of the membranes.
A. ANCILLARY TESTS
1. Fetal scalp blood sampling
Capillary blood collected from the fetal scalp typically has a pH lower than arterial blood. A pH of 7.20 was initially believed to be the critical value to identify serious fetal stress and an increase in the incidence of low Apgar scores. However, there is much debate over the accuracy of scalp pH in predicting fetal distress with subsequent neurologic sequelae. Continuous scalp pH during labor was highly successful in defining abnormal FHR patterns associated with acidosis, although the advanced technical skill and expense prohibited widespread use. In fact, despite the correlation with FHR, fetal scalp pH is no longer used in many institutions. The only proven benefits reported for scalp pH testing were demonstration of adverse neurologic outcome with pH < 7.1, and fewer cesarean sections for fetal distress.
2. Fetal lactate levels
Collected in the same fashion as scalp pH, lactate levels demonstrated a higher predictive value than pH as markers of neurologic disability.
3. Fetal pulse oximetry
This has been studied over the past 10 years. Controversy exists over its potential clinical value. There is debate about its accuracy in correlating with acidemia. Studies have demonstrated no benefit in relation to FHR patterns, or in detecting neurologically-compromised fetuses. A recent report demonstrating a reduction in the rate of cesarean section for a diagnosis of distress, without an actual decrease in the incidence of cesareans compared with the control group, raised questions about the usefulness of the test, since it was hoped that it could reduce the cesarean section rate in a manner similar to scalp pH and lactate assays. Clearly, more studies need to be initiated to demonstrate a clear benefit to this test.
B. FETAL HEART RATE PATTERNS
1. Reassuring fetal heart rate patterns
Slight deviations from the normal baseline of 120–160 bpm and some periodic changes are innocuous in the continuum of the fetal heart rate pattern. Early decelerations and bradycardia of 100–119 bpm are believed to be vagally mediated due to fetal head compression, and are not associated with fetal acidosis or poor neonatal outcome. Certain cardiac arrhythmias also pose no threat to the fetus while the fetal heart rate pattern deviates from what is considered “normal.” In fact, the majority of fetal arrhythmias are benign and spontaneously convert to normal sinus rhythm by 24 hours postpartum. Persistent tachyarrythmias are well tolerated, but may proceed to fetal hydrops if present for many hours to days. Persistent bradyarrhythmias are often associated with fetal heart disease, but are seldom associated with hypoxia or acidosis in fetal life or labor. Accelerations and variable decelerations of variable shape and timing are indicative of a normal autonomic nervous system.
2. Nonreassuring fetal heart rate patterns
This category is of more concern to the clinician, and while there is still evidence that the fetus is not acidotic, continuation or worsening of the clinical situation may result in fetal distress. Late deceleration is a smooth fall in the fetal heart rate beginning after the contraction has started, and ending after the contraction has ended. They are associated with a fall in fetal pH and a potential for perinatal morbidity and mortality. Another nonreassuring pattern is the sinusoidal heart rate. It is best defined as a pattern of regular variability resembling a sine wave with a fixed period of 3–5 cycles per minute and an amplitude of 5–40 bpm. The mechanism for the sinusoidal pattern is believed to be a response to moderate fetal hypoxemia, including secondary to fetal anemia. It was previously thought to carry a high perinatal mortality. However, follow-up with serial scalp pH has been successfully performed with no adverse outcome. The significance of sinusoidal heart rate patterns depends on the clinical setting. Variable decelerations may be divided into categories, with the deciding characteristic being the onset and the timing of the return to baseline. If a variable deceleration, no matter how deep, does not have a late component, then the pattern is benign and at most is mild cord compression not associated with acidosis or low Apgar scores. When there is a late recovery, the fetal pH falls progressively during the period of deceleration.
3. Fetal distress patterns
Considerable confusion surrounds the diagnosis of fetal distress. Fetal distress should be defined operationally as a pathological condition of the fetus that is likely to cause fetal or neonatal death or damage to the newborn if left uncorrected for a period of greater than 1 hour. It is often, but not always, associated with fetal acidemia and hypoxemia. These metabolic changes are highly correlated with a decompensated fetal homeostasis, but not necessarily with all nonreassuring .
FHR patterns. There are numerous causes and multiple factors associated with fetal distress; however, only a few fetal heart rate patterns are associated with true fetal distress, including:
a. Undulating baseline
Alternating tachycardia and bradycardia with wide swings, often with reduced variability in between.
b. Severe bradycardia
Fetal heart rate below 100 bpm for a prolonged period of time of at least 10 minutes.
c. Tachycardia with diminished variability unrelated to drugs
d. Tachycardia associated with additional nonreassuring periodic patterns such as late decelerations or variable decelerations with late recovery
With careful interpretation, FHR patterns can be a useful screening test for fetal acidemia and hypoxemia. The monitoring and interpretation of the fetal heart rate is ideally used as a screening tool. The presence of a reassuring FHR pattern is just that, reassuring that there is no fetal acidemia at that time. The absence of a reassuring tracing is not necessarily problematic, and ancillary testing can be performed to eliminate false positives. However, it must be remembered that a given segment of FHR monitoring is a single point in time. Pregnancy and labor are ongoing dynamic states. Maternal and fetal conditions and the processes of gestation, especially labor, are stresses which challenge fetal homeostasis. Fetal stress may be manifested in the FHR pattern, while the fetus remains compensated. The clinician must discriminate between stress and distress, using interpretation and ancillary testing. All monitoring techniques are to be ultimately used as supplements to clinical judgment, to obtain the best outcome of pregnancy.
CONCLUSIONS
Assessing pregnancy to determine risk as well as carefully monitoring pregnancies with a recognized risk begins early in the gestation. Preconceptual counseling of patients with known medical or genetic disorders helps to optimize outcomes. Early and frequent prenatal care allow the care provider to screen his or her patient population to identify pregnancies at risk and act accordingly. Additionally, pregnancies identified as complicated by one or more issues can be followed by assortments of maternal and fetal surveillance techniques to maximize therapeutic treatment.
As technology advances and our ability to both diagnose and treat improve, the methods for assessment and care of the pregnancy at risk will be a constantly changing field.

Abdominal Incisions and Sutures in Gynecologic Surgery

Location and type :
Abdominal incisions for gynecologic surgery requires consideration of several factors. These factors include the disease process, patient’s weight, operative exposure, simplicity, and speed of the procedure. The most important factor is adequate exposure to the operative field. Complications during surgery can occur due to inadequate exposure, which often is due to the unwillingness of the surgeon to extend the incision. Incision location is particularly important when the patient has a gynecologic malignancy. These patients may need a colostomy, urinary diversion, or extraperitoneal lymph node dissection to satisfactorily treat their disease. This article reviews pertinent abdominal wall anatomy, discusses various options for abdominal incisions, and examines various sutures available to surgeons.
Anatomy :
A thorough understanding of abdominal wall anatomy is essential for choosing and making the proper surgical incision. The musculature of the abdominal wall is composed of 2 groups of muscles. One group, the flat muscles, consists of the external oblique, internal oblique, and the transversus abdominis. The second group is composed of 2 muscles that run vertically, the rectus abdominis and the pyramidalis.
The external oblique muscle is the largest and most superficial of the flat muscles of the abdominal wall. Arising from the lower 8 ribs, the external oblique courses transversely to insert upon the iliac crests. The aponeurosis is a strong tendinous sheath that ends medially in the linea alba. The internal oblique muscle arises from the upper surface of the inguinal ligament, the iliac crest, and the thoracolumbar fascia. This muscle courses at a right angle to the fibers of the external oblique muscle. The aponeurosis of the internal oblique splits at the edge of the rectus muscle to envelope the rectus. The anterior layer blends with the aponeurosis of the external oblique. Posterior to the rectus muscle, this aponeurosis blends with the aponeurosis of the transversus abdominis to form a portion of the posterior rectus sheath.
The innermost of the flat muscles is the transversus abdominis. This muscle arises from the inguinal ligament, the iliac crest, the thoracolumbar fascia, and the lower costal cartilages. Coursing transversely to the midline, the upper three fourths of the transversus aponeurosis lies behind the rectus muscle. The lower one fourth of the aponeurosis passes in front of the rectus muscle. The aponeurosis of each flat muscle joins medial to the rectus muscle to form the linea alba.
Originating from the pubic crest, the rectus muscle runs vertically to insert into the xiphoid process and the fifth, sixth, and seventh costal cartilages. The muscle fibers contain 3 fibrous insertions known as the linea transversae. The rectus is surrounded by the rectus sheath, which consists of the aponeuroses of the oblique muscles and the transversus abdominis. A small, vestigial, triangular-shaped muscle, the pyramidalis, arises from the symphysis and inserts upon the linea alba. This muscle marks the midline and assists in the identification of the medial borders of the rectus muscle.
Two important surgical landmarks are formed by the aponeuroses of the muscles of the abdominal wall. The linea alba is in the midline between the 2 rectus muscles. Formed by the fusion of the aponeuroses of the external oblique, internal oblique, and transversus abdominis, identifying this structure during a midline incision is important. A second surgical landmark is the arcuate line that is found below the rectus muscle, approximately halfway between the umbilicus and the symphysis pubis. Above the arcuate line, the aponeuroses of the internal oblique and transversus abdominis fuse to form the posterior rectus sheath. Below the arcuate line, the posterior rectus sheath is absent. This anatomic finding occurs as the aponeuroses of the oblique muscles and the transversus pass in front of the rectus muscle.
Blood supply
The primary blood supply to the abdominal wall is from the inferior and superior epigastric arteries, the deep circumflex arteries, and the musculophrenic arteries. The inferior epigastric artery originates from the external iliac artery and courses posterior to the lateral one third of the rectus muscle. Another branch of the external iliac is the deep circumflex artery, which courses cephalad lateral to the inferior epigastric artery. The superior epigastric artery is the terminal branch of the internal thoracic artery. This artery has multiple branches leading to the rectus muscle and has an anastomosis with the inferior epigastric artery. The internal thoracic artery is the source of the musculophrenic artery, which has an anastomosis with the deep circumflex artery. A larger network of vascular anastomoses exists in the abdominal wall and provides an excellent blood supply to all areas of the abdominal wall.
Nerve supply
Innervation of the abdominal wall is by the thoracoabdominal nerves, the ilioinguinal nerves, and the iliohypogastric nerves. The thoracoabdominal nerves travel caudad between the transversus abdominis and the internal oblique. These nerves innervate the flat muscles of the abdominal wall and the rectus muscle. Innervating the lower abdominal wall are the iliohypogastric nerves and the ilioinguinal nerves. Both of these nerves arise primarily from the first lumbar nerve root. Damage to these nerves results in sensory changes in the mons pubis and the labia majora.
Types of abdominal incisions :
Vertical incision
Several types of vertical abdominal incisions have been used in gynecologic surgery, including midline, paramedian, and wide paramedian incisions. A midline incision is almost exclusively the type of vertical incision used in gynecologic oncology surgery. The midline incision is the easiest and most versatile vertical incision for performing gynecologic cancer surgery. This incision allows quick entry into the abdominal cavity with little blood loss, and it easily can be extended in length to accommodate the operative findings. The disadvantages of this incision include an increase risk of wound dehiscence and hernia formation (compared to a transverse incision).
For a midline incision, the skin and subcutaneous fat is incised down to the level of the fascia. The scalpel or electrocautery can be used to incise this tissue. Some surgeons believe the infection rate is higher with the use of electrocautery, but randomized control trials comparing these 2 techniques are lacking. Using either instrument, the principle is to make long smooth strokes through the subcutaneous fat to the fascia. Do not dissect the subcutaneous fat from the fascia because this creates unnecessary dead space. Next, the fascia is incised and the rectus muscles separated vertically in the midline. The midline may not be evident in patients with previous abdominal surgery. Identifying where the rectus muscles diverge around the umbilicus or locating the pyramidalis muscles assists in identifying the midline. Once the rectus muscles are divided, the peritoneum is grasped between 2 hemostats, opened with a scalpel, and extended the length of the incision.
If the operative findings necessitate extending the incision above the umbilicus, avoid cutting through the umbilicus. Postoperative wound infections may be increased due to bacterial colonization of the umbilicus. Extension of the incision should pass to the left of the umbilicus to avoid cutting through the ligamentum teres.
Closure of the midline incision has evolved over the last 2 decades. Layered closure using interrupted sutures previously was the choice of many surgeons. Today, many surgeons prefer to close the abdominal wall using a continuous running suture. The use of a continuous suture to close the fascia is faster, with dehiscence rates comparable to interrupted closures. Two basic techniques are used to close the abdomen with continuous suture, the single-layer mass closure and the internal mass closure. The single-layer mass closure involves using a heavy monofilament delayed-absorbable or permanent suture. Fascial closure involves penetrating the fascia 1.5 cm from the edge with the suture. The suture also should include the underlying muscle and peritoneum.
Some surgeons close the wound using the internal mass closure technique advocated by Smead-Jones. This is a far-far, near-near suturing technique. The anterior fascia is included in the near-near bite. The initial stitch is similar to the single-layer mass closure. The second bite only includes the anterior rectus fascia, approximately 0.5 cm from the fascial edge. Either technique requires starting from each end of the incision. Securing the suture with 5 knots at each end is sufficient. In thin patients, burying the knot is helpful. Some surgeons place a small hemoclip above each knot to prevent unraveling.
Transverse incision
Several useful transverse abdominal incisions are available to the surgeon performing gynecologic cancer surgery. Historically, the obstetrician-gynecologist has preferred this type of incision. Reported advantages include better cosmetic results, less pain, and low incidence of hernia formation. Gynecologic oncologists have embraced certain types of transverse incisions for specific gynecologic cancer operations. However, several disadvantages to the transverse incision exist. These incisions limit exploration of the upper abdomen, are associated with greater blood loss, and are more prone to hematoma formation when compared to a midline incision. An increased risk of injury to nerves innervating the area also exists, thus leading to subsequent anesthesia of the overlying skin.
Pfannenstiel incision
The Pfannenstiel incision results in good exposure to the central pelvis but limits exposure to the lateral pelvis and upper abdomen. These factors limit the usefulness of this incision for gynecologic cancer surgery. If the patient is thin and has a gynecoid or platypelloid pelvis, this incision can be used for a radical hysterectomy and pelvic lymph node dissection.
The incision usually is made 1-2 fingerbreadths above the pubic crest. Use of a marking pen is helpful to keep the incision symmetric. An incision length of 10-14 cm is sufficient. Increasing the length of the skin incision usually does not improve exposure due to the rectus muscles. The incision is made through the subcutaneous fat to the fascia. The superficial epigastric vessels often are near the lateral edges of the incision.
The anterior fascia is incised in the midline with a scalpel. Using curved scissors or electrocautery, the fascia is incised in a curvilinear fashion 1-2 cm lateral to the rectus muscle. The upper edge of the fascia is grasped with 2 Kocher clamps on either side of the midline. Using electrocautery, the rectus muscle is dissected free from the fascia. Electrocautery allows coagulation of multiple small vessels that perforate the rectus muscle to the fascia. The rectus muscles are mobilized off the fascia to the level of the umbilicus. Next, the lower fascial edge is grasped with Kocher clamps. Electrocautery is used again to dissect the rectus muscles and the pyramidalis muscle from the fascia. The rectus muscles are separated. The peritoneum is opened and incised vertically to complete a Pfannenstiel incision.
Closure of the Pfannenstiel incision is straightforward. The peritoneum is closed with an absorbable suture. Some surgeons elect not to suture this layer, citing little information clearly indicating a benefit. Regardless of whether the peritoneum is closed, thoroughly irrigate the rectus muscles with water or saline, and cauterize or ligate any bleeding areas. Bleeding from small perforating vessels through the rectus muscle is the most common source of subfascial hematoma. The fascia is approximated with an absorbable suture. Usually, a separate suture is started at each end of the fascial incision, and they incorporate all layers of the anterior rectus sheath. Unless a large area of dead space exists between the fascia and skin, closure of the Scarpa fascia is not needed.
Maylard incision
In an effort to improve surgical exposure to the lateral pelvic sidewall with a transverse incision, Maylard proposed a transverse muscle-splitting incision. This incision usually refers to a subumbilical transverse incision. For gynecologic surgery, the incision is made 3-8 cm superior to the pubis symphysis. The anterior rectus sheath is cut transversely. The inferior epigastric vessels are identified under the lateral edge of each rectus muscle. After ligating these vessels, the rectus muscles are incised transversely with electrocautery. The peritoneum is opened and cut laterally.
To facilitate closure of a Maylard incision, flex the operating table. Close the peritoneum with an absorbable suture. Next, inspect the ties placed on each inferior epigastric vessel, and irrigate with water. Examine the cut edges of the rectus muscles for any bleeding areas. The fascia and underlying rectus muscle can be closed with a monofilament absorbable suture.
Cherney incision
Cherney described a transverse incision that allows excellent surgical exposure to the space of Retzius and the pelvic sidewall. The skin and fascia are cut in a manner similar to a Maylard incision. The rectus muscles are separated to the pubis symphysis and separated from the pyramidalis muscles. A plane is developed between the fibrous tendons of the rectus muscle and the underlying transversalis fascia. Using electrocautery, the rectus tendons are cut from the pubic bone. The rectus muscles are retracted and the peritoneum opened.
Closing a Cherney incision begins with closure of the peritoneum. Attach the cut ends of the rectus muscle to the distal end of the anterior rectus sheath with interrupted nonabsorbable sutures. Fixing the rectus muscle to the pubis symphysis can result in osteomyelitis. Next, the fascia is closed with 2, running, continuous, delayed-absorbable sutures.
Several types of incisions facilitate extraperitoneal paraaortic lymph node dissection. An upper abdominal transverse incision, which is a high Maylard incision, is made approximately 2 cm above the umbilicus. The incision is extended laterally and caudad to the anterior superior iliac spines. The fascia and rectus muscles are incised transversely, usually requiring ligation of the inferior and superior epigastric vessels. Next, the transversus abdominis muscle is cut, exposing the peritoneum. Using blunt dissection, the peritoneal sac is dissected caudad to cephalad to expose the psoas muscle, the aorta, and the common iliac vessels. Often, a drain needs to be placed in the area of the lymph node dissection.
Modified Gibson incision
Some gynecologic oncologists perform an extraperitoneal lymph node dissection using a modification of the Gibson incision. This incision can be made on each side of the midline, but often, the skin is cut only on the left. The incision is started 3 cm superior and parallel to the inguinal ligament. Extension is made vertically 3 cm medial to the anterior superior iliac spine to the level of the umbilicus. The fascia is cut and the peritoneum bluntly dissected, as described above. The round ligament and the inferior epigastric vessels are ligated to facilitate surgical exposure. Care is needed when exposing the lymph nodes using only a left-sided incision. Too much traction on the peritoneum can result in avulsion of the inferior mesenteric vessels.
Incisions in obese patients :
Surgery in patients who are obese and morbidly obese represents a challenge for every surgeon. Wound complication rates uniformly are higher in patients who are obese, regardless of the type of incision. Obtaining adequate surgical exposure requires patience, understanding of changes in anatomical landmarks, and proper surgical equipment.
The abdominal wall landmarks are distorted in patients who are obese, particularly if a large panniculus is present. The umbilicus is located caudad to its normal position. If a vertical incision is needed, first pull the panniculus downward. A periumbilical incision is made and the fascia incised to the symphysis. Care is needed not to buttonhole the skin under the panniculus. Use of a ring retractor, such as the Bookwalter, optimizes surgical exposure.
The site of a transverse incision in patients who are obese should never be made under the fold of the panniculus because wound infection rates are invariably higher. Make a transverse incision close to the umbilicus. However, in some patients, this incision may be too far from the pelvic organs. The surgeon may find the distance to the pelvic structures exceeds the length of the surgical instruments and the retractors. In this scenario, perform a panniculectomy. A panniculectomy allows the fascial incision to be within several centimeters of the pubis symphysis, allowing easier access to the pelvic organs. Place large suction drains above the fascial closure with a panniculectomy, and keep them in place until the drainage is less than 25 cc in 24 hours.
Sutures :
A suture is any strand of material used to approximate tissue or ligate vessels. Various materials have been used for sutures throughout history. Materials incorporated into sutures include horsehair, linen, silk, animal intestines, and wire. The ideal suture has yet to be created. Qualities important in a suture include uniform tensile strength, knot security, nonallergenic properties, and high tensile-strength retention during wound healing. Choosing the correct suture requires knowledge of the healing characteristics of tissues and understanding of the physical properties of various suture materials.
Absorbable sutures
Today, sutures are classified based on their absorptive properties. Absorbable sutures are prepared from the collagen of animals or synthetic polymers. These sutures are removed from the body by enzymatic action or hydrolysis. The ability of the suture to retain tensile strength dictates where the suture should be used in wound closure. Do not confuse the loss of tensile strength with the rate of absorption. Sutures can maintain adequate tensile strength until wound healing is complete, followed by rapid absorption. Conversely, some sutures may lose tensile strength rapidly and undergo slow absorption. All absorbable sutures eventually completely dissolve.
Absorbable sutures have some limitations. For patients with fever, infection, or poor nutritional status, absorption of absorbable suture may accelerate and lead to premature diminution of tensile strength. If these sutures are exposed to significant moisture, such as ascites, absorption rates are accelerated. The common absorbable sutures used in gynecologic surgery are as follows:
Surgical gut
Plain
Chromic
Fast absorbing
Polyglactin 910 (Vicryl)
Uncoated
Coated
Polyglycolic acid (Dexon)
Poliglecaprone (Monocryl)
Polydioxanone (PDS)
Polyglyconate (Maxon)
Poly (L-lactide/glycolide)(Panacryl)
Surgical gut sutures can be used to reapproximate mucosal surfaces or peritoneal edges, but they lack the tensile strength for use in fascial closure.
Synthetic absorbable sutures are used extensively in most gynecologic surgeries. Polyglactin (Vicryl) and polyglycolic acid (Dexon) often are used during a hysterectomy. These 2 sutures retain enough tensile strength to be used in fascial closure. Poliglecaprone 25 (Monocryl) is a newer absorbable suture that retains 50% of its tensile strength after 2 weeks.
Two monofilament absorbable sutures useful in fascial closure are polyglyconate (Maxon) and polydioxanone (PDS). Both of these sutures invoke little tissue reaction and maintain 50% of their tensile strength at 4 weeks. These sutures often are used with midline incision closures, especially in patients with cancer or other major comorbidities. Poly (L-lactide/glycolide) (Panacryl) is a new absorbable suture that is useful in patients with delayed wound healing. At 40 weeks, these sutures retain 50% of their tensile strength.
Nonabsorbable sutures
Enzymatic activity or hydrolysis does not digest nonabsorbable sutures. These sutures are composed of multiple filaments of metal, synthetic fibers, and organic fibers fashioned into a strand by twisting, braiding, or spinning. The commonly used nonabsorbable sutures are as follows:
Natural
Silk
Cotton
Stainless-steel wire (Flexon)
Nylon (Dermalon, Surgilon)
Polypropylene (Prolene, Novofil)
Braided synthetics (Dacron, Tevdek)
Use of nonabsorbable sutures, polypropylene (Prolene) or polybutester (Novofil), is recommended to close the fascia in the presence of infection. Tie these sutures with at least 6 throws.

CONTRACEPTION

Introduction :
The contraceptive user has an array of methods from which to choose. Appropriate considerations include the user's age, need for concomitant protection against sexually transmitted infections, future plans for childbearing, health status, pattern of sexual activity, and feeling about method options. Method safety and efficiency are usually the two issues of greatest concern for users and clinicians. The morbidity for any methods of contraception is low.
The important trends in ensuring the safest possible use of contraception include the following:
Use of low-dose oral contraceptive products (i.e., ≤35 µg of estrogen, low-potency progestin).
Use of long-lasting progestins when estrogen may not be safely used.
Proper patient selection for the intrauterine device (IUD).
Use of barrier methods to decrease risk of sexually transmitted disease (STD), HIV, and hepatitis B virus transmission are sometimes used in addition to other contraceptives.
Careful counseling concerning sterilization including counseling the partner on the safety of vasectomy.
Use of emergency contraception (EC): postcoital.
Early recognition and diagnosis of pregnancy and ectopic pregnancy.
I. Oral contraceptives :
are the second most commonly used method overall and the most common method for patients younger than 30. The pill has undergone substantial changes since its development in the 1950s. Most important is the reduction in the amount of estrogen. Initially, pills contained 40 to 80 µg of ethinyl estradiol, whereas today 30 to 35 µg is the standard. This reduction of estrogen almost eliminates concern about cardiovascular risk in healthy nonsmoking women. Cardiovascular risk seems to be related to the thrombotic effect of estrogen, which is dose-related. At 35 µg the risk is not any higher than the baseline risk of a healthy woman. Figure 22.1 is a chart on relative potency of estrogens and progestins in currently available oral contraceptives.
A. Types of pills
Combined pills when used perfectly have a very low failure rate of approximately 0.1% to 3.0%. They provide a daily dose of estrogen and progestin for 21 days in a 28-day cycle. Almost all pills today are comparable in efficacy, side effects, and complications.
Estrogen acts by inhibiting FSH production and decreasing follicle development thereby limiting ovulation. It also may prevent implantation and potentiates the effects of progestins. Estrogen also stabilizes the endometrium.
Progestins inhibit luteinizing hormone (LH) release and, therefore, can interfere with ovulation. The endometrium atrophies, the cervical mucus becomes thick and hostile to sperm, and the fallopian tubes have decreased motility. Bleeding occurs when the estrogen and progestin are withdrawn, usually during the last 7 days of the 28-day cycle.
There are several different progestins used in oral contraceptives.
They are of varying potency but in each formulation potency is compensated by the dosage.
Progestins have an androgenic pharmacology and may affect lipid levels adversely; however, clinically this is rarely a problem.
Of the progestins, norethynodrel may produce estrogenic effects, and norethindrone acetate and norgestrel may produce antiestrogenic or androgenic effects or both. There had been some concern that the so-called newer progestins (gestodene, desogestrel, and norgestimate) present in third generation OCPs may incur higher thromboembolic risks. However, more recent data does not support this hypothesis .
Multiphasic preparations contain varying daily dosages of estrogen and progestin. Theoretically, this decreases the progestin dose and androgenic effects. Clinically, however, there is very little difference between the monophasic and multiphasic preparations.
The minipill contains progestin only and is taken continuously at the same time of day and with no cyclic interruption for maximum effectiveness. The preparation's main effects are on the endometrium, cervix, and fallopian tubes.
Failure rates of the minipill when it is used correctly are only slightly higher than combination pills, 0.5% to 3.0%.
It causes anovulation in only 40% to 60% of users.
Since the minipill has no estrogen, it is recommended for women who have a contraindication to the combined pill .
Minipills are often well tolerated by women who experience side effects, such as headaches, when using combined pills.
It is likely that some noncontraceptive benefits of pills, such as protection against pelvic inflammatory disease (PID), are mediated by progestin.
B. Contraindications and risk factors.
Certain systemic conditions contraindicate the use of the pill.
Women with absolute contraindication should never be given the pill.
For those with strong relative contraindications, risk and benefits should be weighed carefully.
C. Evaluation issues
When discussing options with the patient, it is important to determine whether or not she has any of the risk factors. It is also important to discuss lifestyle issues, noncontraceptive benefits, side effects, and severe complications. Recent evidence has confirmed that combined oral contraceptives are extremely safe. Some authors have suggested that pills should be available over-the-counter without a prescription.
Noncontraceptive benefits. The pill offers many benefits other than contraception and is used in the treatment of several clinical conditions. The following is a summary of these benefits:
Decreased menstrual flow, dysmenorrhea, and anemia.
Decreased fibrocystic changes of the breast with prolonged use.
Decreased risk of PID, although the risk of cervicitis may be increased.
Decreased acne.
Decreased ovarian and endometrial cancer risks. The risk of breast cancer may be slightly increased but tumors, when found, tend to be diagnosed earlier and are of a less aggressive type .
Decreased risk of ovarian cysts, although this may not be as true with the low-dose pills.
Decreased risk of rheumatoid arthritis.
Fewer ectopic pregnancies and abortions owing to its contraceptive effectiveness.
Lifestyle and other issues.
It must be stressed that pills do not provide protection from STDs, HIV, or hepatitis B transmission. Patients who are not mutually monogamous should be encouraged to also use a barrier method with the pill.
Family history should be explored to determine if occult risk factors exist .
Discussions with patients will reveal fears and misinformation that the clinician can correct.
A good understanding of the pill's benefits, risks, and method of use will increase compliance and effectiveness.
D. Dosage and type.
The axiom for determining pill dosage is to use the lowest dosage that provides effective protection from pregnancy.
Most women should be prescribed a 35-µg or less estrogen pill.
These pills contain the more potent ethinyl estradiol and may not have a markedly lower estrogenic effect than do pills containing 50 µg of mestranol.
Spotting or failure to have withdrawal bleeding are common problems associated with use of low-dose pills. Patients should be warned of these problems and advised that they often spontaneously resolve after three cycles.
Pills containing more than 50 µg estrogen (80 or 100 µg) are for the most part unavailable now. Pills containing 50 µg estrogen may occasionally be appropriate for women with severe acne, dysfunctional bleeding, or endometriosis.
Progestin-only pills may be the initial pill choice for postpartum or nursing mothers, women older than 30 to 35 years, or women who have vascular headaches.
The minipill is also a good choice for women who do not tolerate combined pills or for those who develop relative contraindications to the use of combined pills.
E. Instructions
Clinicians.
A thorough history including the foregoing risk factors, lifestyles, and considerations must be obtained.
A thorough examination including blood pressure, breast examination, Papanicolaou (Pap) smear and pelvic examination is done.
Be sure that every pill user is aware of the pill danger signs .
New users may benefit from an initial follow-up visit at 3 months to check blood pressure and review problems. Most users who discontinue use do so because of side effects. Thus, it is very important to emphasize that most of these side effects resolve spontaneously within the first 3 months of use .
Thereafter, annual examinations and Pap smears are appropriate.
For women older than 35 who may have risk factors, a blood sugar concentration and lipid panel should be checked. Healthy women with no family history do not need these tests.
Documentation of counseling and examination findings is essential.
It is important that the patient fully understands the method of taking the pill, the side effects, and the severe complications. She should know when and whom to call with any questions.
Patients.
Every pill user should memorize the five pill danger signs. The first letter of each symptom spells the acronym ACHES:
Abdominal pain.
Chest pain or shortness of breath.
Headaches.
Eye problems, such as blurred vision, flashing lights, or blindness.
Severe leg pain.
A pill user who develops a breast lump, notices growth or change in a mole, develops liver disease or jaundice, or becomes depressed should contact her clinician.
Pill users should know how to report problems to the clinician and know what to do if they experience bleeding, skip a period, or forget to take one or more pills.
A new pill user should start the first pack of pills within the first 5 days of menses.
Most can start on a Sunday, which makes it easy to remember and relegates menses to the weekdays.
If she cannot start within the first 5 days, a backup method for the first full cycle should be used.
Starting a package beyond the first 6 to 7 days may increase the failure rate.
In adolescents with a negative pregnancy test, an immediate start may be helpful to prevent forgetfulness. A backup method must be used for the first cycle.
Patients should take one pill a day at about the same time of day.
F. Sequelae
Pill hormones affect virtually every organ system, and about 40% of users notice side effects or noncontraceptive benefits. Severe complications are rare.
Complications and side effects. The major complications of pills are cardiovascular. These, however, are primarily limited to women older than 35 who smoke or have a history of other cardiovascular problems or diabetes.
Life-threatening complications:
Thrombophlebitis.
Deep pelvic vein thrombosis.
Pulmonary embolism.
Arterial thromboembolic events resulting in cerebrovascular accident or myocardial infarction.
Hepatic adenomas. These may regress after discontinuation of the pill.
Serious side effects include:
Hypertension.
Gallbladder disease.
Vascular headache.
Depression.
Other minor side effects, which usually improve with time, include:
Nausea.
Weight gain.
Breast tenderness.
Breakthrough bleeding.
Decreased libido.
Women who develop acne may want to discontinue use or change to formulations with lower androgen-potency progestins. Orthotricycline has been approved to treat acne.
Higher rates of cervical neoplasia (dysplasia, carcinoma in situ, and invasive carcinoma) have been reported for pill users. Whether this is an effect of the pill or of lifestyle is unclear. The pill can be continued with very careful follow-up.
Pill effects on subsequent fertility.
Resumption of ovulation is usually within the first 14 to 21 days of discontinuing the pill.
The pregnancy rate in the first 3 months lags behind that of users of other methods. However, within a year the rates are relatively the same.
There is no indication that infertility is increased by the pill.
Older data indicate that the higher dose pill may have caused a pregnancy rate lag of up to 42 months.
Noncontraceptive benefits. Use of the pill is associated with a decreased incidence of PID, ovarian and endometrial cancer, ectopic pregnancy, iron-deficiency anemia, rheumatoid arthritis, ovarian functional cysts, benign breast lumps, dysmenorrhea, and acne .
G. Clinical dilemmas
Optimal management of pill problems involves numerous clinical dilemmas.
Forgotten pills.
A woman who forgets to take one pill should double up the next day.
If two pills are missed, she should double up for 2 days and use a backup method of birth control until the next menstrual period.
If three or more pills are missed, the user should start a new pack of pills and use a second method of contraception as well.
If she is a Sunday starter, she may continue the pills until Sunday and then start a new package.
Breakthrough bleeding is a common occurrence in the first 3 months of starting the pill. If breakthrough bleeding persists beyond that time, a different formulation may be tried or a small amount of estrogen may be added in the first 7 days of the cycle (1.25 mg of conjugated estrogens or 1 mg of estradiol).
Skipped periods or amenorrhea. The pill's effect on the endometrium is dominated by progestin and causes atrophy. Amenorrhea may be a response to continued progestin stimulation.
If the patient takes the pills regularly and she is not concerned about the lack of a “withdrawal period,” nothing need be done. It may be advisable to check a pregnancy test, if there is any doubt about whether the pills are taken correctly.
If the patient is concerned, a period may be induced by adding estrogen, 1.25 mg of conjugated estrogens or 1 mg of estradiol for 21 days of the cycle. This can be done for one or two cycles to thicken the endometrial lining.
Alternatively, a patient may be switched to an oral contraceptive with a lower progestin potency.
Development of vascular headaches, hypertension, or cholestasis are reasons to discontinue the pill.
Development of cervical dysplasia is not a reason to discontinue the pill. Pap smear or colposcopy surveillance is necessary. These patients may be at risk for other STDs, HIV, and hepatitis B transmission and should be counseled to use a barrier method as well as the pill.
H. Special considerations
Adolescents may benefit in many ways by using the pill.
Cycles are regulated, are less painful, and have decreased blood loss.
There is less risk for PID, although the pill does nothing to mitigate against STDs, HIV, and hepatitis B transmission.
Adolescents who are not mutually monogamous should use a barrier method in addition to the pill.
Women older than 35 who are perimenopausal benefit from pill use.
The pill will regulate cycles.
There is increased bone density and less risk of rheumatoid arthritis.
It is an extremely effective method of birth control that should not be denied simply because of age.
“Morning-after pill” . Minipills may be given to women who have relative contraindications to the combination pills. It must be taken every day at the same time. If a pill is missed, a backup method must be used.
Postpartum and breast-feeding women also need effective protection.
Combination pills can be started after 3 weeks if postpartum and not breast-feeding.
A patient exclusively breast-feeding may start the minipill 6 weeks postpartum.
Combination pills are not recommended in women who are breast-feeding because estrogen can decrease the amount and quality of breast milk.
II. Injectable combination contraceptive :

