Dr. Alaa Mosbah, MD OBS & GYN

Bacterial Infections and Pregnancy

2011-04-22T14:29:00.000-07:00

Bacterial Infections and Pregnancy

DR ALAA MOSBAH ; LECTURER OF OBS & GYN MANSOURA FACULTY OF MEDICINE ,EGYPT 2011

Fetal and Newborn Infections

-In utero (transplacentally) ,congenital syphilis

-During labor (vertical transmission) , E. coli, group B streptococci, ;conjunctivitis due to chlamydia, gonorrhea or Listeria monocytogenes, and a number of infections due to gram-negative anaerobic bacilli.

-In the neonatal period (i.e., during the first 28 days following birth) , tuberculosis and tetanus

Group B Streptococcus (GBS)

Clinical spectrum

Because only 0.5-1% of mothers who carry GBS develop signs and symptoms of disease, clinical diagnosis of GBS can be problematic.

In pregnant women, GBS is a cause of cystitis, amnionitis, endometritis, and stillbirth. Occasionally, GBS has been a cause of endocarditis and meningitis, while in postpartum women, it has been identified as a cause of urinary tract infections (UTIs) and pelvic abscesses.
Prenatal screening for this condition is now established practice in North America, Australasia and many parts of Europe
The UK and Finland stand out as the only two countries to have consciously resisted this trend, and this is, at least in part, because the incidence of early onset neonatal infection in the UK is less than a third of what it was in America

Group B Streptococcus – background

Streptococcus agalactiae:

Group B Strep, Strep B, beta haemolytic Strep, GBS

Colonisation

Intestinal (up to 30% of adults) & vaginal (up to 25% of women)

Asymptomatic

May be intermittent

90% of adults possess no protective antibodies to GBS

Infection

Infections in adults: the elderly, pregnant women, others with other disease

Most common cause of life-threatening infection in newborn babies

Underlying rate ~ 1/1000 live births overall

GBS infection in babies

Early Onset

Up to 80% of GBS infection in babies

0-6 days (usually less than 24 hours)

Usually septicaemia, also meningitis & pneumonia

11% die

Late onset

Up to 20% of GBS infection in babies
Start 7 or more days after delivery
Usually septicaemia, and meningitis
5% die

Reducing risk of GBS infection in babies

Late onset GBS infection

No medical intervention proven to prevent

Good hygiene

Education / alert

In future – vaccination of women before/during pregnancy

Will prevent EO/LO and adult GBS infection
Reducing risk of GBS infection in babies

Early onset GBS infection

-Intrapartum antibiotic prophylaxis (IAP)

Only proven effective method of prevention available

-Oral antibiotics

No evidence it reduces EOGBS infection

Used to treat GBS in urine

-Intramuscular antibiotics before labour

May eradicate GBS colonisation for up to 6 weeks

-Vaginal flushing with chlorhexidine

No evidence it reduces EOGBS infection

Recognised risk factors for EOGBS infection

Previous baby with GBS infection x 10

GBS bacteriuria during pregnancy x 4

Intrapartum fever x 3

Preterm labour x 3

Prolonged rupture of membranes x 3

Maternal GBS colonisation during pregnancy x 4

But … there’s no way to know a woman is carrying GBS unless we look for it

Testing for GBS carriage

When to swab?

Before 35 weeks of pregnancy

35-37 weeks of pregnancy

Intrapartum
Where to swab? (not speculum)

-High vaginal swab

-Low vaginal swab

-Low vagina & anorectal swab/s (more than 30% more effective than vaginal or cervical alone)

Who to swab?
Pregnant woman

What culture method to use?

Direct agar plate - 24-48 hours to grow culture in lab

Selective Enriched Culture Medium (ECM) - 24-48 hours to grow culture in lab

Polymerase Chain Reaction (PCR) – minutes to hours to grow culture

PCR requires special equipment and special training

Who should be offered intrapartum antibiotic prophylaxis?

-Women with recognised risk factors:

50-60% cases prevented

-GBS carriers this pregnancy:

80-90% cases prevented

-GBS carriers this pregnancy who have risk factors:

less than 50% cases prevented

UK – RCOG guideline summary

Antenatal

Routine screening for GBS not recommended

Antenatal treatment with penicillin is not recommended

Intrapartum

Clinicians should discuss the use of IAP in the presence of known risk factors including incidental carriage.

Risk factors include:

Prematurity less than 37 weeks

prolonged rupture of membranes more than 18 hours

fever in labour more than 38C

The argument for prophylaxis becomes stronger for mor than 2 risk factors.

IAP should be considered if GBS is detected incidentally in the vagina or the urine in the current pregnancy

IAP offered to women with a previous baby with neonatal GBS disease.

IAP regime is Penicillin G as soon as possible after the onset of labour and at least 2 hours before delivery.

If chorioamnionitis is suspected, broad-spectrum antibiotic therapy including an agent active against GBS should replace GBS-specific antibiotic prophylaxis

Mother should receive antibiotics

mother should receive antibiotics using the following criteria:

Previously delivered infant with invasive GBS infection

GBS bacteriuria during current pregnancy

Delivery at less than 37 weeks' gestation

Duration of ruptured membranes longer than 18 hours

Intrapartum temperature of more than 100.4°F (38°C)

Treatment
During labor, 5 million U of penicillin G should be given as an intravenous loading dose, followed by 12-24 million U/d in 4 divided doses.

An alternative therapy is 2 g of ampicillin as an intravenous loading dose, followed by 1 g every 4 hours until delivery.

In case of penicillin allergy, clindamycin 900 mg IV every 8 hours until delivery or erythromycin 500 mg IV every 6 hours until delivery may be given.

Neonates delivered from a mother who received prophylaxis require careful observation for signs and symptoms of disease.

URINARY TRACT INFECTIONS

Women are predisposed to UTIs compared with men because of :

their anatomically shorter urethra,

the proximity of the urethra to the well-colonized anus and vagina, and

trauma during sexual intercourse.

UTIs are an especially important topic in pregnancy because even asymptomatic bacteruria can lead to complications such as pyelonephritis and premature labor.

Etiology

The most common causative organisms are as follows:

Escherichia coli

Klebsiella species

Enterobacter species

Enterococcus species

Group B Streptococcus

Staphylococcus saprophyticus

Proteus mirabilis

Pseudomonas aeruginosa

Citrobacter diversus

Clinical spectrum

Infection can involve the lower and upper urinary tracts, and patients can present with asymptomatic bacteriuria, cystitis, or pyelonephritis.

Bacteriuria that does not manifest symptoms apparently does not occur more frequently with pregnancy but is more likely to result in acute pyelonephritis in pregnant women.

Approximately 28% of pregnant women with untreated bacteriuria develop pyelonephritis. Some of the complications of bacteriuria observed in pregnancy include maternal anemia, low neonatal birth weight, hypertension, and prematurity.

Cystitis does not occur more frequently in pregnant women. The symptoms of cystitis are often confused with symptoms noted in normal pregnancy. These findings include urgency, frequency, suprapubic discomfort, and dysuria without fever or costovertebral angle tenderness. Urine culture findings are positive, and urinalysis reveals occasional hematuria or pyuria.

Acute pyelonephritis occurs with increased frequency in pregnant women (rate of 1-2%) and is most likely due to stasis of urine and bacteria in the urinary tract because of relative obstruction. This is caused by the dilatation of the ureters secondary to progesterone in early pregnancy and to the mechanical obstruction from the gravid uterus later in pregnancy.

Glycosuria, proteinuria, and aminoaciduria found in pregnancy also facilitate bacterial growth.

Acute pyelonephritis is confirmed by the presence of spiking fever (which sometimes reaches 104°F [40°C]), costovertebral angle tenderness, urinalysis findings with white blood cells and bacteria, and a urine culture result with positive growth of the causative organisms.

The scope of pyelonephritis may encompass many complications, including hyperthermia, anemia, leukocytosis, thrombocytopenia, decreased creatinine clearance, and adult respiratory distress syndrome. Fetal outcomes include low birth weight and prematurity.

Screening and diagnosis

Because asymptomatic bacteriuria is clinically significant in pregnancy, it should be aggressively sought, diagnosed, and treated in all stages. The various screening techniques used to detect bacteriuria include urinalysis, leukocyte esterase activity, a nitrite test, and urine cultures.

Treatment

Any overt UTI or asymptomatic bacteriuria in pregnancy must be treated.
Sulfonamides, amoxicillin, amoxicillin-clavulanate, cephalexin, and nitrofurantoin are all acceptable antibiotics. However, avoid sulfonamides in the last few weeks of gestation in order to prevent kernicterus and hyperbilirubinemia in the newborn.
A 7-day regimen eradicates bacteriuria in 70-80% of patients and is recommended for acute cystitis.
Single-dose therapy is less effective.
A 3-day course of treatment may provide the best balance of achieving adequate therapy and minimizing drug administration in pregnancy and is recommended for asymptomatic bacteriuria.

Cystitis can generally be treated in the same manner as asymptomatic bacteriuria, Women treated for cystitis must be monitored with frequent urine cultures (at monthly intervals) because 25% of women who have cystitis experience another UTI during the course of their pregnancy.

Patients with pyelonephritis in pregnancy: Although mild cases may be treated in an outpatient setting, many of these women need hospitalization and require intravenous antibiotics in addition to parenteral hydration to combat nausea, vomiting, and dehydration.

Initial antibiotic therapy may be empirical, followed by tailoring to the pathogen grown in the urine.

Most patients show symptomatic improvement within 1-2 days of beginning therapy.

If no improvement is observed, consider resistant organisms, nephrolithiasis, abscess formation, and obstruction as causes of therapy failure. Follow-up care in women after an episode of acute pyelonephritis should be frequent with close monitoring of urine cultures.

LISTERIOSIS

Etiology

Listeria monocytogenes is a gram-positive, aerobic, motile bacillus with aerobic and facultative anaerobic characteristics. The organism is found in soil and water and can be carried by animals that do not appear ill, leading to contamination of food of animal origin such as meats and dairy products. Unpasteurized raw milks are also sources of Listeria organisms.

Transmission

Pregnant women are 20 times more likely to contract listeriosis, and approximately one third of all cases of listeriosis occur during pregnancy. Transmission has mainly been by contaminated food, although rare cases of nosocomial transmission and transmission by direct contact with infected animals (which causes a local disease of the skin) have been noted.

The organism is found in soil and water. Vegetables become contaminated from the use of fertilizer, while animals may be asymptomatic carriers transmitting disease to individuals who eat their infected meat.

Outbreaks of listeriosis are still reported. Contaminated turkey meat caused a multistate outbreak in 2002 and led to 46 cases with 7 deaths and 2 stillbirths.

Clinical spectrum
Pregnant patients with listeriosis are often asymptomatic, or, they may have a febrile illness similar to influenza with symptoms of fever, muscle aches, and, sometimes, nausea or diarrhea during the bacteremic phase of the disease. Although the symptoms may be mild during pregnancy, listeriosis can still lead to premature delivery, infection of the newborn, or even stillbirth.
Placental transfer of the organism to the fetus can cause amnionitis, which usually results in either spontaneous septic abortion or premature labor with delivery of an infected baby. Fetal infection may manifest as septicemia, meningoencephalitis, or disseminated granulomatous lesions with microabscesses.

In neonates, the mortality rate is approximately 50%. Mortality is more likely in early-onset neonatal sepsis. Late-onset listeriosis typically manifests as meningitis at age 3-4 weeks

CDC recommendations for prevention

Thoroughly cook raw food from animal sources.

Thoroughly wash raw vegetables before eating.

Keep uncooked meats separate from vegetables, cooked foods, and ready-to-eat foods.

Avoid unpasteurized milk or foods made from raw milk.

Wash hands, knives, and cutting boards after handling uncooked foods.

Avoid soft cheeses.

Cook leftover food or ready-to-eat foods until they are steaming hot.
Diagnosis

Results of blood and cerebrospinal fluid cultures are positive in 60-75% of cases when central nervous system infection is present as indicated by fever or meningeal symptoms. Serological testing is not reliable for confirming a diagnosis, and stool cultures are not sensitive or specific.

Treatment

Ampicillin is the drug of choice for treating listeriosis; a 2-week course is required for bacteremia. A dose of 2 g every 4 hours is recommended.

Trimethoprim/sulfamethoxazole, the usual alternative for penicillin-allergic patients, has not been approved for use in pregnancy.

Syphilis

Caused by Treponema pallidum a helical, tightly coiled, motile spirochete..

Treponemes appear able to cross the placenta at any time during pregnancy, thereby infecting the fetus.

Early diagnosis and treatment are extremely important for preventing the effects syphilis may have on pregnant women and their infants. Untreated primary or secondary syphilis in pregnant women can lead to congenital syphilis in 40-50% of cases.
Lack of prenatal care and failure to properly diagnose and treat syphilis in the mother are the most important factors leading to congenital syphilis, and these areas should be the focus of preventive efforts.

Clinical spectrum

The stage of maternal disease during which the fetus is exposed to infection determines the morbidity; the earlier the disease stage, the higher the morbidity. Untreated primary or secondary syphilis in pregnancy causes almost a 100% rate of infection in the fetus. The disease can cause stillbirth, neonatal death, or congenital syphilis.

The stages of disease mirror the stages in nonpregnant women. In the first stage, primary syphilis, a hard, painless red ulcer forms on the vulva, cervix, or vagina. Secondary syphilis predominantly manifests as a nonpruritic rash that may involve the palms and soles. Fever and joint pain are less common manifestations of secondary syphilis. The latent phase causes no symptoms, and, although the disease may not be transmitted to sexual partners, it is still transmissible to the fetus. One third of patients may progress to tertiary syphilis, during which the organism can damage the heart, eyes, brain, nervous system, bones, or joints.

Screening

Even when syphilis is considered unlikely, routine antenatal screening is warranted for prevention and surveillance. The earlier in pregnancy the treatment, the more efficacious it is. Therefore, serologic tests should be performed at the initial prenatal visit. If the patient is considered to be at high risk, tests should be repeated at 28 weeks' gestation and at delivery.
The nontreponemal antibody tests are generally used for screening. These tests are highly sensitive but are nonspecific. They include the rapid plasmin reagin and VDRL tests. Pregnancy often causes false-positive nontreponemal antibody test results; therefore, positive findings should be confirmed with specific antitreponemal antibody tests such as the microhemagglutination assay-T pallidum and the fluorescent treponemal antibody absorption test.
Diagnosis

The diagnosis can be made in the same manner as for a nonpregnant woman. In primary syphilis, the diagnosis can be confirmed by identifying T pallidum in dark-field examination of material taken from a lesion. Because most pregnant women do not have visible lesions, serologic screening as mentioned previously is the primary means of establishing the diagnosis.

Treatment

Once a diagnosis is made, consider other sexually transmitted diseases before starting treatment. Treatment is the same as for nonpregnant women, with a single dose of 2.4 million U of benzathine penicillin for primary and secondary syphilis, but some experts recommend a second dose of benzathine penicillin G 1 week after the initial dose, especially in the third trimester or in the case of secondary syphilis.

In latent syphilis, treatment consists of 3 doses of benzathine penicillin (as for nonpregnant women). If results of the monthly quantitative VDRL or equivalent test show a 4-fold increase, re-treat the patient and perform a lumbar puncture to rule out neurosyphilis.

Penicillin-allergic women must be desensitized and then treated with penicillin because the accepted alternatives to treatment are erythromycin and tetracycline. Erythromycin may not prevent congenital syphilis, and tetracycline and doxycycline are not recommended for pregnant women.
Using penicillin therapy in pregnant women with early syphilis can cause a Jarisch-Herxheimer reaction. Pregnant women, apart from the usual manifestations, can present with uterine contractions, preterm labor, and premature delivery.

Chlamydia

Chlamydia trachomatis - obligate, intracellular bacterium with 15 immunotypes:

A-C - trachoma

D-K - genital tract infections

L1-L3 - lymphogranuloma venereum

One of the leading causes of infertility in women.

Etiology

Chlamydia trachomatis is an obligate intracellular organism. Initially considered a virus, it is now classified as a bacterium based on its sensitivity to antibiotics and its reproduction cycle.

Transmission

The usual mode of transmission to the fetus is vertical during the second stage of labor. The major routes of entry are the eye and the nasopharynx.

Clinical spectrum
Approximately 75% of women with chlamydia are asymptomatic.
The disease can cause endometritis, cervicitis, acute PID, and acute urethral syndrome in all women and chorioamnionitis, postpartum endometritis, and gestational bleeding in pregnant women.

Diagnosis

Chlamydial cervicitis should be considered in the presence of a yellow or green vaginal discharge, greater than 10 polymorphonuclear leukocytes per high-power field, and bleeding or edema of the cervix.

The following are the accepted screening methods according to the CDC:

A nucleic acid amplification test performed on an endocervical swab specimen or on urine

An unamplified nucleic acid hybridization test, an enzyme immunoassay, or direct fluorescent antibody test performed on an endocervical swab specimen

Culture performed on an endocervical swab specimen

Monoclonal antibodies labeled with fluorescein to detect elementary bodies of Chlamydia species (MicroTrak) or enzyme-linked immunosorbent assay is used for screening.