A. Lunelle, a combination of medroxyprogesterone acetate and estradiol cypionate, has received Food and Drug Administration (FDA) approval as a monthly injectable contraceptive. In comparison to the oral combination pill, contraceptive effectiveness is very high since the problem of forgetting pills is eliminated. In an initial study over the course of 1 year, there were no pregnancies in 782 women.
B. Side effects
are expected to be similar to that of the OCP. There seems to be higher rates of irregular bleeding during the initial months of use when compared with corresponding rates in OCP users.
C. return to fertility
Compared with long-acting progestins, return to fertility after discontinuation of this method is more rapid. Ovulation can occur as early as 6 weeks after the last injection. For this reason it is also important to receive follow-up injections within 5 days of the prescribed 28-day injection schedule.
III. Long-acting progestin contraceptives :
Since 1992, long-acting injectable forms of progestins have been approved in the United States. Medroxyprogesterone acetate (Depo-Provera) has been used around the world for more than a decade. Levonorgestrel implants (Norplant system), silastic capsules that release progestin for up to 5 years, were approved in 1990. The mechanisms of action for these forms of progestin are the same as with the combined pill and the minipill. Progestin interferes with endometrial growth, cervical mucus production, and possibly fallopian tube transport. It may suppress LH surge and prevent ovulation but this is not consistent. About one third to one half of cycles are ovulatory. Effectiveness has been shown to be excellent, exceeding even that of sterilization in one large study.
A. Types of progestins
Norplant system is six silastic subdermal capsules that contain levonorgestrel.
Each capsule is 34 mm long and 2.4 mm in diameter. The levonorgestrel is very stable and is released over a period of 5 years. During the first year, 80 µg/day is released, which is comparable with the minipill and is about 50% of the progestin in the combined pills. Gradually, the release decreases to 30 to 40 µg/day. At 5 years, the amount released is not enough to provide adequate protection.
Very obese women may have relatively lower serum levels and, therefore, less contraceptive efficacy.
A modification of the Norplant system (Norplant II) has only two subdermal capsules. Implanon has only one subdermal capsule .
Depo-Provera is the depot form of medroxyprogesterone acetate. It is given as an injection of 150 mg every 3 months. The contraceptive effects may last up to 4 months.
B. Failure rate
The failure rates for either method are extremely low, from 0.2% to 0.3% in the first year. Most of the “failures” were in women who were pregnant at the time of insertion or injection. The Norplant failure rate increases with time until at 5 years it is as high as1.1%.
C. Contraindications and risk factors
are fewer than with the combined pills.
These methods may be safely used in women who may have contraindications to the combined pills (i.e., estrogen).
Theoretically, there are concerns with progestins' effects on lipid levels. However, studies do not show a significant change in lipids or carbohydrate metabolism.
D. Evaluation and counseling considerations.
Long-acting progestins have noncontraceptive benefits similar to those of the pill , except that there is no protection from ovarian cysts. In fact, ovarian cysts can occur more frequently.
E. Complications and side effects
Early animal research with Depo-Provera suggested increased breast tumors in beagle dogs. Worldwide use and many years of follow-up have alleviated fears of this severe complication. A multinational study showed a slightly increased risk ratio of 1.2 in women younger than 35 only in the first 4 years of use. Risks were not increased in women who had used this method longer than 5 years.
Serious side effects are rare. However, many side effects are such nuisances that patients discontinue use.
The most common side effect is irregular bleeding from the lack of estrogen's stabilizing influence on the endometrium.
Bleeding patterns are unpredictable.
Amenorrhea can occur.
Other side effects include:
Headaches.
Nausea.
Weight gain.
Acne.
Ovarian cysts.
Hyperpigmentation over the Norplant site.
Depression, which can be severe, more so with Depo-Provera than with Norplant implants.
Other considerations.
This method does not interrupt sex for contraception.
It provides no protection against STDs, HIV, or hepatitis B transmission.
Long-acting progestins are not as accessible as other methods. Norplant requires an appointment to have it inserted and removed.
In some cases it is costly because it involves a procedure charge.
Depo-Provera must be given every 3 months so patients must remember (or be reminded) to return regularly for injections.
There are no long-term effects on fertility. Most women ovulate in the first month after discontinuing this method. However, medium-range delays in ovulation (up to 9 months) can occur with Depo-Provera.
F. Instructions
Clinicians should discuss all of the foregoing considerations with the patient .
Some practitioners recommend a trial of a minipill before committing to the injection or Norplant system.
It is ideal to begin the progestin within the first 7 days of menses.
A pregnancy test is recommended before administering the first dose of Depo-Provera or inserting the Norplant.
The Norplant insertion procedure is not difficult and takes about 15 to 20 minutes. Wyeth-Ayerst can be contacted for training materials.
Removal of Norplant can take longer and may be complicated by an initial irregular placement or by a fracture of the silastic capsule.
Patients should be aware of possible side effects and may want to keep track of bleeding.
Patients should call in with any change in the bleeding pattern since a pregnancy test may be indicated.
G. Clinical dilemmas
If spotting or irregular bleeding continues, the patient may be treated with
Ibuprofen (Motrin), 800 mg PO tid for 5 days.
Conjugated estrogens, 1.25 mg PO or estradiol, 1 mg PO every day for 7 days.
Ethinyl estradiol, 20 µg PO every day for 25 days.
Methyltestosterone with conjugated estrogens (Premarin), 2.5 mg every day for 25 days.
Some clinicians use low-dose birth control pills such as ethinyl estradiol-norethindrone (Ovcon 35) for one cycle.
If all of the foregoing methods fail and the woman wishes to continue treatment, then a hysteroscopy and a D & C can be done to rule out intrauterine pathology.
A barrier method should be used with any estrogen-only method of treatment as it may decrease the effectiveness of the progestins by thinning cervical mucus.
If a patient develops amenorrhea, a pregnancy test should be obtained. The patient can be reassured that the method is still effective even without a period.
It is important to remember that many patients still ovulate while taking progestins. If there is any change in a regular pattern of bleeding, a pregnancy test is advised.
Headaches, severe acne, and depression may be indications for discontinuing this method.
H. Special considerations
Both Depo-Provera and Norplant may be used by lactating women.
Adolescents and women older than 35 may be well suited to one of these methods for the same reasons as those discussed for the combined pills .
Mentally disabled patients may particularly benefit from this method.
IV. IUDs :
have been used since the beginning of the twentieth century. This is a popular method of birth control worldwide but less so in the United States. With proper patient selection and counseling, products could be used more often. IUDs are believed to inhibit pregnancy by producing a local inflammatory response in the endometrium. This hostile environment is thought to be spermicidal and there is theoretical evidence that tubal motility is affected. It is important to realize that IUDs are thought to be contraceptive not abortifacient. Failure rates of any IUDs are low. The Progestasert fails between 2% and 3% of the time, whereas the failure rate for the CuT 380A is between 0.5% and 0.8%.
A. Types of IUDs
Nonmedicated IUDs are no longer available in the United States but some women still have them. Among the more common types are the Lippes Loop and the Saf-T-Coil. These types of IUDs work indefinitely and there is no need to remove and replace them.
Copper T-380A (ParaGard) is a copper-containing device in a T-shape, 36 mm long by 32 mm wide. It is currently approved for up to 10 years of use.
Progestasert contains progesterone that is released locally, has progestin (atrophic) effects on the endometrium, and affects the cervical mucus. This particular progestin IUD must be replaced every year.
Mirena is a new levonorgestrel-releasing IUD that has received FDA approval. This IUD can be used for up to 5 years.
B. Contraindications and risk factors
PID and pregnancy are absolute contraindications for use of an IUD.
The risk of developing PID for the first time while using an IUD is dependent on the sexual activity of the woman and her partner.
A woman in a mutually monogamous relationship will have little increased risk of developing PID while using the IUD.
A previous ectopic pregnancy is no longer considered an absolute contraindication.
The newer copper IUDs protect against ectopic as well as intrauterine pregnancy.
The Progestasert offers less protection against ectopic pregnancy.
Experimental levonorgestrel IUDs offer good protection against ectopic pregnancies, probably by interfering with ovulation..
C. Counseling considerations
The manufacturers of IUDs have developed extensive consent forms that the provider should review with the patient.
The best candidate for an IUD is a multiparous (proven fertility) woman involved in a mutually monogamous relationship.
As with the pill, it must be stressed that this method provides no protection against STDs, HIV, or hepatitis B transmission.
Wearing an IUD and contracting an STD can lead to severe PID and possibly abscesses.
Selecting the type of IUD. Most patients will prefer to have the longer lasting CuT 380A (ParaGard).
Progestasert may decrease the severity of dysmenorrhea and anemia in some women.
Mirena has the same benefits as Progestasert, with the additional advantage of needing replacement only once in 5 years instead of yearly.
Risks at the time of insertion include perforation and infection. There is about a 5% expulsion rate.
Patients should expect some cramping and discomfort for a few months.
There can also be heavy menses, spotting, or an increase in vaginal discharge.
These symptoms can be treated with standard doses of nonsteroidal antiinflammatory drugs.
Approximately 10% of patients will discontinue this method because of these problems.
Return of fertility is as rapid as with barrier methods. The endometrial cavity returns to normal almost immediately after removing the IUD.
D. Instructions
Clinicians should be well skilled in how to insert the different types of IUDs.
It is best to insert the IUD during menses or just after an abortion. This is not a strict rule as long as pregnancy has been completely ruled out.
If there is a suspicion of STDs, cultures need to be taken and results obtained prior to inserting the IUD.
Perform a bimanual examination to determine size and position of the uterus.
Grasp the anterior lip of the cervix with a tenaculum and sound the uterus slowly and gently.
Load the IUD into the inserter barrel and with slow steady traction on the tenaculum slide the IUD inserter barrel into the uterus.
Gently remove the inserter, being careful not to tug the IUD string.
Clip the strings about 3 to 5 cm from the os. Leaving them longer initially allows for some retraction over the next several days as the IUD becomes seated within the uterine cavity. If the strings are cut too short, the partner may feel them.
Paracervical injection of 10 to 20 mL of 0.5% lidocaine provides an effective anesthetic block for difficult or painful insertion. However, a paracervical block is usually not needed for insertion.
Since the risk of perforation is greatest at the time of insertion, patients should return in 2 to 3 weeks to have the placement checked and to rule out expulsion or perforation. At this return visit, preferably after a menses, the string length can be cut shorter if needed.
Patients. Be sure each patient knows how to check for her IUD strings and does so regularly. If the strings are absent or if a period is missed, the patient should contact the clinician.
A second method of birth control is recommended during the first 3 months after insertion.
Each user should know what type of IUD she has and when her IUD should be replaced.
Most important, she should memorize the IUD danger signs. The first letter of each sign spells the acronym PAINS.
Period late or missing.
Abdominal pain.
Increased temperature.
Noticeable discharge.
Spotting.
E. Sequelae
Potential IUD complications are listed in order of decreasing severity.
Infection is the cause of most IUD-associated hospitalizations and deaths. IUD users are two to eight times more likely to require hospitalization for PID than women using no contraception. Infection rates are highest among women at high risk for PID, including young women with multiple sexual partners in areas where STD rates are high.
IUD infection can occur without any obvious sign of systemic sepsis and without fever. Symptoms, such as abnormal discharge, bleeding, or pelvic pain, should be treated as infection until proven otherwise.
Because fertility impairment can be a consequence, IUD infection warrants immediate aggressive management.
Uterine perforation, embedment, or cervical perforation can occur silently (with no symptoms) and may be discovered when IUD removal is attempted or when unintended pregnancy occurs. Symptoms may include pain, bleeding, and disappearance of IUD strings.
Ultrasound is often helpful in determining the location of an IUD but may not be accurate for a woman with large fibroids.
Cervical perforation may occur as an IUD is being expelled.
The Dalkon Shield is not visible on x-ray films. Although it has been off the market since the 1980s, a few women may still have it.
Pregnancy. Whenever pregnancy occurs in an IUD user, the probability of ectopic pregnancy must be carefully evaluated. Although IUD use does not cause ectopic pregnancy, the IUD's effectiveness in preventing conception with ectopic implantation is lower than its effectiveness in preventing intrauterine pregnancy.
If pregnancy occurs, the IUD should be removed when the string is still visible.
If the string is not visible, patients should be counseled that there is a 50% spontaneous abortion rate and elective termination may be offered.
Ectopic pregnancy should always be considered and ruled out by ultrasound or D & C, if appropriate.
Lost IUD strings are a common complaint. In most cases the string may be seen inside the cervical canal. Narrow forceps can be used to probe the cervical canal in an attempt to bring the strings into view.
Consider pregnancy if the strings are not visible on careful examination. If pregnancy is ruled out, then a search must be made for the IUD.
Ultrasound will be able to determine if it is inside the cavity or if it has eroded into the myometrium.
IUDs that are totally inside the cavity may be left in place.
In many places worldwide, IUDs are routinely placed without strings.
If ultrasound is unable to identify the IUD, a three-way x-ray of the abdomen should be obtained to ensure that it is not floating in the abdominal cavity.
If the IUD is in the abdominal cavity, the patient should be referred for laparoscopic removal.
If the IUD is not seen on x-ray examination, most likely it was expelled without the patient's awareness. Remember that the Dalkon Shield is not visible on x-ray films.
Spotting and bleeding may vary depending on the type of IUD. Unusual spotting or cramping may represent pregnancy or mild infection and should always be considered prior to any treatment.
The progestin-type IUDs generally lead to hypomenorrhea, but long-time use can cause atrophy and irregular spotting.
Copper IUDs are more likely to cause irregular spotting and cramping than are progestin-containing ones. Nonsteroidal antiinflammatory drugs can decrease these problems:
Difficult removal of an IUD. Removal of the IUD during menses is generally easy. An IUD should be removed with gentle traction on the string.
In older IUDs, the string may pull off or the IUD may not move from its position, indicating that it may be partially embedded.
A narrow packing forceps may be used to grab the end of the IUD.
Sometimes, a paracervical block and cervical dilation may be necessary.
If this is unsuccessful, an IUD hook may be used inside the cavity.
A “Novak” curette, used for endometrial biopsies, is useful because of the serrations at the end of the curette.
The patient should be referred for hysteroscopic removal when other methods have failed.
IUD expulsion. Between 5% and 20% of users expel the IUD within the first year of use.
Expulsion or partial expulsion is often entirely asymptomatic. Symptoms may include the following:
Unusual vaginal discharge.
Cramping or pain.
Spotting.
Dyspareunia.
Lengthening of the IUD strings.
Feeling the plastic of the IUD.
Noting the passage of the IUD from the vagina.
Replacement of an IUD can be done in one office visit. Preprocedural antibiotic coverage, such as doxycycline 200 mg PO, may be used. Although a recent study showed no benefit to the use of prophylactic antibiotics in reducing pelvic infection rates in new IUD placements (18).
Cramping and pain should not be accepted as normal consequences of IUD use. The possibility of ectopic pregnancy or infection must be carefully evaluated. Increased menstrual cramping or intermittent cramping can occur, especially with larger IUDs.
F. Special considerations
Postcoital contraception. Insertion of a copper IUD within 5 days after unprotected intercourse provides effective postcoital contraception. This approach to morning-after treatment is logical only for women who wish to continue using the IUD as a method of contraception and who have no contraindications.
It is contraindicated in nulliparas, adolescents, and rape victims.
All of the previously discussed contraindications and risk factors must be considered .
Effectiveness has been reported to be >99%.
Newer, very effective, hormonal methods of postcoital or emergency contraception (EC) have been approved for safe and effective use by the FDA. These approaches make IUD insertion for this indication less attractive.
The IUD may be an ideal method for the perimenopausal patient who has completed her family and does not want to risk another pregnancy.
G. Clinical dilemmas
Most of the problems arising with an IUD in place can be mimicked by pregnancy. Therefore, always consider pregnancy.
Infection, especially PID, can occur in users of IUDs and may develop serious sequelae.
Be sure that the patient does not have an ectopic pregnancy.
Any patient with a suspicion of PID should be treated immediately and probably hospitalized.
Frank PID must treated with antibiotics.
After the first dose is given, the IUD should then be removed.
An ultrasound should be obtained, if an abscess cannot be ruled out on clinical examination.
If the infection seems to be limited to the cervix (i.e., cervicitis, asymptomatic positive Chlamydia or gonorrhea culture), it can be treated without removing the IUD and with very close follow-up.
Following an episode of PID, a woman should wait at least 3 months (preferably 1 year) for insertion of another IUD.
If future fertility is a goal, then should be avoided.
Uterine or cervical perforation.
When partial cervical perforation occurs, the IUD can usually be removed by using alligator forceps to push the device back into the uterine cavity and then removing the IUD by grasping it with forceps or pulling gently on the string.
In a nonpregnant woman, an IUD located outside the uterus (intraperitoneal) usually can be removed through a laparoscope.
Management of pregnancy. Obtain a serum pregnancy test to exclude ectopic or intrauterine pregnancy for any IUD user who has missed one or more periods. If pregnancy is intrauterine, the IUD should be removed because of the high risk (50%) of spontaneous abortion and, often, of associated infections. IUD removal reduces but does not eliminate the possibility of miscarriage.
If the strings cannot be seen or located in the cervical os, IUD removal cannot be attempted and therapeutic abortion should be considered.
If a woman decides to continue a pregnancy with an IUD in place, she should be warned about the 50% risk of spontaneous abortion and should be educated about signs of infection.
Ectopic pregnancy should always be considered and ruled out by ultrasound or D & C, if appropriate.
Most of the IUD-associated deaths have been the result of rapidly progressive infection with incomplete spontaneous abortion.
Management of lengthening string.
When an IUD is partially expelled, in many cases the string descends through the cervix and appears longer. The possibility of expulsion must be excluded before other causes are considered. Pelvic sonography and examination of the endocervical canal with a sterile swab can assist in this determination.
The string can also lengthen if, after insertion, part of the string remained in the uterine cavity and the clinician cut the string based on the segment visible in the canal.
Indications for IUD removal.
Pregnancy, pelvic infection, and partial expulsion are indications for immediate IUD removal.
Removal is also indicated when persistent pain is a problem, excessive bleeding causes a drop of 5% or more in hematocrit, or the patient requests removal.
An IUD can be removed at any time in the menstrual cycle. If the patient has had midcycle intercourse and the IUD is removed immediately thereafter, there may be some reduction in IUD efficacy for that cycle.
V. Barrier methods :
Although possibly more cumbersome than the methods already discussed, barrier methods, specifically condoms, have assumed new importance in this age of the potentially life-threatening STD—HIV—as well as other problematic STDs such as hepatitis B, HPV (human papillomavirus), HSV (herpes simplex virus), Chlamydia, and gonorrhea. It is important to explain to sexually active couples that prevention does require different or supplementary measures in conjunction with pregnancy prevention.
A. Diaphragm
The diaphragm acts as a barrier and serves as a receptacle to hold spermicide against the cervical os. Diaphragms are ineffective unless used with spermicide. Failure rates are related to the motivation of the patient and range from 6% to 18%. There are several types of diaphragms and familiarity with them will help the practitioner recommend the appropriate one to the patient.
Types of diaphragms. Each diaphragm is available in size increments of 5 mm.
Arcing-spring rim. This diaphragm provides the sturdiest of spring strengths; the rim arcs can be folded, thus facilitating insertion for some women. Available sizes range from 55 to 95 mm.
Two arcing-spring products, Koro-Flex and Bendex, fold at only two points along the rim.
The Ortho product, All-Flex, folds at any point, although it is less sturdy than the other two.
Flat-spring rim. This diaphragm has a thin rim, with gentle spring strength. The rim folds flat for insertion and is available in sizes 55 to 95. It is slightly harder than others to place correctly, but comfortable once placed behind the pubic bone.
Coil-spring rim. The coil-spring diaphragm has firm spring strength and is available in sizes 50 to 95. It folds flat for insertion and can also be used with an introducer.
Wide-seal rim. This diaphragm has an arcing-spring or a coil-spring rim with an additional soft flange along the inner edge to create a seal with the vaginal mucosa. It is available through Milex Products in sizes 65 to 85.
Contraindications and risk factors include the following:
Allergy to latex or spermicide.
Recurrent urinary tract infection.
Introital or pelvic pain.
Active lesions that interfere with comfortable fitting or insertion.
History of toxic shock syndrome (TSS) or colonization with Staphylococcus aureus.
Lack of medical staff to fit and instruct adequately on diaphragm use.
Inability of the patient to master correct insertion or removal.
Anatomic abnormalities. Diminished vaginal muscle tone, previous obstetric laceration, uterine prolapse, cystocele, rectocele, extreme and fixed retroversion, vaginal fistula, and vaginal septum may make diaphragm fitting or use impossible.
Fitting may not be accurate for a woman who has had a full-term delivery in the past 6 weeks.
How to determine correct size and fit. Select the largest rim size that is comfortable for the user. Since vaginal depth increases during sexual arousal, a diaphragm that is too small may slip out of place. On the other hand, a diaphragm that is too large may cause discomfort or recurrent urinary infection.
The anterior rim should tuck just behind the symphysis pubis and the posterior portion of the rim resides snugly in the posterior vaginal fornix.
The diaphragms or rings used for fitting should be washed with soap and water and then immersed in a 70% alcohol solution for 20 minutes after each use.
Many clinicians rely primarily on the arcing-spring diaphragm since it fits most women and is easy to insert. The arcing-spring diaphragm is also useful for a woman with a long and firm cervix.
The coil-spring or flat-spring diaphragm may provide a comfortable fit for a woman who has firm vaginal tone, who finds the arcing spring uncomfortable, or who has had problems with recurrent urinary infections.
Instructions.
Clinicians.
Be sure each user is able to insert and remove her diaphragm and can verify correct position by palpating her cervix.
Have her practice placement and removal while in the office.
Ensure that she is comfortable with the method and answer any questions.
The importance of spermicide and consistent use should be stressed. Spermicide must be used with initial coitus and replenished with subsequent acts without removal of the diaphragm.
Each patient should also be aware that TSS could occur with diaphragm use if not removed within 24 hours.
Patients.
Apply 1 tablespoon of spermicide cream or gel to the inner dome of the diaphragm and along the rim.
If the diaphragm is placed in the vagina more than 6 hours before intercourse, another applicator full of spermicide should be inserted.
Insert the diaphragm by pushing the rim downward and toward the back wall of the vagina. The rim should fit just behind the pubic bone and should reach back behind the cervix.
Always check to make certain the diaphragm is covering the cervix.
Leave the diaphragm in place for at least 6 hours after intercourse. If you have intercourse again during the 6-hour time, insert an applicator full of spermicide, but do not remove the diaphragm.
Remove the diaphragm any time after 6 hours, wash it with soap and water, and let it dry. It can then be reinserted with new spermicide or stored in its case until again needed.
Avoid leaving the diaphragm in place any longer than 24 hours, but do keep to the 6-hour minimum time.
Do not use talcum or perfumed powder or any petroleum products (e.g., Vaseline) on your diaphragm.
If you experience danger signs of possible TSS while using the diaphragm, contact your clinician immediately. The danger signs are:
Fever of 100°F or more.
Diarrhea and vomiting.
Muscle aches.
Rash (like sunburn).
Diaphragm size should be reassessed after childbirth, or when approximately 10% of body weight is gained or lost.
Sequelae.
Side effects. Overall, the diaphragm is a very safe method of contraception.
TSS is the most serious potential problem, but is very rare. A handful of TSS cases, however, have been reported in association with prolonged diaphragm placement. These cases did not arise during menses as is more typical for TSS. Any patient who experiences TSS danger signs must be evaluated promptly, which includes diaphragm removal, vaginal culture for S. aureus, and prompt antibiotic treatment when indicated.
Other problems that can occur with diaphragm use include
See section on spermicides discussed in C, below.
Recurrent cystitis.
The size of the diaphragm should be checked.
If size is not the problem, the patient should be counseled to void prior to and after intercourse.
In some cases an antibiotic may be given prophylactically [i.e., nitrofurantoin (Macrodantin), 50 mg PO, or sulfamethoxazole-trimethoprim (Bactrim or Septra), PO after coitus].
Allergic reactions to latex or spermicide. If the reaction is to the spermicide, try different brands. It may, in fact, be a reaction to perfume or other additives.
Irritation from spermicide.
Foul-smelling vaginal discharge when a diaphragm is left in place too long.
Recurrent candidiasis if the diaphragm is not thoroughly cleaned out and dried after use.
Pelvic discomfort from rim pressure.
Patient or partner discomfort. There are many ways this may manifest itself. There has to be a level of comfort in the relationship to incorporate the use of barrier methods. Furthermore, some patients may have physical discomfort with the diaphragm. If it is too small, the partner may notice it as well as it will move around in the vagina during coitus.
Noncontraceptive benefits. Use of a diaphragm and spermicide may provide significant protection against STDs. Their use is associated with a decreased risk of developing cervical dysplasia.
B. Cervical cap
The soft, thimble-shaped cup fits over the cervix and is held in place by suction. Pregnancy is prevented through the cap's action as a barrier over the cervix and by its ability to hold spermicide in place. The reported failure rate is similar to that of the diaphragm. Manufactured and long used in England, the Prentif cap was approved by the FDA for use in the United States in 1988.
The cervical cap has a deep dome with a groove inside the firm rim to aid suction and it is available in four sizes, ranging from 22- to 31-mm internal rim diameter.
Contraindications and risk factors are the same as for the diaphragm, with the following exceptions:
Cap use is contraindicated for a woman who has Pap smear evidence of HPV infection, cervical intraepithelial neoplasia, or cervical dysplasia.
Cap use should not be initiated if the woman has acute PID, acute cervicitis, or vaginal infection or has undergone cervical biopsy or cryosurgery within the past 6 to 12 weeks.
The cap should not be used during the first 6 weeks after full-term delivery, when vaginal bleeding is occurring after spontaneous or induced abortion, or during normal menses.
How to determine correct size and fit. Because of variations in normal anatomy and the limited number of cap sizes available, it is not possible to fit every patient satisfactorily. Only about 50% of women can use this method successfully.
The cap must fit snugly over the cervix and remains by suction.
The cap dome should be deep enough so that it does not rest on the cervical os.
The cap should not be easily dislodged with a fingertip.
The cap user should check carefully for cap dislodgment after intercourse.
Instructions are the same as for the diaphragm, with the following exceptions:
Spermicide is not necessary. If used, it should fill the dome of the cap one third full. Using spermicide may prolong the wearing time.
The cap should be left in place at least 6 hours after intercourse but can be in for up to 36 hours.
Sequelae.
Little is documented concerning possible side effects or complications of the cervical cap.
Reports have noted vaginal lacerations and abrasions caused by the Vimule cap (not currently available in the United States) and abnormal thickening of the vaginal mucosa, possibly a reaction to chronic irritation (2).
Other researchers have expressed concerns about pelvic infection, acute cervicitis, and abnormal Pap smears possibly linked to cap use.
Failures occur when the cap is dislodged during intercourse.
Any noncontraceptive benefits are likely to be similar to those afforded by diaphragm use .
C. Spermicides and the contraceptive sponge.
Spermicidal contraceptives consist of two components: an inert substance, such as foam, gel, cream, or in the case of the sponge (currently unavailable), polyurethane; and a spermicidal agent (non-oxynol 9). Spermicides immobilize and kill sperm. In addition, the sponge provides a barrier between the sperm and the cervical os and traps the sperm within the sponge. The typical failure rates are 21% to 28%.
Although contraceptive sponges have been discontinued, they may again become available. Spermicidal agents are often used in combination with condoms to provide an extremely effective method of contraception, with a failure rate possibly lower than 1:100 woman-years. In the United States, the active spermicidal agent for products is non-oxynol 9. This is a surface-active substance that destroys cell membranes of sperm. Currently, controversy exists as to the practical effectiveness of non-oxynol 9 in destroying many organisms that cause STDs. In the laboratory, the chemical is lethal to organisms that cause gonorrhea, genital herpes, syphilis, trichomonas, and HIV. However, the evidence that non-oxynol 9 decreases STD risks (including HIV) in human studies has been mixed. There is even some concern that frequent non-oxynol 9 use can irritate the mucosa of the vagina and skin of the vulva, possibly increasing susceptibility to HIV. Also, cystitis (discussed later) may be increased by non-oxynol 9 use, which allows for intravaginal proliferation of Eschericia coli, which is a frequent cause of cystitis .
Type of spermicidal method. All methods are available without prescription.
Foam. Used alone, there is a wide disparity between perfect-use effectiveness and actual-use effectiveness. Common mistakes include inconsistent or careless use, using too little foam, failing to shake the container vigorously enough, not placing the foam high enough in the vagina, and douching too soon after intercourse.
Cream and gel. When used alone, these are slightly less effective than other spermicides. Cream products have better dispersion to cover the cervix and vagina than do gels. Cream and gel are often used in conjunction with the diaphragm or cervical cap.
Suppositories and tablets dissolve over a period of 10 to 30 minutes after placement in the vagina but retain their full effectiveness for less than 1 hour. Mistakes arise from not allowing the tablet or suppository to dissolve, failing to remove the wrapper, placing the spermicide incorrectly, or having intercourse after the fully effective interval.
Contraceptive sponge. In the future, this method may again become available. The polyurethane sponge incorporates 1 g of nonoxynol-9. Approximately 200 mg of spermicide is released during the initial 24 hours of use. It has a concave dimple on one side that fits over the cervix and a woven loop to facilitate removal.
Contraindications and risk factors.
Contraindications to spermicide use include allergy to the active ingredient or base or physical inability to insert or use the product correctly.
Additional contraindications specific to sponge use include:
Anatomic abnormalities such as uterine prolapse, rectocele, cystocele, extreme uterine retroflexion, or vaginal septum when they interfere with placement or retention of the sponge.
History of TSS or vaginal colonization with S. aureus.
Prevention against STDs, HIV, and hepatitis B transmission is less ensured when these methods are used alone.
Instructions. Different formulations of spermicides have different effective times. Most must be placed within 1 hour of intercourse. The length of time protection lasts varies from 1 to 8 hours.
Correct use of a spermicide entails following package instructions carefully:
Removing the wrapper from tablets or suppositories.
Filling the applicator completely with foam, cream, or gel.
Placing the spermicide as close to the cervix as possible.
Applying additional spermicide for each act of intercourse.
Inserting the spermicide before intercourse.
Not douching for at least 6 hours after intercourse.
The sponge.
Correct use requires moistening the sponge with clean water, placing it over the cervix, and leaving it in place for at least 8 hours after intercourse.
The sponge should not be worn for longer than 24 hours.
Each user should learn the danger signs of TSS and know how to contact her clinician if these signs occur. TSS symptoms include high fever, rash, diarrhea, vomiting, and muscle aches.
Sequelae.
Spermicides.
Possible complications of spermicide use include irritation, allergic reaction, and failure of suppository or tablet to melt or foam.
Noncontraceptive benefits include decreased incidence of gonorrhea and trichomoniasis, augmented vaginal lubrication, and possibly some protection against cervical neoplasia.
Contraceptive sponge.
Sponge use involves the possible complications of spermicide .
Some users also experience dryness of the vagina and difficulty with removal or tearing of the sponge.
It is not known whether or not sponge use increases the risk of TSS.
Noncontraceptive benefits of the sponge include those listed for spermicides as well as absorption of vaginal secretions and ejaculate.
Clinical dilemma. When spermicide users experience an allergic reaction, the offending agent is often the perfume or base, although it may be the active spermicidal ingredient. Recommend a nonperfumed spermicide. Check the ingredients of the problem product and consider recommending one containing different ingredients.
D. Condoms
Mechanical barriers to cover the penis during intercourse have been used for hundreds of years. Synthetic condoms were developed after 1840. The popularity of condoms has made this the third most commonly used contraceptive method in the United States. Reported failure rates range from 2 to 12 pregnancies per 100 woman-years.
Types of condoms.
Most condoms are made of latex. About 1% are made from lamb cecum (“natural” skin condoms). Newer polyurethane (plastic) condoms are available and are also useful for those with latex allergy.
Condoms are available lubricated or nonlubricated, straight or tapered, and with or without reservoir tip. Some condoms have external ribbing.
Latex and plastic condoms can prevent transmission of all STDs, including the viral ones (HIV, HPV, HSV, hepatitis B), but natural or lambskin do not prevent transmission of viral STDs.
When protection against transmission of HIV is a consideration, latex condoms in conjunction with spermicide use are recommended. Skin condoms (natural) are more porous than latex, and small particles such as HIV may traverse the intact condom barrier.
Female condoms are available. These are pouches of plastic that line the vagina and cover the cervix.
Contraindications and risk factors.
Allergy to latex is a contraindication. Natural or plastic condoms can still be used.
Some men report difficulty maintaining an erection when using condoms, although others find that condom use is helpful for this.
Instructions. A new condom must be used for every act of intercourse and placed on the penis before any vaginal entry.
Patients should be instructed to place the condom on the erect penis before the penis touches the partner.
The end of the condom should extend beyond the tip of the penis and air should be removed to form a small receptacle.
Lubricants should be water-based only. Oil-based lubricants can weaken the condom.
After intercourse, the penis should be withdrawn while it is still erect, taking care to keep the bottom of the condom from coming off the base of the penis.
Jewelry, fingernails, and sex toys may tear the condom.
Average breaking rates for latex condoms are 1% to 2% and are greater for plastic, up to 7%. If breakage occurs, concomitant use of spermicides substantially decreases the risk of pregnancy.
Condoms should be stored in a cool, dry place and should not be reused.
Petroleum jelly can cause a condom to deteriorate.
Couples using condoms need to know about morning-after hormonal treatment.
Sequelae.
Complications.
The condom may reduce sensitivity of the glans penis. In some cases, use of the natural skin condoms may help.
Some users object to interruption in lovemaking to place the condom on the penis.
Very rarely, an allergic reaction to latex or lubricant can occur.
Noncontraceptive benefits. Condom use is one of the few opportunities for men to play an active role in contraception.
Condoms greatly reduce the transmission of STDs, hepatitis B, and HIV and diminish the likelihood of cervical cancer.
Condoms may also be of help in treatment of premature ejaculation and in preventing exposure to ejaculate for a woman who is allergic to her partner's semen or develops antibodies that cause infertility.
VI. Fertility awareness :
is also called natural family planning. The various methods include rhythm, basal body temperature (BBT), Billings (mucus) method, and the symptothermal methods. All these methods require periodic abstinence with unsafe days determined by physiologic changes that occur during a woman's menstrual cycle. Women who are well educated concerning their cyclic changes, have regular menses, are disciplined, and are willing to cope with possible pregnancy may have good success with fertility awareness. Some users choose to monitor several cyclic changes or combine fertility awareness with alternative contraceptive methods or both.
Failure rates range from 2% to 35%, depending on the method used and on whether alternative birth control was employed. Best success is reported for couples who abstain throughout the preovulatory phase and do not have intercourse until the fourth day after ovulation is clearly documented. Most failures occur because of intercourse during “early safe” days, when ovulation occurs a few days earlier than anticipated. Temperature and mucus changes do not predict ovulation accurately enough to avoid this problem.
VII. Sterilization :
is the most commonly used method of birth control in the United States. The pregnancy rates are 0.2 to 0.4 for tubal ligation and 0.15 for vasectomy per 100 woman-years. For the purpose of decision making about sterilization, these procedures should be considered irreversible.
A. Types of sterilization
Vasectomy.
This operation for men is a simple and safe procedure that prevents sperm passage by blocking the vas deferens. The clinician can ligate the vas deferens through a small incision of the scrotum.
Reversal is moderately successful. Depending on the type of vasectomy performed and the time interval to vasovasostomy, vasectomy reversal procedures can result in clinical success up to 50% of the time. Success diminishes if the vasectomy was performed over 10 years ago.
Tubal ligation. The fallopian tube can be blocked by ligation, coagulation, or mechanical occlusion with clips, bands, or rings. Tubal reanastomosis is generally less successful than is vasovasostomy and will be recommended only if a substantial portion of undamaged fallopian tube is available for repair. Reversal rates as high as 50%, however, have been reported for reanastomosis after clip ligation or surgical ligation with minimal damage. This rate is much lower when electrocautery has been used. The types of tubal ligation include the following:
Abdominal approach. More than 100 variations of abdominal tubal ligation have been developed. Two of the most commonly used methods are laparoscopy and minilaparotomy. Both procedures can be performed under local or general anesthesia.
For laparoscopy, one or two 1-in. incisions may be required, one for the laparoscope and one through which the tubes are grasped with forceps for coagulation or clip applications.
For minilaparotomy, a 2- to 3-cm incision approximately 3 cm above the symphysis pubis allows the surgeon to grasp the fallopian tube for ligation. Minilaparotomy is most feasible for patients with minimal abdominal wall fat.
Vaginal approach. The fallopian tubes can be approached by vaginal culdotomy or rarely by culdoscopy. Because of high complication rates, the advantages of an unobtrusive scar and rapid recovery are less attractive.
Hysterectomy. At one time, hysterectomy was the most common method of sterilization. This approach may be considered for women who are likely to require later hysterectomy because of known gynecologic disease but should not be a routine recommendation. Hysterectomy mortality is 10 to 100 times higher than that of tubal ligation, and the associated morbidity as well as cost in money and time is much greater.
B. Contraindications and risk factors
Ambivalence is a strict contraindication. Only a patient who wishes to terminate fertility should undergo sterilization. In reaching a decision, the possible impact of divorce or family tragedy should be considered. Remarriage is the most common reason cited for requesting reversal.
A patient who is obese, has cardiovascular disease, or has a serious medical condition that might increase anesthesia or surgery risks should be encouraged to consider alternative methods of fertility control.
C. Counseling
Every patient must understand that sterilization surgery is not 100% effective and that pregnancy can occur in rare cases. Because of the permanent and completely elective nature of sterilization surgery, informed choice and informed consent are crucial. The mnemonic BRAIDED has been developed for the essential components of informed consent counseling.
Benefits: It is effective and convenient.
Risk: Risk of method including consequences of method failure.
Alternatives: The patient must be informed about possible alternatives, including advantages and disadvantages of each.
Inquiries: Any questions the patient may have should be answered fully by the clinician.
Decision: The patient must feel free to decide against the proposed method, without implied pressure or coercion.
Explanation: The procedure planned must be explained in specific detail.
Documentation: Information provided to the patient should be entered in the medical record, along with a written consent form signed by the patient.
D. Sequelae
Male sterilization.
Vasectomy is a very safe procedure. Complications are generally minor and short term. Swelling, discoloration, and discomfort are common during the first few days after surgery.
More significant, but uncommon, complications are hematoma, granuloma, epididymitis, and wound infection.
One half to two thirds of men develop sperm antibodies after vasectomy, but the possible significance of this is unknown.
Approximately 0.4% of vasectomy procedures fail to terminate fertility. In most cases, failure is evident within a few weeks, as postoperative semen shows continuing sperm release.
Sperm counts should be obtained after 20 ejaculations and a repeat sperm count done at 2 months.
Approximately 10% will need to repeat the sperm count 1 to 2 months later to ensure that the count has decreased.
It is recommended that all men have a repeat sperm count 6 months after the vasectomy.
A backup method of contraception should be used until the semen no longer shows sperm release.
Female sterilization. Tubal ligation is also extremely safe. The greatest risk is in the type of anesthesia used with general anesthesia having the highest risk.
Complications of tubal ligation could involve damage to one or both ovaries or to the ovarian blood supply, and this could cause menstrual disturbance or a change in the hormonal milieu. Whether such problems can be linked to uncomplicated tubal ligation, however, has been an issue of controversy. Long-term follow-up in large case-control studies have found menstrual disturbances equally as frequent among controls as among sterilization cases.
Complications occur in fewer than 2% to 3% of women undergoing minilaparotomy and include infection, hematoma, uterine perforation, and bladder injury.
Complications are also rare with laparoscopy. The procedure can cause mesosalpingeal tear, bowel burn, uterine perforation, or hemorrhage.
Vaginal tubal ligation complication rates are approximately twice as high as those for laparoscopy or minilaparotomy, with infection and hemorrhage accounting for most of the problems.
Tubal ligation failure rates depend on the specific surgical method used.
Following laparoscopy, approximately 0.25% of patients experience failure. Ectopic pregnancy and pregnancy already established at the time of the surgery are the most common.
Postpartum tubal ligation, sterilization at the time of caesarean section delivery, and abdominal ligation by the Pomeroy method have somewhat higher failure rates.
VIII. Abortion :
Approximately 1.6 million abortions are performed annually in the United States; more than 90% are performed early in pregnancy using vacuum aspiration. Although the complication rate for abortion is as low as, or lower than, any other method of fertility control, very few women choose it as a primary fertility control method. Patient acceptance of effective contraception is extremely high at the time of unintended pregnancy, so birth control information and supplies are an important part of clinical management. Early identification and confirmation of pregnancy are also crucial tasks for all family-planning clinicians.
With the marked increase in ectopic pregnancy rate, early pregnancy identification can be lifesaving. Early confirmation also permits optimal initiation of prenatal precautions and care and early termination if abortion is the patient's decision. Abortion risks are lowest at approximately 7 to 8 weeks gestation and double for every 2-week delay thereafter. This method is not accepted in Islamic .
IX. Postcoital or EC :
has been mentioned in other sections. Practitioners need to be more aware of this option and feel comfortable using it. Patients need to be counseled that it is available as a backup if one of the foregoing methods is not used correctly (i.e., a failed condom). EC prevents ≈ 75% of expected pregnancies, probably closer to 95% when used within 24 hours of intercourse. In a recent review article about EC, Glasier thoroughly discusses the mode of action of these hormonal techniques and states, “The prevention of pregnancy before implantation is contraception and not abortion” . There is considerable current advocacy to make EC available without prescription in the United States. Evidence exists that this approach could reduce the unwanted pregnancy rate without risk to the users. There are two methods of postcoital contraception, hormonal and the IUD.
There are two main hormonal approaches to EC using either combination estrogen and progestin OCPs or progestin-only contraceptive pills. Together these are referred to as emergency contraceptive pills (ECPs). In 1997 the FDA declared the combination method of ECP use both safe and effective for use in pregnancy prevention. Previously studied, but not currently used, methods include danazol (an antigonadotropin) and high-dose estrogen-only regimens. It may be that antiprogesterone, mifepristone (RU-486), will be used for postcoital contraception. Effective contraception must be used within 72 hours of unprotected sex.
Combination estrogen and progestin methods include a large number of easily available formulations.
In all cases two doses are required, the first within 72 hours of intercourse, the second 12 hours after the first dose.
All use ethinyl estradiol 100 to 120 mcg and levonorgestrel 0.50 to 0.60 mg per dose. This is convenient because many conventional OCPs contain appropriate dosages of these hormones when taken in multiples.
For example, Ovral contains 50 mcg ethinyl estradiol and 0.25 mg levonorgestrel. Thus, taking two Ovral pills 12 hours apart provides the correct dose of ECPs.
Similarly, Lo/Ovral contains 30 mcg ethinyl estradiol and 0.15 mg levonorgestrel. Thus, four Lo/Ovral pills per each dose provides the correct dose.
One commercially available product, Preven, contains four tablets each containing 50 mcg of ethinyl estradiol and 0.25 mg levonorgestrel.
Progestin-only method. Currently, only one such method is commercially available; “Plan B,” which contains a single pill containing 0.75 mg of levonorgestrel, is taken within 72 hours of intercourse. This method was shown in a large multinational trial to be as effective as the combination estrogen and progestin regimen and may be preferred because of its low incidence of nausea and ease of single dosing.
The most common side effect of ECPs is nausea. Using combination pills, the incidence of nausea is 30% to 50% and approximately 20% have emesis. These rates drop by more than half with the progestin-only method. If vomiting does occur within 3 hours of either dose, some feel it should be repeated with an antiemetic.
Although the ECPs may slightly alter the expected menstrual interval, patients should expect to see their menses by 21 days after treatment. If the pregnancy ensues, the patient should be counseled appropriately concerning an undesired pregnancy. If she opts to continue the pregnancy, there is no evidence of teratogenic effects.
IUD placement within 5 days of conception can successfully prevent pregnancy with failure rates of less than 1%. .