Treatment

In asymptomatic women with positive culture findings and in symptomatic women,

500 mg of erythromycin 4 times daily for 7 days is the treatment of choice.

Single-dose therapy with 1 g of azithromycin is an alternative.

Tetracycline, the drug of choice for treating chlamydia in other situations, is contraindicated in pregnancy. Retest treated women after 3-4 weeks, and evaluate and treat sexual contacts.

GONORRHEA

Gonorrhea is caused by Neisseria gonorrhoeae, a gram-negative diplococcus.

Gonorrhea is transmitted vertically during the birth process. No evidence suggests placental transmission

Gonococcal infections cause no symptoms in approximately 50% of patients and thus warrant screening in pregnancy.

Clinical spectrum

Gonorrhea can infect the uterus, cervix, and fallopian tubes, leading to ectopic pregnancy and infertility.

During pregnancy, women with gonorrhea may be asymptomatic, although reports have been received of endocervicitis, premature rupture of membranes, chorioamnionitis, septic abortion, intrauterine growth retardation, prematurity, and postpartum sepsis.

Newborns exposed to gonorrhea during vaginal delivery can develop an acute conjunctivitis known as ophthalmia neonatorum.
Pregnancy is a predisposing factor in the development of disseminated gonococcal infection. The classic presentation of disseminated disease is the triad of arthritis, skin lesions, and fever. The rash is vesicular and pustular, usually over the distal joints.

Diagnosis

A Gram stain of the endocervical secretions should be performed when an immediate diagnosis is necessary. Gram-negative diplococci in polymorphonuclear leukocytes are diagnostic.

A culture specimen should be taken directly from the endocervix onto Thayer-Martin media. Other sites, such as the pharynx, rectum, and urethra, should also be cultured as indicated.
Enzyme immunoassay is another rapid means of diagnosis.

Treatment

The treatment of choice for uncomplicated cervicitis is a single dose of 250 mg of ceftriaxone intramuscularly. Penicillin-allergic pregnant women can be treated with spectinomycin. Although ciprofloxacin is one of the standard drugs of choice, it is contraindicated in pregnancy.

All patients treated for gonococcal infection should also be empirically treated for chlamydial infection.

BACTERIAL VAGINOSIS
Bacterial vaginosis is an infection caused by excessive growth of bacteria that may normally be present in the vagina.
In the United States, the rate of bacterial vaginosis in pregnancy is approximately 16%
Infection can be transmitted via the placenta to the fetus and cause intrauterine fetal death.

Etiology

The etiology is polymicrobial in nature and is associated with G vaginalis, Bacteroides species, Mobiluncus species, Peptococcus species, and Mycoplasma hominis.

Clinical spectrum

Abnormal vaginal discharge with an unpleasant, fishlike odor, especially after sexual intercourse. The discharge is generally white or gray, and women may have dysuria or itching around the vagina.

The bacteria can ascend and colonize the amniotic membranes, decreasing the tensile strength of the membranes and causing the weakened membranes to rupture. G vaginalis can also cause prostaglandin production and lead to premature labor unresponsive to tocolytic therapy.

Diagnosis

When using the clinical criteria, 3 of the following 4 should be present:

A homogenous, white, noninflammatory discharge that smoothly coats the vaginal wall

Clue cells, ie, vaginal epithelial cells that have a stippled appearance due to aggregates of coccobacilli

Vaginal fluid pH of more than 4.5

A positive whiff test result, ie, a fishy odor to the vaginal discharge before or after the addition of 10% potassium hydroxide solution
When using Gram stain to make a diagnosis, determine the relative concentration of the bacterial morphotypes characteristic of the altered flora of bacterial vaginosis.
Treatment

Metronidazole at 500 mg twice a day for 7 days or metronidazole gel 0.75% intravaginally twice a day for 5 days is the treatment of choice. Avoid the gel in the first trimester of pregnancy.

Clindamycin 300 mg twice a day for 7 days

Antibiotic Use During Pregnancy And Birth Defects: Study Examines Associations

Crider and her colleagues (2009) analyzed data on more than 13,000 women whose babies had one of more than 30 birth defects. They compared the women's rates of antibiotic usage, from the month leading up to pregnancy through the end of the first trimester, with that of almost 5,000 women whose children did not have a birth defect.

November 2009, Archives of Pediatrics & Adolescent Medicine
Although penicillin and several other antibacterial medications commonly taken by pregnant women do not appear to be associated with many birth defects, other antibiotics, such as sulfonamides and nitrofurantoins, may be associated with several severe birth defects and require additional scrutiny, a new study has found

November 2009, Archives of Pediatrics & Adolescent Medicine

Antibiotics (anti-microbials)
Commonly used antibiotics

Penicillins (category B): These are the most widely used antibiotics in pregnancy because of their wide margin of safety and lack of known toxicity. In the collaborative perinatal project, 3546 women used penicillin during the first trimester and no adverse effects were demonstrated. Ticarcillin, however, has shown some toxicity in animals and may not be safe in pregnancy.

Cephalosporins (category B): This group has not been well studied in the first trimester and should therefore not be considered the first line of treatment in the first trimester of pregnancy. Generally, these drugs are considered safe and have shown no teratogenicity

Sulfonamides (category C): Avoid sulfonamides in the third trimester of pregnancy and during breastfeeding. Although these agents cause no known damage in utero, they can cause hyperbilirubinemia and kernicterus if the drug is still present in the neonate after birth. In mothers with G-6-PD deficiency, sulfonamide use has been associated with hemolysis. The combination of sulfonamides with trimethoprim in the first trimester has been associated with cardiovascular birth defects.

Sulfonamides were also tied to an increased risk for hypoplastic left heart syndrome and coarctation of the aorta, choanal atresia (a blockage of the nasal passage), transverse limb deficiency , diaphragmatic hernia and anencephaly

November 2009, Archives of Pediatrics & Adolescent Medicine

Tetracyclines (category D):

-Pregnant women are susceptible to acute fatty necrosis of the liver, pancreatitis, and renal damage.

-In the fetus, these agents can cause stunting of growth, discoloration of teeth, and hypoplasia of dental enamel.

Nitrofurantoin (category B): The collaborative perinatal project showed no increased risk of anomalies in 590 women who were exposed to the drug. In mothers with G-6-PD deficiency, it has caused hemolysis in both the mother and the fetus and should therefore be avoided near delivery.

Nitrofurantoins were also associated with multiple birth defects, including anophthalmia and microphthalmos , a cleft lip or cleft palate and several congenital heart defects

November 2009, Archives of Pediatrics & Adolescent Medicine

Quinolones (category C): Although animal studies have shown arthropathies, no human studies have been conducted and no cases of teratogenicity have been reported. These agents have a high affinity for bone and cartilage.

Metronidazole (category B): Metronidazole should not be used in the first trimester or during lactation. When used in the second or third trimester, large single-dose treatments should be avoided.

Macrolides (category B): These agents have not been associated with birth defects and are considered safe for use in pregnancy.

Clindamycin (category B): This drug has not been associated with birth defects

Ovarian Hyperstimulation Syndrome

2011-03-11T12:55:00.000-08:00

Background Definition Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of assisted reproduction technology. OHSS usually develops several days after assisted ovulation following gonadotropin therapy. This syndrome is characterized by ovarian enlargement due to multiple ovarian cysts and an acute fluid shift into the extravascular space. Results include ascites, hemoconcentration, hypovolemia, and electrolyte imbalances. The prevalence of therapy with assisted reproduction technology is increasing. Therefore, gynecologists, internists, and emergency physicians must be aware of this rare condition and its myriad of clinical presentations, which can cause multiorgan dysfunction and, potentially, death Classification To understand OHSS and its management, one must first be aware of its classifications of severity.