SEXUALLY TRANSMITTED DISEASES

Introduction :
Twenty or more infectious diseases may be transmitted by sexual contact. This chapter reviews those associated with cervicitis, gonorrhea and chlamydia, and those characterized by genital ulcers, syphilis, herpes, chancroid, lymphogranuloma venereum, and granuloma inguinale as well as the parasitic skin infestations, pediculosis pubis and scabies. Sexually transmitted diseases (STDs) often coexist. It is strongly recommended that whenever serologic testing is done, screening for syphilis (rapid plasma reagin test [RPR], HIV, hepatitis B surface antigen (HBsAg) and hepatitis C titer should be included routinely.
I. Gonorrhea.
Urogenital purulent inflammation is the most common form of infection with the gram-negative, intracellular diplococcus Neisseria gonorrhoeae, which has an avidity for columnar and transitional epithelium. Transmission is almost always by sexual contact, with a usual incubation period of 2 to 8 days. In the United States, an estimated 600,000 new infections are reported annually.
A. History.
The acute attack usually follows sexual exposure or a menstrual period. Symptoms include vaginal discharge, urinary frequency and dysuria, menstrual irregularity, and bilateral lower abdominal pain. An asymptomatic carrier state is common in both sexes. The incidence of asymptomatic gonorrhea in men has been estimated to be as low as 12% and as high as 50%. The estimated incidence for asymptomatic women ranges from 50% to 80%. Infections in other mucosal sites, such as the oropharynx and anorectal area, are usually asymptomatic, but may lead to complaints of pain and discharge. Hematogenous spread may occur, causing manifestations such as septic arthritis and skin lesions. The most common dissemination, however, is by mucosal passage to the fallopian tubes and ovaries, resulting in pelvic inflammatory disease (PID), occurring in 10% to 15% of infected women .
B. Physical examination.
In the asymptomatic case, the physical examination may be entirely normal. There may be a purulent discharge, or Skene's or Bartholin's glands may be inflamed. However, these are nonspecific signs, and the diagnosis is dependent on bacteriologic investigations. The classic presentation of acute gonococcal PID, with fever, abdominal and adnexal tenderness, and a purulent discharge, is often absent.
C. Investigative procedures
A Gram stain of urethral or cervical secretions is unreliable since there is a 60% to 70% false-negative rate in female patients.
Gonorrhea culture, on Thayer-Martin or equivalent medium. The culture should be placed in a candle jar since the organism is fastidious, requiring aerobic conditions with an increased carbon dioxide atmosphere to grow. Incubation should begin as early as possible. Depending on the history, cultures may also be required from the pharynx and rectum.
Enzyme immunoassay (ELISA), polymerase chain reaction (PCR), and ligase chain reaction (LCR) assays on endocervical or urine samples have largely replaced culture methods of diagnosis and are at least as accurate.
Serologic testing for syphilis should be done on all patients. HIV testing and screening for HBsAg and hepatitis C are strongly recommended.
Chlamydia testing should be done at the same time the gonorrhea culture is obtained.
D. Management.
Therapy is based on antibiotic sensitivity, site of infection, and concurrent STDs. Antibiotic resistance is mediated through two genetic mechanisms: chromosomal-mediated resistant N. gonorrhoeae and plasmid-mediated resistance. Two types of plasmids are important: one for penicillinase and one for high-level tetracycline resistance. Rectal infections are relatively refractory to amoxicillin and tetracycline, and pharyngeal infections to amoxicillin and spectinomycin. Chlamydia trachomatis is a common coinfective agent and should be covered with empiric therapy. A summary of the guidelines for treatment recommended by the Centers for Disease Control and Prevention (CDC), Atlanta, in 1998 follows.
Treatment of adults
Uncomplicated gonococcal infections are treated with empiric single-dose therapy consisting of ceftriaxone, 125 mg IM once. Mixing 1% lidocaine reduces the discomfort of the injection. Other recommended single-dose regimens include cefixime, 400 mg PO; or ciprofloxacin, 500 mg PO; or ofloxacin, 400 mg PO. Alternative regimens include spectinomycin, 2.0 g IM for patients who cannot tolerate cephalosporins or quinolones. Injectable cephalosporins that are also effective include ceftizoxime, 500 mg IM; cefotaxime, 500 mg IM; cefotetan, 1 g IM; and cefoxitin, 2 g IM. Oral cephalosporin regimens include cefuroxime axetil, 1 g PO; and cefpodoxime proxetil, 200 mg PO. These two regimens are less effective against pharyngeal infections. Other quinolone regimens include enoxacin, 400 mg PO; lomefloxacin, 400 mg PO; and norfloxacin, 800 mg PO. Many other antibiotics are effective, and this does not represent a comprehensive list of all suitable treatments.
All treatment regimens should include a single dose of azithromycin 1 g PO or a 7-day course of oral tetracycline or doxycycline to eradicate concurrent chlamydial infection, which has been documented in up to 45% of gonorrheal cases in some populations. These drugs are not considered adequate therapy for gonorrhea. Generic doxycycline costs a little more than tetracycline but provides the advantage of a 100-mg bid dosage unrelated to meals, compared with a 500-mg qid dosage between meals with tetracycline. The alternative regimen is erythromycin stearate, 500 mg; erythromycin ethylsuccinate, 800 mg; or erythromycin base, 500 mg PO qid for 7 days .
All patients should have a serologic test for syphilis and should be offered counseling and testing for HIV infection. Most patients with incubating syphilis (in who there is no clinical evidence and who are seronegative) may be cured by any of the foregoing regimens, with the exception of spectinomycin and the quinolones. Patients treated with these drugs should have a syphilis serologic workup in 1 month.
Pharyngeal infections should be treated with ceftriaxone, 125 mg IM. Those who cannot receive this drug should be treated with ciprofloxacin, 500 mg PO, as a single dose; and these patients require repeat culture 5 to 7 days later. Trimethoprim, 720 mg; sulfamethoxazole, 3600 mg PO once daily for 5 days may be an effective alternative therapy.
Sexual partners should be identified, examined, cultured, and treated presumptively.
Follow-up culture (so-called test of cure) following combined ceftriaxone-azithromycin or doxycycline therapy is not essential since treatment failure is rare. Reculture 1 to 2 months later (rescreening) detects both treatment failures and reinfections. Patients treated with other regimens and those with persistent symptoms should have cultures 4 to 7 days after completion of therapy.
Treatment failures after one of the recommended regimens are usually due to reinfection, indicating a need for improved contact tracing and patient education. Nevertheless, antibiotic sensitivities and chlamydial cultures are indicated. Additional treatment with ceftriaxone and azithromycin or doxycycline should be given.
Pregnant women should be treated with ceftriaxone, 125 mg IM, plus azithromycin 1 g PO or erythromycin base, 500 mg PO qid for 7 days. (Erythromycin stearate, 500 mg; erythromycin ethylsuccinate, 800 mg; or an equivalent may be substituted for erythromycin base). Tetracyclines (including doxycycline) and the quinolones are contraindicated in pregnancy because of possible adverse fetal effects. Pregnant women allergic to beta-lactams should be treated with spectinomycin, 2 g IM, followed by erythromycin. Test of cure is required for these cases.
Disseminated gonococcal infection (arthritis-dermatitis syndrome). The condition may be monoarticular or polyarticular. Skin lesions are commonly present with the arthritis. They begin as small red papules, evolving through vesicular and pustular stages to lesions with a necrotic center superimposed on a hemorrhagic base. Healing is usually spontaneous. Hospitalization is usually indicated, especially for those who cannot reliably comply with therapy or who have an uncertain diagnosis, purulent joint effusions, or other complications. Treatment schedules for this syndrome are included in the CDC guidelines but are outside the scope of this chapter.
Miscellaneous. The CDC guidelines also recommend schedules of therapy for infants born to mothers with gonococcal infections, for gonococcal ophthalmia in adults, and for neonatal infections. These are problems seldom encountered in a medical or gynecologic outpatient department. However, adolescents may be seen and should receive similar regimens. Children weighing more than 100 lb (45 kg) receive adult dosage while those weighing less receive dosages adjusted to weight. In all pediatric cases, the possibility of sexual abuse must be considered.
E. Sequelae.
The short-term and long-term complications and sequelae of gonococcal infections are mainly related to gonococcal PID .
II. Syphilis.
The infectious agent is a spirochete, Treponema pallidum. Spread is by sexual intercourse or by intrauterine transmission (congenital syphilis). The incubation period is usually 2 to 6 weeks, with a primary sore (chancre) appearing at the site of infection and remaining for 1 to 6 weeks. Manifestations of the secondary stage may appear 2 to 12 weeks later. During early latency (1–4 years), relapses with mucocutaneous lesions may occur. Thereafter, there are no relapses and the syphilis is noninfectious, except transplacentally. Late symptomatic syphilis is generally characterized by cardiovascular or neurologic disease, although any tissue can be involved.
The incidence of syphilis in the United States in 1995 was 9 cases per 100,000 population.
A. Early (primary, secondary, latent less than 1 year)
History. The primary chancre usually appears on the genitalia, mouth, or anus and is painless. The secondary stage may present with ulcerations of mucous membranes or skin eruptions. Frequently there is only a flulike syndrome with a fever, sore throat, and muscle pain. During the latent phase, the patient is generally asymptomatic. Nearly two thirds of patients pass through the primary and secondary stages without realizing it. The clinical spectrum of syphilis acquired in utero includes stillbirth, neonatal death, neonatal illness, and development of the stigmata of congenital syphilis in later life.
Physical examination. Chancres vary in appearance but the usual feature is that of a nontender clean-cut ulcer with an indurated base and an associated regional adenopathy. The secondary-stage skin lesions tend to be widespread and symmetric, with 60% to 80% of patients having lesions on their palms and soles. Cutaneous lesions tend to be maculopapular. Condylomata latum are intertriginous papules formed at areas of friction and moisture, such as the vulva. Mucosal or mucocutaneous lesions appear in 21% to 58% and include pharyngitis, tonsillitis, and the “mucous patch” (a papule with a central erosion found on the oral and genital mucosa). Lymphadenopathy is a very common finding in the secondary stage.
Investigative procedures. Dark-field microscopy of fluid expressed from lesions may demonstrate the organism. In practice, serologic tests are of major importance in diagnosis. Nontreponemal tests (Veneral Disease Research Laboratories test [VDRL] and RPR) are used for screening and may be repeated quantitatively as a guide to therapeutic response. The tests become positive 1 or 2 weeks after the appearance of the chancre. They are positive in approximately 66% of primary cases, in 99% of secondary cases, and in about 70% of late cases. These tests are nonspecific, with biologic false-positive results occurring in association with other infections and diseases (e.g., infectious mononucleosis, collagen vascular diseases). The titer is usually low (no more than 1:8), with a false-positive test. Treponemal tests (fluorescent treponemal antibody absorption test [FTA-ABS], Treponema pallidum immobilization test [TPI]) are specific, but are not quantitative, and remain positive even after adequate therapy. The treponemal tests, therefore, are used to confirm the diagnosis. The FTA-ABS test is positive in 85% of primary and 100% of secondary cases and may be the only positive test in tertiary cases. Positive serologic studies in the newborn may be passively acquired, but most physicians treat all VDRL-positive neonates. All patients with evidence of latent syphilis should have a lumbar puncture with a cerebrospinal fluid (CSF) VDRL to rule out neurosyphilis .
Management. The CDC recommendations (1998) are summarized as follows:
Drug therapy for early syphilis is benzathine penicillin G, 2.4 million units IM in a single dose. Penicillin-allergic patients should receive doxycycline, 100 mg PO bid; or tetracycline hydrochloride, 500 mg PO qid for 14 days. An alternative regimen is erythromycin, 500 mg PO qid for 14 days. Various ceftriaxone regimens may also be considered. Pregnant patients are treated similarly, but tetracyclines are contraindicated. Penicillin is the only acceptable therapy for the pregnant patient. Following documentation of penicillin allergy by skin testing, reactive patients should be desensitized and treated with penicillin. Desensitization should be performed in consultation with an expert and only where adequate emergency facilities are available.
Quantitative nontreponemal tests should be repeated at 3, 6, and 12 months after treatment. Pregnant women who are treated should have monthly tests until delivery.
Retreatment may be indicated if there is a fourfold increase in titer, an initial high titer fails to show a fourfold decrease within a year, or clinical signs persist or recur. Retreatment should consist of schedules recommended for late syphilis .Pregnant women who are treated and who do not show a fourfold decrease in titer in a 3-month period should be retreated.
Miscellaneous. Cases of syphilis should be reported within 48 hours of diagnosis to a local or state health department, which usually offers referral and follow-up services. Sexual partners are notified without identification of the index case.
Sequelae. One third of all untreated patients develop sequelae that are generally confined to the CNS and cardiovascular system.
B. Late (neurosyphilis, latent more than 1 year)
History, antecedent treatment, and previous serologic tests are important in establishing the diagnosis. Patients with latent symptomatic syphilis present with complaints relevant to the particular organs involved (see section II.B.2). The latent stage prior to clinical presentation ranges from 3 to 20 years.
Physical examination. The typical lesion of late syphilis is the gumma. These nodular ulcerative lesions can involve skin, mucous membranes, skeletal system, and viscera. Cardiovascular syphilis manifests with aortitis, aneurysm, or aortic regurgitation. Neurosyphilis may be asymptomatic or symptomatic, presenting as tabes dorsalis, meningovascular syphilis, or general paralysis of the insane. Iritis, choroidoretinitis, and leukoplakia may occur.
Investigative procedures. CSF VDRL should be done for clinical signs and symptoms consistent with a CNS lesion and for patients with syphilis of more than 1-year duration to exclude asymptomatic disease.
Management
Recommendations for therapy of cardiovascular, late benign syphilis, and syphilis of more than 1-year duration are as follows: benzathine penicillin G, 2.4 million units IM weekly for 3 weeks; or if penicillin-allergic, doxycycline, 100 mg PO bid, or tetracycline hydrochloride, 500 mg PO qid, for 30 days. Alternatively, if the patient is pregnant or unable to tolerate tetracyclines, desensitization in consultation with an expert may be indicated.
Neurosyphilis may be treated with aqueous crystalline penicillin G, 12 to 24 million units, administered as 2 to 4 million units q4h IV for 10 to 14 days. An alternative regimen is procaine penicillin, 2 to 4 million units IM daily, with probenecid, 500 mg PO qid, both for 10 to 14 days. After completion of these regimens, many authorities recommend the addition of benzathine penicillin G, 2.4 million units IM. Patients allergic to penicillin should be skin-tested and desensitized in consultation with an expert.
Up to 80% of patients treated during the late stages of syphilis remain seropositive indefinitely, although their titers should decrease over time.
The provider should keep in mind that the Jarisch–Herxheimer reaction can occur, producing fever, myalgia, tachycardia, and hypotension within 24 hours of treatment. Some authors recommend hospitalization of pregnant patients since this reaction places mother and fetus at increased risk.
III. C. trachomatis
is a bacterial intracellular parasite that causes a wide range of infections. In women, these include cervicitis, salpingitis, perihepatitis, and urethritis. There are 15 serotypes, and those associated with genital infection are D to K, whereas the L strains are associated with lymphogranuloma venereum. In the United States, approximately 4% to 5% of sexually active women carry Chlamydia in their cervix; and this site appears to play a central role in transmission, with the horizontal spread to male partners and the vertical spread to neonates. There are an estimated 4 million cases annually in the United States.
A. History.
Chlamydial cervicitis is frequently asymptomatic. However, a purulent discharge may be found. Dysuria and frequency (urethral syndrome) may be present. A history of nongonococcal urethritis in the male partner is associated with a 50% isolation of Chlamydia from the female partner. Neonates born to infected mothers have a 60% to 70% risk of infection, including a 10% to 20% risk of pneumonia and a 25% to 55% risk of conjunctivitis.
B. Physical examination.
Although the cervix may appear normal, there is often a significant increase in the incidence of cervical ectopy, erythema, and friability, as well as the presence of mucopus readily seen on a cotton-tipped swab. Mucopurulent cervicitis is caused by chlamydial infection in approximately 50% of cases.
C. Investigative procedures. Culture
is the only reliable way to establish the diagnosis. Endocervical samples are required and should be frozen if not cultured immediately. The organism must be grown in cell culture, and characteristic intracytoplasmic inclusions are identified after staining. If chlamydial cultures are not available, treatment should be given if the diagnosis is strongly suggested on clinical grounds. Direct tests for chlamydial antigen utilizing monoclonal antibodies, enzyme immunoassay, or a DNA probe are useful for screening high-prevalence populations. In low-prevalence groups, there are a significant number of false-positive results. Serologic testing is of little value.
D. Management.
Tetracycline, erythromycin, and azithromycin are highly effective, with cure rates approaching 95%. Additional drugs that have demonstrated activity against Chlamydia include sulfamethoxazole-trimethoprim, rifampin, clindamycin, ofloxacin, and amoxicillin.
The CDC-recommended regimens are azithromycin 1 g PO in a single dose or doxycycline, 100 mg PO bid for 7 days. Alternative regimens are ofloxacin, 300 mg PO bid for 7 days; erythromycin base, 500 mg PO qid for 7 days; erythromycin ethylsuccinate, 800 mg PO qid for 7 days; or sulfisoxazole, 500 mg PO qid for 10 days (this has inferior efficacy to other regimens) (3).
The CDC-recommended regimen for pregnant women azithromycin, 1 g PO or erythromycin base, 500 mg PO qid for 7 days. Alternative regimens include erythromycin base, 250 mg PO qid for 14 days or erythromycin ethylsuccinate, 800 mg PO qid for 7 days or 400 mg PO qid for 14 days. If erythromycin cannot be tolerated, amoxicillin, 500 mg PO tid for 7 to 10 days or clindamycin, 300 mg PO tid for 7 days, are recommended. Limited data exist on these regimens.
Sexual partners should be evaluated and treated.
Follow-up testing is unnecessary unless symptoms persist or reinfection is suspected. Pregnant patients, however, should be retested. At least 3 weeks must elapse after completion of therapy before retesting.
IV. Genital herpes simplex virus.
Venereal transmission through intercourse or orogenital contact is common for herpesvirus, a DNA virus. After the genital skin is inoculated, the virus infects peripheral nerve endings and travels to the lumbosacral dorsal root ganglia. A persistent, but subclinical, infection is established in the ganglion cells. Periodically, the virus becomes active and travels by peripheral nerves to the skin, inducing the characteristic focal recurrent lesion. Infections with herpesvirus type I or II are the most common cause of vesiculoulcerative lesions of the female genital tract. Type I generally causes oral lesions (fever blisters), and 75% to 80% of genital lesions are type II. However, these percentages vary with the population screened. About 50% to 70% of patients with primary infection experience recurrence. The attack rate (percentage of those who contract herpes simplex virus after exposure) for susceptible individuals is believed to be about 75%. There are an estimated 500,000 new cases in the United States annually, with more than 20 million episodes of recurrence.
A. History.
Incubation periods range from 1 to 30 days (median, 6–8 days). Generally, the presenting complaint is of blisters or ulcers on the vulva or severe vulvar pain. Much less often, severe dysuria, general malaise, fever, and enlarged inguinal nodes are the presenting features. The lesions typically evolve from vesicles to pustules to ulcers to crusts, with healing occurring over 14 to 21 days. They may be preceded by pruritus, burning, or hyperesthesia of the skin. Some patients may have no symptoms; thus it is not uncommon to miss the first infection. Recurrent infections are generally less severe than the primary infection and may be triggered by emotional stress, menses, intercourse, or may be totally unpredictable. Systemic symptoms rarely occur, and lesions last from 7 to 10 days. Recurrent lesions represent a reactivation of latent virus, not reinfection.
B. Physical examination.
Exquisitely sensitive vesicles and erosions of the labia, vaginal canal, perineum, and oropharynx may be found. Intense edema of the labia and urethra, as well as inguinal adenopathy may be present. Recurrent disease follows essentially the same course except that it is less debilitating, there are few ulcers, and adenopathy is seldom present. It is generally believed that there is no clinical difference between the lesions caused by the two virus types.
C. Investigative procedures.
The vesicles and ulcers characteristic of the disease are easily recognized, especially if there is a positive history. Cervical herpes virus is less obvious clinically. A Papanicolaou (Pap) smear of cervical herpes virus contains characteristic multinucleate giant cells in about 30% to 50% of patients. Definitive diagnosis can be confirmed by viral culture. Specimens should be taken using cotton-tipped or Dacron-tipped swabs placed in viral transport medium and held at 4°C until cultured. Direct detection of viral antigens using immunodiagnostic methods is available and provides sensitivities of 85% to 90%. These methods are much less sensitive in detecting asymptomatic viral shedding. Herpes virus antibodies appear within 4 days of primary infection and are present thereafter; therefore, they are not helpful in recurrent infection unless a change in titer is documented. Since herpesvirus is an STD, culture for gonorrhea and chlamydia infections and a serologic workup for syphilis, HIV, and hepatitis B and C should be obtained.
D. Management
General measures include keeping the vulva and perineum as dry as possible, wearing cotton underwear, and exposing the vulva to a heat lamp or a hair dryer, which may be soothing. Analgesics may be required because of pain and hypnotics may be required if there is interference with sleep. Occasionally, urinary retention may necessitate the use of an indwelling catheter. Sitz baths and local anesthetic creams may be helpful.
Specific measures. Oral acyclovir, valacyclovir, and famciclovir provide partial control of the symptoms and signs of herpes episodes but do not eradicate latent virus. Topical therapy is less effective and its use is discouraged. The CDC guidelines are as follows:
For first clinical episodes of genital herpes, the recommended regimen is acyclovir, 200 mg PO 5 times a day for 7 to 10 days or until clinical resolution. Alternatives are famciclovir 250 mg PO 3 times a day for 7 to 10 days or valacyclovir 1 g PO twice a day for 10 days. The dose of acyclovir is doubled for herpes proctitis and treatment is for 10 days, experience with famciclovir or valacyclovir in proctitis is lacking.
When treatment for recurrent episodes starts during the prodrome or within 2 days of lesion onset, limited benefit may result. The recommended regimen is acyclovir, 200 mg PO 5 times a day for 5 days or 400 mg PO tid for 5 days or 800 mg PO bid for 5 days. Drug therapy begun more than 2 days after onset of lesions has not been proven to be of benefit. Alternatives are famciclovir 125 mg PO twice a day for 5 days or valacyclovir 500 mg PO twice a day for 5 days.
Daily suppressive therapy reduces recurrences by at least 75% in patients having six or more episodes per year. Safety and efficacy have been reported for as long as 6 years. Asymptomatic viral shedding and the potential for transmission are not totally eliminated. After 1 year, therapy should be discontinued to reassess the rate of recurrence. The recommended regimen is acyclovir, 400 mg PO bid or famciclovir 250 mg PO bid or valacyclovir 500 mg PO bid or valacyclovir 1000 mg PO once a day.
For patients who have severe symptoms or complications that necessitate hospitalization, intravenous acyclovir shortens the median course of first episodes by approximately 7 days.
Acyclovir has not been adequately tested in pregnant or lactating women. Use in pregnancy is recommended only in the presence of life-threatening maternal infection. However, evidence of adverse effects has not been shown in ongoing registries, and therefore first clinical episodes in pregnancy may also be treated with acyclovir.
Patients should be counseled about the disease and advised to abstain from sexual intercourse while lesions are present. The risk of transmitting herpes simplex virus during asymptomatic periods is unknown. The use of condoms should be encouraged during all sexual exposures. Women also need to be instructed to inform their clinicians of their history of genital herpes early in pregnancy since serious neonatal infection may occur during parturition.
E. Sequelae.
In addition to a possible link with cervical neoplasia and neonatal infections, patients with the disease also have a high incidence of depression and sexual dysfunction. Much of the burden of this disease is of an emotional and social nature. Self-help groups, such as the American Social Health Association, may be of great assistance in helping herpes simplex virus patients cope with their problems.
V. Chancroid
is an ulcerating disease of the genital region caused by Haemophilus ducreyi. Its exact incidence is unknown, although clinical infection is rare in women. The incubation period is generally 4 to 7 days, the male to female ratio is 10:1.
A. CDC guidelines.
Chancroid is probably underreported because of the difficulty in proving the diagnosis. In an attempt to obtain more accurate incidence figures, the CDC has changed its reporting guidelines. The new case classification is:
Probable: a clinically compatible case with one or more painful genital ulcers and both
No evidence of T. pallidum by dark-field examination of ulcer exudate or by a serologic test for syphilis performed at least 7 days after the onset of ulcers.
Clinical presentation of the ulcer is not typical of a disease caused by herpes simplex virus, or an HSV culture is negative.
Confirmed: A case that is laboratory confirmed. Recently there has been a documented association of chancroid and HIV. The presence of HIV infection predisposes women to chancroid and increases the possibility of treatment failure.
B. History.
The patient usually presents with the complaint of a painful lesion.
C. Physical examination.
The initial lesion in women occurs on the fourchette, labia minora, urethra, cervix, or anus. Extragenital lesions may occur but are uncommon. Chancroid begins as an inflammatory pustule or papule that quickly ruptures to form a painful, nonindurated, shallow ulceration. Women tend to have multiple ulcers, with an average of four. The ulcer is 1 to 2 cm in diameter with ragged undermined edges, and the base is often covered with a purulent exudate. Approximately 1 week after the initial ulcer, lymphadenopathy, which is usually unilateral, develops in 50% of patients. This subsides without suppuration in more than half of the patients; however, if left untreated, the lymphadenitis may undergo unilocular suppuration. The involved nodes are inflamed and tender, and the overlying skin is erythematous. These nodes then break down, forming a single drainage sinus and/or fever may occur.
D. Investigative procedures
A presumptive diagnosis of chancroid may be made in the presence of a genital ulcer(s) with a negative examination for syphilis (dark-field examination, serologic tests, or both) and no evidence of herpesvirus during follow-up visits.
A definitive diagnosis is made by isolation of the organism from ulcers of lymph nodes on an appropriate selective medium, but the organism is difficult to culture.
DNA probes and the use of PCR may make diagnosis easier in the future.
E. Management
Drug therapy. Recommended regimens include azithromycin, 1 g orally; or ceftriaxone, 250 mg IM or ciprofloxacin, 500 mg PO bid for 3 days; or erythromycin, 500 mg PO qid for 7 days.
Fluctuant nodes should be aspirated through healthy adjacent skin as often as necessary to prevent the formation of a draining sinus. Incision and drainage of buboes may be necessary.
All sexual partners should be treated.
As with all STDs, examination should be undertaken for the presence of other STDs, HIV, and hepatitis B and C.
All patients should be counseled about the risk of transmitting chancroid and the risk of either transmitting or acquiring HIV and hepatitis B and C through sexual intercourse. Patients should be encouraged to abstain from intercourse until all lesions have healed. Condoms have also been shown to prevent the transmission of chancroid.
VI. Lymphogranuloma venereum
(LGV) is a granulomatous disease of the genital region that is primarily sexually transmitted. The causative organism is C. trachomatis, and the serotype is different from that which causes cervicitis. The incubation period is unknown. It is more common in men than women. LGV is rare in the United States, however, the actual prevalence is unknown.
A. History.
The presenting complaints may include a painless lesion, lymphadenopathy, lower abdominal pain, rectal bleeding, rectal purulent discharge, and proctitis with tenesmus, depending on the stage of development.
B. Physical examination
The initial lesion is a painless vesicopapule that appears on the external genitalia, vaginal walls, or cervix in women. It appears a few days to a few weeks after exposure. This quickly breaks down to form a small erosion that heals rapidly in men, but more slowly in women. As many as 50% of these lesions are asymptomatic and heal without scarring.
The secondary stage is characterized by lymphadenopathy, which is usually unilateral, but involves multiple nodes. This results in the formation of a large nodal mass with inflamed overlying skin. The involvement of inguinal and femoral nodes with a depressed area over the inguinal ligament (groove sign) is almost pathognomonic for LGV. These nodes then develop multiple foci of suppuration, followed by skin breakdown and formation of multiple draining sinuses (as opposed to chancroid, which has a single area of suppuration and one draining site). Genital mutilation often develops.
The inguinal adenopathy typically resolves after 2 to 3 months if untreated. However, in the tertiary stage involvement of internal nodes (perirectal and perivaginal) leads to an anorectal syndrome with lower abdominal complaints and proctitis with tenesmus, rectal bleeding, and a purulent discharge. This may lead to rectal strictures, elephantiasis of the labia, and rectovaginal fistulae. Although extragenital lesions are rare, LGV is associated with significant systemic signs such as fever, malaise, myalgias, and arthritis.
C. Investigative procedures
The diagnosis of LGV is best made by complement fixation titers, which are available through most laboratories. However, there is cross-reaction with other chlamydial serotypes. A fourfold increase in titer or a titer of greater than 1:64 should be considered diagnostic. A titer of 1:16 to 1:64 is suggestive, but can occur in individuals with other chlamydial infections. The organism can be recovered from nodal aspirations, but culture is technically difficult, expensive, and rarely available.
D. Management
Drug therapy. The recommended regimen is doxycycline 100 mg PO bid for 21 days. An alternative regimen is erythromycin 500 mg PO qid for 21 days.
As with chancroid, involved lymph nodes (buboes) should be aspirated through adjacent normal skin, and incision and drainage may be indicated.
Sexual contacts should be examined and treated.
Investigation for the presence of other STDs, including HIV and hepatitis B and C, should be undertaken.
VII. Granuloma inguinale
is generally considered a disease of tropical and subtropical regions. It is rare in the United States. The causative organism is an intracellular gram-negative bacterium, Calymmatobacterium granulomatis.
A. History.
The presenting complaint is usually of an enlarging painless ulcer.
B. Physical examination.
The initial lesion is a painless ulcer that has little undermining and is usually located on the labia or fourchette. There is no lymphadenopathy unless the lesion is secondarily infected. Occasionally, a deep granuloma may appear to be a fluctuant node. These “pseudobuboes” may erode through skin and slowly extend by local enlargement. Constitutional symptoms are absent. If left untreated, these lesions progress insidiously, often along skin folds, and take on a granulomatous appearance. The central portions of the ulcer may heal spontaneously, leaving gray, fibrous scars with active advancing borders. These scars can produce deformities and strictures. Long-standing lesions often produce elephantiasis-like enlargement of the labia and extensive ulceration of the perineum. Extragenital lesions can occur almost anywhere by direct spread, and systemic dissemination (presumably blood-borne) has been described. In advanced cases, general debilitation may lead to death. The incidence of squamous cell carcinoma is increased within the chronic ulcers.
C. Investigative procedures.
The diagnosis of granuloma inguinale should be considered in any genital ulcer lasting more than several weeks, especially in the absence of lymphadenopathy. The diagnosis is best made by finding the typical organisms (Donovan bodies) with histiocytes on stained smears or tissue sections from the edge of lesions. The tissue should be crushed and spread between two glass slides and stained with Wright's or Giemsa stain. The Donovan bodies exhibit bipolar staining and are commonly described as having a “safety pin” appearance.
D. Management
Drug therapy. The recommended regimens include doxycycline, 100 mg bid for 3 weeks or until all lesions have healed (from 2–12 weeks); trimethoprim-sulfamethoxazole DS (160/800) bid for at least 3 weeks; erythromycin, 500 mg qid for 2 to 3 weeks; or ciprofloxacin 750 mg PO bid for at least 3 weeks.
Sexual partners should be examined and treated.
Patients should also be examined for the presence of other STDs.
VIII. Pediculosis pubis.
The causative organism for pubic lice is Phthirus pubis (crab louse), which is different from body or head lice. Its life cycle is approximately 25 days and can be completed entirely on the human host. Soon after reaching maturity, impregnated females begin laying eggs (nits) that hatch in 7 to 8 days. Each egg is cemented to a single hair shaft.
Transmission is generally by direct body contact, usually sexual. The risk of transmission from fomites is negligible. Pubic lice are the most contagious STD known, and the risk of acquiring the infestation is approximately 95% after a single exposure. The incidence is higher in young women from 15 to 19 years of age and is higher in men older than 20 years. There is no racial difference. Although pubic lice can be transmitted without sexual contact, abuse should be considered in any infection in a child.
A. History.
The chief complaint of infested persons is pruritus and, because of autosensitization, it is not always localized to the affected sites. Patients may report seeing organisms move in their pubic hair.
B. Physical examination.
The louse is usually found in the pubic area, eyebrows, and eyelashes. Nits may be seen at the base of the hair shafts in these areas. Scratching may lead to secondary excoriations, which may predispose to lymphadenitis or pyoderma. The infested patient may also present with a symptomatic, bluish, nonblanching, nodular rash on the lower trunk and upper thighs, known as maculae ceruleae. This rash is believed to be either secondary to altered blood pigments in the patient or an excretory substance from the louse's salivary glands.
C. Investigative procedures.
A magnifying glass may be helpful in visualizing the lice or nits. They may also be placed on a slide with a drop of mineral oil and examined under the microscope. The lice look like miniature crabs.
D. Management
For pubic infestation, treatment with gamma benzene hexachloride (lindane [Kwell]), a solution of pyrethrins with piperonyl butoxide (RID), or a 1% permethrin creme rinse (Nix) is equally effective.
Lindane is available by prescription only, is absorbed through the skin, and can cause CNS toxicity (although this has been described only when it was used improperly or taken orally). It should not be used in pregnant or lactating women or on children younger than 2 years. The lotion is applied to the affected area, left on for 12 hours, and repeated in 1 week. The shampoo is massaged into the pubic hair and worked into a lather, left on for 4 minutes, and washed off. It is usually not necessary to repeat the application. Nits remaining after either treatment can be removed with forceps or a fine-toothed comb.
The pyrethrin solution is available without prescription and is poorly absorbed through intact skin, so it is apparently free of toxicity. Two ounces are massaged into dry pubic hair, left on for 10 minutes, and washed off. One treatment is all that is necessary, and remaining nits can be removed in the manner described previously. This is the treatment of choice in pregnancy and lactation.
1% permethrin creme rinse is available by prescription only. It should be applied to pubic hair and washed off after 10 minutes. This treatment should be repeated in 10 days, and remaining nits can be removed as discussed previously.
For infestation of the eyelashes, apply petrolatum bid for 8 days and remove the nits by hand.
Even though fomite transmission rarely (if ever) occurs, patients should be advised to wash and dry sheets, bedding, and clothing in the hot cycle. Sprays are available for use on inanimate objects, but are unnecessary and potentially dangerous and their use should be discouraged.
All sexual contacts should be treated simultaneously, and the patient should be examined for the presence of other STDs, including hepatitis B and HIV, since one third to one half of all patients have another STD.
Follow-up after 1 week if symptoms persist. Nonresponders should be retreated with an alternative regimen.
IX. Scabies infestation
is caused by the mite Sarcoptes scabiei. Like the crab louse, its entire life cycle can be completed on humans. The adult female burrows into the skin and remains there for life, approximately 30 days. She rapidly begins laying two to three eggs per day, which become adult mites in 10 days. However, fewer than 10% of the eggs become adults. The average patient with scabies only has 10 to 15 live adult female mites on the body at any time. The mites can survive for only 2 to 3 days at room temperature apart from humans. However, they can survive longer in warm humid areas such as nursing homes than in cool, dry climates.
Several different types of scabies have been described. These include scabies incognito, occurring in persons receiving steroids, which alter the clinical presentation; scabies in the clean, found in those with good hygiene and in whom physical findings are minimal; and nodular scabies, which present as reddish-brown pruritic nodules in the usual scabetic distribution and appear to represent a hypersensitivity reaction; Norwegian scabies, which is rare, highly contagious, and usually found in institutions with a propensity for mentally retarded and debilitated persons; and animal-transmitted scabies, with dogs as the major source of infection. All of these types are treated the same except the latter. The animal mite cannot complete its life cycle on the human host, so the infestation is self-limited (several weeks), and the animal must be treated to prevent reinfestation.
Transmission is by close personal contact, usually sexual. Scabies are rarely transmitted by fomites or by casual contact. It is more common in men than women.
A. History.
The primary symptoms are pruritus and a rash that is caused by sensitization to the mite. In primary infestation, it takes 4 to 6 weeks for these to occur, although in reinfestation, symptoms may appear within 24 hours. The pruritus is typically nocturnal. Since the immune system must be intact for a response, patients with a depressed immune system may not itch.
B. Physical examination.
The rash is usually symmetric and located primarily on the hands (especially finger webs and sides of digits), wrists, elbows, female breasts, waist, penis, and the lower portion of the buttocks. The pathognomonic lesion is the burrow, which is a short, wavy, dirty-appearing line. This lesion is seen very infrequently now even though the incidence of scabies is not decreasing. Excoriations of these lesions can lead to secondary infection.
C. Investigative procedures.
A presumptive diagnosis is made by observing the typical burrows in a symptomatic patient. A definitive diagnosis can be made by demonstrating the mite, the fecal pellets, or the burrow by special tests.
A drop of mineral oil can be placed on the skin lesions, which are then scraped with a scalpel blade and transferred to a slide for observation through the microscope.
The lesions can be moistened with alcohol, then scraped and transferred to a microscopic slide. Adding 20% potassium hydroxide to the slide and heating gently aids in clearing epidermal debris.
In the tetracycline test, a liquid tetracycline solution is applied to areas where burrows are usually found. After drying, the area is cleaned vigorously with isopropyl alcohol and then observed with a Wood's lamp. Burrows that have retained the tetracycline appear as yellow-green lines.
The ink test, similar to the tetracycline test, involves rubbing a fountain pen over the suspected area, then cleaning with alcohol, and looking for burrows that the ink has penetrated.
D. Management
Several treatments are effective.
Lindane (1%) lotion is applied thinly but thoroughly from the neck down and left on for 12 hours. The application is repeated in 1 week only for those with evidence of treatment failure or reinfestation. Lindane should not be used in pregnancy or lactation or in children younger than 2 years. Bathing prior to application is not recommended since it can potentiate absorption of the drug. The usual amount needed for adults is 30 mL.
Permethrin, 5% cream (Elimite), is an excellent scabicide and less toxic than lindane. This is used as a single application in the same way as lindane and washed off after 10 hours. Over-the-counter permethrim products are lower strength, designed to treat pediculosis, and are ineffective in the treatment of scabies.
Sulfur, as a 6% solution is applied nightly for 3 nights and washed off 24 hours after each application. Its efficacy and toxicity are not well established, and it is unpleasant to use.
Treatment should include brushing the formulation under the ends of the fingernails. In children and elderly patients, the face, head, and especially the postauricular fold should be included in treatment.
Bedding and clothing should be decontaminated via washing and hot cycle drying. Fumigation of living areas is unnecessary.
All persons in close personal contact with the patient should also be treated with one of the foregoing regimens.
For the pruritus, an oral antihistamine, such as hydroxyzine hydrochloride (Atarax), 25 mg tid; or diphenhydramine (Benadryl), 25 mg qid, as needed can be used simultaneously with the scabicide, or a 1% hydrocortisone cream can be used after treatment.

Female Sexual Dysfunction

Definition :
Female sexual dysfunction (FSD) is defined as a disorder of sexual desire, arousal, or orgasm, and/or sexual pain, which results in personal distress and has an impact on quality of life and interpersonal relationships. It is a compilation of problems that has both biologic and psychosocial components and is multifactorial in etiology.

Introduction :
Female sexual dysfunction (FSD) is defined as a disorder of sexual desire, arousal, and orgasm, and/or sexual pain that results in significant personal distress and might have an impact on the quality of life and interpersonal relationships . It affects approximately 4 out of 10 women in the United States, and according to the 1995 American College of Obstretricians and Gynecologists (ACOG) Technical Bulletin, sexual dysfunction occurs in as many as 35% of US women, with lack of libido being the most common symptom reported . Based on self-reported complaints from US census data, 10 million women between the ages of 50 and 74 report diminished lubri-cation, pain with intercourse, decreased arousal, and difficulty achieving orgasm . Several animal and human studies have documented that FSD is a progressive, age-related, hormone-sensitive condition .
A significant proportion of postmenopausal women are predisposed to experience FSD . In addition to the physical changes associated with menopause, FSD can significantly alter self-esteem and intimate relationships .
Female sexual dysfunction was previously thought to be caused by primarily psychological factors and interpersonal issues, and male sexual dysfunction was thought to be caused by physical and biologic changes. FSD, however, is a compilation of problems that has both biologic and psychosocial components. It is only recently that FSD has been considered to have a multifactorial etiology . Our improved understanding of normal female sexual function and age-related changes have helped us to better classify the types of dysfunction. FSD can also be associated with conditions that cause male erectile dysfunction, such as hypertension, smoking, elevated cholesterol, and pelvic surgery .
Models of Normal Human Sexual Functioning
In 1966, Masters and Johnson described the human sexual response that has remained a classic teaching model. This linear model, which focuses primarily on the vascular and neurologic changes, includes four stages: 1) excitement; 2) plateau; 3) orgasm; and 4) resolution.
Excitement refers to changes in the central nervous system(CNS) that cause vasodilation and increased blood flow to the genitalia. Several hormones play key roles in this process. The outcome of these complex physiologic processes results in lubrication and expansion of the vagina, increased labial girth, and exposure of the introitus, due to opening of the labia. A well-estrogenized vagina has prominent rugae, particularly in the lower third. These rugations allow the vagina to distend and increase frictional tension with coitus . The clitoris elongates and increases in diameter while the uterus elevates over the levator plate . Although the clitoris arises from the same embryologic structure as the penis, the genital tubercle, it lacks the bilaminar tunica albuginea and venous plexus. Therefore, during sexual stimulation the clitoris becomes engorged, but not erect. The uterus and cervix also add to lubrication by secreting mucus during this phase of stimulation.
Interruption of the vascular supply and innervation during pelvic surgery has remained a controversial issue in the topic of postoperative FSD. Ovarian atrophy and fibrosis of the vagina and clitoris can occur after disruption of the uterine vessels and removal of the uterus . Previous studies, however, have shown conflicting results of pelvic surgery on sexual function postoperatively . This might reflect the limited use of validated questionnaires rather than sexual dysfunctions related to pelvic surgery.
In older women, changes associated with excitement begin to diminish. Labial swelling and clitoral engorgement rarely occur in women older than age 60 . Vaginal lubrication, which usually takes seconds in young women, can take 1 to 3 minutes in women older than 40, if it occurs at all. The ability of the vagina to elongate, widen, and expand is reduced.
Excitement is followed by plateau, in the Masters and Johnson model. During this phase, the labia become engorged and the clitoris retracts. The Bartholin glands secrete fluid, and congestion of the outer third of the vagina occurs. The upper two thirds of the vagina expand, and pelvic--floor muscle tension builds. The combination of neurovascular injury and/or loss of muscular tone, due to birth trauma, surgery, menopause, vascular insufficiency, and aging in general can result in vaginal anesthesia, lack of orgasm with coitus, or coital incontinence .
Kaplan later modified this model by dividing the excitement phase into desire and arousal, and eliminating the plateau phase . In his model, desire results from neurogenic changes and arousal from vasogenic changes. The new diagnostic criteria for FSD are based on this revision.
Orgasm occurs when the levator ani muscles contract. This altered state of consciousness consists of 8 to 12 contractions of musculature at specified intervals, followed by vaginal and uterine contractions. Sensory afferent stimulation from the clitoris, labia, vagina, and periurethral glands travel to supraspinal structures. Adequate sensory information results in a discharge of central neurotransmitters and causes the contractile phase of orgasm. Some sensory information is also relayed to the cortical pleasure sites. The final result is massive release of muscular tension.
The postmenopausal uterus tends to be smaller and does not enlarge to premenopausal magnitude. Some women even experience painful contractions during orgasm .
Resolution was described by Masters and Johnson as the end of the sexual response and is characterized by pleasant, gradual diminishing of sexual tension following the above phases. Although this model accurately reflects the physiologic characteristics of the human sexual response, it is limited by the omission of social and psychological factors.
The biopsychosocial model postulates that biologic or physiologic processes alone cannot characterize female sexual response. It is, instead, a combination of biology, psychology, sociocultural influences, and interpersonal relationships. This model suggests that emotional intimacy, feeling emotional closeness, commitment, sharing, and tenderness to another person is often required for a woman to respond to sexual stimuli. This theory holds that a woman's sexual experience is initiated by a response to intimacy and a desire to share themselves emotionally and physically rather than being provoked by sexual fantasies or thoughts. Once the woman is emotionally aroused, she can then become sexually aroused, which will in turn lead her to sexual desire, and the ultimate culmination of the event for sexual reasons . Sexual arousal can be triggered by various stimuli ranging from conversation to music to direct physical contact. Therefore, a woman's lack of spontaneous sexual desire should not always be viewed as a dysfunction. There might simply be a lack of emotional connectedness to the person directing the sexual advances. Another point is that this model does not place orgasm as the goal of a sexual experience. Instead personal satisfaction, regardless of whether orgasm is reached, becomes the goal .
Physiology of Normal Sexual Function
Physicians, women, and their partners can comprehend abnormal sexual functioning once they appreciate the basic physiology behind normal sexual function. This usually begins with understanding the structures and bioactive substances involved in sexual function. There are several organs that are vital to a normal sexual response-the brain, however, is the center of the sexual universe. The five senses (smell, sight, sound, taste, touch) help to relay sexual images, fantasies, and ideas to the brain. The brain accepts these signals and translates them into messages the body can understand. These messages include signals to increase vascular blood flow and release sex hormones, such as estrogen, testosterone, and vasoactive substances.
The central nervous system is affected by both internal and external factors that result in a need or want to partake in sexual activity. The limbic and paralimbic systems emit signals that are responsible for a woman's arousal . Munarriz states that, in the biology of sexual function, desire consists of three areas: biologic, which is controlled in part by sex hormones and neurotransmitters; motivational roots, which are partly based on intimacy; and pleasure,relationship issues, and cognitive factors, such as risk and wish. Arousal results from central mechanisms, dreams, fantasies and thoughts, nongenital peripheral mechanisms, salivation, sweating, cutaneous vasodilatation, nipple erection, and genital engorgement.
Estrogen increases blood flow to the brain and the vagina. This might be related to estrogen's ability to stimulate the release of substances such as nitric oxide from endothelial cells, which act in a vasoactive manner to induce dilation. Levels of estradiol that are below 50 pg/mL have been correlated with sexual complaints . Decreased blood flow, sensation, and sex drive are all associated with low estrogen levels. In vivo studies in rabbits and rats have demonstrated that pelvic nerve stimulation causes a response that mimics genital arousal from sexual stimulation . Using these models, several studies have shown the importance of ovarian substances and hormones in modulating genital blood flow, vaginal lubrication, and vaginal tissue structural integrity . There is some evidence that this hormone might have effects on the urethral, vaginal, and clitoral blood flow through prevention of atherosclerotic plaque formation in the pelvic vasculature . Estrogen also increases vibratory sensation peripherally, and has a positive effect on nerve growth and nerve transmission .
Testosterone also serves an important role in women. Its concentration is 7 to 10 times higher in the brain than estrogen, and it is the primary precursor for estradiol biosynthesis in the brain . Testosterone is thought to work peripherally by either directly affecting arterial blood flow, or indirectly by increasing the availability of estrogen. Additionally, the hypothalamus, which controls sexual function and mood, contains dense estrogen and testosterone receptors. A study by DeCherney suggests that the testosterone receptors in the brain are linked to sex drive. The study implies that testosterone has a central role in controlling sex drive through receptor-mediated activities.
Normally, the clitoris and vagina are under the contractile tone of the pudendal, autonomic, and somatic nerves. Based on rabbit models, sexual stimulation results in release of neurogenic and endothelial nitric oxide (NO) . This might play a role in clitoral cavernosal artery inflow and helicine arteriolar smooth muscle relaxation during arousal .
Vaginal lubrication might be mediated by several neuro-transmitters, including NO and vasoactive intestinal peptide (VIP) .These substances modulate vascular and smooth muscle relaxation, causing capillary inflow that overwhelms normal sodium reabsorption, resulting in 3 to 5 mL of vaginal secretions. Smooth muscle relaxation that increases the length and caliber of the vagina, particularly in the distal two thirds, might also be due to these substances. Phosphodiesterase type V enzyme has been found in human clitoral cavernosal smooth muscle, which degrades cyclic guanosine monophosphate (cGMP) .Inhibition of this substance might result in relaxation of clitoral and vaginal smooth muscle and improve arousal .Other factors and hormones such as oxytocin and endorphins act on the brain to promote sexuality.
Diagnostic Classifications of Female Sexual Dysfunction
Inconsistency in classifying FSD has existed for years. In the past, many researchers created their own definitions for sexual disorders, which inevitably led to confusing and incongruent results. An attempt to address this issue was made through a panel of experts at the Consensus Development Conference on FSD in 1998 . The panel created a new classification of FSD that was published in the Journal of Urology, and reprinted with invited expert comment in the Journal of Sex and Marital Therapy [2001]. This system can be used in FSD caused by either medical or psychosocial etiologies, and it includes some modifications to the Diagnostic and Statistical Manual [of Mental Disorders] IV (DSM IV) system. Some experts would argue that this system is still based on the male linear model of sexual function . They argue that women can experience satisfaction and pleasure without experiencing every phase of the sexual response cycle. Our continuing quest to understand female sexual function and dysfunction might result in modifications of this classification system with time. The current system classifies the following disorders.
Hypoactive sexual desire disorder
Includes persistent or recurrent lack of sexual thoughts and/or receptivity to sexual activity, which causes personal distress. This can be secondary to medical causes (ie, endocrine) or related to psychological or emotional dis-orders. There are currently no validated, research-proven treatments for hypoactive sexual desire disorder, but lack of the estrogenic and androgenic effects on the female sex drive has been implicated as a possible cause.
Sexual aversion disorder
Sexual aversion disorder is the persistent or recurring phobic aversion to and avoidance of sexual contact with a sexual partner, which causes personal distress. This dis-order is usually caused by an underlying emotional or psychological problem, commonly physical or sexual abuse or childhood trauma.
Sexual arousal disorder
Sexual arousal disorder is the persistent or recurrent inability to attain or maintain sexual excitement, which causes personal distress. These disorders can be primarily physiologic in origin, resulting from insufficient vaginal lubrication, poor vascular blood flow to the genitalia, or neurologic etiologies. It can be secondary to medical/surgical therapy, pelvic floor disorders, and deficiencies in relaxation of pelvic floor musculature. This disorder can result from psychological factors, but is more commonly associated with organic factors. Sexual arousal disorder has been the focus of most of the basic science and clinical research in FSD.
Orgasmic disorder
Orgasmic disorder is defined as the persistent or recurrent loss of orgasmic potential after sufficient sexual stimulation and arousal, which causes personal distress. Orgasmic disorder can be primary (never achieved orgasm) or secondary, caused by traumatic nerve injury after pelvic floor surgery or spinal cord injury. There are several approaches to therapy, including addressing emotional trauma or medical/physical factors.
Sexual pain disorder
Sexual pain disorder is a persistent or recurrent genital pain associated with noncoital sexual stimulation, which causes personal stress. This disorder is further subtyped into dyspareunia, vaginismus, and other sexual pain disorder induced by noncoital sexual stimulation.
Clinical Evaluation of the Female Patient with Sexual Dysfunction
In the general gynecology or primary care setting, patients do not commonly present with FSD symptoms, even when a good rapport has been established. Many patients are reluctant to ask questions during evaluation, despite a high prevalence rate of FSD. For this reason, patients might be more comfortable answering questions presented on a standard history intake form. A recent study by Nusbaum et al. demonstrated the prevalence of sexual concerns in women seeking routine gynecologic care. Of the 964 (65%) respondents, 98% of this group reported one or more sexual concerns. Women might respond to an anonymous survey, but most women are hesitant to actively address these issues at annual examinations. This might be due to the perception or the actuality that the physician is too busy, or they are not approachable. Similarly, most health care providers fail to address sexual history as a part of the medical history. Societal, cultural, and religious values also play an important role in a woman's comfort level for discussing sexual function .
Once a problem is uncovered, clinicians might consider behavioral modification first. Reading articles/books on the symptoms can empower a woman and help educate the partner. Self-examination of the genitalia should be encouraged routinely. Educating a patient about their genital anatomy can help address body-image issues. Prolonged touching, both by a partner or the patient herself, can improve vaginal blood flow and potentially enhance orgasm. Changing routine sexual practices and experimenting with different places and positions can result in improved function for some. Creative thinking can help to bring excitement into a love life without significant medical intervention. Clinicians can focus on these techniques initially, instead of making a diagnosis.
Caregivers should also stress the importance of changes in lifestyle. Postmenopausal women who complain of decreased desire might benefit from aerobic training. Exercise, particularly strength training, has been shown to improve body image, decrease depression, and increase libido and levels of testosterone .Exercise of the pelvic floor also enhances pelvic blood flow, and possibly enhances orgasm by improving awareness . Smoking can decrease vaginal flow and worsen atherosclerotic disease in the aorto-iliac vessels.
For patients who have not benefited from behavioral modifications, a complete evaluation should be performed, including history, review of medications, completion of a sexual function questionnaire, a hormonal profile, when indicated, and physical examination. This examination should delineate if estrogen therapy is indicated and if there are painful trigger points.
Treatment of Female Sexual Dysfunction
Addressing FSD in a clinical setting should begin with an open discussion about the importance of nonpharmacologic therapies. Ultimately, the goal of therapy is to achieve satisfying and pleasurable experiences. The approach to therapy should start with identification of the disorders from a biologic or physical standpoint. Tantamount to defining the medical problem is to address relational, situational, and psychological issues. Couples should first engage in open conversation about their preferences in a way that is nonjudgmental or intimidating. Many couples benefit from short-term counseling to develop effective means of communicating. Couples should also address expectations of sexual frequency. It is important to educate patients and their partners that each sexual encounter does not have to culminate in orgasm to be pleasurable or satisfying.
Pain disorders
Addressing pain disorders should begin with obtaining a complete history of a woman's experiences. Depending on the population surveyed, between 20% and 66% of women have been sexually or physically abused at some point in their lives . Caregivers should specifically ask if date rape or forced intercourse during a steady relationship has occurred. Mental and verbal abuse, which is highly prevalent and underestimated, can also manifest as pain. Women who have been abused often dissociate from their bodies as a defense mechanism. Later in life, this can result in unconscious spasms or painful coitus.
A diagram of the female genital tract should be shown prior to examination. It is helpful for the caregiver to explain how the examination will proceed and for the woman to point out the painful area prior to examination. A mirror might be utilized while the examination is conducted. Begin with reviewing the external genitalia and asking again where the pain occurs. Women with vestibulodynia might have diffuse or local disease that causes pain on insertion. Patients with vaginismus involuntarily contract their pelvic floor even prior to examination or coitus. Both disorders can benefit from education, pelvic-floor physical therapy (including biofeedback and myofascial release), and psychological counseling, if indicated. The presence of endometriosis and/or pelvic adhesions can also cause deep or 'bump' dyspareunia, and thus might require medical or surgical intervention. In postmenopausal women with atrophic vaginitis, vaginal administration of estrogen has shown a clear benefit in decreasing pain on insertion, improving lubrication, and decreasing vaginal burning . Estrogen can be administered in a variety of methods: cream, tablet, or a ring. Some women also experience coincident changes in desire and arousal, which can result in pain if they are not fully aroused. A psychotherapist or a sex therapist can address relational issues. Patients should attend to situational factors such as fatigue and emotional exhaustion.
The presence of incontinence and/or prolapse does not prohibit women from functioning sexually and/or having satisfying activity . However, women undergoing procedures to correct incontinence and/or prolapse might experience complaints of pain postoperatively . Weber et al. demonstrated improved or unchanged sexual function after surgery for prolapse/incontinence, but higher rates of dyspareunia were noted after repair of the posterior wall. Routine repair of posterior wall defects should be challenged, owing to common patient complaints of pain and inability to have intercourse after such procedures.
Orgasm disorder
Women who have never achieved orgasm, primary anorgasmia, often need a referral to a sex therapist. Sociocultural values can inhibit a woman's ability to process pleasurable stimuli. Several techniques, such as sensate focus, systematic desensitization, and directed masturbation, have shown to be effective in treating primary and secondary anorgasmia and hypo-orgasmia . More women achieve orgasm with clitoral stimulation than from penile-vaginal intercourse. Caregivers should educate and reassure the couple that this is normal.
Secondary anorgasmia might be the result of depression or medications for depression. Switching to bupropion for women using selective serotonin-reuptake inhibitors (SSRIs) can be helpful. Bupropion has been shown to be more helpful than placebo in nondepressed women . The mechanism of action might be to increase NO synthase activity and subsequent NO availability .
Pelvic floor rehabilitation with Kegels, vaginal weights, and/or pelvic floor physical therapy can be used to strengthen pelvic-floor muscles and improve pelvic-floor blood flow and orgasm. Vaginal weights are useful in performing pelvic floor exercises, in that contraction of the pelvic floor musculature is required to retain the weight. The patient progressively moves through the weights until she can hold the heaviest weight in the vagina without any effort. Some women might benefit from sessions with a physical therapist and biofeedback. Home biofeedback units are also available. Recently, the FDA approved the EROS clitoral therapy device (EROS-CTD, St. Paul, MN). The device applies gentle suction to the clitoris and has been shown to improve orgasm, sensation, and lubrication in patients with and without FSD. Women who experience change in orgasm function after surgery or menopause might benefit from this device. Relational and situational variables can be dealt with by open communication between partners.
Arousal disorder
In the traditional model of sexual function, women become aroused after a desire or 'hunger' is initiated by sexual thoughts and fantasies. Recent research has indicated that this process is much more complex . Arousal involves 'a mind sexually awakened and a body physiologically prepared for sexual activity' in the context of emotional intimacy . Desire becomes a response to subjective awareness of this type of arousal. In women, the mere presence of genital congestion does not translate into sexual arousal. In fact, several studies have demonstrated an obvious disconcordance between genital arousal and subjective awareness of this physical process . Several reports have demonstrated increased vaginal pulse amplitude (VPA) with viewing erotic video, while reporting absent or minimal subjective arousal . This understanding can give patients and clinicians insight to treatment.
Postmenopausal women who complain of lack of lubrication and swelling might certainly benefit from vaginally administered estrogen. The role of oral estrogen is less clear. In vivo studies have shown estrogen prevents clitoral and vaginal fibrosis and, therefore, permits genital arousal . Although oral estrogens might improve end-organ function, they also increase sex-hormone binding globulin, which decreases free-testosterone and sexual desire. Sarrel reported that improvements of symptoms were seen at estradiol concentrations of more than 50 pg/mL. These levels also improved clitoral sensitivity and orgasm, and, in particular, increase desire and activity. Other studies have not validated improvement of arousal or orgasm with oral estrogen replacement therapy (ERT) . Premenopausal women who are lactating or on low-dose oral contraceptives might also benefit from short-term topical estrogen. These women are also the focus of sildenafil research on women who can achieve mental excitement but lack the genital stimulation.
Although sildenafil revolutionized male sexual dysfunction, research and reimbursement by third-party payers for women were, until recently, lacking, at best. Many women had hoped that this revolutionary sex drug would be equally effective for FSD. Current research demonstrates that patients and physicians must know who are appropriate candidates for this medical therapy. Several studies have been published that do not demonstrate improved sexual arousal. Laan et al. evaluated healthy premenopausal women without FSD. In this cross-over study, patients were given an oral 50-mg dose of sildenafil or placebo in the first session and the alternate in the next session. Despite significant increases in vaginal vasocongestion in the treatment group, there was no difference between the treatment group and the control group on subjective sexual arousal experience. In women with self-described FSD, Kaplan et al. reported changes in vaginal lubrication and clitoral sensitivity, but no significant improvement in sexual function. Conversely, Caruso et al. reported improved sexual arousal and sexuality with 25 mg and 50 mg of sildenafil in premenopausal women with arousal disorder. Basson et al. recently presented data from 577 estrogenized and 204 estrogen-deficient women with sexual arousal disorder. Patients were randomized to sildenafil 10 to 100 mg or matching placebo. Patients completed efficacy, satisfaction, and sexual function questionnaires. Neither group perceived an improvement in sexual response. Basson et al. pointed out that there might be subtypes of women with arousal disorder who might benefit from treatment: those with intact desire but limited genital function.
Sildenafil shows some promise in treating patients with antidepressant-associated sexual dysfunction (AASD). Approximately 30% to 70% of patients using SSRIs have AASD . In a review of the literature from 1989 to 1996, Shen et al. found that sildenafil reversed the AASD caused by SSRIs. The more recent studies have not focused on women, but do show improvement favoring sildenafil.
Sildenafil is not without risks. Several studies report headache, flushing, nausea, dyspepsia, and visual changes. The drug is also associated with sudden cardiac death and possibly stroke in high-risk patients.
Encouraging partners to uncover psychological and relational factors with a therapist or counselor can improve sexual experiences. Women with an arousal or desire disorder might benefit from viewing erotic videos with or without their partner. Increasing sexual fantasies might improve satisfaction and enjoyment in subsequent physical encounters.
Desire disorders
Disorders of desire are the most common presentation of FSD. A survey of 964 women presenting for annual examinations noted 67% of women complained of low desire . Dysfunction exists if a woman expresses a persistent or recurrent lack of sexual thoughts and/or receptivity to sexual activity, which causes personal distress. The development of desire results from the interaction of neurotransmitters and their target organs. The brain, however, is the central mediator of this process. Fantasies and sexual thoughts initiate the activation of this biochemical cascade in men. Women, however, seek out sexual stimuli in the context of emotional intimacy, based on the biopsychosocial model .Therefore, loss of this 'drive' is more commonly the result of alterations in intimacy, rather than biologic factors. Psychological, relational, or situational issues are factors that should be addressed before considering pharmacotherapy. If elucidated in the history, referral for professional counseling might be suggested. Many women experience a lack of desire due to the mental and physical exhaustion associated with daily activities and responsibilities. Emphasis on a healthy lifestyle, exercise, and rest are important to re-establishing desire.
Women who have undergone bilateral oophorectomy often complain of loss of desire. ERT improves vasomotor symptoms as well as atrophic vaginitis, but does not improve libido. ERT might actually cause or exacerbate loss of desire by increasing sex hormone binding globulin (SHBG) and decreasing free testosterone. Mixed results have been reported in postmenopausal women regarding testosterone replacement and improved desire . Rako suggests that testosterone deficiency can result in 1) global loss of sexual desire, lack of sexual fantasy and lack of sexual dreams; 2) decreased sensitivity to sexual stimulation in the nipples and in the clitoris; 3) diminished vital energy and sense of well-being. She states that even if total and free testosterone levels are normal, women who experience symptoms of depletion are candidates for replacement of testosterone. Rako also notes that women who undergo hysterectomy without adnexectomy might still suffer from testosterone depletion due to interruption of the uterine arteries and ovarian atrophy. This can have a profound effect, particularly for younger women who undergo hysterectomy, with or without oophorectomy. Premenopausal women using oral contraceptives can also benefit from testosterone replacement, because oral contraceptive pills decrease free testosterone levels.
There are many methods to replace testosterone, but there are no current guidelines for androgen therapy in FSD . Methyltestosterone and combined estrogen/testosterone are commonly prescribed by clinicians. Although these formulations are well tolerated, patients should be counseled on their effects on serum high-density lipoprotein (HDL) and liver function. Cosmetic effects such as acne and hirsutism can result, but irreversible virilization is rare. Transdermal testosterone replacement can also be administered. Shifren et al. showed a beneficial effect in a double-blinded, randomized, placebo-controlled, crossover-designed trial of 75 surgically induced menopausal patients. Supraphysiologic replacement improved measures of desire, orgasm pleasure, and general well being. Most studies showing benefit with testosterone report correction to premenopausal levels .