Grades of OHSS are as follows: Mild OHSS Grade 1 - Abdominal distention and discomfort Grade 2 - Grade 1 disease plus nausea, vomiting, and/or diarrhea plus ovarian enlargement from 5-12 cm Moderate OHSS Grade 3 - Features of mild OHSS plus ultrasonographic evidence of ascites Severe OHSS Grade 4 - Features of moderate OHSS plus clinical evidence of ascites and/or hydrothorax and breathing difficulties Grade 5 - All of the above plus a change in the blood volume, increased blood viscosity due to hemoconcentration, coagulation abnormalities, and diminished renal perfusion and function Pathophysiology The pathogenesis of ovarian hyperstimulation syndrome is unknown, but the process is related to increased vascular permeability in the region surrounding the ovaries and their vasculature

Beta-human chorionic gonadotropin (hCG) and its analogs, estrogen, estradiol, prolactin, histamine, and prostaglandins have all been implicated in the past. Vasoactive substances such as interleukins, tumor necrosis factor (TNF)-alpha, endothelin-1, and vascular endothelial growth factor (VEGF) secreted by the ovaries have been implicated in increasing vascular permeability. Withholding hCG decreases OHSS. Hence, it plays a critical role in enhancing ovarian angiogenesis and triggering the cascade of vascular permeability in ovarian vessels that leads to third spacing and OHSS. Both exogenous and endogenous gonadotropins from molar pregnancy, gonadotroph adenomas, and even pregnancy can aggravate OHSS.These changes in the ovarian vasculature are exaggerated responses to normal luteinizing hormone (LH). The function of hCG is similar to that of LH. As a result, the actions of hCG mimic these changes. Moreover, hCG exerts a follicle stimulating hormone–like action in stimulating the ovaries. In addition, it has a prolonged half-life. All of these properties of hCG lead to ovarian stimulation and changes in periovarian vasculature even after ovulation. These effects lead to poor control of the induction process, initiating and/or aggravating OHSS. Abdominal pain, nausea, and vomiting Enlargement of the ovaries causes abdominal pain, nausea, and vomiting. The enlargement is sometimes as much as 25 cm. Another consequence is discomfort resulting from increased intra-abdominal pressure due to ascites. Ascites and tense distention Ascites and tense distention occur because of the extravasation of protein-rich fluid and increasing leakage from the intravascular space due to an osmolar differential. Leakage of fluid from follicles, increased capillary permeability leading to third spacing (due to the release of vasoactive substances), or frank rupture of follicles can all cause ascites. Localized or generalized peritonitis Localized or generalized peritonitis is caused by peritoneal irritation secondary to blood from ruptured cysts, protein-rich fluid, and inflammatory mediators. Acute abdominal pain Acute abdominal pain may be due to ovarian torsion, intraperitoneal hemorrhage, or rupture of cysts secondary to enlarged ovaries with fragile walls. Hypotension and/or hypovolemia Follicular fluid and perifollicular blood containing large amounts of VEGF, which is thought to increase vascular permeability, escapes into the peritoneal cavity. The fluid is then absorbed into the general vascular bed. Blood vessels both within and outside the ovary become functionally impaired, and the result is the leakage of fluid through those vessels and a massive fluid shift from the intravascular bed to the third compartment. This process results in intravascular hypovolemia with the concomitant development of edema, ascites, hydrothorax, and/or hydropericardium. Hypotension and/or hypovolemia are also caused by compression of the inferior vena cava because of enlarged cysts or ascites. As a result, both venous return and preload decrease. Eventual outcomes are decreased cardiac output and hypotension. Dyspnea Pulmonary function may be compromised as enlarged ovaries and ascites restrict diaphragmatic movement. Other possible causes of dyspnea are the relatively rare manifestations of OHSS, such as pleural effusion, pulmonary edema, atelectasis, pulmonary embolism, acute respiratory distress syndrome (ARDS), and pericardial effusion. Hypercoagulable state A hypercoagulable state is likely due to hemoconcentration and hypovolemia resulting from third spacing and fluid shift. It is also related to increased estrogen levels. Patients have an increased risk of developing deep venous thromboses and pulmonary embolisms. Electrolyte imbalance Electrolyte imbalance occurs due to the extravasation of fluid and resultant renal dysfunction resulting from decreased perfusion. Increased reabsorption of sodium and water occurs in the proximal tubule, leading to oliguria and low urinary sodium excretion. The exchange of hydrogen and potassium for sodium in the distal tubule is reduced. As a result, hydrogen and potassium ions accumulate and cause hyperkalemia and a tendency to develop acidosis. Compensatory and electrolyte-retaining mechanisms fail. Acute renal failure The hypovolemia of OHSS leads to hemoconcentration and creates a hypercoagulable state. Microthrombi form in tubules, leading to decreased renal perfusion. Acute renal failure may result. Frequency International The rate of ovarian hyperstimulation syndrome depends on definitions, risk factors, stimulation protocols, and conception. Rates of OHSS are as follows:

Mild, 8-23% Moderate, 1-7% Severe, 0.25-5% The frequency of OHSS may increase if the ovary is overstimulated, as documented by high levels of estradiol and depicted as increased number of follicles on ultrasonography. The incidence is increased when protocols combine luteinizing hormone-releasing hormone (LHRH) agonists and gonadotropins, as compared with gonadotropins alone, to induce ovulation. In the ideal situation, induction should stimulate the ovaries to a desired level. However, the unpredictable response of the ovaries to induction make the prediction and prevention of OHSS difficult.Hence, heightened clinical suspicion and early intervention are paramount for decreasing morbidity and mortality. Women of young age, as well as those with low body weight, polycystic ovarian syndrome, or previous episodes of hyperstimulation are all at increased risk for developing OHSS. In addition, an increased number of small- and medium-sized follicles and elevated estradiol levels around the assumed time of ovulation increase the incidence. According to Martin et al, if the pre-hCG estradiol amount is greater than 6000 mcg and/or if more than 30 follicles are present, the rate of severe OHSS approaches 80%.[11 ] Mortality/Morbidity Morbidity may be clinically significant in cases of severe and critical ovarian hyperstimulation syndrome, and fatalities do occur. Race No racial predisposition is reported in ovarian hyperstimulation syndrome. Sex Ovarian hyperstimulation syndrome affects only women. Age Only women of childbearing age are affected by ovarian hyperstimulation syndrome. The risk is increased in younger women. Clinical History The patient who has ovarian hyperstimulation syndrome (OHSS) is a woman who recently had gonadotropin stimulation to induce ovulation or one who was treated with assisted reproductive technologies such as in vitro fertilization. Early OHSS is usually moderate or severe and manifests 3-7 days after the administration of hCG. Late OHSS is usually severe and occurs 12-17 days after hCG treatment.The former type is due to exogenously administered hormone, and the latter often occurs during an implanting or implanted pregnancy because pregnancy hCG exacerbates the disease. Signs of OHSS Signs of OHSS include the features listed below.(Percentages refer to all classes of OHSS.) -Ascites -Hypercoagulability (6.2%) -Thrombosis -Pleural effusion and pericardial effusion -Hemoconcentration -Leukocytosis (WBC count, >20,000/mm3) -Electrolyte abnormalities (eg, hyponatremia, hyperkalemia) -Elevated transaminase values (26%) -Acute respiratory distress syndrome (2%) -Pulmonary embolism (2%) -Acute renal failure (1%) Symptoms of OHSS Symptoms of OHSS include those listed below.(Percentages refer to cases of severe OHSS.) -Shortness of breath (92%) -Abdominal discomfort (99%) -GI disturbances - Nausea, vomiting, diarrhea (54%) -Oliguria (30%) -Peripheral edema (13%) -Lethargy -Rapid weight gain -Although OHSS usually manifests with a constellation of symptoms, atypical presentations can occur. Rare presentations such as thromboembolism, both venous and arterial, have been observed. Atypical locations of venous thromboembolism include the internal jugular vein, the subclavian vein, the inferior vena cava, the ileofemoral veins, and the intracerebral veins. Other abnormal forms of presentation include isolated hydrothorax and isolated thromboembolism. Additional situations leading to elevated hCG concentrations, such as in molar pregnancy and gonadotroph adenomas may lead to mild forms of OHSS in rare cases. Physical Physical findings of ovarian hyperstimulation syndrome include right or left lower quadrant pain below the umbilicus, as well as edema. Of note, abdominal palpation must be performed gently to avoid the possibility of rupturing a large cyst. Pelvic examination should be deferred in favor of ultrasonography of the pelvis. Causes No single cause of ovarian hyperstimulation syndrome has been identified. The etiology appears to be multifactorial, though the cardinal events are ovarian enlargement, ascites, and hypovolemia. The hormone hCG and its analogs estrogen, estradiol, histamine, TNF-alpha, endothelin-1, and especially VEGF have all been implicated in OHSS.Increased vascular permeability in periovarian vasculature brought about by the factors described above plays an important role in OHSS.A young age, a decreased body mass index, and a history of OHSS increase the risk. Exogenous induction agents (recombinant hCG) precipitates OHSS more than endogenous agents (gonadotropin-releasing hormone [GnRH] analogs). Other precipitating factors are induction in a hyperestrogenic state and poor timing. Differential Diagnoses Acute Respiratory Distress Syndrome Pelvic Inflammatory Disease/Tubo-ovarian Abscess Appendicitis Pericardial Effusion Appendicitis, Acute Peritonitis and Abdominal Sepsis Cholecystitis Pleural Effusion Ectopic Pregnancy Pulmonary Embolism Ovarian Cysts Salpingitis Ovarian Torsion Hemorrhagic cyst

Pulmonary edema

Ruptured ovarian cyst Workup Laboratory Studies In ovarian hyperstimulation syndrome (OHSS), the hematocrit is the most important measure in deciding if a patient should be hospitalized. If the patient's hematocrit level is greater than 60% and if she has ascites, hospitalize her immediately. Laboratory monitoring may involve the following parameters: -CBC with differential: This is helpful because decreased intravascular volume leads to hemoconcentration and an increased hematocrit. -Complete metabolic panel -Liver function: Liver function is decreased, as indicated by increased concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase. -Kidney function: Renal function is reduced, BUN and creatinine values are increased, whereas albumin and protein levels are decreased. Electrolyte imbalances, hyperkalemia, and acidosis may be present. -Coagulation profile, including the prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ratio (INR): These findings aid in detecting a hypercoagulable state and in monitoring anticoagulation. -Leukocyte count: This count is related to the seriousness of OHSS and to the risk of thromboembolism. -Beta-hCG concentration: A beta-hCG measurement is especially useful at more than 12 days after an injection of hCG. A positive result at this stage indicates pregnancy, an endogenous source of hCG for OHSS. hCG upregulates vascular endothelial growth factor (VEGF) receptors, and this upregulation increases third spacing.Mild OHSS may deteriorate to severe OHSS because of the increased availability of hCG. -Estradiol levels: Values are increased. -Laboratory findings of a serum estradiol concentration greater than 2000 pg/mL and a progesterone concentration greater than 30 ng/mL in the early part of the luteal phase are warning signs of developing OHSS. Signs that may indicate a progression in severity are increases in hCG level, hematocrit, hypoproteinemia, and hypoalbuminemia (third spacing). Additional signs are decreasing renal and liver function. OHSS is critical when the signs and symptoms of severe OHSS are present with any of the following findings: renal failure, ARDS, thromboembolism, or a hematocrit level greater than 60%.

Imaging Studies :

-Ultrasonography may be needed to measure the size of the ovaries, to assess the follicles, and to evaluate ascites

-Chest radiography may be indicated if dyspnea is present.

Treatment :

Treatment Based on Degree of Hyperstimulation Mild hyperstimulation Treatment for ovarian hyperstimulation syndrome (OHSS) is supportive, as needed. Mild ovarian hyperstimulation can develop into moderate or severe disease, especially if conception ensues. Therefore, women with mild disease should be observed for enlarging abdominal girth, acute weight gain, and abdominal discomfort on an ambulatory basis for at least 2 weeks or until menstrual bleeding occurs. Moderate hyperstimulation Treatment of moderate OHSS consists of observation, bed rest, provision of adequate fluids, and sonographic monitoring of the size of cysts. Serum electrolyte concentrations, hematocrits, and creatinine levels should also be evaluated. Some physicians have their outpatients keep track of their fluid intake and output. Intake or output less than 1000 mL/d or a discrepancy in fluid balance greater than 1000 mL/d is a cause for concern. The beginning of the resolution of OHSS is apparent when the cysts shrink, as seen on 2 consecutive ultrasonographic examinations, and when clinical symptoms recede. In contrast, early detection of progression to the severe form of the syndrome is marked by continuous weight gain (>2 lb/d), increased severity of existing symptoms, or appearance of new symptoms (eg, vomiting, diarrhea, or dyspnea). Severe hyperstimulation -Experience with severe OHSS is mandatory for appropriate treatment. One should transfer the patient to a different center if no one who is experienced in managing severe OHSS is available at the present location. -Severe OHSS is not common, but it is dangerous. Severe and critical forms of OHSS are potentially lethal disorders, and history taking and physical examination are paramount at the time of admission. In most clinical situations, patients require bed rest. Daily physical examination should consist of measuring the patient's weight and abdominal girth. Fluid balance must be assessed every 4 hours. -Medical treatment of severe hyperstimulation is directed at maintaining intravascular blood volume. Simultaneous goals are correcting the disturbed fluid and electrolyte balance, relieving secondary complications of ascites and hydrothorax, and preventing thromboembolic phenomena. -The main interventions are fluid management and correction of hypovolemia. These measures consists of initial fast intravenous administration of normal saline. Dextrose 5% in normal saline or normal saline is infused at a rate of 125-150 mL/h with 4-hour tabulations of urine production. If urine production is restored or improved, a maintenance protocol is started. The patient should be closely monitored for clinical signs of overhydration. If urine output is unsatisfactory, hyperosmolar intravenous therapy is indicated with an infusion of 200 mL of 25% human albumin. The use of diuretics in patients with low urine production and hypovolemia is counterproductive and dangerous. -Close surveillance of fluid management is necessary. Intravenous fluid administration is stopped when urine production, appetite, or interest in drinking increases and when an overall clinical improvement is observed. In the resolution phase of severe OHSS, the patient's fluid intake should be restricted to avoid renewed hemodilution. -To prevent thrombosis, subcutaneous heparin 5000-7500 U/d is begun on the first day of admission. It is stopped after adequate mobilization is achieved. -To manage ascites, ultrasonographic-guided vaginal paracentesis is indicated if the patient has severe discomfort or pain or if she has pulmonary or renal compromise.The procedure entails the same setup as that used for transvaginal follicular puncture. Whelan and Vlahos advise that an anesthesiologist be present. Paracentesis may be repeated if required. Critical hyperstimulation Critical OHSS may include renal failure, hepatic damage, thromboembolic phenomena, ARDS, and multiorgan failure.Its management and treatment requires intensive care in a critical care unit. Intensive care should include invasive monitoring of circulatory indicators, including venous pressure and wedge pressure. The patient may need extra oxygenation (assisted ventilation). If renal failure is present, an intravenous dopamine regimen should be started. To treat thromboembolism, therapeutic doses of anticoagulants should be administered. Thoracocentesis should be performed in the case of severe hydrothorax. Finally, if a pregnancy is maintaining a life-threatening OHSS, therapeutic abortion must be considered. Clinical Pearls What not to do Aggressive palpation of the abdomen: This can precipitate follicular rupture. Early surgical intervention: Early surgery may cause extensive bleeding from ovarian cysts. However, surgery is mandated if torsion or rupture has occurred. Neglect of deterioration in organs and systems: Remember that OHSS is a syndrome of multiorgan dysfunction. What to do Maintain a high degree of clinical suspicion and a low threshold for admission. Implement early surgical intervention in cases of ovarian torsion or hemorrhage. Perform paracentesis to address ascites. This decreases pressure on inferior vena cava and diaphragm. Place a transthoracic tube to manage pleural effusions. Resolution After several days, third-space fluid begins to re-enter the intravascular space, hemoconcentration reverses, and natural diuresis ensues. Intravenous fluids may be tapered as the patient's oral intake increases. Complete resolution typically takes 10-14 days from the onset of initial symptoms. Careful maintenance of blood volume, correction of electrolyte imbalances, and relief of secondary complications of ascites and hydrothorax are generally sufficient to support the patient during the severe phase of ovarian hyperstimulation. Anticoagulant therapy is usually unnecessary if these therapies are promptly administered. Blood coagulation may be monitored because of the danger of disseminated intravascular clotting. Surgical Care Ovarian hyperstimulation syndrome is a self-limiting disease. Therefore, treatment should be conservative and directed at symptoms. Medical therapy suffices for most patients. Women with severe symptoms often require intensive medical care. Surgery is necessary only in extreme cases, such as in the case of a ruptured cyst, ovarian torsion, or internal hemorrhage. Surgical management further aggravates electrolyte imbalances and increases morbidity. Ascites can be tapped by means of paracentesis. Harvesting of eggs in women with OHSS can lead to hemorrhage and peritonitis. However, tapping follicles when they are of moderate size may prevent OHSS. Laparotomy during torsion and intraperitoneal hemorrhage is life saving and recommended. Consultations In severe cases of OHSS, consultation with a physician specializing in fluid and electrolyte imbalances is warranted. For some cases, aggressive treatment in the surgical intensive care unit may be required. Diet Ensure that patient receives plenty of hydration. Activity Activity should be minimal. Physical examination should be performed gently because of the tendency of follicles to rupture.

Medication :

Medical therapy is aimed at the correction of fluid and electrolyte balance. Thrombosis can occur in the arteries (25%) and veins (75%). Therefore, use of heparin, low molecular weight heparin (enoxaparin sodium [Lovenox]), antiembolism stockings, and sequential compression devices (boots) are all recommended as prophylaxis against thrombosis. Heparin prophylaxis is usually started in patients with a history of thrombosis, factor V Leiden deficiency, or other thrombophilic states before the induction of ovulation. Anticoagulant These agents inhibit key factors involved in thrombogenesis.