Evidence Based Management of Androgen Insufficiency in Women with Female Sexual Dysfunction

In 2000, the International Consensus Development Conference on Female Sexual Dysfunction1 defined Sexual Desire Disorder as a persistent or recurrent deficiency of sexual fantasies or thoughts, and/or desire or receptivity to sexual activity accompanied by personal distress. The most severe form of this is sexual aversion disorder. The hallmark epidemiological study was done by Laumann2 and reported in J.A.M.A. in 1999. In all, 43% of women ages 18 to 59 years, suffer from some form of sexual dysfunction. The incidence of decreased libido remained constant in all decades studied at about 30-32%. How many of these women have decreased androgens is unknown. In a study in the UK, Dunn3 determined by postal questionnaire that 41% of women 18 to 75 years old had some form of sexual dysfunction.
As in men, decreased libido in women has been linked to decreased testosterone levels. Decreased sexual desire is multifaceted and often multiple causes are found in any single individual. Anxiety and depression have traditionally been linked to decreased libido, as well as relationship disorders. Acute and chronic illnesses, along with various medications have been implicated. Decreased sexual desire has been often noted to accompany the menopausal transition, and estrogen deficiency has been studied along with androgen deficiency.
The Princeton Consensus Conference4 in 2002 defined female androgen deficiency as consisting of a pattern of clinical symptoms in the presence of decreased bioavailable testosterone and normal estrogen status. Besides decreased libido, changes in sexual function include decreased sexual receptivity and pleasure. As in men, decreased androgens may cause a diminished sense of well-being and unexplained fatigue and loss of energy. Vasomotor instability and decreased lubrication can occur even if the patient is adequately estrogenized. Decreased muscle strength and bone loss may also occur.
In men, androgens are made primarily in the Leydig cells of the testicles. In women, half of the androgens and androgen precursors are produced in the ovary with the other half being derived from the adrenal glands. Also, half of the active androgens are produced by the peripheral conversion of precursors in various tissues. Therefore, damage to the pituitary gland, ovaries or adrenal glands will produce a deficiency. Also, blocking the function of these organs will impede their androgen production. Examples of this are cortisone, birth control pills, or even perimenopausal hormone replacement.
Androgens have been given during menopause for many years. Greenblatt5 compared the effect of various combinations of androgens and estrogens during the menopause in 1950. The combination resulted in improved well-being and libido when compared to estrogen alone. Sherwin6, recently in 2002, summarized a number of randomized clinical trials showing that adding androgens to the standard estrogen replacement had added benefit to well-being, sexual desire and interest, frequency of intercourse, and frequency of orgasm.
There are problems in considering the use of androgens in women. The use of testosterone for androgen replacement is not approved for use in the United States and in many other countries. There is a lack of knowledge on the exact normal range for testosterone by age, although we know that androgen precursors and testosterone decrease with age in both men and women. This is compounded by the lack of sensitive and specific testosterone assays in women. Because of this a free androgen index or a calculated free testosterone value is felt to be more precise.
Zumoff7, in 1995, published a curve showing decreasing testosterone levels in women from ages 20 to 50. There were only 33 women and none were screened for sexual difficulties. The mean testosterone levels declined from approximately 38 ng/dL at age 20 to approximately 12 ng/dL at age 50. There was no sudden decline associated with the menopausal years. Guay8 and colleagues recently presented the androgens values in 60 women for the same 30-year period, and these women were screened for sexual dysfunction, especially decreased libido. In doing this, and presumably eliminating some women with low testosterone from the normal pool, the normal range increases substantially. In this study, total testosterone ranged from 46 to 58 ng/dL for women aged 20-29 (n=17), 28 to 40 ng/dL for women aged 30-39 (n=23), and 27 to 39 ng/dL for women aged 40-49 (n=20). More normal range studies are needed with many more women to verify this finding.
Products are being developed to deliver testosterone to deficient women. Shiffren et al9 studied women with impaired sexual function who were menopausal after oophorectomy. Testosterone or placebo was administered by transdermal patch to the women who were receiving standard estrogen replacement. The total testosterone was raised above the normal range despite the SHBG decreasing, but the free and bioavailable testosterone remained within the normal range. Sexual frequency and orgasm increased significantly with the testosterone, along with an increase in well-being and mood. No adverse effects on skin and lipids were noted but the study did have a high placebo response as well as possible supraphysiological levels of total testosterone and dihydrotestosterone at the higher treatment dose level. The study did confirm that testosterone therapy augmented the standard estrogen replacement in menopause and actually did have added benefits, especially in the area of sexual function.
Very few studies have been done in premenopausal women complaining of sexual dysfunction. Guay et al10 studied women, ages 20-49, who appeared healthy but who complained of sexual dysfunction. They, and an age-matched group of women with no sexual complaints, had regular menses and were taking no medications or birth control pills. The two groups were separated significantly by a sexual function questionnaire. The women complaining of sexual dysfunction had significantly lower adrenal androgen precursors and testosterone levels than their age-matched controls. This included decreased levels of pregnenolone, 17-OH pregnenolone, DHEA-S, total testosterone and free testosterone. The cortisol part of adrenal gland function remained quite normal.
Goldstat, et al11, also studied premenopausal women complaining of decreased libido. They were found to have testosterone levels in the lower third of the presumed normal range for young women. These women received testosterone cream or placebo for 12 weeks. The women on testosterone therapy had significantly increased well-being as well as increased sexual desire and activity. The mean decrease in a depression inventory score approached significance. Androgens play an important role in general well-being and energy as well as in sexual function, but more research is needed in developing the data and tools needed to outline androgen deficiency more precisely.
References
Basson R, Berman J, Burnett A, et al. Report of the international consensus development conference on female sexual dysfunction: definitions and classifications. J. Urol 2000; 163: 888 - 893.
Laumann EL, Paik A, Rosen RC. Sexual dysfunction in the United States: prevalence and predictors. JAMA 1999;10: 537-545.
Dunn KM, Croft PR, Hackett GI. Sexual problems: a study of the prevalence and need for health care in the general population. Family Practice 1998; 15: 519-524.
Bachmann GA, Bancroft J, Braunstein G, et al. Female androgen insufficiency: the Princeton consensus statement on definition, classification, and assessment. Fert. & Ster. 2002; 77: 660-665.
Greenblatt RB, Barfield WE, Garner JF, et al. Evaluation of an estrogen, androgen, estrogen-androgen combination and a placebo in the treatment of the menopause. J. Clin. Endocrinol. Metab. 1950; 10: 1547-1552.
Sherwin BB. Randomized clinical trials of combined estrogen-androgen preparations: effect on sexual functioning. Fert. & Ster. 2002; 77: S49.
Zumoff B, Strain G, Miller L, et al. Age-related decrease in total testosterone in women. J. Clin. Endocrinol. Metab. 1995; 80: 1429-1430.
Guay A, Munarriz R, Jacobson J, et al. Serum androgen levels in women aged 20-49 years with no complaints of sexual dysfunction. Int. J. Imp. Res. 2004; 16: 112-120.
Shifren JL, Braunstein GD, Simon JA, et al. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Eng J Med 2000;343: 682-688.
Guay A, Jacobson J, Munarriz R, et al. Serum androgen and androgen precursor hormone levels in women with and without sexual dysfunction. Int. J. Imp. Res.: J. Sex. Med. 2004; 16: 121-129.
Goldstat R, Briganti E, Tran J, et al. Transdermal testosterone therapy improves well-being, mood and sexual function in pre-menopausal women. Menopause 2003; 10: 390-398.

ABNORMAL UTERINE BLEEDING

Introduction :
Abnormal uterine bleeding is the most common presenting gynecologic complaint. Although often assumed to be uterine in origin by both patient and physician, abnormal bleeding can occur from other sites. A systematic approach to the problem will identify the source and lead to an explanation for the abnormal bleeding.
I. Normal menstruation.
The normal menstrual cycle involves a series of complex hormonal events integrating hypothalamic, pituitary, ovarian, and uterine functions. The local hormonal milieu achieved during ovarian follicular maturation and ovulation induces secretory changes in the endometrium to facilitate implantation of the fertilized ovum. Normal menstrual bleeding occurs in the absence of endometrial implantation of the fertilized ovum. The menstrual flow represents sloughing of the endometrial lining and is the direct result of the withdrawal of hormonal stimulation in the absence of early pregnancy.
A. Normal volume of menstrual blood loss
is less than 80 mL, with an average volume loss of 30 mL .
B. Normal interval between menstrual cycles
is considered to be 28 days (±7 days) .
C. Duration of flow
ranges between 2 and 7 days for normal menses.
II. Overview of abnormal bleeding.
The appropriate management of patients with abnormal bleeding is dependent upon an accurate diagnosis. It is important to remember that not all bleeding originates from the uterus, or even the genital tract; therefore, a thorough investigation of potential bleeding sites is mandatory
A. General etiologies
for abnormal bleeding fall into four categories :
Dysfunctional bleeding, with no evidence of organic lesions.
Pregnancy and its complications.
Organic pelvic lesions, benign or malignant.
Extragenital problems (coagulopathies, endocrinopathies, iatrogenic).
B. Age-dependent causes
of abnormal bleeding should be considered during the investigation. This way of approaching the problem directs the evaluation toward the most probable etiologies in each age category. This chapter focuses on the potential diagnostic considerations in the prepubertal, perimenarcheal, reproductive, and postmenopausal age groups and discusses their management.
III. Dysfunctional uterine bleeding
(DUB) results from a loss of coordinated cyclic hormonal changes and excludes organic lesions (e.g., neoplasms, polyps, leiomyomas). The age of the patient will determine the likelihood that DUB is the primary cause.
A. Age categories
Menarche to 20 years. Majority of these patients will have abnormal bleeding secondary to anovulatory DUB.
Age 20 to 40 years. Less than 20% of abnormal bleeding is due to anovulatory DUB. More common etiologies include pregnancy and its complications, pelvic inflammatory disease, intrauterine devices, oral contraceptives (OCPs), neoplasia, thyroid disease, endometriosis, and adenomyosis.
Age greater than 40 years. Anovulation again becomes a prominent cause of abnormal bleeding until menopause. However, neoplasia must be ruled out prior to attributing the bleeding to DUB.
B. Etiologies.
DUB is usually associated with anovulatory cycles but it can also be seen in ovulatory cycles. The differentiation between anovulatory and ovulatory DUB is based on bleeding patterns and predisposing factors. These differences are elaborated in the following paragraphs:
Anovulatory DUB is often seen in the adolescent and perimenopausal age groups. In these age groups, 90% of DUB is anovulatory . In regular ovulatory cycles, estrogen causes endometrial proliferation. Progesterone provides stromal support and acts as an antiestrogen to prevent excessive proliferation, thereby controlling endometrial height. Endometrial shedding occurs following cyclic withdrawal of estrogen and progesterone. In an anovulatory cycle, the prolonged effect of estrogen on the endometrium results in abnormal proliferation and hyperplasia. Once the endometrial height is greater than the stromal support, irregular menstrual shedding occurs, which can lead to excessive and prolonged bleeding.
Ovulatory DUB can result in midcycle bleeding or abnormal menstrual cycles. Midcycle bleeding occurs when estrogen levels are reduced at ovulation (i.e., estrogen withdrawal bleeding) . Abnormal intervals between cycles can manifest as polymenorrhea or oligomenorrhea. Corpus luteum insufficiency (or luteal phase defect) can result from inadequate progesterone production or a shortened period of progesterone secretion, which usually leads to unexpected early menses.
IV. Prepubertal bleeding
or bleeding that occurs prior to the age of 9 years is abnormal. The average age of menarche in the United States is 12 years . A complete history and physical examination are essential for diagnosis.
A. History.
In addition to questions concerning the character of the bleeding, the following should be elucidated:
The possibility of maternal diethylstilbestrol (DES) use during pregnancy.
Ingestion of steroid-containing substances (e.g., OCPs).
A family history of blood dyscrasias or sexual precocity.
B. Physical examination
The physical examination should be done with a proper pediatric-sized speculum, a long otoscope, or a long nasal speculum.
Materials for culturing and biopsy should be readily available for use as indicated.
The recto-vaginal-abdominal examination can often detect vaginal masses or foreign bodies.
The extremely small child may require vaginoscopy and cystoscopy under anesthesia to ensure completeness of the evaluation.
The status of secondary sexual characteristics such as breast development and pubic hair should be noted to look for signs of sexual precocity.
If the physical examination is not helpful in establishing the cause of bleeding, one must consider whether the child actually bled.
C. Etiologies
of vaginal bleeding usually are easily recognized in this age group. Management strategies for the following diagnoses are discussed in their context.
Vulvovaginitis is the most common cause of pediatric gynecologic complaints . The offending organisms are usually bacterial, monilial, and occasionally protozoan. Superinfection associated with a vaginal foreign body is a common finding.
The clinical presentation includes pruritus, burning, erythema, discharge, and occasionally a small amount of bleeding.
Poor hygiene is often the cause but other etiologies include irritation from soap, cosmetics, clothing, and sand.
The vaginitis can result from a sexually transmitted infection which would require careful and sensitive questioning of the child, her parents and/or caregivers.
The diagnosis is established by gentle examination, looking for evidence of a foreign body.
Any discharge should be sent for routine cultures as well as cultures for gonorrhea and chlamydia.
If a sexually transmitted disease is strongly suspected, then throat and anal cultures, as well as the Venereal Disease Research Laboratories (VDRL) test and HIV test, should be done.
Treatment is specific to the etiology. Antibiotics are necessary for identified bacterial infections, and the dose should be calculated for the age and weight of the child. Instruction in hygiene is valuable to avoid repeat infections.
Trauma to the perineum is another common cause of bleeding in children. Since a child's vulva lacks subcutaneous fat, it is less able to withstand trauma compared with an adult's vulva.
Sexual molestation of the child is a potential cause of perineal or vaginal lacerations. Any suspicion should be pursued in a discreet investigation.
Treatment of large lacerations should be carried out in the operating room under anesthesia to allow better exposure and to minimize further trauma to the child. Examination under anesthesia is also necessary to rule out intraabdominal perforation or rectal entry. Large hematomas should be observed for further enlargement. Retroperitoneal bleeds with unilateral back pain can follow development of a large hematoma. A continuing fall in hematocrit is an indication for laparotomy.
Prolapse of the urethra can also cause bleeding. It usually occurs in girls aged 6 to 9 years and is more common in blacks than whites.
Predisposing factors are congenital weakness, mucosal redundancy, increased intraabdominal pressure, and external trauma.
Presenting symptoms include bleeding, pain, and dysuria.
Examination will reveal tender, grayish or dark-red tissue outside the urethral meatus.
Management is initiated with the use of estrogen cream, which is often effective and may eliminate the need for surgery. If unsuccessful, then ligation, cautery, or surgical excision of the prolapsed tissue is indicated. Manual repositioning of the prolapsed tissue and sitz baths are no longer recommended for conservative therapy since recurrence is common.
Genital neoplasms are distinctly uncommon in the prepubertal age group.
Benign growths include vaginal and cervical polyps, vaginal adenosis, and vaginal and vulvar hemangiomas . Biopsy of the latter can lead to massive hemorrhage.
Malignant tumors include sarcoma botryoides, adenocarcinoma of the cervix or vagina (especially in DES progeny), and ovarian tumors. Ovarian tumors, such as granulosa-theca cell tumors and other sex-cord stromal tumors, as well as dysgerminomas, can cause vaginal bleeding and incomplete isosexual precocity as a result of estrogen production .
Diagnosis usually requires biopsy. Ultrasound is useful in looking for ovarian or other pelvic tumors.
Management of malignant tumors requires referral to a gynecologic oncologist. Vaginal bleeding associated with sexual precocity also may require evaluation by a pediatric or gynecologic endocrinologist.
V. Perimenarcheal bleeding.
Anovulatory DUB is the most common cause of abnormal bleeding in this age group, usually representing an immature hypothalamic-pituitary-ovarian axis. Following menarche at an average of 12 to 13 years, 80% of menstrual cycles are anovulatory in the first year. Regular ovulatory menstrual cycles are usually not established until the second year, with some irregularity persisting up to 5 years. It is well to remember that coagulation defects, especially Von Willebrand's disease, can cause 20% of excessive abnormal uterine bleeding in this age group .If a patient has severe anemia (hemoglobin <10 g/dL) because of menorrhagia, the risk of a coagulopathy increases to 45% .
A. History.
A history of irregular, heavy menses is classic for anovulatory DUB in this age group. In general, patients should be queried about onset of menses, duration and amount of flow, dysmenorrhea, sexual activity, and excessive bleeding resulting from minor surgical procedures (often dental procedures). A history of DES exposure leads to a search for vaginal or cervical adenosis or adenocarcinoma .
B. Physical examination.
The adolescent should be examined carefully and with sensitivity. DUB is often the precipitating event that leads to the first pelvic examination.
Abnormalities of the genital tract should be noted.
Signs of pregnancy should be sought.
In most adolescents with abnormal bleeding, the examination will be normal.
In the virginal patient, clinical judgment will decide the extent of the pelvic examination.
C. Investigative procedures
A complete blood cell count (CBC) is often all that is needed to document the presence of anemia or thrombocytopenia. If anemia is present, the red cell indices should be noted since not all anemia is due to excessive menstruation.
Prothrombin (PT), partial thromboplastin (PTT), and bleeding time tests should be done if a coagulopathy is suspected.
Thyroid function tests should be done for evaluating thyroid dysfunction.
A pregnancy test should be considered if sexual activity is suspected. Teenagers will often deny sexual activity.
A Papanicolaou (Pap) smear is indicated in the sexually active adolescent.
Cultures for gonorrhea and chlamydial infections should be done in the sexually active teenager.
Gonadotropin levels are rarely necessary to investigate abnormal bleeding in this age group.
Ultrasound is usually unnecessary unless a palpable mass is present.
Uterine curettage is rarely necessary unless an organic etiology is suspected or the patient fails hormonal treatment. Pregnancy must first be ruled out.
Diagnostic hysteroscopy may be a better choice to investigate the uterine cavity.
D. Management.
Hormonal treatment will usually be effective if anovulatory DUB is the etiology of the bleeding. The lack of response to hormonal treatment should make the clinician suspicious of another cause for the abnormal bleeding. Other determined etiologies should be addressed specifically (e.g., pregnancy, pelvic inflammatory disease).
OCPs are the treatment of choice, especially if the teenager is sexually active.
Any OCP can be used in a dose of 1 tablet qid for 5 to 7 days. This is followed by use of a low-dose estrogen pill daily for 21 days.
This regimen is then followed by 7 days of withdrawal that usually leads to a heavy menses. The patient and her family should be warned to expect this heavy period since this may be interpreted as failure of therapy.
After several cycles of the pill, each succeeding period will become lighter. The pill can then be discontinued, and the patient can be followed for the onset of regular menses.
The pill can also be continued in the sexually active patient, in those with a history of severe anemia, or in patients who are anxious about recurrence of heavy bleeding.
Progestational agents
Medroxyprogesterone (Provera), 10 mg qd, or norethindrone, 5 to 10 mg qd to bid, can be used. Patients must understand that this regimen does not provide contraception.
This is continued for several days and then withdrawal bleeding is allowed. Since the withdrawal bleeding will be heavy, the patient must be warned that this does not represent treatment failure.
OCPs can then be used cyclically.
Alternatively, medroxyprogesterone, 10 mg qd for 10 days at the beginning of each month may be used to induce regular withdrawal bleeding.
Profuse, persistent bleeding associated with anemia or hemodynamic changes is treated differently.
Blood transfusion is indicated for severe anemia or unstable hemodynamics.
Intravenous conjugated estrogens (Premarin), 25 mg IV, can be given every 4 hours for up to three doses to stop acute bleeding . Failure to control bleeding with this regimen mandates further investigation and usually requires curettage. After the acute bleeding stops with this regimen, OCPs or progesterone, as described earlier, should be started immediately to continue to control the bleeding.
VI. Reproductive age.
DUB is less common in this age group. Pregnancy and its complications must be ruled out.
A. History
A detailed menstrual history, including the last menstrual period, age at menarche, frequency, duration, and amount of menstrual flow, must be obtained from all patients with abnormal bleeding.
The abnormal bleeding episode(s) should be described in detail and related chronologically to the patient's menstrual pattern.
Coexisting as well as precipitating factors, such as medical illnesses, medications, stress situations, changes in weight, dietary alterations, pain, dyspareunia, and any other relevant symptomatology, should be carefully sought.
A comprehensive medical history should be obtained, looking for systemic causes for abnormal uterine bleeding. The possibility of a cagulopathy should be considered.
Bleeding from other orifices should be considered as a possibility.
Endocrinopathies, such as thyroid or adrenal diseases, should be noted. The combination of hirsutism, obesity, and oligomenorrhea suggests polycystic ovarian syndrome.
B. Physical examination
A general physical examination should be performed.
Signs of anemia and chronic systemic diseases are sought.
Obesity and hirsutism are noted if present.
Pain or masses should be noted.
A thorough pelvic examination, beginning with careful inspection of the external genitalia, urethral meatus, perineum, and perianal area is performed. The vaginal walls and cervix are inspected for the presence of gross lesions and retained foreign objects.
Bimanual examination will document the shape and contour of the uterus and adnexa, as well as the presence of any tenderness or masses.
Rectovaginal examination will evaluate the presence of lesions in the cul-de-sac or primary rectal lesions.
C. Investigative procedures
Cultures for gonorrhea and chlamydial infection should be taken.
Cervical cytologic studies are done to screen for cervical dysplasia or cancer.
Gross lesions of the cervix, vagina, and external genitalia are biopsied for pathologic identification unless obvious.
All lesions suspicious for malignancy must be biopsied.
Patients with abnormal Pap smears showing dysplasia should be referred for colposcopy.
Stool occult blood screening should be done to evaluate potential gastrointestinal sources for the bleeding.
A CBC is useful to document anemia and/or thrombocytopenia.
PT, PTT, and a bleeding time should be obtained if a coagulopathy is suspected.
Thyroid function tests and prolactin levels are done to rule out endocrinopathies.
Urinalysis is done to look for hematuria which can be caused by urinary tract infection, stones, or tumor.
A pregnancy test is necessary to rule out pregnancy and its complications, such as abortion or ectopic gestation. Current urine pregnancy tests are sensitive; however, if doubt persists after a negative urine pregnancy test, a serum assay for the beta-subunit of human chorionic gonadotropin (hCG) will settle the issue.
Pelvic ultrasound should be done for any palpable mass.
D. Management
is dependent upon the determined etiology of the bleeding. Treatment issues pertaining to specific causes of abnormal bleeding, such as pelvic inflammatory disease, leiomyomas or neoplasms and pregnancy complications, are not covered in this chapter.
Ovulatory DUB is usually due to midcycle bleeding or abnormal corpus luteum function.
Midcycle bleeding occurs at the time of ovulation when the level of estrogen drops. It commonly manifests only as spotting and is usually not bothersome. In those patients who have bleeding and require treatment, oral estrogen therapy is used. Conjugated estrogens (Premarin), 1.25 to 2.5 mg, or ethinyl estradiol, 20 µg, is given daily from 3 days before to 2 days after ovulation.
Abnormal corpus luteum function is usually diagnosed in association with infertility. It is suspected by menstrual cycles that have a shortened interval (<24 days). It is diagnosed with an endometrial biopsy that shows endometrial maturation 1 to 2 days outof-phase in the secretory period. Its treatment is controversial.
If the patient desires pregnancy, then vaginal progesterone suppositories are sometimes used to augment the endogenously produced progesterone.
Clomiphene citrate (Clomid) is often used instead (see Infertility.
OCPs can be used if contraception is desired.
If neither fertility nor contraception is important, then it is not necessary to treat the patient unless the irregular menstruation is bothersome, in which case, OCPs will serve well.
Anovulatory DUB that occurs during reproductive years is often due to polycystic ovarian syndrome or obesity. These women often have prolonged amenorrhea or oligomenorrhea followed by menorrhagia. On the other hand, women who experience significant stress, perform strenuous exercise (marathon runners), or lose excessive weight (e.g., anorexics) have amenorrhea or oligomenorrhea with hypomenorrhea. This latter pattern results from hypothalamic hypogonadism .
Anovulatory cycles associated with amenorrhea or oligomenorrhea, due to resulting from polycystic ovarian syndrome or obesity, lead to excessive estrogen exposure on the endometrium. The absence of a corpus luteum means that progesterone is not produced to balance the estrogen-stimulated proliferation. This persistently estrogen-stimulated endometrium is at risk to develop hyperplasia or cancer.
Endometrial biopsy is indicated in patients older than 30 years with 12 months or more of anovulatory DUB and in occasional patients older than 20 years with frequent, prolonged, or excessive periods . This is necessary to identify those patients at risk for endometrial hyperplasia, atypical hyperplasia, or rarely cancer. Most often, biopsy will show evidence of hyperplasia.
Infertility is a common problem in this group because anovulation results in no ovum being available for fertilization in the cycle.
Hirsutism is also common. It results from chronic exposure to excessive ovarian production of androgens, primarily androstenedione .
Treatment depends on the patient's desire for fertility.
If pregnancy is desired, then ovulation induction is indicated .
To regulate menses when pregnancy is not desired, supplemental progesterone or OCP is used.
The patient can be treated with medroxyprogesterone (Provera), 10 mg qd, for 10 days each month, followed by withdrawal bleeding.
Occasionally, sporadic ovulation occurs in these patients, and thus, they are at risk for pregnancy.
If the patient desires to avoid pregnancy, then low-dose estrogen OCPs can be used instead. The OCPs have the added advantage of helping to control hirsutism .
Functional ovarian cysts are often responsible for abnormal periods. They are either follicular cysts or persistent corpus luteum cysts. They are referred to as functional cysts because they produce hormones.
They are often palpable and can reach 6 cm in diameter.
Any adnexal mass of 6 cm or more requires further investigation .
Use of OCPs may be successful in suppressing the cysts.
Failure to resolve within 1 to 2 months, with or without use of OCPs, requires further evaluation to rule out a neoplasm.
Functional ovarian tumors are neoplastic growths that do not resolve spontaneously and are not suppressible with OCPs. They also produce hormones, usually either estrogen or androgens. These include granulosa cell and theca cell tumors, arrhenoblastomas, and some malignant ovarian tumors. The management is primarily surgical.
Menorrhagia or intermenstrual bleeding is a common menstrual disorder. It is one of the most common causes of iron deficiency anemia . When not associated with DUB, it often represents anatomic abnormalities. The differential diagnosis includes uterine fibroids, endometrial polyps, endometriosis, adenomyosis, chronic pelvic inflammatory disease, ovarian abnormalities, massive obesity, coagulopathies, severe hypothyroidism, and endometrial hyperplasia or carcinoma. Pregnancy and its complications must be ruled out. Some evaluation of the uterine cavity is indicated by endometrial biopsy, formal dilation and curettage (D & C), or hysteroscopy.
Diagnostic hysteroscopy has become popular in the evaluation of abnormal uterine bleeding because of its ability to visualize the uterine cavity directly. There is literature to suggest that it is more accurate in defining the exact pathology compared to endometrial biopsy since hysteroscopy can visualize the entire cavity, whereas endometrial sampling recovers only 1% of the endometrial volume .
Hysteroscopic surgery is commonly performed for the treatment of uterine bleeding disorders. In skilled hands, submucous leiomyomas and endometrial polyps can easily be removed using a resectoscope .
If no specific pathologic process can be found and the patient has persistent menorrhagia, then endometrial ablation can be used to destroy the endometrium, with resultant cessation or decrease of menses.
Current methods for endometrial destruction involve laser ablation, use of the resectoscope, “roller-ball” cautery, or the thermal balloon. Roller-ball cautery is still the most common method used .
Endometrial atypia, pregnancy, or cancer must be ruled out prior to endometrial ablation.
The endometrium should be hormonally prepared with medroxyprogesterone (Provera or Depo-Provera), danazol, gonadotropin-releasing hormone (GnRH) agonists, or OCPs. The specifics for hormonal preparation are beyond the scope of this book.
Nonsteroidal antiinflammatory agents are sometimes effective in controlling menorrhagia. Agents that have been used include mefenamic acid (Ponstel), 500 mg tid, and naproxen (Naprosyn), 500 mg as an initial dose followed by 250 mg tid. Gastrointestinal side effects are diminished if taken with food .
Hysterectomy has been used to control menorrhagia as a last resort when medical therapy and uterine curettage fail.
VII. Perimenopausal bleeding.
The causes of bleeding in this age group include those mentioned for the reproductive-age group . Anovulatory DUB again becomes a common cause of abnormal bleeding. This occurs as a result of the greatly diminished number of follicles remaining in the ovary and the growing refractoriness of the residual follicles to gonadotropin stimulation . As a consequence, follicle-stimulating hormone (FSH) levels are elevated and circulating estradiol levels are lower, compared with the reproductive years. As the follicles fail to ovulate, corpus luteum function ceases. Unopposed estrogen leads to endometrial proliferation, hyperplasia, and sometimes endometrial cancer. The irregular menstrual shedding is responsible for the abnormal bleeding.
A. Evaluation
of the perimenopausal woman with abnormal bleeding is the same as in the reproductive-aged woman.
Pregnancy is an unusual cause but should be ruled out if the sexually active woman is not using birth control.
A menstrual history should be taken, as well as a description of the abnormal bleeding episodes.
A careful pelvic examination is mandatory, looking for evidence of neoplasia or other anatomic causes for the bleeding.
A Pap smear must be done.
A CBC should be obtained to determine whether anemia is present if bleeding has been excessive.
Endometrial sampling is necessary to rule out endometrial hyperplasia (with or without atypia) or endometrial cancer.
An ultrasound should be obtained to rule out fibroids.
B. Treatment
of anovulatory DUB in the perimenopausal woman involves use of progesterone to counterbalance the effects of unopposed estrogen on the endometrium. If the endometrial sampling shows simple proliferation or simple, adenomatous, or cystic hyperplasia without atypia, then the condition should respond to progestin therapy.
Medroxyprogesterone, 10 mg qd for 10 to 14 days each month, is used until menopause occurs.
If the initial pathologic workup revealed endometrial hyperplasia, then repeat endometrial sampling is done in 3 to 6 months to demonstrate the reversal of the endometrial hyperplasia. Preferably, the timing should be after completion of 10 days of progesterone therapy and prior to the next menses to show the secretory effects on the endometrium.
The presence of atypical hyperplasia or cancer requires hysterectomy for definitive treatment since these conditions will not resolve with progestin therapy.
VIII. Postmenopausal bleeding
is defined as any amount of bleeding that occurs after a 12-month cessation of regular menstrual flow. The irregular, acyclic bleeding that characterizes the perimenopausal period can make it difficult to determine when menopause has begun. Bleeding that occurs 1 year after cessation of flow or that begins after the onset of vasomotor changes demands investigation. Those at risk for endometrial cancer, such as obese, hypertensive, or diabetic patients or those receiving unopposed estrogen therapy, should have investigation as soon as possible.
A. History.
A complete description of the bleeding episode as well as a thorough medical history must be obtained.
Any history of systemic diseases, particularly diabetes mellitus, hypertension, liver disease, or obesity, should be noted.
Use of medications, especially that of estrogen or progesterone, is especially relevant.
B. Physical examination
includes a general examination, with careful attention to the abdominal and pelvic examination.
C. Investigative procedures
Routine pap smear.
Cultures for gonorrhea and chlamydia. These infections may be considered but are an unusual cause of bleeding in the postmenopausal woman.
CBC.
Stool occult blood testing.
Urinalysis for hematuria.
Pelvic ultrasound. Any palpable mass requires this procedure.
Endometrial sampling by endometrial biopsy or D & C. An endocervical curettage or cytobrush sampling should also be done to rule out endocervical disease.
If a diagnosis is made by endometrial biopsy, then a formal D & C is not necessary.
Lesions can still be missed in the uterine cavity with the four-quadrant technique.
If the pathologic findings on endometrial biopsy are not consistent with the clinical impression, then a formal D & C or hysteroscopy should be performed.
Diagnostic hysteroscopy .
D. Etiology
The benign causes of postmenopausal bleeding are most common.
Atrophic vaginitis is due to lack of estrogen stimulation. The vaginal wall becomes thin and atrophic, with loss of rugae (folds). It is susceptible to bleeding resulting from the slightest trauma.
Atrophic endometrium also results from estrogen deficiency. The endometrium becomes thin, with simple tubular glands and occasionally, cystically dilated glands. The stroma is dense, cellular, and compact . The thin endometrium is susceptible to bleeding, usually manifesting as spotting. Endometrial sampling will demonstrate atrophy. Unfortunately, endometrial cancer can be present in limited foci with surrounding atrophic endometrium. Persistent postmenopausal bleeding in a patient with atrophic endometrium should have further evaluation by formal D & C or hysteroscopy or both.
Endometrial or endocervical polyps occasionally contribute to vaginal spotting.
Cervical polyps are almost invariably benign. They can be removed by twisting off with a ring forceps.
Endometrial polyps can be missed, even with the most careful curettage. Often they are discovered only at hysteroscopy or after hysterectomy.
Endometrial hyperplasia is caused by excess endogenous estrogen (as seen in obesity and diabetes) or unopposed estrogen therapy.
The malignant causes should be ruled out systematically. Malignancy is more likely the longer the interval since cessation of menses.
Endometrial adenocarcinoma is seen in about 20% of postmenopausal women who present with bleeding . Atypical endometrial hyperplasia is considered a precursor and can be documented with endometrial sampling.
Cervical cancer can be found on routine screening with a Pap smear. Gross cervical lesions should be biopsied even if the Pap smear is negative.
Ovarian cancer occasionally produces hormones (estrogen or androgens) that can lead to postmenopausal bleeding.
Fallopian tube cancer classically presents with a watery vaginal discharge and a pelvic mass, but more commonly, scant vaginal bleeding occurs. If endometrial sampling fails to yield a diagnosis, ultrasound should be done.
Gastrointestinal and urinary tract cancers also cause bleeding, and bleeding from the rectum or urethra can be misinterpreted as vaginal bleeding.
E. Management
of postmenopausal bleeding is primarily directed at determining the etiology of the bleeding and then providing appropriate treatment.
Atrophic changes of either the vulva or vagina can readily be treated with exogenous estrogen replacement.
Conjugated estrogens, 0.625 mg/day, is sufficient to reverse atrophy of the vagina. Alternatively, estrogen cream will suffice to treat atrophic vaginitis on a short-term basis
Progesterone is needed to counterbalance the effects of estrogen on the endometrium. This can be accomplished by cyclic regimens or continuous, combined hormone replacement therapies.
Medroxyprogesterone, 5 to 10 mg qd is given for 10 to 14 days each month. This is sufficient to reverse the effects of estrogen on the endometrium.
Continuous, combined estrogen and progesterone regimens reduce the doses of progesterone needed. Conjugated estrogens, 0.625 mg, and medroxyprogesterone, 2.5 to 5 mg, are each given daily. Irregular spotting is common for the first 3 to 6 months. A baseline endometrial biopsy is recommended prior to starting therapy to ensure that the baseline endometrium is benign.
Adenomatous hyperplasia in the postmenopausal woman is abnormal and represents either unopposed exogenous estrogen therapy or excess endogenous estrogen production.
The diabetic, hypertensive, or obese patient is at risk for endogenous estrogen production.
Hysterectomy and bilateral salpingo-oophorectomy is indicated for definitive treatment.
In those patients who are not candidates for surgery, high-dose progesterone therapy (e.g., Megace) can be considered as an alternative.
Repeat endometrial sampling is mandatory to document that the lesion has not progressed to cancer.
Endometrial cancer and other malignancies in their early stages are amenable to therapy by surgery, radiation, or chemotherapy. These malignancies are best managed in consultation with a gynecologic oncologist.

PREMENSTRUAL SYNDROME

Introduction :
Premenstrual syndrome (PMS) is a diverse constellation of cyclic physical and emotional symptoms, occurring monthly during the luteal phase of the menstrual cycle (ovulation to menstruation). This phase is followed by a symptom-free period of at least 1 week, beginning after the onset of menses. Of all the symptoms, the emotional and behavioral symptoms are the most devastating. In an attempt to define and treat the psychological symptoms, the American Psychiatric Association has described premenstrual dysphoric disorder (PMDD). PMDD requires the presence of at least one of 4 core symptoms (irritability, dysphoria, labile mood, tension) and at least 5 of 11 other symptoms. Symptoms must markedly impair functioning and interfere with normal activities.
I. Incidence.
It has been reported that 70% to 90% of the female population will admit to recurrent menstrual problems. Between 20% and 40% report some degree of temporary mental and physical dysfunction and 2% to 5% may be incapacitated.
PMS is cross-cultural and affects women of all races, socioeconomic status, and professions. There may be an increased incidence with age and major life stresses. Demographic data are contradictory concerning genetic contribution, effects of number of pregnancies, and educational level. Women with severe PMS may have a lifetime increased incidence of affective disorders.
II. Etiology.
Evidence supports the association of PMS with abnormal neurotransmitter response to normal ovarian function. Recent research has confirmed that women with PMS have normal levels of both estrogen and progesterone, are not vitamin or mineral deficient, have normal prolactin and thyroid levels, and are euglycemic. Of the possible mediators of ovarian steroid action in the central nervous system, serotonin, gamma-amino butyric acid (GABA) receptors, and beta-endorphins are the best studied.
A. Serotonin.
The association of serotonin with mood and appetite disturbances is well documented, and the sex steroidal hormones do modulate serotonergic activity. Women with PMS have significantly lower serotonin levels during the luteal phase, as measured in peripheral blood, compared with normal controls. This may be due to impaired postsynaptic serotonergic response in PMS patients. Compounds that increase serotonin levels have been shown to decrease symptoms of PMS.
B. Beta-endorphin
levels may be lower in PMS patients during both the periovulatory and premenstrual phases of the menstrual cycle. Substances that increase beta-endorphins improve PMS symptoms.
C. GABA receptors
The GABA receptors, associated with control of anxiety, are stimulated by progesterone, which may be a mechanism in the modulation of anxiety in PMS.
III. History.
PMS is a polysymptomatic disorder and the syndrome may last anywhere from 3 to 21 days. Symptoms do not all begin on the same day nor will women have the same symptoms each month or throughout their lives. The following is a partial list of symptoms:
A. Behavioral symptoms:
depression, irritability, tension, lethargy, mood swings, anger, uncontrolled crying, aggression, panic attacks, anxiety, social withdrawal, change in memory or concentration, change in libido, poor impulse control.
B. Physical symptoms
Neurologic: migraines and other headaches, syncope, vertigo.
EtiologyMetabolic: breast tenderness, edema.
Cardiovascular: palpitations, ectopic beats, paroxysmal tachycardia.
Gastrointestinal: nausea, abdominal bloating, flatulence, constipation, diarrhea.
Urinary: oliguria, urethritis, cystitis, enuresis, urinary retention.
Dermatologic: acne, urticaria.
Musculoskeletal: pain and swelling of the joints and muscles.
C. Chronic medical problems, such as diabetes and asthma, as well as psychological disorders may worsen premenstrually, a condition termed premenstrual magnification.
IV. Physical examination.
A complete physical examination including a pelvic examination is necessary to rule out other causes such as ovarian cysts, fibroids, pelvic inflammatory disease, endometriosis, and thyroid disease. It is also important to perform a complete mental status examination to rule out psychopathology. There are no characteristic physical findings of PMS.
V. Investigative procedures.
The diagnosis of PMS depends on the temporal relationship of psychological and somatic symptoms with menstruation rather than the presence of symptoms alone. It is the recurring symptoms during the luteal phase followed by a symptom-free time that defines PMS. A thorough medical, sexual, and psychological history as well as physical examination and laboratory studies are necessary to identify PMS and to rule out other disorders.
A. Menstrual chart.
Evaluation should include a detailed diary of symptoms charted against the menstrual cycle .
The chart should show the length of the menstrual cycle, duration of bleeding, and regularity or irregularity of menstruation. By definition, PMS occurs only during ovulatory cycles.
Each symptom along with its severity can be charted each day. The patient should be sure to include eating patterns if they vary with the cycle.
A full three cycles are optimal for evaluation.
Posthysterectomy patients may still experience PMS if they retained their ovaries, so their 3-month chart will show the same characteristic pattern.
B. Laboratory tests
should be ordered as indicated by history and/or examination to rule out other disease as a source of the patient's symptoms.
VI. Management.
Since PMS represents an abnormal response to the physiologic ovulatory cycle, management can be directed to:
Altering the cycle.
Changing the body's response to the cycle.
Treating the symptoms themselves.
A. Self-help steps
Education is one of the most important components in the management of PMS.
Knowledge of the menstrual cycle, as well as female anatomy and physiology can aid in understanding this disorder.
It is also helpful to read the available literature on PMS.
Keeping a menstrual chart helps a woman achieve awareness of her menstrual cycle as well as her premenstrual symptoms.
Exercise. Regular aerobic exercise at least three or four times per week, continuing through the premenstrual phase, may reduce symptoms of PMS. This is especially true of the physical symptoms including breast tenderness, fluid retention, and abdominal cramping. Exercise has been shown to reduce stress and anxiety, increasing one's sense of well-being.
Stress management. Women should be encouraged to reduce the demands that they make on themselves and on others. Relaxation, visualization, and hypnosis are some other important methods of stress reduction. Supportive psychotherapy and reflexology may also be beneficial .
Diet and nutrition improves one's overall feeling of health and may be helpful with PMS. Recommended dietary changes include increasing complex carbohydrates and green vegetables and decreasing simple sugars, fats, and processed foods. Unfortunately, specific studies of the effect of diet on PMS have not demonstrated a benefit, with the exception of eliminating caffeine, which helps reduce breast tenderness and low salt/low fat diet, which improves fluid retention.
B. Food supplements
Vitamin B6. Pyridoxine is a coenzyme in the biosynthesis of serotonin and dopamine, probable mediators of PMS. Some studies have shown a benefit with vitamin B6 in doses well above the recommended daily allowance (RDA), starting at 25 mg twice daily and increasing to 100 mg per day. Higher doses to 300 mg have been studied but carry a significant risk of peripheral neuropathy.
Vitamin E in doses of 400 to 600 IU/day has, in some studies, alleviated the symptom of breast tenderness associated with PMS.
Calcium improves symptoms of water retention, abdominal cramps, and mood changes in doses of 1,000 mg/day. One study has also shown improvement with food cravings.
Magnesium supplementation, 300 to 500 mg daily during the luteal phase, has been shown to improve symptoms of mood changes and fluid retention in small randomized crossover trials.
There are now many PMS formulae that combine vitamins and mineral supplements. Of these only a few, Lurline PMS tablets and Optivite have been studied and shown to have some efficacy.
The use of cis-linoleic acid (evening primrose oil), 1,500 mg bid, is an old remedy for depression and anxiety symptoms of PMS. Randomized, double-blind trials have been unable to substantiate its efficacy.
C. Drug therapy.
Drug therapy can be tailored to alleviate specific symptoms or to obliterate the menstrual cycle itself.
Oral contraceptive pills (OCPs) are often used as a first-line treatment for premenstrual symptoms but few studies have substantiated efficacy except with some physical symptoms such as cramps and bloating.
Monophasic preparations may be more effective than triphasic combinations.
Patients should be warned that psychological symptoms could worsen when taking OCPs.
In the past, progesterone was widely used for PMS, but well designed studies do not demonstrate efficacy. The general popularity of using progesterone for PMS may be due to its mildly sedative properties.
Synthetic progestins (medroxyprogesterone acetate, norethindrone) are used as contraceptives or to regulate menstrual flow.
In some women, medroxyprogesterone acetate (Depo-Provera) eliminates the menstrual cycle and can in this way improve some of the physical symptoms of PMS.
Progestins should be used with caution in women with PMS because they can exacerbate psychological symptoms, especially anxiety and depression.
Gonadotropin releasing hormone (GnRH) agonists obliterate the menstrual cycle and are therefore very effective in controlling symptoms of PMS. Randomized trials have demonstrated significant improvement in PMS symptoms; however, psychological symptoms are not as consistently improved as physical symptoms.
These medications are expensive and must be used with add-back estrogen and progesterone to reduce menopausal side effects such as osteoporosis.
Use of GnRH agonists without add-back hormonal replacement must be limited to less than 6 months.
Leuprolide acetate, 3.75 mg IM monthly OR 11.25 mg q 3 months OR
Goserelin, 3.6 mg SQ implant monthly, OR
Nafarelin, 200 g bid intranasally, are the most commonly used preparations.
Selective serotonin reuptake inhibitors (SSRIs) are highly effective in the treatment of severe PMS. Multiple controlled double-blind studies have shown efficacy, with resolution of symptoms nearly immediately and in smaller doses than is normally used for depression.
Fluoxetine has been studied in the most detail and is effective in doses as small as 5 mg and up to 20 mg po qd. Efficacy has been shown with a daily dose throughout the month and also with treatment only during the luteal phase of the menstrual cycle (i.e., with symptoms). Although generally well tolerated, side effects include insomnia, anxiety, gastrointestinal disturbances, and sexual dysfunction.
Paroxetine, 5 to 30 mg/day, and sertraline, 25 to 150 mg/day, have not been as extensively studied as fluoxetine for PMS but are probably equally as effective.
Clomipramine, a tricyclic antidepressant with serotonin and noradrenaline reuptake inhibiting properties, has been successfully used to treat severe psychological symptoms of PMS.
Effective doses are 25 to 75 mg PO qd during the luteal phase of the menstrual cycle.
Side effects including fatigue, weight gain, nausea, seizures, and dry mouth may limit its usefulness.
Anxiolytics
Buspirone may be useful in patients with predominant symptoms of anxiety and it is neither sedating nor habit forming. The initial dosage is 5 mg tid, gradually increasing to cessation of symptoms with a maximum dose of 60 mg/day.
Alprazolam controls anxiety and irritability if given during the symptomatic period.
However, its use is associated with sedation, tolerance, and dependence and it should be used cautiously.
Dosage is 0.25 mg tid, increasing to a total daily dose of 4 mg. At the beginning of menses, the dose should be decreased by 25% each day.
Diuretics. Abdominal bloating and water retention are some of the most common symptoms of PMS. Despite this, actual weight gain and change in total body water have not been well demonstrated in studies. In this light, diuretics should be used with caution. Spironolactone, 25 mg tid or qid, during the luteal phase of the menstrual cycle may be effective for abdominal bloating and also may improve irritability, depression, and food cravings.
Danazol, a synthetic androgen, is effective in suppressing symptoms of PMS. However, its side effects, including weight gain and virilization may be unacceptable to patients.
D. Surgery.
Bilateral oophorectomy is rarely indicated in PMS treatment and should be reserved only for patients with severe PMS and after failure of all conservative measures. Complete resolution should be demonstrated with GnRH agonist suppression prior to undertaking surgery. Consideration should also be made of the number of years left until menopause.

Caesarean Section (C.S)

An operative procedure to deliver a viable foetus or more (i.e. after 28 weeks or
20 weeks according to the ACOG) through an abdominal and uterine incisions.
Incidence:
increased from 5% in 1970 to 25% in 1990 due to:
1.Procedures as high forceps and difficult mid forceps are
abandoned in favour of C.S.
2. Increased C.S delivery in breech presentation.
3. Destructive operations are abandoned in favour of C.S.
4.Decreased morbidity and mortality due to C.S encourages its
use.
5. Increased repeated C.S due to increased primary C.S.
Indications:
(A) Maternal indications:
1. Contracted pelvis and cephalopelvic disproportion (see before).
2.Pelvic tumours especially if impacted in the pelvis or cancer
cervix.
3. Antepartum haemorrhage .
4. Hypertensive disorders with pregnancy .
5. Abnormal uterine action .
6. Previous uterine scar as hysterotomy or metroplasty.
7. Previous successful repair of vesico-vaginal fistula.
8. Previous caesarean section if,
i- the cause of the previous section is permanent e.g.
contracted pelvis.
ii- previous section was upper segment.
iii- suspected weak scar as evidenced by:
- History of puerperal infection after the previous
section.
- Hysterosalpingography or hysteroscopy done
after the previous section reveals a defect in the
scar.
- Vaginal bleeding during current labour.
- Marked tenderness over the scar during current
labour.
iv- Associated conditions as antepartum haemorrhage or
malpresentations.
(B) Foetal indications:
1. Malpresentations and malposition .
2.Prolapsed pulsating cord or foetal distress before full cervical
dilatation.
3. Diabetes mellitus (see before).
4.Bad obstetric history as recurrent intrauterine foetal death in last
weeks of pregnancy or repeated intranatal foetal death.
5.Post-mortem C.S. done within 10 minutes of maternal death
to save a living baby.

Contraindications:
1- Dead foetus: except in;
- Extreme degree of pelvic contraction.
- Neglected shoulder.
- Severe accidental haemorrhage.
2- Disseminated intravascular coagulation: to minimise blood loss.
3- Extensive scar or pyogenic infection in the abdominal wall e.g. in
burns.
Types of Caesarean Section:
(A) According to timing:
1.Elective caesarean section: The operation is done at a
pre-selected time before onset of labour, usually at completed 39 weeks .
2.Selective caesarean section: The operation is done after onset of labour
(B) According to the site of uterine incision:
1.Upper segment caesarean section (classical C.S.): The incision
is done in the upper uterine segment and it is always vertical.
2.Lower segment caesarean section (LSCS) : It is the
commoner type. The incision is done in the lower uterine
segment and may be transverse ( the usual) or vertical in the following coditions :
i- Presence of lateral varicosities.
ii- Constriction ring to cut through it.
iii- Deeply engaged head.
(C) According to number of the operation:

1. Primary caesarean section: for the first time.
2.Repeated caesarean section : with previous caesarean
section(s).
(D) According to opening the peritoneal cavity:
1.Transperitoneal : The ordinary operation where the peritoneal
cavity is opened before incising the uterus.
2.Extraperitoneal: The peritoneal cavity is not opened and the
lower uterine segment is reached either laterally or inferiorly
by reflecting the peritoneum of the vesico-uterine pouch . It is
indicated in case of infected uterine contents as
chorioamnionitis.
Advantages of elective C.S:
1.Pre - operative good preparation as regard sterilisation and
antiseptic measures, fasting and bowel preparation.
2. The risk of puerperal sepsis is minimised.
3. The operation is scheduled and working is in ease.
Disadvantages of elective C.S:
1. The risk of immaturity of the foetus or its lung is present.
2. Higher incidence of respiratory distress syndrome.
3. The lower segment may be not well formed.
4. Postpartum haemorrhage is more liable to occur.
5.Imperfect drainage of lochia as the cervix is closed so it
should be dilated by the index finger introduced abdominally through the uterine incision .
Procedure of Lower Segment Caesarean Section:
Anaesthesia: General inhalation anaesthesia with nitrous oxide
+ oxygen ( the most commonly used) , epidural, spinal or
rarely local infiltration anaesthesia.

Position : Tilting the patient 15o to the left in the dorsal
position minimise the aorto-caval compression.
Skin incision: pfannenstiel ( transverse suprapubic) incision is
the most commonly used, but midline or paramedian vertical
suprapubic incisions may be used. If the patient had a previous
C.S incise in the same incision with trimming of the fibrosed
edges of the wound to help good healing.
Pfannenstiel incision has a better cosmetic appearance, better healing and less
incidence of incisional hernia but it is more time consuming associated with
more blood loss and gives less exposure.
The subcutaneous fat is incised.
The anterior rectus sheath is incised transversely in case of
pfannenstiel incision and longitudinally in case of vertical
incisions.
The rectus muscles : are separated in the midline in pfannenstiel
incision or retracted laterally in case of vertical incisions. The parietal peritoneum: is opened vertically.
The uterus is centralised, the bowel and omentum are packed off
with moist laparotomy pads, however this is usually
unnecessary.
The loose peritoneum over the lower uterine segment is held and
incised transversely, for about 10 cm in a semilunar fashion with
its edges directed upwards.
The bladder is dissected downward and is retained behind a
Doyne retractor placed over the symphysis.
A stay suture may be taken superficially in the lower segment
below the assumed site of uterine incision to help in its
identification after evacuation of the uterus.
he uterus is incised : in the same semilunar fashion by one of
the following methods:
A semilunar mark is made by the scalpel cutting
partially through the myometrium for 10 cm. A short
(3cm) cut is made in the middle of this incision mark
reaching up to but not through the membranes. The
incision is completed by the 2 index fingers along the
incision mark. If the lower uterine segment is very
thin , injury of the foetus can be avoided by using the
handle of the scalpel or a haemostat ( an artery
forceps) to open the uterus.
The short ( 3cm) middle incision may be enlarged by a
bandage scissors over 2 fingers introduced into the
uterus to protect the foetus.
Membranes are ruptured by toothed or Kocker’s forceps. The head is delivered by :
i- introducing the right hand gently below it and lifting it
up helped by fundal pressure done by the assistant,
ii- using one blade of the forceps or,
iii- using Wrigley’s forceps.
If the head is deep in the pelvis it can be pushed up vaginally by
an assistant.
The Doyen’s retractor is removed after the hand or forceps blade
is applied and before head extraction.
Suction for the foetus is carried out before delivery of the head.
In breech or transverse lie the foetus is extracted as breech.
The placenta is removed.

Closure of the uterine incision is done in 3 layers.
- The first is a continuous locking suture taking most of the
myometrium but not passing through the decidua to guard
against endometriosis and weakness of the scar.
- The second is a continuous or interrupted one inverting
the first layer.
- The third is a continuous or interrupted layer to close the
visceral peritoneum of the uterus. Closure of visceral
and/or parietal peritoneum is omitted by some surgeons.
The abdomen is then closed in layers .
Upper Segment Caesarean Section :
Indications:
1.Dense adhesions, extensive varicosity or myoma in the lower
uterine segment making its exposure or incising through it
difficult.
2. Impacted shoulder presentation.
3. Anterior placenta praevia.
4. Defective scar in the upper segment.
5. Cancer cervix.
6. Rapid delivery is indicated.
7. If a concomitant tubal sterilisation will be done.
8. Previous successful repair of high vesico-vaginal or
cervico-vaginal fistula.
9. Post-mortem hysterectomy.

Procedure:
Abdominal incision: is vertical.
Uterine incision : 10 cm vertical incision is made in the midline
of upper uterine segment without incising the peritoneal coat
separately as it is adherent in the upper segment.
Extraction of the foetus: as a breech in cephalic presentation.
The last layer of the uterine incision closure includes the
superficial part of the myometrium with the peritoneal covering.
The remainder of the procedure is as lower segment C.S.
Special problems encountered during caesarean section:
(I) Anterior placenta praevia:
Try to pass beside the placenta to reach the foetus if this is impossible cut
through it but severe bleeding will result which may affect the foetus.
(II) Narrow uterine incision:
Extension of the lower uterine segment incision may be done by:
a- "J" shaped or hockey-stick incision : i.e. extension of one end of the
transverse semilunar incision upwards.
b- "U"- shaped or trap-door incision: i.e. extension of both ends upwards.
c- An inverted T incision: i.e. cutting upwards from the middle of the
transverse incision. This is the worst choice because of its difficult
repair and poor healing.
Advantages of the lower segment over the upper segment operation:
1.Less blood loss: due to less vascularity and the placental bed
is away from the incision.
2. Easier to repair.

3. The resultant uterine scar is stronger due to:
a- Better coaptation of the edges as the lower segment is
thin.
b- Better healing as the lower segment is more passive
during puerperium.
c- The scar is distant from the subsequent site of placental
implantation which may penetrate it.
So subsequent rupture uterus is less (0.2% versus 2% in
upper segment).
4. Less subsequent adhesions to the bowel and omentum.
5. Less liability to acute gastric dilatation and paralytic ileus.
6. Less liability to peritonitis due to better peritonization and
healing.
Mode of Delivery in Subsequent Pregnancies:
The rule that "caesarean always caesarean" had been replaced since a long time
by "caesarean always hospital delivery". If the cause of the previous section is
not permanent as contracted pelvis, vaginal delivery can be tried.
Caesarean Hysterectomy:
Hysterectomy is carried out after caesarean section in the same sitting for one
of the following reasons:
1- Uncontrollable postpartum haemorrhage.
2- Unrepairable rupture uterus.
3- Operable cancer cervix.
4- Couvelaire’s uterus.
5- Placenta accreta cannot be separated.
6- Severe uterine infection particularly that caused by Cl. welchii.
7- Multiple uterine myomas in a woman not desiring future pregnancy although
it is preferred to do it 3 months later.
Caesarean Sterilisation:
Tubal sterilisation is usually advised during the fourth caesarean section.
Complications of Caesarean Section:
(I) Operative:
1- Primary maternal mortality is 4 times that of vaginal delivery which
may be due to:
i- shock .
ii- Anaesthetic complications particularly Mendelson’s
syndrome
iii- Haemorrhage usually due to extension of the uterine
incision to the uterine vessels, atony of the uterus or DIC.
2- Injuries to the bladder or ureter.
3- Foetal injuries.
(II) Post-operative:
(A) Early:
1. Thrombosis and pulmonary embolism.
2. Acute dilatation of the stomach and paralytic ileus.
3. Wound infection, puerperal sepsis and burst abdomen.
4. Chest infection.
(B) Late :
1. Rupture of the uterine scar.
2. Incisional hernia.

Deep Vein Thrombosis in Pregnancy

Introduction :
Deep vein thrombosis (DVT) is a rare but serious complication that can occur during pregnancy. Thromboembolic events can include venous thrombosis of the leg, calf, or pelvis, and also the most serious and life-threatening complication: pulmonary embolism (PE). Thromboembolic events during pregnancy and postpartum are a leading cause of maternal mortality in the United States and in the United Kingdom .
Pregnancy is recognized as a physiological state that substantially increases the risk of thromboembolic disease and its complications; a pregnant woman has a five times greater risk of thrombi formation than a non-pregnant woman of similar age
Incidence and Risk Factors :

The reported incidence of DVT in the literature varies widely. The incidence of venous thrombosis as approximately 1:1000–2000 pregnancies. Other sources report the incidence to be lower . The prevalence of thrombosis varies with the mode of delivery and the gestational length of the pregnancy . Risk factors for forming a DVT include advanced age, prolonged bed rest or immobility, pelvic or leg trauma, obesity, coagulation disorders, and certain chronic diseases . Risk factors that may be influenced by pregnancy include preeclampsia, Cesarean section, instrument-assisted delivery, hemorrhage, multiparity, and varicose veins . Women with a previous history of a thromboembolic event are at increased risk during their pregnancy as are women who have hereditary or acquired thrombophilias such as Factor V Leiden.
Thrombophilia is a disorder in which there is a tendency for the formation of thrombi or clots. It is estimated that 15% of the general population has a thrombophilia reports that in the presence of thrombophilia the maternal risk for thrombosis is increased by a factor of 8. According to . approximately 50% of all episodes of venous thromboembolism in pregnancy and postpartum are linked to acquired and congenital thrombophilias. Management of pregnant women with thrombophilia is based on individual assessment of risk factors and history . Although a comprehensive discussion about thrombophilias and pregnancy is beyond the scope of this article, interested readers should view the reference list for appropriate articles that discuss thrombophilias in more detail.
Thromboembolic disease may occur at any point in pregnancy. ,in a review of 165 cases of thrombosis over 15+ years, found that DVT occurred more frequently during the antepartum period than the postpartum period. One hypothesis for this is that women working outside the home during pregnancy must sit for prolonged periods of time, thus increasing their risk. Concerning where thrombosis is more often seen in pregnancy, most cases of thrombosis in the legs are in the ileofemoral veins than the calf veins . Clots located in the deep veins such as the ileofemoral veins are more likely to cause pulmonary embolus than those of the superficial veins of the legs . Approximately 90% of thrombi are located on the left side, which may be related to the anatomy of the veins and arteries on the left side . The enlarging uterus may provide additional compression on the vessels and further reduce venous flow .
Pathophysiology :

In 1999, Rosendaal reported that thrombosis is a multicausal disease in which risk factors, acquired and congenital, dynamically interact, rarely occurring without risk factors. Pregnancy unquestionably places certain women in a higher risk category. In the 1800s, Virchow described a triad of predisposing factors for thrombosis that still exist today: Venous stasis, endothelial or vascular damage, and hypercoagulability . Venous stasis exists as a normal course of pregnancy; the gravid uterus exerts mechanical compression on the inferior vena cava and pelvic veins as it enlarges, and the effects of some hormones, such as progesterone, increase venous distensibility . In addition, vascular and endothelial damage can occur during the course of a normal or instrumental vaginal delivery or during a Cesarean delivery. Intravenous catheters or medications may also cause vessel wall injury .
Hypercoagulability is a normal physiologic change in pregnancy, and might be so because the body is preparing for control of blood loss after delivery of the placenta. Fibrinogen levels double during pregnancy in preparation for the separation of the placenta and the development of a fibrin layer in its place .In addition, clotting factor levels (Factors V, VII, VIII, IX, X, XII) increase during pregnancy .
Although levels of Protein C remain normal, levels of Protein S decrease in pregnancy. Consequently fibrinolytic activity (the splitting up or dissolving of clots) decreases from inhibitory substances produced by the placenta. Although the levels of some coagulation factors do not change remarkable during pregnancy (i.e., the platelet count), by 3 weeks postpartum the levels of affected coagulation factors return to normal. The risk of developing a thrombosis continues until approximately 12 weeks postpartum.
Diagnosis of DVT and PE :

In the general population, diagnosis of DVTs is difficult and clinical findings can be unreliable, leading to delays in diagnosis and treatment which can be life threatening. The reason for the difficulty in diagnosis is that approximately one-half of all DVTs are asymptomatic. The physical signs of DVT will depend upon the development of collateral circulation, location, and size of the thrombus, and the degree of vessel obstruction. The pregnant woman poses significant challenges to diagnosis, based on expected body changes. Swelling, aches, and pains in the lower extremities are common by the second and third trimesters, and those are the symptoms of DVT. When examining a lower extremity for DVT diagnosis, a 2 cm difference between calf measurements in the affected and unaffected leg is common. Pain, heat, redness, tenderness, edema, changes in skin color, and a palpable cord may be seen. The woman may have a positive Homan’s sign (dorsiflexion of the foot which produces pain in the calf or popliteal area), although this is not present in all women with DVT. Phlegmasia alba dolens (white leg) or phlegmasia cerula dolens (blue leg) may develop with obstruction of the large veins. In postpartum women, it is more common to have phlegmsasia alba dolens (milk leg), which creates the milky white appearance in the affected leg, occurring due to spasms of the arterioles .
Diagnostic tests used in evaluating a suspected case of thrombosis include venography, impedance plethysmography (IPG), and Doppler ultrasound. Venogram has been considered the gold standard for making the diagnosis of DVT, but is invasive and involves using contrast dye to visualize the veins in the legs. Because the use of dye and radiation involve potential risk to the mother and the fetus, noninvasive tests should be used as initial screening tools for pregnant women, although noninvasive tests could miss thrombi of the pelvic veins.
Ultrasound, a noninvasive procedure, used in combination with Doppler analysis, can be an appropriate screening test for DVT. Doppler combined with ultrasound is known as the duplex study; real -time imaging provides visualization of vessels, and Doppler measures change in blood flow through the vessels. Doppler imaging is more sensitive to the veins in the femoral or popliteal area than the calf. Another test is impedance plethysmography, a non-invasive test that measures change in venous volume through electrical resistance; however, it is not very specific for the distal veins of the legs.
Pulmonary thrombi that embolize from DVTs may present as an acute event. Symptoms may include dyspnea, tachypnea, color changes, air hunger, anxiety, chest pain, tachycardia, cough, changes in heart sounds, rales in the lung fields, and hemoptysis, with dyspnea and tachypnea being the predominant presenting signs. Because PE can occur and can be life threatening, any patient with a suspected or confirmed DVT should be monitored for PE.
Diagnostic work-up for suspected PE includes arterial blood gas sampling, ventilation-perfusion scan, angiography, chest radiography, and electrocardiogram. Many of these tests are nonspecific. Blood gas sampling with a SpO2 <>90%. Scans with high probability are good indicators, but low or intermediate probabilities are less useful clinically. Pulmonary angiography is more invasive, and does expose the fetus to minimal radiation. Angiogram is useful if other noninvasive tests are inconclusive.
Women who develop DVT or PE during or after their pregnancy should have a thrombophilia work-up. Testing that may be ordered may include Factor V Leiden, Anti-thrombin III, prothrombin gene mutation, Protein C and S, Lupus anticoagulant, and Anticardiolipin antibodies (ACOG, 2000b). The American College of Obstetricians and Gynecologists (2000a) recommends individualized thromboprophylaxis for all pregnant women who are at high risk for developing thrombosis.
Treatment :

Treatment for confirmed or suspected cases of DVT or PE is immediate anticoagulation therapy. The goals of treatment in the pregnant woman are to reduce morbidity and mortality and to protect the fetus. Anticoagulation is started when there is a high suspicion that either a DVT is present or PE is possible. Anticoagulant agents are used to prevent the extension of existing clots and the formation of new thrombi. Drugs used include unfractionated heparin, low molecular weight heparin (LMWH), and warfarin (Coumadin). Each drug prevents the blood from clotting normally at different points during the clotting sequence. Traditionally, unfractionated heparin has been the gold standard for treatment of acute thrombosis and for thromboprophylaxis during pregnancy. However, LMWH is being used with increased frequency.
Heparin works by inhibiting the formation of thrombin and fibrin thereby reducing clot formation and extension and is the preferred treatment for pregnant women because it does not cross the placental barrier and therefore does not affect the fetus. However, heparin does have potential side effects. The mother is at risk for osteoporosis, thrombocytopenia, and hemorrhage. The risk of osteoporosis may be related to dosing and length of treatment . Heparinization for active thromboembolitic disease may vary between institutions and practitioners. Treatment protocols may vary but the literature supports management of DVT/PE in the pregnant woman with intravenous unfractionated heparin for 5–10 days followed by subcutaneous injections of heparin every 12 hours. Intravenous infusion dosing is based on achieving a therapeutic range of the activated partial thromboplastin time (aPTT) at 1.5–2 times normal. Several protocols are available in the literature; . The usual concentration is heparin 25,000 units per 250–500 cc. An initial bolus is given, usually 5000–10,000 units, and then a maintenance dose of approximately 800–1200 units is continued. The aPTT is measured every 6 hours until therapeutic and then testing can be done daily thereafter. The therapeutic range of the aPTT is generally between 60–80 seconds but may vary. Periodic testing of platelet counts should be done for patients on prolonged therapy. Long-term heparin use is known to cause osteoporosis as well as thrombocytopenia, but these side effects appear less often with LMWH use . Oral calcium supplements should be given to minimize the potential for osteoporosis development.
The switch to subcutaneous heparin injections after initial heparinization is controversial. Antepartum patients with DVT, especially thrombi in the iliac or femoral veins that are more likely to embolize, may benefit from more precise anticoagulation. Some advocate continuing heparin infusion during the antepartum period because it is difficult to achieve therapeutic levels with subcutaneous injections. Anti-Xa levels measure the therapeutics of subcutaneous heparin. The target range is usually 0.2–0.70µ/ml. Unfractionated heparin infusions may be desirable for those patients who may be clinically unstable or when delivery may be imminent.
LMWH is being used with increasing frequency as a result of clinical research demonstrating safety and efficacy during pregnancy . It has the advantage of being administered once daily and has a longer half-life, but is more expensive than traditional therapy. LMWH also appears to cause less osteoporosis and heparin-induced thrombocytopenia . Enoxaparin (Lovenox) and dalteparin (Fragmin) are two of the most widely used LMWHs. LMWH works by inhibiting factor Xa in the clotting cascade thereby preventing the formation of thrombi. Dosing of the LMWH is based on weight and rounded to the nearest available prepackaged dose. The usual dose for Lovenox is 1 mg/kg every 12 hours. A dose of 40 mg is reported to be effective for pregnancy.
Recommendations for dosing with LMWH depend upon the basis for requiring anticoagulation and the practitioner’s preference. Once daily dosing may provide sufficient coverage for prophylaxis in a patient with no previous thrombophilia history or event, whereas twice-daily dosing may be needed to achieve therapeutic levels in a patient with active thrombolic disease or event. Chan et al. (2001) suggest that twice daily dosing of LMWH may be needed in the pregnant woman because physiological changes such as increases in glomerular filtration rate metabolize the drug more quickly. Patients being treated for an acute event may benefit from testing of therapeutic levels. Antifactor Xa levels can be obtained 4 hours after administration to monitor dosing requirements.
Warfarin (Coumadin) can be used as well but it is traditionally used in the postpartum period, and for specific diseases such as for women with artificial heart valves. Warfarin does cross the placenta and can have tetratogenic effects. During the first 6 to 9 weeks gestation, warfarin has been shown to cause fetal embryopathy such as limb and nasal hyperplasia, scoliosis, stippling of the bone epiphyses, microcephaly, and nasal hypoplasia, and should not be used. At any point in the pregnancy, warfarin has been documented to place the fetus at risk for central nervous system and eye abnormalities as well as hemorrhage. Additionally, there is a risk of placental abruption. Therefore, warfarin should be considered for long-term use in pregnant women who have prosthetic heart valves and have contraindications to heparin therapy. Warfarin works by inhibiting the formation of several vitamin K-dependent clotting proteins. Historically, it is started shortly after heparin therapy is initiated and most recently it is being used with LMWH. Dosing is individualized and is titrated to achieve a target range of the International Normalized Ratio (INR) of 2.0 to 3.0. Heparin is usually discontinued after the INR reaches >2.0. It takes approximately 2 to 7 days for the body to deplete the stores of clotting proteins and the INR to be near the therapeutic range. Treatment is usually continued for at least 3 to 6 months or longer if indicated. Warfarin is safe for women intending to breastfeed in the postpartum period. Small amounts of warfarin will be transmitted through the breast milk to newborns; therefore, parents should be aware of potential side effects to the newborn. Parents should be taught to observe the infant for bleeding, bruising, or the development of petechia. Any of these changes should be reported to the pediatrician .
Thrombectomy and vena cava filter are two treatment options that are less widely used. Vena caval filter is considered for pregnant woman to prevent pulmonary embolization from unstable venous clots. The filter is used for patients who continue to have recurrent pulmonary emboli despite adequate heparinization or who may be unstable and anticoagulation is contraindicated. Thrombectomy is usually limited to severe cases with massive PE or limb-threatening disease.
Superficial venous thrombosis is typically seen in the superficial veins of the calf, usually associated with varicosities and intravenous insertion sites. The risk of embolization is rare. Treatment includes rest, elevation, analgesia, and elastic compression stockings.
Management in Labor :

Women receiving anticoagulation in labor should be cared for by providers skilled in high-risk care. Management of the pregnant woman on anticoagulants during the intrapartum period is dictated by the reason for the therapy; therefore, the treatment will vary. Patients who are receiving thromboprophylaxis can usually have their heparin therapy discontinued during labor, but LMWH has a longer half-life and needs to be discontinued sooner. If needed, anticoagulation therapy can be restarted 4 to 6 hours postpartum, with the exception of women with mechanical heart valves or serious thrombophilia.
Therapeutic heparin infusions during labor can be continued, and the rate adjusted to maintain the aPTT at 1.5x’s normal. This mode of treatment is ideal for those patients who are at increased risk of hemorrhage (i.e., placenta previa or placental abruption).
Regional anesthesia is not recommended for women on LMWH, for the literature raises concerns about reports of hematoma formation in nonpregnant patients receiving heparin after epidural placement . Consultation with the anesthesia service is recommended. For planned inductions or Cesarean deliveries, dosages of LMWH can be timed so that peak levels are achieved before anesthesia is needed. Certain patients receiving LMWH can be switched to heparin injections toward the pregnancy’s end so that regional anesthesia is an option in the event of spontaneous labor or induction. In general, at least 4 hours should pass after unfractionated heparin is administered and at least 12 to 24 hours since the last dose of LMWH is given before regional anesthesia can safely be given. If epidural anesthesia is given, LMWH can usually be restarted at least 3 hours after the catheter is removed.
After delivery, many women will be restarted on anticoagulation for 6 to 12 weeks postpartum. Women who had been treated for active thrombosis during pregnancy may have therapy continued longer than 12 weeks, and may be treated up to 6 months or longer.
Nursing Implications :

Treatment modalities will vary between practitioners, but nurses can be active in educating patients about risk factors, prevention, and treatment options for thromboembolic disease .Patients being treated for active thrombosis will need prolonged anticoagulation therapy. Whether it be for treatment of active disease or for prophylaxis, patient compliance is essential for successful anticoagulation, and nurses can be essential in helping women to understand the necessity of continued treatment. In addition to educating women about pharmacologic treatment for or prevention of thrombosis, nurses must teach women about signs of clots, side effects of drug treatment, self-injection techniques, labor support, prevention of complications such as embolization and postthrombolic insufficiency, and when to seek medical attention. Nursing care should include not only teaching but frequent assessments for bleeding from anticoagulant therapy and complications resulting from DVT/PE.
The woman who has active thromboembolic disease or who is receiving anticoagulation poses challenges to any perinatal nurse. Education must be offered to pregnant and postpartum women, especially those women with additional risk factors such as obesity, preeclampsia, or hypertension. Women taking warfarin will require specialized teaching on drug interactions and dietary restrictions. Women should also be counseled to take adequate calcium supplementation and perform weight-bearing exercise as tolerated while taking heparin to lessen the potential for heparin-induced osteoporosis.
Bleeding is a major side effect of any anticoagulant used. Special attention should be paid to monitoring for bleeding and educating the patient about the risk of bleeding and the need to notify the healthcare provider immediately if bleeding should occur. Women in active labor should be assessed frequently during labor and postpartum for abnormal bleeding. Protamine sulfate can be used to reverse the effects of both LMWH and unfractionated heparin; therefore, it should be readily available minutes to prevent hypotension. Long-term therapy with heparin should consist of periodic testing of the platelet count. Women receiving heparin therapy who present in labor or for evaluation should have the platelet count measured.
Properly fitting antiembolitic stockings or elastic compression stockings promote the fluid movement of blood through the veins of the leg by exerting pressure. Women who are on prolonged bed rest, are undergoing Cesarean section, or are at high-risk due to obesity or preeclampsia should be fitted for elastic stockings in knee or thigh length. Knee-length stockings are generally believed to be easier to apply and to fit properly, thereby being more effective. Stockings that are too loose provide no compression; those that are too tight may promote venous stasis. Proper fit is best obtained by measuring the calf diameter and selecting a size that corresponds to the manufacturer’s recommendations. The stockings should be removed once per day and the legs inspected. Other devices that can be used to reduce the pooling of blood in the venous system are external pneumatic compression and venous foot pumps. Women on bed rest should be taught to perform active and passive resistance exercises to prevent muscle wasting and promote venous return.
Postpartum women who will be taking warfarin need extensive teaching about the drug and its effects. Warfarin interacts adversely with many prescriptions and over the counter medications. Patients should be instructed to call their physician before taking other medications, and to limit foods rich in Vitamin K (e.g., broccoli, lettuce, spinach). If the woman desires more children, she should be warned about possible tetratogenic effects to the fetus while she is taking the drug, and the essential nature of birth control during this time. Women taking warfarin must be told to notify their physician if they do become pregnant or plan to conceive while taking warfarin. As with any medication or anticoagulant, the patient should be aware of possible side effects including bleeding from the gums, dark or red stool or urine, heavy menses, heavy bleeding from cuts; patients should be advised to notify their healthcare provider should any of these side effects occur.