Heparin Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse but can inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis. Dosing Adult 5000-7500 U SC qd Interactions Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, dextran, dipyridamole, and hydroxychloroquine may increase heparin toxicity Contraindications Documented hypersensitivity; subacute bacterial endocarditis, active bleeding, history of heparin-induced thrombocytopenia Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Electrolyte supplement, parenteral Used to replenish intravascular and extravascular volume.

Normal saline Used to restore interstitial and intravascular volume. Dosing Adult 1-2 L IV initially, given as fast bolus; assess hemodynamic response, then 125-150 mL/h until urine production improves; followed by maintenance dose Interactions May decrease lithium levels when administered concurrently Contraindications Edema in brain or lungs (pulmonary edema may contribute to ARDS); hypernatremia Precautions Pregnancy A - Fetal risk not revealed in controlled studies in humans Precautions Exercise caution to prevent fluid overload; monitor cardiovascular and pulmonary function; stop fluids when desired hemodynamic response observed or pulmonary edema develops; interstitial edema may occur; caution in congestive heart failure, hypertension, edema, liver cirrhosis, or renal insufficiency Blood product derivatives These agents are used to expand plasma volume. Albumin (Albuminar, Albumisol, Albunex, Albutein, Buminate) Major plasma protein responsible for colloid oncotic pressure of blood. Pooled from blood, serum, plasma, or placenta from healthy donors. Given in certain types of shock or impending shock. Use 5% solution to expand plasma volume and maintain cardiac output. Use 25% solution to raise oncotic pressure. Dosing Adult 200 mL of 25% solution IV over 20-30 min, then assess hemodynamic and renal response Interactions None reported Contraindications Documented hypersensitivity; pulmonary edema; severe congestive heart failure or anemia; protein load of 5% albumin (tends to exacerbate renal insufficiency, a potential complication of septic shock) Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus Precautions Caution in renal or hepatic failure, may cause protein overload; rapid infusion may cause vascular overload or hypotension; monitor for volume overload; caution in sodium-restricted patients; common adverse effects include congestive heart failure, hypotension, tachycardia, fever, chills, and pulmonary edema; do not dilute albumin 25% with sterile water for injection (produces hypotonic solution and, if administered, may result in life-threatening hemolysis and acute renal failure) Adrenergic agonist agent These agents increase blood pressure. Dopamine (Intropin) Naturally occurring endogenous catecholamine that stimulates beta1-adrenergic, alpha1-adrenergic, and dopaminergic receptors in dose-dependent fashion; stimulates release of norepinephrine.At low dosages (2-5 mcg/kg/min), acts on dopaminergic receptors in renal and splanchnic vascular beds, causing vasodilation-selective dilation of renal vasculature, enhancing renal perfusion. Also reduces sodium absorption, decreasing energy requirement of damaged tubules. This enhances urine flow, which, in turn, helps prevent tubular cast obstruction. Most clinical studies have failed to establish this beneficial role of renal-dose dopamine infusion.At midrange dosages (5-15 mcg/kg/min), acts on beta-adrenergic receptors to increase heart rate and contractility.At high dosages (15-20 mcg/kg/min), acts on alpha-adrenergic receptors to increase systemic vascular resistance and raise blood pressure. Dosing Adult 1-5 mcg/kg/min IV Interactions Monoamine oxidase inhibitors (MAOIs) may prolong effects; beta-blockers may antagonize peripheral vasoconstriction caused by high doses; butyrophenones (eg, haloperidol) and phenothiazines can suppress dopaminergic renal and mesenteric vasodilation induced with low-dose infusion; low doses concurrently administered with diuretics may produce additive effects on urine flow; hypotension and bradycardia may occur with phenytoin; may decrease effects of phenytoin Contraindications Documented hypersensitivity; pheochromocytoma or ventricular fibrillation Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus Precautions Closely monitor urine flow, cardiac output, pulmonary wedge pressure, and blood pressure during infusion; before infusion, correct hypovolemia with whole blood or plasma, as indicated; monitoring of central venous pressure or left ventricular filling pressure may help in detecting and treating hypovolemia; in patients who have received MAOIs the last 2-3 weeks, doses should not exceed 1/10th the initial dose of dopamine; ventricular arrhythmias and hypertension may occur in patients receiving cyclopropane or halogenated hydrocarbon anesthetics

Follow-up Deterrence/Prevention -Ovarian hyperstimulation syndrome (OHSS) is a self-limiting disease of the luteal phase. Without luteinizing hormone (LH) or its imitator hCG, ovulation or the luteal phase does not occur. Avoidance of hCG during ovarian stimulation offers an opportunity to prevent OHSS in high-risk patients. However, those patients do not conceive. Other options are delaying hCG (coasting) for 1-3 days until estradiol levels plateau or decline (<2500 pg/mL), using a GnRH agonist to induce ovulation, or lowering doses of hCG. -The best preventive method is to adapt the treatment and to closely monitor patients at risk. Remember that women at risk are those with high levels of estrogen and many follicles at the assumed time of ovulation. Patients with polycystic ovarian syndrome should be closely monitored as well. -Laboratory findings of a serum estradiol concentration greater than 2000 pg/mL and a progesterone concentration greater than 30 ng/mL in the early part of the luteal phase are warning signs of developing OHSS. -Vaginal intercourse is restricted in women with any grade of OHSS because of the risk of rupturing a cyst. Patients should also avoid impact-type activities or strenuous exertion. Prognosis The prognosis is excellent if ovarian hyperstimulation syndrome is mild or moderate. In severe OHSS, the prognosis is optimistic if good treatment is given. Hypercoagulability may endanger the patient. Death from OHSS is largely due to hypovolemic shock and electrolyte imbalance, hemorrhage, and thromboemboli. Estimated fatality rates are 1 per 400,000-500,000 stimulated cycles. Patient Education Patients are instructed to record their weight on a daily basis, to avoid exercise and intercourse, and to maintain adequate hydration after in vitro fertilization. They should measure their abdominal girth, intake, and output, and they should report urinary output of less than 1000 mL in any 24-hour period. Patients are educated to report progressive bloating, abdominal discomfort, decreases or increases in urination, cramping, dizziness, shortness of breath, and weight gain of more than 5 lb/wk.