External version

The aim :
1. To detect cephalo-pelvic disproportion.
2. Cephalic delivery is safer for the mother and foetus.

Success rate:
50-70%.
Indications
Breech presentation ,transverse lie
Do not perform this procedure before 37 weeks.
Technique :
• Have the woman lie on her back, and elevate the foot of the bed.
• Listen to and note the fetal heart rate. If there are fetal heart rate abnormalities (less than 100 or more than 180 beats per minute), do not proceed with external version.
• Palpate the abdomen to confirm presentation and position of the fetal head, back and hips.
• To mobilize the breech, gently lift the lowest part of the fetus from the pelvic inlet by grasping above the pubic bone (Fig P-5 A).
• Bring the head and buttocks of the fetus closer to each other to achieve forward rotation. Rotate the fetus slowly by guiding the head in a forward roll as the buttocks are lifted (Fig P-5 B–C).
• Listen to the fetal heart rate. If an abnormality is detected:
- Have the woman turn on to her left side;
- Give oxygen at 4-6 L per minute by mask or nasal cannulae;
- Reassess every 15 minutes.
• If the procedure is successful, have the woman remain lying down for 15 minutes. Counsel her to return if bleeding or pain occurs or if she believes the baby has returned to the previous presentation.
• If the procedure is unsuccessful, try again using a backward roll (Fig P-5 D).
• If the procedure is still unsuccessful and fetal heart rate is good, tocolytics may increase the chances of successful version. Give:
- terbutaline 250 mcg IV slowly over 5 minutes;
- OR salbutamol 0.5 mg IV slowly over 5 minutes.
• If the procedure is still unsuccessful, attempt version again after 1 week or if the woman presents in early labour with breech or transverse lie.
• If they are fetal heart abnormalities:
- Turn the woman onto her left side;
- Reassess the fetal heart rate every 5 minutes;
- If the fetal heart rate does not stabilize within the next 30 minutes, deliver by caesarean section .
Causes of failure:

1- Large sized foetus.
2- Oligo - or polyhydramnios.
3- Short umbilical cord.
4- Uterine anomalies as bicornuate or septate uterus.
5- Irritable uterus. Tocolytic drugs may be started 15 minutes before the procedure to overcome this.
6- Obesity.
7- Rigid abdominal wall.
8- Frank breech because the legs act as a splint.
Contraindications:
1- Contracted pelvis.
2- Multiple pregnancy.
3- Hydrocephalus.
4- Antepartum haemorrhage.
5- Uterine scar.
6- Hypertension as the placenta is more susceptible to separation.
7- Elderly primigravida.
8- Ruptured membranes.

9-Anaesthesia during version is contraindicated as pain is a safeguard against rough manipulations.
Complications:
1- Accidental haemorrhage due to separation of the placenta.
2- Rupture of membranes .
3- Preterm labour.
4- Foetal distress.
5- Cord presentation or prolapse.
6- Entangling of the cord around the foetus.
7- Isoimmunization in Rh-negative mothers due to foeto - maternal transfusion.

Diagnostic hysteroscopy ,DR. Alaa Mosbah M.D OBS&GYN

Introduction
Endoscopy began in 1805 with Bozzini , but it was Pantaleoni who, in 1869, performed the first hysteroscopy, not only diagnosing an endometrial polyp with the aid of an endoscope, but cauterizing it with silver nitrate. A second generation of endoscopes was developed by Nitze in 1879 who constructed a cystoscope with a lens system and a light source inside the endoscopic tube. With this innovation, vision was clearer, lighting more intense and the field of vision wider.
In spite of these early attempts, hysteroscopy was more a curiosity than a truly useful technique until the 1970s when technical improvements in lenses and distension media resolved some of the difficulties that had prevented its widespread use before that time. It was Hamou who revolutionized the field of hysteroscopy with new, improved visual optics and instruments of fine diameter ( 4 mm). Improved optics, simpler techniques and the ability to perform the examination in the outpatient clinic without anaesthesia or cervical dilatation have further popularised hysteroscopy in the 1980s and 90s .Failure rates due to either cervical stenosis or pain can be as low as 3% .The acccuracy of diagnostic hysteroscopy in detecting uterine anomalies is recognized by most experts in the field today.As interest in hysteroscopy grows as a consequence of these advances, there is an urgent need to introduce the technique more widely into routine gynaecological practice.
Indications
The remarkable progress made and the relative simplicity of the technique have widened the indications for hysteroscopy. Today diagnostic hysteroscopy can be considered the optimal method of assessing all cases where visualizing the cervical canal, uterine cavity and tubal ostea will improve diagnostic accuracy and guide therapeutic management. It is in the field of improved diagnosis that hysteroscopy has made the most significant progress, mainly because the ability to use fine diameter instruments makes it feasible to avoid both anaesthesia and cervical dilatation. The procedure may therefore be performed in an outpatient setting without the need for hospitalization.
1. Infertility
While hysterosalpingography (HSG) and endometrial biopsy are important and well established techniques in the investigation of infertility, only hysteroscopy permits an accurate assessment of the of the genital tract in infertile women. Direct visualization of the uterine cavity and tubal ostia coupled with targeted endometrial biopsy provide more specific information which may clarify the cause of the infertility. HSG has limitations as a diagnostic tool. Dubious or erroneous results have been reported in as many as 40% of the cases when HSG is compared with hysteroscopy and laparoscopy .The need for hysteroscopy becomes clear when filling defects are seen on HSG .A study conducted in 1983 showed that the uterine cavity as seen at hysteroscopy was normal in 45% of the women in whom a prior HSG had suggested a uterine anomaly .
Hysteroscopy is recommended for the diagnosis and treatment of intrauterine adhesions, to assess the anatomical and functional condition of the uterotubal ostia, to determine and guide post surgical management of metroplasty and salpingoplasty, to identify and treat suspected intrauterine pathology such as submucous myomas, endometrial polyps and hyperplasia and to assess the status of the uterine cavity in cases of repeated abortion.
Hysteroscopy aids both the diagnosis and management of intrauterine adhesions. It allows a panoramic as well as a close-up view with magnification. At x20 magnification, three different histological types of adhesions may be seen: endometrial, myofibrous, and connective .Endometrial adhesions are usually fragile, soft, and whitish in appearence and are easily divided. Myofibrous adhesions on the other hand, require a more aggressive technique. Connective tissue adhesions, which are greyish and dense, are the most difficult to divide .Successful management can be achieved in most cases. In our experience a normal menstrual flow followed in 86.7% of the cases with a pregnancy rate of 44.4% .
Hysteroscopy is the best means of studying and evaluating the anatomy and function of the uterotubal ostium. HSG may give false results because pressure of distension medium in the uterine cavity and intramural portion of the fallopian tube may provoke contraction of the sphincteric muscle. Hysteroscopy allows the observation of the ostium under almost normal conditions. Falloposcopy, which may be controlled with or without hysteroscopy allows examination of the tubal lumen as far as teh isthmo-ampullary junction and, occasionally, as far as the fimbrial opening .This is less invasive and traumatic than laparoscopic salpingoscopy or intraoperative microbiopsy .
Intra-uterine pathology, including submucous myomas, polyps, and hyperplasia, may occur in a relatively high percentage of asymptomatic, infertile patients .These conditions can be easily identified and classified through hysteroscopy.
Endometrial biopsy is useful in the cases of polyps or hyperplasia. Although the role of endometrial pathology in infertility is debatable, the presence of gross intracavitary pathology can easily interfere with the process of nidation. In our experience, the percentage of asymptomatic submucous myomas in infertile patients is 5.2% .Additional pathology which can interfere with embryo implantation and development are uterine malformations, particularly a septate uterus, although uterine malformations are usually associated with pregnancy wastage, not infertility. Hysteroscopy and laparoscopy allow precise classification and consequently appropriate treatment of uterine malformations. When facing the problem of recurrent abortion, visualization of the uterine cavity becomes indispensable for a correct diagnosis, and forms the basis for an appropriate therapy .
2. Abnormal Uterine Bleeding (AUB)
One third of all gynaecologic consultations are because of AUB and this constitutes the second indication for hysteroscopy. This proportion rises to more that two thirds when the peri- and postmenopausal age groups are considered .Excessive mestrual blood loss is a strong indication for exploring the uterine cavity and determining the underlying pathology. The only other method available in such cases is Dilatation and Curettage (D&C). D&C provides a histological diagnosis, but it often requires general anesthesia and, in many hospitals an overnight stay. The main drawback of D&C is that it is a blind procedure that may not identify focal lesions. The correct diagnosis may be missed even in the presence of endometrial polyps, myomas and neoplasia. Published information places diagnostic failures of D&C at between 10% and 25% .In our own experience, hysteroscopy with an endometrial biopsy is the procedure of choice in patients with abnormal uterine bleeding .Biopsy is especially important if hyperplasia, polyps or endometrial cancer are suspected. The reliability of hysteroscopy approaches 100% in endometrial neoplasia, and has been estimated at 87.5% in "high risk hyperplasia" and 65.2% in "low risk hyperplasia" .Over 50% of patients over 45 years with AUB have a normal endometrium.
The diagnosis cannot rely exclusively on hysteroscopy, but its diagnostic accuracy is greater than any other technique in use today.
3. Endometrial Hyperplasia and Cancer
The third area in which hysteroscopy can provide valuable information is in the prevention and early diagnosis of neoplastic lesions of the endometrium. Early diagnosis of endometrial adenocarcinoma may be difficult in pre-menopausal women, since this type of neoplasm may be asymptomatic for a long period. Although D&C and endometrial biopsy are also reliable for the diagnosis of endometrial neoplasia, hysteroscopy has the advantage of permitting a targeted biopsy in the event of localized lesions, reducing the possibility of false negatives. In addition, it permits proper classification of the extent and degree of hyperplasia.
Although there is no specific appearance for each histological type of endometrial hyperplasia, endoscopic classifications have been developed that can be applied clinically .The hysteroscopic appearance of low risk endometrial hyperplasia (EH) includes an increase in the thickness of the endometrium, its dyshomogeneous regeneration, increased vascularization and the presence of ciliated images, cystic dilatation, increased bleeding, polypoid formation, necrotic zones and the concentration and irregular arrangement of the glandular openings. If one or more of these elements are found, hyperplasia must be suspected. Guided endometrial biopsy can then be performed.
The hysteroscopic appearance of high risk endometrial hyperplasia or endometrial intraepithelial neoplasia (EIN) clearly defines these pre-neoplastic and neoplastic lesions: Polyps are often present and abnormal vascularization produces an arborescent appearance which surrounds groups of glandular orifices. The architecture and organization of the uterine cavity is altered. The endoscopist can easily confirm the hysteroscopic suspicion with endometrial sampling of specific areas.
In its initial stages, endometrial cancer shows a papillary appearance with irregular polylobate excrescences which are friable and partly necrotic or haemorrhagic. Vascularization is irregular and anarchic. Often there is a clear dividing line between cancerous and normal endometrium. Neoplastic lesions can be focal and localized at the tubal cornua. Some authors . believe that irrigation of the endometrial cavity with saline during hysteroscopy may disseminate endometrial cancer cells into the peritoneal cavity and may alter the prognosis and the course of treatment. There are several arguments against this hypothesis. First, bimanual examination, curettage or even hysterectomy will cause intravasation and passage of cells into the peritoneal cavity through the fallopian tubes without increasing the risk of metastatic implantation .Second, Tanizawa et al . showed that of 1040 patients with endometrial cancer examined by hysteroscopy, the number of tumour cells in the peritoneal cavity was not significantly different from those who had not had hysteroscopy. Hysteroscopy had no effect on metastasis in the peritoneal cavity and in the prognosis of these patients. Finally, it must be stressed that if diagnostic hysteroscopy is performed with CO2 it carries fewer cells through the fallopian tubes than if a liquid medium were used.
In order to check the diagnostic accuracy of hysteroscopy, we have compared visual images to histologic results . and found a good correlation in 87% of the cases of EH, in 92% of the cases of adenomatous hyperplasia with atypia or EIN, and in 94% of adenocarcinomas. Considering that AUB, either per se, or in association with risk factors for endometrial adenocarcinoma such as obesity, diabetes, hypertension or the unopposed use of estrogens in peri-and post-menopausal patients, leads to a suspicion of endometrial cancer, it should not be surprising that hysteroscopy must be considered the examination of choice in these patients.
Contraindications
Most of the classic contraindications of diagnostic hysteroscopy, such as the presence of an active pelvic infection or cervical cancer, are not considered any more as absolute, but rather as relative. In these cases the examination can be performed, but the surgeon must observe adequate precautions.The potential spread of an infection caused by intrauterine manipulation and the pressure of the distending medium may increase the risk of spreading infection so prophylactic antibiotics should be given. Hysteroscopy can be performed without any major risk of spreading malignant cells in patients with invasive cervical carcinoma. However, hysteroscopy in the presence of invasive cervical cancer has no practical value if we exclude the differential diagnosis of a primitive adenocarcinoma of the endocervix, a very rare form of cancer.
Special care is required in discussing hysteroscopy in early pregnancy. This can be performed without affecting the pregnancy, although the indications are few. They include the removal of a "lost IUCD" to avoid the risk of a septic abortion.
Equipment
Light Source: Light is an indispensable component of endoscopy. Satisfactory sources of "cold" light using halogen or xenon lamps have been available for for several years. The power required varies from 100 to 300 watts. A fibroptic cable transmits light from the source to the endoscope. In general, 150 watts are enough to obtain a satisfactory view. Higher power is used for filming or photography. However it is preferable to use a videocamera in performing diagnostic hysteroscopy to allow colleagues and even the patient to participate and to make video recordings. Furthermore the utilization of videoendoscopy is considered fundamental for proper training.
Distension of the uterine cavity: It is necessary to distend the uterine cavity to obtain a panoramic view. Distension media include gas, low viscosity fluids (dextrose, lactated Ringer’s, glycine, sorbitol, saline solution) and high viscosity fluids. The preferred technique is insufflation of carbon dioxide with an automatic pressure control. This was introduced in 1971 by Lindemann and has been constantly improved. Recent innovations have led to high reliability making CO2 distension the best method in current use. A steady flow of CO2 assures an even dilatation. In order to keep a safe, constant flow of carbon dioxide, a pre-set insufflator which automatically maintain pressure at between 80 and 100 mm Hg, with a flow of 60-80 ml/min should be used. Early fears of possible gas embolism were allayed when Lindemann and Rubin reported on 90.000 insufflations performed by 380 different surgeons without complications. This is because the levels of CO2 capable of producing toxicity far exceed those used during an entire hysteroscopic examination.Low viscosity fluids such as dextrose, water, glycine, sorbitol, lactate Ringer’s and saline solution can also be used to produce uterine distension. They must be introduced under pressure since they pass easily through the tubal openings and also flow back through the cervical canal. A system of infusion/aspiration allows the creation of a continuous flow in the uterine cavity that mantains a constant, clear view with proper uterine distension. The use of a continuous stream of low-viscosity fluids requires less skill and allows adequate vision even in the presence of blood. Low viscosity fluids are readily absorbed from the peritoneal cavity and their cost is low. Their disadvantage is that they mix easily with blood and therefore visibility may be compromised unless they are used with a continuous lavage system which makes the use of an automatic pump for infusion/aspiration mandatory. Intravasation or excessive vascular uptake of fluid from the uterine vessel may produce complications.Dextran 70 (Hyskon) is a high viscosity solution with a molecular weight of 70.000. It is normaly infused along the hysteroscope sheath using a 50 ml syringe. Generally, 100 ml are sufficient to distend the uterine cavity and the peritoneum is not harmed by spillage into it. Simplicity of use and excellent light transimission are among the advantages of Dextran 70. The advantages of its high viscosity are that it does not escape easily through the fallopian tubes or cervix and so maintains uterine distension and that it does not mix with blood. The disadvantages are that it may be difficult to infuse through the hysteroscope and that the instruments must be washed immediately in warm water to prevent crystallization of the fluid and blockage of stop-cocks. There have also been occasional reports of allergic reactions and even death.
Optical systems: Optical systems are either rigid or flexible. Flexible systems have not gained in popularity because of their high cost and fragility. Three types of rigid lens systems are in use: Hopkins, Lumina and Olympus. Technical improvements aim at maintaining high resolution at various distances and with various magnifications. Optical systems have angles of vision ranging from 0 (180 degrees) to 30 (150 degrees), the latter being the most popular. Their external diameter can be as little as 1.2 mm. This diameter makes the device less durable but does not reduce visibility. An instrument 4 to 5 mm in diameter is considered preferable for routine use because it still permits endoscopic examination without anesthesia or cervical dilatation. Hamou's microhysteroscope has two advantages over other systems for diagnostic hysteroscopy: a fine diameter (5 mm) essential for performing the examination in the outpatient clinic and a system of lenses controlled by a push button switch which offers 4 magnifications: x1, x20, x60 and x150. Lower magnifications (x1 and x20) are used to obtain a panoramic view of the uterine cavity. This is similar to the view obtained with a colposcope for the ectocervix and comparable to the traditional hysteroscope for the examination of the cervical canal and uterine cavity. Higher magnifications of x60 and x150) require contact vision after vital staining of the area and show the structure and arrangement of the surface cellular layers. Changing the magnification is easy and carried out by simply pressing a push-button switch on the side of the device during the course of the examination. The narrow diameter of the hysteroscope and its manouverability permit easy and relatively painless exploration of both the cervical canal and the uterine cavity. The continuous insufflation of CO2 which is introduced into the space between a single flow sheath and the hysteroscope creates the desired dilatation of the cervical canal as well as of the uterine cavity. Distension with a continuous flow of liquid requires a double sheath for infusion and aspiration. Continuous liquid flow is indicated in patients with bleeding because always it can mantain a clear vision.
Technique
The patient should be examined and a speculum introduced. A tenaculum is placed on the anterior lip of the cervix for traction. At this time local anesthesia can be used, if appropriate, by injecting a few ml of carbocaine 2% into the cervix. The flow rate of CO2 is set at 60 ml/min. The hysteroscope is gently introduced in the cervical canal and advanced under visual control into the uterine cavity. The ectocervix and vaginal fornix, cervical canal and uterine cavity may be explored.
During examination of the ectocervix low magnification (x1, x20) provides results that are comparable with those obtained by colposcopy, although traditional colposcopy presents clear advantages because the colposcope allows a more accurate observation of fine details which are so crucial in cervical pathology. The field of vision of the colposcope is wider and is not deformed by the 30 degree angle view afforded by the hysteroscope. Microcolposcopic contact vision, with x60 and x150 magnifications shows the superficial layers of the epithelium with a field depth of about 80 micron and provides a microscopic view of the nucleus and cytoplasm. Such high magnification requires prior staining with Lugol and Watermann blue solution.
Low magnification gives a panoramic view and can provide important information on the integrity of the anatomical structure of the cervical canal. The application of a few millilitres of 2% acetic acid may often show the squamous-columnar junction (SCJ), when this has risen inside the cervical canal. The SCJ is always visible and clearly defined after vital staining with Watermann blue solution using contact viewing and magnifications of x60 or x150 It is possible to judge exactly how far the instrument has advanced into the cervical canal.
During the examination of the uterine cavity simple panoramic viewing at x1 or x20 magnification has proved extremely useful in identifying all types of endometrial pathology .Microscopic contact viewing requires some form of anaesthesia because of the relatively long time needed for the examination and the consequent discomfort to the patient and should be reserved for cases where its use is specifically indicated. Problems such as pain, bleeding obscuring the endoscopic vision, or poor distension of the uterine cavity are directly related to the experience of the endoscopist .
Complications
Diagnostic hysteroscopy is a safe procedure. Complications mainly occur when inappropriate instruments or techniques are used.
The prevalence of vagal reaction depends on the ability of the endoscopist and on the diameter of the scope. It can be prevented with the administration of 0.5 ml of atropine 20 minutes prior to commencing the procedure. Atropine should not be given if the patient suffers from cardiocirculatory problems.
The most frequent complications seen during hysteroscopy are the result of over distension of the uterine cavity. The uterus can be adequately distended with a pressure of 60 to 80 mm Hg of carbon dioxide. Automatic "hysteroflators" keep of CO2 flow under 80 ml/min and maintain an intrauterine pressure less than 100 mm Hg and make the procedure very safe. Gaseous intravasation usually occurs only at CO2 pressures above 400 mm Hg. When this occurs there is a decrease in PO2 and an increase in PCO2.
Complications can also occur when using Dextran-70 ("Hyskon"). They include pulmonary edema, anaphylactic reactions and coagulopathy consequent to intravasation. Liquid intravasation can provoke pulmonary edema also with low viscosity fluids such as saline solution and Ringer’s lactate but this can be easily managed by intravenous diuretics. Saline and Ringer’s lactate cannot be used with electrosurgery because they contain electrolytes. The risk of complications increases with the duration of the intervention and when intrauterine manipulations are performed. Loffer reported an incidence of intravasation of 1.1% when performing hysteroscopic myomectomy but did not report an incidence for diagnostic hysteroscopy.
The golden rule to avoid intravasation with any liquid distension media is to measure the difference between the quantity of liquid infused into the patient and the quantity reaspirated and always maintain the deficit at under 1 liter.
Uterine perforation is a rare event. It occurs in 4 out of 1000 cases of diagnostic hysteroscopy. Perforation usually occurs in difficult cases during dilatation of the cervix .Perforation occurs more frequently at the level of the fundus without significant bleeding. When perforation occurs laparoscopy should be performed and antibiotics and oxytocin administered for at least two days. Salat Baroux et al have reported an incidence of 0.2% of infection in over 4000 diagnostic hysteroscopies.
Conclusion
Truly useful techniques and procedures frequently evolve slowly in medicine. They are usually developed to answer a specific need. For this reason, their evolution depends on many factors.
While it may be true that the first hysteroscopies date from the beginning of the 20th century, enthusiasm for its use has only recently gained momentum and has now begun to expand exponentially. It should not be surprising that the development of practical hysteroscopic techniques is proceeding parallel to the development of highly sophisticated endoscopic methods of visualizing other body cavities, as one technique feeds and reinforces the others. In spite of this, there is still a reluctance to incorporate this procedure into routine office gynecologic practice. Yet, the potential of hysteroscopy ranging from diagnosis of abnormal uterine uterine bleeding to the microscopic confirmation of cervical precancerous lesions permits us to predict that it will play an increasing role in our ability to diagnose diseases of the female reproductive tract quickly and accurately.
Hysteroscopy also offers advantages in the diagnosis and management of infertility and repeated abortion. The use of diagnostic hysteroscopy in the management of abnormal uterine bleeding may, in many instances, replace procedures such as D&C. The magnifying power of the microhysteroscope and its ability to penetrate the cervical canal to regions inaccessible to the colposcope suggest a very real role in the assessment of precancerous and cancerous lesions of the endometrium.

Ultrasound in obstetrics /DR. Alaa Mosbah , M.D OBS & GYN

- Obstetric ultrasound is the use of ultrasound scans in pregnancy. Since its introduction in the late I950's ultrasonography has become a very useful diagnostic tool in Obstetrics.
- Currently used equipments are known as real-time scanners, with which a continuous picture of the moving fetus can be depicted on a monitor screen. Very high frequency sound waves of between 3.5 to 7.0 megahertz (i.e. 3.5 to 7 million cycles per second) are generally used for this purpose. They are emitted from a transducer which is placed in contact with the maternal abdomen, and is moved to "look at" (likened to a light shined from a torch) any particular content of the uterus. Repetitive arrays of ultrasound beams scan the fetus in thin slices and are reflected back onto the same transducer. The information obtained from different reflections are recomposed back into a picture on the monitor screen (a sonogram, or ultrasonogram). Movements such as fetal heart beat and malformations in the fetus can be assessed and measurements can be made accurately on the images displayed on the screen. Such measurements form the cornerstone in the assessment of gestational age, size and growth in the fetus.

The main uses of ultrasonography are in the following areas:
1- Diagnosis and assessment of early pregnancy:
The gestational sac can be visualized as early as four and a half weeks of gestation and the yolk sac at about five weeks. The embryo can be observed and measured by about five and a half weeks.

2- Threatened miscarriage.
The viability of the fetus can be documented in the presence of vaginal bleeding in early pregnancy. A visible heartbeat could be seen and detectable by pulsed Doppler ultrasound at 6 weeks and is usually clearly visible by 7 weeks. If this is observed, the probability of a continued pregnancy is greater than 83 percent. Missed abortion and blighted ovum will usually give typical pictures of a deformed gestational sac and absence of fetal poles or heart beat. Ultrasonography is also useful in the early diagnosis of ectopic pregnancies and molar pregnancies.

3- Determination of gestational age and assessment of fetal size
Fetal body measurements reflect the gestational age of the fetus. This is particularly true in early gestation. In patients with uncertain last menstrual periods, such measurements must be made as early as possible in pregnancy to arrive at a correct dating for the patient. In the latter part of pregnancy measuring body parameters will allow assessment of the size and growth of the fetus and will greatly assist in the diagnosis and management of intrauterine growth retardation (IUGR).

The following measurements are usually made:
a) The Crown-rump length (CRL)
This measurement can be made between 7 to 13 weeks and gives very accurate estimation of the gestational age. Dating with the CRL can be within 3-4 days of the last menstrual period.
b) The Biparietal diameter (BPD)
The diameter between the 2 sides of the head. This is measured after 13 weeks. It increases from about 2.4 cm at 13 weeks to about 9.5 cm at term. Different babies of the same weight can have different head size, therefore dating in the later part of pregnancy is generally considered unreliable.
c) The Femur length (FL)
Measures the longest bone in the body and reflects the longitudinal growth of the fetus. Its usefulness is similar to the BPD. It increases from about 1.5 cm at 14 weeks to about 7.8 cm at term.
d) The Abdominal circumference (AC)
The single most important measurement to make in late pregnancy. It reflects more of fetal size and weight rather than age. Serial measurements are useful in monitoring growth of the fetus.

4- Placental localization.
Ultrasonography has become indispensible in the diagnosis or exclusion of placenta praevia, and other placental abnormalities as in diabetes, fetal hydrops, Rh isoimmunization and severe intrauterine growth retardation.
5- Multiple pregnancies.
In this situation, ultrasonography is valuable in determining the number of fetuses, the chorionicity, fetal presentations, evidence of growth retardation and fetal anomaly, the presence of placenta praevia, and any suggestion of twin-to-twin transfusion.
6- Hydramnios and oligohydramnios.
Excessive or decreased amount of liquor (amniotic fluid) can be clearly depicted by ultrasound. In both these situations, careful ultrasound examination should be made to exclude intrauterine growth retardation and congenital malformation in the fetus such as intestinal atresia, hydrops fetalis or renal dysplasia.
7- Fetal malformation.
Many structural abnormalities in the fetus can be reliably diagnosed by an ultrasound scan, and these can usually be made before 20 weeks. Common examples include hydrocephalus, anencephaly, myelomeningocoele, achondroplasia and other dwarfism, spina bifida, exomphalos, Gastroschisis, duodenal atresia and fetal hydrops. With more recent equipment, conditions such as cleft lips/ palate and congenital cardiac abnormalities are more readily diagnosed and at an earlier gestational age.
First trimester ultrasonic 'soft' markers for chromosomal abnormalities such as the absence of fetal nasal bone, an increased fetal nuchal translucency (the area at the back of the neck) are now in common use to enable detection of Down syndrome fetuses. Ultrasound can also assist in other diagnostic procedures in prenatal diagnosis such as amniocentesis, chorionic villus sampling, cordocentesis (percutaneous umbilical blood sampling) and in fetal therapy.

8- Other areas.
Ultrasonography is of great value in other obstetric conditions such as:
a) confirmation of intrauterine death.
b) confirmation of fetal presentation in uncertain cases.
d) evaluating fetal movements, tone and breathing in the Biophysical Profile.
d) diagnosis of uterine and pelvic abnormalities during pregnancy e.g. fibromyomata and ovarian cyst.

Transvaginal Scans
With specially designed probes, ultrasound scanning can be done with the probe placed in the vagina of the patient. This method usually provides better images (and therefore more information) in patients who are obese and/ or in the early stages of pregnancy. The better images are the result of the scan head's closer proximity to the uterus and the higher frequency used in the transducer array resulting in higher resolving power, Fetal cardiac pulsation can be clearly observed as early as 6 weeks of gestation. Vaginal scans are also becoming indispensable in the early diagnosis of ectopic pregnancies. An increasing number of fetal abnormalities are also being diagnosed in the first trimester using the vaginal scan. Transvaginal scans are also useful in the second trimester in the diagnosis of congenital anomalies.

Doppler Ultrasound
The doppler shift principle has been used for a long time in fetal heart rate detectors. Further developments in doppler ultrasound technology in recent years have enabled a great expansion in it's application in Obstetrics, particularly in the area of assessing and monitoring the well-being of the fetus, and the diagnosis of cardiac malformations. Doppler ultrasound is presently most widely employed in the detection of fetal cardiac pulsations and pulsations in the various fetal blood vessels. Doppler examinations can be performed abdominally and via the transvaginal route. The power emitted by a doppler device is generally greater than that used in a conventional 2-D scan.

3-D Ultrasound
The scan requires special probes and software to accumulate and render the images, and the rendering time has been reduced from minutes to seconds. A good 3D image is often very impressive. Volumetric measurements are more accurate. Present evidence has already suggested that smaller defects such as spina bifida, cleft lips/palate, and polydactyl may be more lucidly demonstrated. Other more subtle features such as low-set ears, facial dysmorphia or clubbing of feet can be better assessed, leading to more effective diagnosis of chromosomal abnormalities. The study of fetal cardiac malformations is also receiving attention. The ability to obtain a good 3D picture is nevertheless still very much dependent on operator skill, the amount of liquor (amniotic fluid) around the fetus, it's position and the degree of maternal obesity, so that a good image is not always readily obtainable.

The Schedule of scanning
There is no hard and fast rule as to the number of scans a woman should have during her pregnancy. A scan is ordered when an abnormality is suspected on clinical grounds. Otherwise a scan is generally booked at about 7 weeks to confirm pregnancy, exclude
ectopic or molar pregnancies, confirm cardiac pulsation and measure the crown-rump length for dating. A second scan is performed at 18 to 20 weeks to look for congenital malformations, exclude multiple pregnancies and to verify dates and growth. Placental position is also determined.

Safety of ultrasound
Harmful effects in cells of experimental animals or humans have not been demonstrated in the large amount of studies that have so far appeared in the medical literature due to the use of diagnostic ultrasound in the clinical setting. Apparent ill-effects such as low birth weight, speech and hearing problems, brain damage and non-right-handedness reported in small studies have not been confirmed or substantiated in larger studies from Europe. The greatest risks arising from the use of ultrasound are the possible over- and under- diagnosis brought about by inadequately trained staff, often working in relative isolation and using poor equipment.

HOW TO PERFORM THE COLPOSCOPIC EXAMINATION

Prepare your patient.
Obtain informed consent and answer her questions. Assure her you will attempt to minimize pain (often a consuming worry) and will use "numbing medicine" (if appropriate). Make sure to know the pregnancy status of your patient. Ibuprofen 800 mg may be offered thirty minutes prior to procedure (be careful on empty stomach), but decreases cramping better if given the night before and morning of the procedure.
A bimanual exam should have been done with the annual exam. If a bimanual examination is needed, perform it here. Quickly examine the vulva for obvious condylomata or other lesions. If cervical biopsy is well tolerated and things are going well, examine the vagina/vulva after the biopsies as the speculum is withdrawn. The excess vinegar from the cervical exam will often stain the vulva. The vulva also can be examined at the time your patient returns for follow-up and/or definitive treatment.
Insert the speculum.
Consider the use of vaginal side wall retractors, a Penrose, or glove thumb with obese or multiparous women with vaginal redundancy (pregnancy too, if you develop colposcopy skills with pregnant patients). Warm the speculum with water (never lubricants), of course.
Examine the cervix.
Is the cervix inflamed or infected-looking? An active cervicitis confounds colposcopic detail. Do cultures if necessary. Repeat Pap only if this is critical information. Even a correctly performed Pap smear may irritate the cervix and often causes bleeding. Gently blot (not wipe) away any excess mucous using normal saline. Look for leukoplakia and abnormal vessels.
Apply 5% acetic acid with a cotton ball held in a ring forceps or a rectal swab. This gently applies lots of vinegar quickly and without trauma. Repeat application every five minutes, as the vinegar effect is only temporary. Warn patients, "this may burn a little." Calling the solution "acetic acid" may help increase the patient's perception of burning. Calling it "vinegar" usually will not.
Start with low power (typically 5x). Scan the entire cervix with white light. Use a vinegar-soaked Q-tip to help manipulate the cervix and transformation zone into view if necessary. The tenaculum is almost never necessary to move the cervix. Kogan endocervical speculum can greatly aid the examination of the distal endocervical canal if necessary. Use higher magnification to carefully document abnormal vascular patterns. The green filter can help find vascular areas.
Is colposcopy satisfactory?
The entire transformation zone, including the entire squamocolumnar junction, must be visualized. The borders of all lesions also must be entirely seen (not disappearing into the canal for instance) for visualization to be adequate. The uncooperative patient or severely flexed uterus with inadequate visualization are potential causes of inadequate colposcopy. Inadequate colposcopy with cytologic evidence of dysplasia frequently requires cervical cone biopsy for work-up. Mentally map abnormal areas. Remember that colposcopic observation's main goal is to highlight areas for biopsy. It is not, per se, a diagnostic tool. However, acetowhite areas that have sharp geographic boarders and a dimension of thickness or roughness are likely to be histologically more severe. Furthermore, all other things being equal, the presence of vessel atypia in any lesion implies more severe dysplasia. Use the following parameters to grade severity of lesions:
Mild acetowhite epithelium < Intensely acetowhite
No blood vessel pattern < Punctation < Mosaic
Diffuse vague borders < Sharp demarcated borders
Follows normal contours of the cervix < "humped up"
Normal iodine reaction (dark) < Iodine-negative epithelium (yellow)
Leukoplakia - usually a very good (condylomata) or a very bad sign (SCC)
Atypical vessels - usually cancer
Lugol's solution (Schiller's test).
May be used by the beginning colposcopist or at any time when further clarification of potential biopsy sites is necessary. It need not be used in all cases. The sharp outlining afforded by Lugol's iodine (Schiller's test) can be dramatic and very helpful. Iodine staining does not interfere with histology. Lugol's solution is often very helpful on the vagina and proximal vulva (non-keratinized skin). It can be used to thoroughly and simultaneously examine the entire vagina for glycogen-deficient areas, which correlate with HPV and/or dysplasia in non-glandular mucosa. It is often reserved for difficult cases when a non-cervical source of cervical Pap smear atypism is suspected (as in "normal cervical colposcopy" with dysplasia on Pap smear or normal ECC histology).
ECC and ECB
If desired, apply topical benzocaine (Hurricaine) solution to the entire face of the cervix using a cotton ball. It will usually be effective in 30 to 45 seconds.
Perform an endocervical curettage (ECC) or endocervical brushing (ECB) if indicated.
Use a Kevorkian curette (preferably without a basket) and scrape the canal, 360 degrees, twice. The sample appears as a coagulum of mucus, blood, and small tissue fragments. Use ring forceps or a cytobrush to gently retrieve the sample. Submit on paper and label "ECC." Do not do an ECC on pregnant patients.
Alternatively, a cervix Pap smear brush (the "pipe-cleaner type brush") may be placed into the os and spun around 5 times. The resulting tissue and blood coagulum may be submitted as a histological specimen in formalin. A short drinking straw may also be placed over the brush to act as a sheath to protect the brush from contamination by the ectocervix while the device is being introduced or withdrawn. Place the brush inside of the straw and place the straw against the os. Then advance the brush, obtain the sample, and withdraw the brush back into the straw for removal. This results in sensitivity about the same as the Kevorkian curette but a higher specificity.
Perform cervical biopsy
Begin by mentally mapping a biopsy strategy. Biopsy posterior areas first to avoid blood dripping over future biopsy sites. The cervix can be manipulated with a Q-tip or hook if necessary to provide an adequate angle for biopsy. Three mm deep is typically all that is necessary. Always include the area with vessel atypism in at least one biopsy site. It is not necessary to include normal- appearing tissue with biopsy samples (i.e., biopsy the margins of lesions). Beginning colposcopists can enhance their skills by initially separating samples from difference biopsy sites in different bottles and subsequently correlating them with colposcopic impression. If bleeding is profuse from a particular site and more biopsies are needed, apply a Q-tip to the area and proceed with the next biopsy. Do not apply Monsel's solution until all biopsies are completed. Monsel's will ruin good histology.
Apply pressure and Monsel's solution to bleeding sites. The Monsel's should be as thick as toothpaste to be most effective. Swab out the excess Monsel and blood debris, which appears as a nasty black substance that eventually will pass and may cause alarm (and potential late night phone calls).
Gently remove the speculum and view the vaginal wall collapse around the receding blades of the speculum. Are any abnormal areas apparent? Have the patient rest supine for at least several minutes and then sit up slowly and rest again. Fainting and light-headedness are not uncommon.
Carefully draw and label a picture of lesions and biopsy sites. Correlate the pictures with the submitted samples, if placed in different containers.
Provide careful post-procedure instructions
Advise no douching, intercourse, or tampons for 1-2 weeks (or until return visit). Patients are instructed to return for foul vaginal odor or discharge, pelvic pain, or fever. Tylenol, ibuprofen, or Aleve may be used for cramps (if any). Otherwise, follow-up is usually in 1 to 3 weeks to discuss histology results.