Dr. Alaa Mosbah

2010-11-16T17:35:00.000-08:00

Dr. Alaa Mosbah

2010-11-16T17:20:00.000-08:00

World Health Organization (WHO) Pandemic Phases

2010-01-14T15:34:00.000-08:00

Groups at High Risk of Influenza-Related Complications

2010-01-14T14:58:00.000-08:00

Structural diagram of the H1N1 virus

2010-01-14T14:46:00.000-08:00

Development of placenta

2008-01-25T16:39:00.000-08:00

Embryo

2008-01-25T16:34:00.000-08:00

Cleavage 2

2008-01-25T16:32:00.000-08:00

Cleavage

2008-01-25T16:30:00.000-08:00

Fertilizes egg

2008-01-25T16:22:00.000-08:00

Follicle development

2008-01-20T17:18:00.000-08:00

Fertilization

2008-01-20T17:01:00.000-08:00

Anatomy of placenta

2008-01-20T16:57:00.000-08:00

Prenatal Diagnosis of Chromosomal Anomalies /DR. Alaa Mosbah , MD OBS & GYN

2008-01-09T15:36:00.000-08:00

Introduction : Prenatal diagnosis of chromosomal anomalies employs a variety of techniques either as a screening procedure for relatively prevalent disorders or as a diagnostic procedure for known familial conditions. The former identifies an increased likelihood of a fetal abnormality in an apparently normal pregnancy, whereas the latter confirms or refutes the existence of an actual anomaly in a fetus believed to be at increased risk . Currently available prenatal non-invasive screening tests are ultrasonography and various biochemical tests, while CVS, amniocentesis, and fetal blood sampling are invasive diagnostic procedures. High-risk pregnancies : include the following 1. Advanced maternal age (age 35 years or more at estimated date of delivery). Some authors also consider paternal age of approximately 50 years or older. 2. Family history (self, spouse, child, parent or sibling) of previous birth of a child with chromosome abnormality / multiple structural defects / ONTDs, or metabolic disorder. 3. Suspicious biochemical results. 4. Abnormal morphological scan. 5. Parent with a chromosome disorder. 6. Parent who are carriers of specific genetic defects such as cystic fibrosis, Tay-Sach dystrophy, sickle cell anemia, Falconis anemia&thalassaemia The most common reason for prenatal diagnosis of chromosome abnormalities is to look for evidence of trisomies, Turner syndrome and triploidy. Trisomy 13, 18, and 21 are the most common, with trisomy 21 comprising about half of all the trisomies identified. Various screening and diagnostic procedures used to detect common chromosomal abnormalities are discussed here. Screening procedures : Non invasive diagnostic procedures : 1.Ultrasonography Ultrasound scanning is offered to all pregnant women. It is non-invasive and has no inherent procedure related loss. First-trimester sonography is offered mainly to confirm the gestational age, to identify singleton or multiple pregnancy and to measure nuchal thickness (NT). Second-trimester ultrasound is generally recommended at 19 to 21 weeks to detect fetal structural defects. Nuchal translucency (NT) : NT refers to the subcutaneous space between the skin and the cervical spine in the fetus. The ultrasonographic findings of NT in the first-trimester of the pregnancy reportedly has been associated with fetal chromosome abnormalities including trisomies 21,18,13 and triploidy and Turner syndrome (45XO). Among karyotypically normal fetuses increased NT may be related to certain birth defects including cardiac septal defects, diaphragmatic hernia, renal defects, omphalocele, body-stalk anomaly, fetal akinesia syndrome, and certain skeletal dysplasias. Certain genetic defects and infections may also lead to increased NT. Various genetic defects associated with increased NT are Arthrogryposis, Noonan's syndrome, Smith-Lemli-Opitz syndrome, Stickler syndrome, Jarco-Levine syndrome, Miller-Dieker syndrome. Increased NT may be found in a normal fetus. Therefore, increased NT does not mean that the fetus is chromosomally abnormal but it does mean an increased risk for some disorders and birth defects. NT measurements can be taken from the sagittal section of the fetus usually used to obtain the crown-rump length, or from a transverse suboccipitobregmatic view of the fetal head. NT values are crown-rump-length-dependent. Measurements equal to or more than 3mm in the first-trimester and more than 6mm in the second-trimester are considered as abnormal. NT is apparently a powerful tool for the detection of aneupolidy, particularly Down's syndrome. For isolated nuchal edema, the risk for trisomy 21 may be 15 times the background. The estimated detection rate for Down's syndrome using NT at 10 to 14 weeks of gestation combined with maternal age is about 80% at a cut off risk of 1 in 300 or higher. However, there is considerable disagreement in the literature as to the precise Down's syndrome detection rate that can be expected with this form of sonography. Cystic hygroma I s caused by the malformation of the fetal lymphatic system and is found commonly in fetuses with Monosomy X (Turner syndrome), and other chromosomal anomalies. An important part of evaluation of nuchal membrane is the evaluation of the subtle signs of hydrops fetalis. Even in the presence of a normal karyotype, perinatal outcome is very poor in the presence of fetal hydrops. Choroid plexus cyst (s) Vast majority of cyst (s) is benign and usually disappears by 24-25 weeks. However, these cysts may be associated with chromosomal anomalies, primarily trisomy 18 but occasionally trisomy 21. Choroid plexus cysts have been reported to be associated with trisomy 18 in 1% to 6 % cases. For isolated choroid plexus cysts, the risk for trisomy 18 and trisomy 21 is about 1.5 times the background. Intracardiac echogenic foci Increased echogenicity (golf ball) located in chordae tendinae is seen in 3 to 5 % of fetuses and is considered by most investigators of no pathological significance. However, they are sometimes associated with chromosomal abnormalities particularly, trisomy 21. For isolated hyperechogenic foci the risk for trisomy 21 may be four times the background. Hyperechogenic fetal bowel Hyperechogenic bowel has been described as a normal variant, but may also be associated with cystic fibrosis, meconium peritonitis, cytomegalovirus infection or trisomy 21. For isolated hyperechogenic bowel, the risk for trisomy 21 may be three times the background. Mild hydronephrosis Minimal pyelectasis in the fetus is common and unlikely to be significant in every case. However, UPJ obstruction and reflux may manifest initially as mild fetal pyelectasis. In addition, karyotype abnormalities, remarkably trisomy 21, are reported to be associated with mild pyelectasis. Long bone biometry Short humeri and short femurs may be found in fetuses with Down's syndrome. Measurements are usually compared with BPD rather than menstrual age due to the uncertainty of the menstrual history. If the femur length is below 5th centile and all other measurements are normal, the fetus is likely to be normal but rather short. However, this finding is rarely related to dwarfism and occasionally trisomy 21. Fetal hand Abnormalities of fetal hand such as polydactyly, over-riding fingers, or abnormal hand positioning, especially if associated with polyhydramnios, have been reported to be associated with fetal chromosomal abnormalities. Club foot / Rocker bottom feet (positional deformities) Club foot has been associated with a variety of chromosomal abnormalities, especially trisomy 13 and 18. Whether or not infants with isolated club foot are at significantly increased risk of chromosomal abnormalities is still unresolved. Rocker bottom feet are also a feature of trisomy 13 and 18. The finding of this deformity should be a stimulus to detailed fetal examination and fetal karyotyping. Single umbilical artery A single umbilical artery is found in 0.5% to 2% of newborns and is associated with structural or other anomalies in 20% to 50% of cases; usually relatively minor anomalies of the renal or genital tracts. Whether or not the presence of an isolated single umbilical artery is an indication for genetic studies is still uncertain. Intrauterine growth restriction A significant percentage of fetuses with chromosomal abnormalities are growth restricted. Some investigators have suggested the presence of IUGR alone is an indication for genetic studies. Many additional abnormalities such as cerebellar hypoplasia, isolated pericardial effusion, sandal-foot, reduction defect of forearm, low set ears or shortened ear length, fetal cholecystomegaly, and polyhydramnios have been found to be associated with chromosomal anomalies. When these findings are seen in isolation, it is still controversial whether or not amniocentesis should be offered. The sensitivity of ultrasonography for detection of fetal trisomic conditions varies with the type of chromosome abnormality, gestational age at the time of sonography, reasons for referral, criteria for positive sonographic findings, and the quality of the sonography. As an estimate, 1 or more sonographic findings can be identified in approximately 90% of fetuses with trisomy 13, 80% of fetuses with trisomy 18, and 50 % to 70% of fetuses with trisomy 21. Clusters of minor sonographic markers greatly increase the likelihood of karyotypic abnormality compared with a single minor marker . Cardiovascular anomalies Since malformations of the heart are the most common birth defect in fetuses with serious chromosomal abnormalities, color Doppler ultrasound evaluation of the cardiovascular system can be used to improve the detection rate of these abnormalities. By the inclusion of color Doppler sonography in genetic ultrasound, 96% of fetuses with Down's syndrome, 98% of all trisomies, and 88 % of all chromosomal abnormalities can be detected . A complete normal ultrasound examination result reduces the risk of abnormal karyotype,by,62%. 2.Biochemical,tests A large number of serum analytes have been found to be associated with chromosomal abnormalities. Various principal biochemical analytes currently available for the prenatal screening of chromosomal abnormalities during first and second-trimester of pregnancy are; pregnancy associated plasma protein-A (PAPP-A), maternal serum alpha-feto-protein (MSAFP), free-beta hCG, total hCG, unconjugated estriol (uE3), and inhibin-A. PAPP-A and free-beta hCG are only biochemical markers identified to be of value in first-trimester screening. Free-beta hCG is the only marker that is effective in both the first and second-trimester pregnancy. PAPP-A It is a homotetrameric glycoprotein (metzincins family of metalloproteases) which is synthesized in chorionic villi [35]. It can be measured in maternal serum; its concentration increases rapidly after 7th week of pregnancy and its potential clinical usefulness is greatest in the first trimester (10th to 14th week of gestation). When the fetus is affected with trisomy 21, PAPP-A levels are decreased by more than half [36]. Low PAPP-A is also associated with trisomy 18 and 13. Using PAPP-A alone, detection rate of Down's syndrome is about 40%. When PAPP-A was combined with maternal age, the detection rate increased to 50% with a 5% screen-positive rate [37]. Decreased production of PAPP-A may cause intrauterine growth restriction [38] as this hormone control the level of insulin -like growth factors (IGF) in the placenta. MSAFP MSAFP is a glycoprotein produced by the fetal yolk sac and fetal liver. Fetal plasma concentration increases to a maximum (approximately 3.0-4.0 g/L) between 13-14 weeks of gestation. Maternal serum levels peak at about 30 weeks (about 250 mg/L). After birth, maternal and infant AFP rapidly declines. High MSAFP levels may occur in the following conditions; 1. Underestimated gestational age 2. Multiple gestation. 