COLPOSCOPIC TERMINOLOGY

Introduction
In the past decade, major changes in our understanding of the epidemiology and science of cervical carcinoma has yielded efforts to develop a unified terminology to be used throughout the international scientific community. The International Federation of Cervical Pathology and Colposcopy (IFCPC) approved a basic colposcopic terminology at its Seventh World Congress in Rome, May, 1990.This outline summarizes this terminology. These terms should be used to describe findings during the colposcopic examination.
OUTLINE OF COLPOSCOPIC TERMINOLOGY
I. Normal colposcopic findings
Original squamous epithelium
Columnar epithelium
Normal transformation zone
Squamocolumnar Junction (SCJ)
Squamous Metaplasia
II. Abnormal colposcopic findings
1.Within the transformation zone
A. Acetowhite epithelium
.Flat
.Micropapillary or microconvoluted
B. Punctation
C.Mosaic
D.Leukoplakia
E.Iodine-negative epithelium
F.Atypical vessels
2.Outside the transformation zone, e.g., ectocervix, vagina
A. Acetowhite epithelium
.Flat
.Micropapillary or microconvoluted
B.Punctation
C.Mosaic
D.Leukoplakia
E.Iodine-negative epithelium
F.Atypical vessels
III. Colposcopically suspect invasive carcinoma
IV. Unsatisfactory colposcopy
Squamocolumnar junction not visible
Severe inflammation or severe atrophy
Cervix not visible
Entire lesion not seen
V. Miscellaneous findings
Non-acetowhite micropapillary surface
Exophytic condyloma
Inflammation
Atrophy
Ulcer
Other

HYPERTENSIVE DISORDERS OF PREGNANCY

I. Classification and definitions
A. Chronic hypertension
Hypertension is defined as elevation either of systolic BP to 140 mm Hg or higher or of diastolic BP to 90 mm Hg or higher.
Chronic hypertension is defined as hypertension diagnosed before pregnancy or before 20 weeks' gestation, or elevated BP that is first diagnosed during pregnancy and persists after 42 days postpartum.
B. Preeclampsia and eclampsia
Preeclampsia is defined as elevated BP and proteinuria after 20 weeks' gestation (except in the presence of trophoblastic disease or multiple gestation, in which cases preeclampsia may appear before 20 weeks' gestation).
Mild preeclampsia. The following criteria must be met to confirm the diagnosis of mild preeclampsia:
BP of 140/90 mm Hg or higher after 20 weeks' gestation, measured on two occasions at least 6 hours apart.
Proteinuria greater than 300 mg in a 24-hour urine collection or a score of 1+ on a random urine dipstick test.
Edema frequently accompanies preeclampsia but is not required for diagnosis.
Edema must be generalized for association with preeclampsia; dependent edema (e.g., low back, legs) is not sufficient.
Fluid retention is evidenced by rapid weight gain (more than 5 lb in 1 week).
Severe preeclampsia. The following criteria are used to confirm the diagnosis of severe preeclampsia:
BP during bed rest of 160 mm Hg systolic or 110 mm Hg diastolic, measured on two occasions at least 6 hours apart
Proteinuria greater than 5 g in a 24-hour collection or a score of 3+ to 4+ on random urine dipstick test
Oliguria, indicated by a 24-hour urine output of less than 400 mL or serum creatinine level higher than 1.2 mg/dL (unless known to be higher previously)
Cerebral or visual disturbances, including altered consciousness, headache, scotomata, blurred vision, or some combination of these
Pulmonary edema or cyanosis
Epigastric or right upper quadrant pain
Impaired liver function without a known cause, indicated by elevated AST level of 70 U/L or higher
Thrombocytopenia, indicated by a platelet count lower than 100,000/mm3, or evidence of microangiopathic hemolytic anemia, such as abnormal findings on peripheral smear, increased bilirubin level (1.2 mg/dL or higher), or elevated lactate dehydrogenase (LDH) level (600 U/L or higher)
Eclampsia is preeclampsia accompanied by seizures.
HELLP syndrome, which consists of hemolysis, elevated liver enzymes, and low platelet count, is a form of severe preeclampsia.
Definition
Thrombocytopenia. A platelet count of less than 100,000/mm3 is the most consistent finding in HELLP syndrome.
Hemolysis is defined as the presence of abnormal peripheral smear results with burr cells and schistocytes, bilirubin level of 1.2 mg/dL or higher, or LDH level higher than 600 U/L.
Elevated liver function test results. AST level is 70 U/L or higher.
Presentation. Typically, HELLP syndrome occurs in a white multiparous patient older than 25 years, but it is not limited to such patients. It may develop antepartum or postpartum. The majority of cases appear to develop antepartum. The patient frequently is remote from term and complains of epigastric or right upper quadrant pain (90%), nausea and vomiting (50%), and sometimes a nonspecific virus-like syndrome. Ninety percent of patients give a history of malaise of several days' duration before presentation. Patients may present with hematuria or GI bleeding. Hypertension may be absent (20%), mild (30%), or severe (50%).
Physical examination may reveal right upper quadrant tenderness (80%) and significant weight gain with edema (60%).
Differential diagnoses include benign thrombocytopenia of pregnancy, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, gallbladder disease, viral hepatitis, pyelonephritis, acute fatty liver of pregnancy, kidney stones, glomerulonephritis, and gastroenteritis.
C. Chronic hypertension with superimposed preeclampsia
is defined as preeclampsia that occurs in a patient with preexisting chronic hypertension. It is often difficult to differentiate chronic hypertension with superimposed preeclampsia from an exacerbation of chronic hypertension.
D. Transient hypertension
Transient hypertension, also known as pregnancy-induced hypertension, is defined as elevated BP during pregnancy or the first 24 hours postpartum without other signs of preeclampsia or chronic hypertension.
Transient hypertension must be differentiated from preeclampsia because transient hypertension is associated with an increased risk of chronic hypertension, whereas preeclampsia or eclampsia is not associated with such a risk.
II. Preeclampsia
A. Epidemiology
Incidence. Preeclampsia is reported to occur in 7–10% of all pregnancies extending beyond 20 weeks. It is the third leading cause of maternal mortality, responsible for over 17% of maternal deaths. It is also a major cause of neonatal morbidity and mortality, both directly, via intrauterine growth restriction, and indirectly, through its association with abruptio placentae and the need for preterm delivery. Preeclampsia has been implicated in 10% of perinatal deaths, 20% of labor inductions, 15% of cesarian sections, and 10% of medically indicated preterm deliveries.
Risk factors for preeclampsia and eclampsia include age younger than 20 years or older than 40 years; nulliparous status; presence of chronic hypertension, lupus erythematosus, diabetes, or renal disease; history of previous eclampsia as primigravida, previous preeclampsia as multipara, or previous superimposed preeclampsia; and positive family history of preeclampsia or eclampsia, multiple gestation, hydatidiform moles, and fetal hydrops.
B. Pathophysiology
The development of preeclampsia requires the presence of trophoblastic tissue but not necessarily a fetus.
There are a number of prominent pathologic features of preeclampsia. Derangements are noticed in vascular reactivity, volume homeostasis, thrombogenesis, and regulation of a number of synthetic processes.
The temporal sequence of these alterations, and which are causal and which consequences of the disorder, are as yet undetermined.
C. Diagnosis
BP values should be recorded with the woman sitting or in a semireclining position. Her right arm should be held consistently, roughly horizontally at heart level. Early measurement of the baseline BP is important because BP normally declines in the second trimester.
Symptoms of preeclampsia or eclampsia may include the following:
Headache
Visual symptoms: blurred vision, scotomata, and blindness (retinal detachment)
Epigastric or right upper quadrant pain
Nausea and vomiting
Dyspnea (from pulmonary edema)
Decreased urine output, hematuria, or rapid weight gain (greater than 5 lb in 1 week)
Constant abdominal pain (resulting from abruptio placentae)
Absence of fetal movement (resulting from fetal compromise)
Premature labor
Physical findings may include the following:
Elevated BP
Proteinuria
Retinal vascular spasm on funduscopic examination
Bibasilar rales on cardiovascular examination
Right upper quadrant tenderness (secondary to hepatic edema causing stretching of the liver capsule)
Uterine tenderness, or uterine tetany secondary to abruptio placentae on abdominal examination
Nondependent edema (face and hands)
Laboratory findings may include the following:
Increase in hematocrit (resulting from decreased intravascular volume)
Proteinuria greater than 300 mg/dL in a 24-hour collection (or score of 1+ or higher on dipstick test)
Uric acid level higher than 5 mg/dL, which is abnormal in pregnancy but is not used to diagnose preeclampsia
Creatinine level of 0.9 mg/dL or higher, which is abnormal in pregnancy .
Elevated liver enzyme levels, indicated by AST level higher than 70 U/L
Platelet count lower than 100,000/mm3
Prolonged prothrombin and partial thromboplastin times, which may be a result of primary coagulopathy or abruptio placentae
Decreased fibrinogen, fibrin degradation products, or both as a result of coagulopathy or abruptio placentae
D. Prevention
Calcium supplementation. Ingestion of 2 g of elemental calcium per day has not been shown to be beneficial in the general population; however, in populations at risk with low calcium intake, supplementation may lower the risk of preeclampsia.
Aspirin. Multicenter randomized clinical trials with aggregate enrollment of more than 27,000 women have demonstrated minimal to no benefit to low-dose aspirin therapy in preventing preeclampsia; therefore, it is not recommended at this time.
Diuretics and salt restriction have no role in the prevention of preeclampsia.
E. Management.
Definitive treatment for preeclampsia or eclampsia and transient hypertension is delivery. For patients presenting at more than 34 weeks' gestation with these conditions, delivery should be considered. The urgency of delivery depends on severity.
Mild preeclampsia. If the gestation is remote from term when mild preeclampsia is discovered, the patient may be managed expectantly. Salt restriction, use of sedatives, and antihypertensive therapy do not improve fetal outcome.
Outpatient management. Some compliant patients with mild preeclampsia may be managed at home with home BP monitoring and twice-weekly fetal testing.
Inpatient management consists of the following measures:
Bed rest
Regular diet (no salt restriction)
BP measurement every 4 hours while awake
Daily review of weight, urine output, and symptoms, with examination for edema, deep tendon reflex check, and fetal movement count
Every-other-day 24-hour urine protein measurement
Twice weekly hematocrit measurement, platelet count, and measurement of AST level
Fetal growth sonogram no more frequently than every 2 weeks
Fetal surveillance with weekly or semiweekly nonstress test (NST) or biophysical profiles
Severe preeclampsia
The mother's safety must be considered above all. The first priority is to assess and stabilize maternal condition, particularly coagulation abnormalities.
At 34 weeks' gestation or later, delivery is the optimal treatment. Immediate delivery by cesarean section is not indicated in every case. Patients in labor, or with a cervical condition favorable to the initiation of labor with oxytocin, can deliver vaginally. Both maternal and fetal conditions must be monitored continuously, however, with hourly assessments and careful attention to intake and output.
Before 34 weeks' gestation, patients may be managed expectantly if their BP can be controlled adequately without antihypertensives and if bed rest reduces their symptoms and produces diuresis.
Between 24 and 34 weeks' gestation, patients who are candidates for expectant management should receive a course of antenatal steroid therapy to induce fetal lung maturity.
At 24 weeks' gestation and earlier, the prognosis for perinatal survival is extremely poor, and termination of the pregnancy should be considered for maternal welfare.
Between 25 and 27 weeks' gestation, in selected cases, aggressive in utero therapy at a tertiary care center in consultation with a maternal-fetal medicine specialist may give the fetus a better chance for perinatal survival than immediate delivery. If the patient has none of the factors that necessitate delivery, aggressive antihypertensive therapy may be used to keep the diastolic BP below 105 until hypertension can no longer be controlled or fetal testing (which may need to be done twice a day) shows increased fetal compromise.
Inpatient management of severe preeclampsia. Patients who are eligible to be followed expectantly should receive the following:
Bed rest
Seizure prophylaxis for the first 24 hours of hospitalization
BP measurement every 4 hours
Daily examination to assess weight, review systems, check for edema, and check deep tendon reflexes; evaluation of 24-hour urine specimen for volume and protein level measurement; CBC
with platelet count; and measurement of AST, LDH, and bilirubin levels
Daily fetal surveillance including fetal movement counts and NST or biophysical profile
HELLP syndrome. Management is the same as for severe preeclampsia—delivery. The average time for resolution of symptoms is 4 days. If, however, the only presenting symptom is thrombocytopenia, without elevated levels on liver function tests, antepartum treatment with steroids may be used in cases of gestation shorter than 28 weeks. Dosage is 10 mg intramuscular/intravenous (IV) dexamethasone every 12 hours until platelets exceed 100,000/mm3. If no response is seen by 24–48 hours or the patient's condition worsens, the patient should be delivered. Postpartum patients with thrombocytopenia may be similarly treated with dexamethasone. Quicker postpartum resolution of signs and symptoms may be achieved by removing all trophoblastic tissue through uterine curettage.
Seizure prophylaxis during labor and for 24 hours postpartum is necessary for all patients with preeclampsia. Some patients with severe preeclampsia need seizure prophylaxis for longer periods before and after delivery than do patients with less severe preeclampsia.
Magnesium sulfate (MgSO4)
Loading dose is 6 g IV administered over 15–20 minutes.
Maintenance dosage is 2 g/hour IV and may be titrated to higher doses.
The therapeutic magnesium level is 4–6 mEq/L.
Magnesium level should be checked 4 hours after administering the loading dose, then every 6 hours as needed.
MgSO4 (50% solution) may also be given intramuscularly into the upper quadrant of the buttocks. Loading dose is 5 g in both buttocks. Maintenance dose is 3 g in alternating buttocks every 4 hours. Therapeutic range and monitoring are the same as with IV administration.
Phenytoin (Dilantin)
Loading dose is based on maternal weight .The first 750 mg of the loading dose should be given at 25 mg/minute and the remainder at 12.5 mg/minute. If the patient shows a normal cardiac rhythm and has no history of heart disease before initiation of therapy, ECG monitoring is not necessary at this rate of infusion.
Thirty to 60 minutes after infusion, a serum phenytoin level should be obtained. The therapeutic level is higher than 12 µg/mL. If the findings show levels lower than 10 µg/mL, reloading with 500 mg should be performed and the level rechecked in 30–60 minutes. If levels of 10–12 µg/mL are found, a reloading dose of 250 mg should be administered and the level rechecked in 30–60 minutes.
If the serum phenytoin level is therapeutic at 30–60 minutes, the level should be rechecked in 12 hours.
Phenytoin has no tocolytic effect.
Comparative efficacy. MgSO4 was shown to be superior to phenytoin in preventing seizures in a recent trial. However, individualization of phenytoin dosage, as recommended here, was not followed in that trial.
Conditions that necessitate delivery irrespective of gestational age include the following:
Eclampsia
Thrombocytopenia with a platelet level of less than 100,000/mm3
Hemolysis (seen on peripheral blood smear)
Elevated liver enzyme levels
Pulmonary edema
Oliguria
Persistent need for antihypertensive medication, except in selected cases between 25 and 27 weeks' gestation .
Antihypertensive therapy is indicated for antepartum, intrapartum, and postpartum patients with a diastolic BP of 105 mm Hg or higher. Acute treatment for severe hypertension in pregnancy involves reducing BP in a controlled manner without reducing uteroplacental perfusion. The goal is not to make the patient normotensive but rather to reduce the patient's diastolic BP to 90–100 mm Hg. A rapid or significant drop in BP interferes with uteroplacental perfusion and results in fetal heart rate decelerations.
Hydralazine hydrochloride, administered IV, is the drug of choice for acute BP control.
The onset of action is 10–20 minutes, with a peak effect in 60 minutes and a duration of effect of 4–6 hours.
Intermittent bolus infusion should be used rather than continuous infusion.
Hydralazine decreases BP without sacrificing uteroplacental blood flow.
Dosing should begin with a 5-mg bolus, and if BP is not in the range of 150–140 mm Hg systolic and 100–90 mm Hg diastolic at 20 minutes, the bolus should be repeated at a dose of 5–10 mg. Boluses may be repeated every 20 minutes, and doses may be increased to a maximum of 20 mg if no response occurs.
A decrease in urine output may occur 2–3 hours after a bolus when diastolic BP is below 90 mm Hg.
Labetalol hydrochloride, administered IV, is an alternative therapy to IV hydralazine for women who cannot be given or have not responded to hydralazine.
Labetalol has a more rapid onset than hydralazine and, like hydralazine, maintains uteroplacental perfusion.
Labetalol is contraindicated if maternal heart block of greater than first degree is present.
Labetalol is given as escalating boluses or a continuous infusion. The escalating bolus protocol begins with boluses every 10 minutes of 20, 40, 80, 80, and 80 mg, to a maximum dose of 300 mg. The continuous-infusion protocol starts at 0.5 mg/kg/hour and increases every 30 minutes by 0.5 mg/kg/hour to a maximum dose of 3 mg/kg/hour.
Conversion from intermittent boluses to infusion may be accomplished by beginning the continuous infusion after the BP has started to rise but not immediately after the last bolus. Infusion should be started at the lowest rate and titrated to the final infusion rate to avoid overdosing the patient.
Intravenous trimethaphan (Arfonad)
Trimethaphan can be used to treat sudden-onset extreme hypertension requiring minute-to-minute titration.
Trimethaphan is a ganglionic blocker and an extremely potent agent, and it is best used for hypertensive emergencies that occur intraoperatively at the time of delivery. The dosage is 5–30 µg/kg/minute. It is most often administered by an anesthesiologist.
Fluid management. Patients with preeclampsia frequently are hypovolemic because of loss of fluid into the interstitial spaces due to low serum oncotic pressure and because of increased capillary permeability. These same abnormalities, however, also put these patients at increased risk for pulmonary edema. IV fluids should be restricted to 84–125 mL/hour.
Oliguria is defined as urine output of less than 100 mL in 4 hours; it is treated with a 500-mL bolus of crystalloid fluid if the lungs are clear. If no response to this treatment occurs, then another 500-mL bolus can be given. If there is still no response after a total of 1 L has been administered, central hemodynamic monitoring should guide further management.
Pulmonary edema. Pulmonary artery catheterization is required to guide therapy for pulmonary edema.
Central venous pressure monitoring does not correlate with pulmonary capillary wedge pressure in all situations; therefore, use of a Swan-Ganz catheter may be required.
Patients usually enter a diuresis phase 12–24 hours after delivery. In cases of severe renal compromise, it may take 72 hours or more for diuresis to appear.
F. Complications of severe preeclampsia
include renal failure (acute tubular necrosis), acute cortical necrosis, cardiac failure, pulmonary edema, thrombocytopenia, disseminated intravascular coagulopathy, and cerebrovascular accidents.
G. Perinatal outcome.
Complication of pregnancy by severe preeclampsia is associated with high perinatal mortality and morbidity rates. These high rates are attributable to extreme prematurity, intrauterine growth retardation (IUGR), abruptio placentae, and perinatal asphyxia. Patients whose onset of severe preeclampsia occurs in the second trimester and those with HELLP syndrome and pulmonary edema are at significant risk of maternal morbidity. HELLP syndrome is associated with particularly poor maternal and perinatal outcomes. The reported perinatal fetal mortality rate ranges from 7.7% to 60.0%, and the reported maternal mortality ranges from 0% to 24%. Maternal morbidity is common. Many patients with HELLP syndrome require transfusions of blood and blood products and are at increased risk of acute renal failure, pulmonary edema, ascites, cerebral edema, and hepatic rupture. HELLP syndrome also is associated with high incidences of abruptio placentae and disseminated intravascular coagulopathy.
III. Eclampsia
is defined as the development of convulsions, coma, or both in a patient with preeclampsia. Eclampsia occurs in 1% of patients with preeclampsia. Although many other conditions can result in seizures during pregnancy, obstetric patients with seizures should be considered eclamptic until proven otherwise. Perinatal mortality in one U.S. series was 12%, attributable to extreme prematurity, abruptio placentae, and IUGR.
A. Clinical presentation.
Maternal complications may include pulmonary edema, aspiration pneumonitis, abruptio placentae with hemorrhage, cardiac failure, intracranial hemorrhage, and transient blindness.
B. Pathophysiology.
The etiology of eclamptic seizures is unknown. It is thought that eclampsia occurs when the patient's mean arterial pressure exceeds the upper limit of cerebral autoregulation. The arterioles then fail to protect the cerebral capillaries from the systemic hypertension. Increased cerebral edema, increased intracranial pressure, or both may play a role.
C. Management.
Eclampsia is an obstetric emergency requiring immediate treatment.
Goals of therapy include the following:
Control of seizures
Correction of hypoxia and acidosis
Control of severe hypertension
Delivery
Methods of therapy
Control of seizures. Magnesium sulfate, administered parenterally, is the treatment of choice for eclamptic seizures in the United States. The alternative treatment is phenytoin. Treatment protocols for both agents are the same as the protocols for seizure prophylaxis .
The magnesium maintenance dosage should be decreased as indicated by clinical factors (absent deep tendon reflexes, decreased respiratory rate, oliguria, or renal insufficiency) or plasma magnesium levels.
Duration of therapy is 24 hours postdelivery or 24 hours after a postpartum seizure.
Magnesium toxicity may occur when therapeutic levels are exceeded. Loss of patellar reflexes occurs at 8–10 mEq/L, respiratory depression or arrest occurs at 12 mEq/L, and mental status changes may occur at levels higher than 12 mEq/L. To treat magnesium toxicity, magnesium administration should be discontinued and plasma magnesium level determined. Therapy should begin, however, based on a clinical diagnosis. Airway and oxygenation should be maintained; mechanical ventilation may be necessary. Ventilation and oxygenation should be monitored by pulse oximetry. Calcium gluconate should be administered in a dose of 1 g IV over at least 3 minutes. ECG changes and arrhythmias may occur if toxicity is severe. Diuretic agents (furosemide, mannitol) may be administered.
The loading dose of MgSO4 is 6 g over 15–20 minutes IV. If the patient has a seizure after administration of the loading dose, another bolus of 2 g of MgSO4 can be administered over 3–5 minutes.
If seizures occur while the patient is receiving magnesium prophylaxis, the magnesium level should be checked. If the level is subtherapeutic (therapeutic range is 4–6 mEq/L), an additional 2-g bolus of MgSO4 should be administered slowly, at a rate not to exceed 1 g/minute. Plasma magnesium level should be measured immediately. If the level is therapeutic, IV phenytoin is used to treat seizures refractory to MgSO4. The treatment protocol for phenytoin is same as the prophylaxis protocol .
Status epilepticus is treated with diazepam, administered IV at a rate of 1 mg/minute, or up to 250 mg of sodium amobarbital, slowly administered IV.
Protection of the patient from harm during seizures. The patient must never be left unattended. Bedside rails should be elevated, and a padded tongue depressor should be available to prevent oral lacerations.
Control of the airway and ventilation. Pulse oximetry should be performed or arterial blood gas levels obtained. The patient may require oxygen administration by mask or endotracheal tube. Difficulty in oxygenating patients with repetitive seizures warrants a chest radiographic examination to rule out aspiration pneumonia.
Treatment of hypertension. Treatment of hypertension in eclampsia is the same as treatment in preeclampsia .Delivery of the fetus Induction of labor may begin, or a cesarean section may be performed, after the patient is stabilized. Although prompt delivery is desirable, vaginal delivery may be attempted in the absence of other maternal or fetal complications. During the acute eclamptic episode, fetal bradycardia is common and usually resolves spontaneously in 3–5 minutes. Immediate delivery for fetal bradycardia is unnecessary. Allowing the fetus to recover in utero from the maternal seizure, hypoxia, and hypercarbia before delivery is advantageous. If the fetal bradycardia persists beyond 10 minutes, however, abruptio placentae should be suspected. Preparation for emergency cesarean section should always be made in case maternal or fetal condition deteriorates.
Limitation of fluids except in cases of excessive fluid loss. Frequent chest auscultation to rule out pulmonary edema and accurate monitoring of urine output using an indwelling Foley catheter are necessary. Pulmonary edema and refractory oliguria are indications for invasive hemodynamic monitoring.
D. Outcome.
Long-term neurologic sequelae of eclampsia are rare. CNS imaging with CT or MRI should be performed if seizures are of late onset (longer than 48 hours after delivery) or if neurologic deficits are clinically evident. The signs and symptoms of preeclampsia usually resolve within 1–2 weeks postpartum. Approximately 25% of eclamptic patients develop preeclampsia in subsequent pregnancies, with a recurrence of eclampsia in 2% of cases.
IV. Chronic hypertension
is defined and graded by diastolic pressure and carries increased risks of preterm delivery, superimposed preeclampsia, abruptio placentae, and IUGR.
A. Grades of chronic hypertension
B. Baseline information
including the following data, should be gathered to aid management.
History of the duration of hypertension
History of current and previous treatments
Other cardiovascular risk factors (smoking, increased plasma lipid levels, obesity, diabetes mellitus)
Other complicating medical factors (e.g., headaches, myocardial infarction or chest pain, prior stroke, renal disease)
Medication with vasoactive drugs (e.g., sympathomimetic amines, nasal decongestants, diet pills)
Baseline blood values, including CBC, serum creatinine, serum urea nitrogen, uric acid, and serum calcium
Urinalysis findings
Twenty-four-hour urine test results for creatinine clearance and protein
ECG, if the patient has not had one in the past 6 months
Twenty-four-hour urine calcium measurement
C. Differential diagnosis
Essential hypertension is the cause in 90% of chronic hypertension cases. Other conditions should be ruled out, however, including renal disease; endocrine disorders such as adrenal disease (primary aldosteronism, congenital
adrenal hyperplasia, Cushing disease, pheochromocytoma), diabetes mellitus, and hyperthyroidism; new onset of a collagen vascular disease such as systemic lupus erythematosus; and cocaine abuse.
Worsening chronic hypertension is difficult to distinguish from superimposed preeclampsia. If seizures, thrombocytopenia, pulmonary edema, unexplained hemolysis, or unexplained elevations in liver enzyme levels develop, superimposed preeclampsia should be presumed and the fetus delivered. If these findings are not present, a 24-hour urine calcium measurement may be useful. Patients with preeclampsia have significantly lower 24-hour urinary calcium findings (42 ± 29 mg/24 hours) than pregnant patients with chronic hypertension (223 ± 41 mg/24 hours).
D. Treatment
Patients with mild hypertension, and some with moderate hypertension, may be managed initially without drug therapy, using the following measures:
Dietary sodium restriction to 4 g
Cessation of smoking and alcohol use
Decrease in activity
Sonography at 18 weeks' gestation, then every 4–6 weeks to follow fetal growth; sonograms may be taken more frequently if indicated, but no more frequently than every 3weeks
Antepartum testing, to begin at 32 weeks' gestation (or earlier if hypertension is severe or IUGR is suspected)
NST or biophysical profile assessment weekly or biweekly depending on the severity of the hypertension
Angiotensin-converting enzyme (ACE) inhibitors and diuretics should be avoided in pregnancy. If, however, a diuretic is an essential component in maintaining control for a patient with severe hypertension, it may be continued.
Drug therapy initiated during pregnancy. Choices for single-agent drug therapy for diastolic BP greater than 105 mm Hg include the following:
Methyldopa (Aldomet), 250 mg three times daily, up to 2 g/day, in four doses. Methyldopa is a centrally acting adrenergic inhibitor that decreases systemic vascular resistance and has been shown to be safe in pregnancy. It can produce hepatic damage, so liver enzyme levels should be checked at least once a trimester.
Hydralazine often is used as a second agent when maximum dosages of methyldopa are reached. Hydralazine should not be used as first-line oral therapy. It is a peripheral direct vasodilator and can be used effectively in combination with methyldopa or a beta-blocker. Hydralazine can produce a lupus-like syndrome, but usually only when used at dosages higher than 200 mg/day for longer than 6 months. It can lead to fluid retention. The dosage starts at 10 mg four times a day initially and may be increased to a maximum of 200 mg/day.
Labetalol is safe for use in pregnancy and can be given to patients who cannot take methyldopa or in whom methyldopa is ineffective. Labetalol is a nonspecific beta- and alpha-blocker, and its use is contraindicated in patients who have greater than first-degree heart block. Labetalol may be used as monotherapy but also works well in combination with hydralazine or a diuretic. The beginning dosage is usually 200 mg two to three times daily; the usual therapeutic dosage is 1600 mg/day, and the maximum dosage is 2400 mg/day.
Drug therapy initiated before pregnancy. If necessary for adequate BP control, most patients can continue to use the antihypertensive agents they used before pregnancy, with the exception of nifedipine and ACE inhibitors.
Thiazide diuretics should not be started late in pregnancy.
Clonidine withdrawal may produce acute hypertension. Clonidine may be used safely in pregnancy.
Beta-blockers may be used safely in pregnancy.
Nifedipine is a calcium channel blocker that is teratogenic in animals but has been used in the third trimester of pregnancy in humans. Nifedipine is potentially hazardous because its use may lead to acute hypotension. It is used as a tocolytic agent and should not be given within 6 hours of MgSO4 administration due to an increased risk of pulmonary edema and hypotension.
ACE inhibitors are contraindicated after the first trimester ofpregnancy. They are not teratogenic but are associated with fetal death in utero and neonatal renal failure.
Emergency treatment for hypertensive crisis
IV therapy for patients with hypertensive emergencies in pregnancy is the same as that for patients with preeclampsia .
Sodium nitroprusside may cause fetal thiocyanate and cyanide poisoning and should be used only as a last resort and for no longer than 30 minutes before delivery.

Vulvodynia /DR. Alaa Mosbah MD OBS&GYN

Introduction & Classification :
In 2003, the International Society for the Study of Vulvovaginal Disease (ISSVD) revised its definition of the frequently used and well-accepted term “vulvodynia.” The new classification acknowledges that vulvar pain can be attributed to diagnosable disorders such as infections, dermatologic disorders, neoplastic processes, and neurologic disorders. The other category is vulvodynia, pain not related to a specific, identifiable disorder. Vulvodynia is often described as a vulvar discomfort with sensations of burning, irritation, or rawness. In addition, the ISSVD further expanded its classification of vulvodynia into generalized and localized pain. These categories are further subdivided to provoked pain or unprovoked pain. Additionally, there is a category for pain that is both provoked and unprovoked (mixed). Vestibulodynia (previously termed vestibulitis) is a pain localized to the vestibule. The suffix “-itis” has been excluded from the recent ISSVD terminology because studies found a lack of association between excised tissue and inflammation. Other terminologies have classified vestibulodynia as primary or secondary; in the primary subset, the pain has been present since the first tampon use or intercourse, and with secondary vestibular pain, women have had painless tampon insertion or intercourse, then the vestibular pain develops at a later time.
Epidemiology :
Until recently, the epidemiology of vulvodynia was largely unknown. The prevalence of vulvodynia has ranged from estimates of as low as 200,000 women in the United States to as high as 15% of women based on a report from a general gynecologic practice population. A study from 1998 reported 1.3% in a female genitourinary medicine clinic population had vulvodynia. A more recent study by Danielsson and coworkers evaluated 3017 women aged 20 to 60 years participating in a screening program for cervical cancer who answered a questionnaire about possible painful coitus. The prevalence was 9.3% for the whole group (13% for women aged 20-29 and 6.5% for women aged 50-60). Women with pain localized to the vestibule (vestibulodynia) have been characterized as white, young (mean age, 32 years), and nulliparous. However, a recent study, performed in 2003, estimated the prevalence of chronic unexplained vulvar pain in an ethnically diverse population-based sample of women. Approximately 16% of respondents (4915 women) reported chronic burning, knife-like pain, or pain on vulvar contact that lasted for at least 3 months or longer. Chronic vulvar pain on contact decreased with increasing age, but the cumulative incidence of chronic burning and knife-like pain was similar across all ages. Contrary to earlier assessments, white and black women reported a similar lifetime prevalence. However, Hispanic women were 80% more likely to experience chronic vulvar pain than were white and black women.
The Etiology of Vulvodynia :
Exactly what causes vulvodynia is unknown, but it most likely occurs from a variety of sources. Proposed etiologies include abnormalities of embryologic development, increased urinary oxalate excretion, genetic and/or immune factors, hormonal factors (association with oral contraception use or menopause), infection (human papillomavirus [HPV] and candida), inflammation, and neuropathies. There may be several different diseases with similar symptoms that are related to vulvodynia.
In the past decade, many of the early theories about vulvodynia have not been substantiated. The majority of recent studies do not support an association with HPV, particularly in pain that is localized to the vestibule. The role of candidiasis in this condition is uncertain. Similarly, the role that inflammation plays in the development of localized vulvar dysesthesia is unclear. Histopathologic specimens from patients with vestibulodynia have been compared with control subjects and similar findings have been found in each population. Many control subjects have nonspecific inflammation. Several papers that mention inflammation and inflammatory cytokines show inconsistent results. Bohm-Starke and colleagues found a low expression of the inflammatory markers cyclooxygenase 2 and inducible nitric oxide synthase in the vestibular mucosa of women with localized vestibular pain as well as in healthy control subjects. A few clinicians believe that vulvodynia occurs directly as a result of psychologic or sexual dysfunction. This viewpoint, however, is rejected both by most patients and by the majority of those working in the field. On the other hand, almost all agree that the presence of chronic pain such as occurs in vulvodynia can secondarily affect a patient's psychologic well-being.
A consensus has been emerging among thought leaders (most recently at an National Institutes of Health [NIH]-sponsored conference on vulvodynia in April 2003) that generalized, nonprovoked vulvodynia is described most accurately when it is thought of as a complex regional pain syndrome (CRPS), similar to other CRPS such as fibromyalgia and interstitial cystitis.
Like women with other CRPS, women with vulvodynia exhibit enhanced systemic pain perception, a process known as central nervous system sensitization. Second, women with vulvodynia are more likely to have other CRPS such as interstitial cystitis. This may be explained by another phenomenon common to CRPS known as “wind-up” in which there is a progressively increasing activity in dorsal horn cells of the spinal cord after repetitive activation of primary afferent C-fibers. Another study found a significant decrease in estrogen receptor expression in the vestibular mucosa of women with vestibulodynia.
Treating Vulvodynia
Numerous treatments have been used for the various forms of vulvodynia, including vulvar care measures; topical, oral, and injectable medications; biofeedback and physical therapy; a low oxalate diet with calcium citrate supplementation; and surgical treatments. Other kinds of treatment include acupuncture, hypnotherapy, topical nitroglycerin, and botulinum toxin, but they are not discussed here. It is important to recognize that rapid resolution of vulvodynia is unusual even with appropriate therapy. Whereas a 100% improvement rate is desired in all patients, most women with vulvodynia do not reach that level. They report markedly less pain at follow up, although many are not cured.
Vulvar Care Measures
Common suggestions for minimizing irritation include the use of 100% cotton underwear during the day and not wearing underwear at night while sleeping. We counsel patients to avoid vulvar irritants and douching, and to use mild soap for bathing without applying soaps to the vulva. We recommend against using facecloths for washing; the interlabial sulci and vestibule can be cleaned easily with water and gentle touch. If menstrual pads are irritating, 100% cotton pads may be helpful. Adequate lubrication for intercourse is recommended. Many different lubricants exist with various bases such as Slippery Stuff, Femglide, Astroglide, Femigel (Australian Bodycare, Denmark) (natural product from tea trees), K-Y Jelly, Lubrin (Aurora Pharmaceuticals, Australia) (a suppository), Moist Again, Replens, Syl

Dr. Alaa Mosbah, MD OBS & GYN

Sunday, January 20, 2008

Fertilization

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