3. Neural tube defects (anencephaly, spina bifida, encephalocele). 3 Abdominal wall defects (omphalocele, gastroschisis) 4. Various other fetal abnormalities such as hydrocephaly, microcephaly, cystic hygroma, cyclopia, tetralogy of Fallot, duodenal atresia, congenital nephropathies, sacrococcygeal teratoma, hydrops fetalis and Turner's syndrome without hygroma. 5. Complications of pregnancy ( fetal distress, growth retardation, early intrauterine death, placental defects, abdominal pregnancy, and maternal proteinuric preeclampsia). 6. Congenital fetal neoplasms, and maternal AFP producing neoplasms. Low MSAFP levels may be associated with 1. Incorrect pregnancy dating (less advanced than originally thought). 2. Complications of pregnancy (missed abortion, spontaneous abortion, late fetal death, molar pregnancy, choriocarcinoma). 3. Some normal pregnancies. 4. Large-for-dates. Very low MSAFP predicts an unusually high rate of large birth weight infants, with increased fetal, intrapartum, and neonatal consequenses. 5. MSAFP less than the median may indicate an increased risk of chromosomal abnormalities such as trisomy 21 and trisomy 18. The level of MSAFP in Down's syndrome pregnancies are about 72% of the normal values for weeks 14 to 21. Using maternal age and MSAFP level, the detection rate of Down's syndrome pregnancies is about 25-33%, at a false positive rate of 5% . Total hCG hCG is a dimeric glycoprotein composed of two non-covalently linked polypeptide sub-units, alpha and beta. It is first secreted by the fertilized ovum and later by placental tissue. Serum hCG levels increase exponentially between 3-10 weeks of pregnancy. Levels reach a peak during the first-trimester (about 100000 m IU/ml) and decline during the second and third-trimesters. In normal second-trimester maternal sera, the level of intact hCG ranges from 20,000-50,000 mIU/ml. In trisomy 21 pregnancies, second -trimester hCG levels are elevated varying from 2.04 to 2.5 MoM or greater while in trisomy 18 and 13, hCG levels are lower than normal. Using maternal age and hCG levels, Down's syndrome detection rate is about 60 % at a false positive rate of 6.7 % . Very high levels of hCG suggest trophoblastic disease. Various workers found a significant increase in the levels of free beta-hCG in trisomy 21, and concluded that this biochemical analyte is superior to intact hCG for the detection of trisomy 21. The levels of this analyte are reduced in the blood of women carrying fetuses with trisomy 18 . Unconjugated estriol (uE3) The substrate for estriol begins as dehydroepiandrosterone (DHEA) made by the fetal adrenal glands. This is later hydroxylated in fetal liver and cleaved by steroid sulphatase in placenta where unconjugated fraction converts to uE3. The amount of estriol in maternal serum is dependent upon a viable fetus, a properly functioning placenta, and maternal wellbeing. In normal pregnancies, uE3 levels increase from about 4 nmol/L at 15 weeks gestation to about 40 nmol/L at delivery. uE3 tends to be lower when trisomy 21or 18 is present and when there is adrenal hypoplasia with anencephaly. Second-trimester maternal serum uE3 levels in Down's syndrome pregnancies are approximated 75% of the values expected in normal pregnancies . Using maternal age and uE3 levels detection rate of about 45.7% at a false positive rate of 9.1 % was found . Inhibin-A Inhibin-A is a heterodimeric glycoprotein of placental origin similar to hCG. Inhibin-A levels in maternal serum are relatively constant through the 15th-18th week of pregnancy. Maternal serum levels of inhibin-A are twice as high in pregnancies affected by Down's syndrome as in unaffected pregnancies while in trisomy 18, inhibin-A levels are lower than normal. Inhibin-A is used with three other analytes (MSAFP, hCG, uE3) and maternal age to characterize more accurately Down's syndrome risk, and a reduction of the false positive rate was detected. Currently available evidences suggest that sensitivity of individual maternal serum markers is substantially low. To improve the sensitivity and specificity of biochemical markers, various combinations of 2, 3, or 4 analytes are offered during first and / or second-trimester screening. Various combinations of analytes include; 1. First-trimester maternal serum double test using PAPP-A and free-beta hCG. This is vastly more effective than any other screening program and is of great advantage because it is available in the first-trimester. The disadvantage is that the test will not detect neural tube defects, so a MSAFP test will still need to be done. After combining PAPP-A and free beta-hCG with maternal age, detection rate of aneuploidy is about 60% at a 5% screen-positive rate. 2. Second-trimester screening includes; double test (MSAFP+ free-beta hCG or total hCG), triple test (MSAFP+hCG+uE3), and quad screen test (MSAFP+hCG+uE3+inhibin-A). When an ultrasound scan is used to estimate gestational age the Down's syndrome detection rate for a 5% false positive rate is estimated to be 59% using the double test (AFP and hCG), 69% using the triple test (AFP,hCG,uE3), and 76% using the quad test (AFP,hCG,uE3, inhibin-A), all in combination with maternal age. Main disadvantage of second-trimester screening is the timing of the test. By the time a definitive diagnosis is made via amniocentesis (after a positive screen result), the option of termination of pregnancy can be difficult. MSAFP is always included as a component of second-trimester biochemical screening because this analyte is widely used for the detection of ONTDs at this stage of pregnancy. Addition of uE3 as an analyte for prenatal screening is controversial. Some authors pointed out that inclusion of this analyte does not improve detection rates, where as in another study a fall in detection rate was noticed. On the other hand, some workers rely on the usefulness of uE3 as a serum marker. In a study, it was found that double test is not worse than the triple test and the double test is preferred because of lower running cost. Comparing free beta-hCG and total hCG, it was found that free beta hCG is better option because it improves the Down's syndrome detection efficiency by 10 % over total hCG at a lower false positive rate. Review of the literature suggests that the combined use of free beta-hCG and AFP instead of total hCG, AFP and uE3, is better screening test because it is more effective, less expensive, and is not limited to 16-20 weeks gestation. The addition of uE3 and inhibin-A adds no significant advantage to the double test. However, some workers recommend triple test while some rely on quad test for better results. Combined screening Since maternal biochemical and sonographic markers are largely independent, combined risk estimate results in even higher detection rate than either alone. Thus combination of a multiple marker test (PAPP-A and free b-hCG) and an ultrasound at 11 to 14 weeks which is targeted to look NT, and maternal age gives a detectable rate of aneuploidy of about 90 % with an invasive testing rate of about 5%. But in many high-risk situations this may still leave the patient at risk. Integrated screening The integrated test includes measurements of PAPP-A and NT in the first-trimester and measurements of MSAFP, uE3, hCG, and inhibin-A in the second-trimester. The integrated test can achieve a high detection rate with a much lower false positive rate (0.9%) than screening based on markers measured in either trimester alone. Consequently the need for amniocentesis or CVS is reduced by four fifths, with a similar reduction in the loss of unaffected fetuses. The estimates of the integrated test's performance are based on there being little or no correlation between the first and second-trimester markers used with the exception of free beta-hCG and total hCG. Disadvantage of the test is that it is expensive, and option of making the diagnosis in the first-trimester is eliminated. Recently, Azuma M, et al used Lens culinaris agglutinin reactive alpha-fetoprotein ratio for the detection of fetal Down's syndrome in combination with traditional serum markers such as AFP, hCG and uE3 and found a detection rate of 83.9% with a 5.1% false positive rate. Various factors affect the accuracy of biochemical tests. Therefore, adjustments are made to take account of these factors when categorizing the result as screen positive or screen negative. These factors are: 1. Gestational age: Measured concentrations of the serum markers vary with gestational age, Between 9 to 14 weeks, maternal serum free beta-hCG decreases, median free beta-hCG also decreases while median PAPP-A increases. Between 14-22 weeks, Median MSAFP and median uE3 increases, median hCG decreases while median inhibin-A is less affected. 2. Maternal weight: Maternal weight has a significant effect on the screening process. There is inverse correlation between body weight and concentration of biochemical markers. If the volume of distribution is greater, the concentration of AFP will be smaller. Maternal weight also has a significant inverse correlation on inhibin-A levels. PAPP-A and free beta-hCG also show a small but significant negative correlation. But there is no correlation for uE3. 3. Smoking: Maternal smoking has a small effect on overall screening performances. Women who smoke are more likely to produce a small amount of PAPP-A. 4. Effect of parity: Parity significantly affects the mean MoM of hCG but did not affect the values for uE3 or MSAFP. 5. Multiple pregnancies: On an average, the levels of MSAFP and free beta-hCG were twice as high in twins and over three times as high in triplets. 6. Difference between races of ethnic groups: Medians are significantly different in races of ethnic groups. Black women, on an average, have higher levels of MSAFP than Caucasian, Asian or Hispanic women. 7. Insulin-dependent diabetes mellitus: MSAFP levels in IDDM have shown an approximately 20% decrement while uE3 and inhibin-A levels are reduced to a smaller extent . Conclusions of multiple marker screening test: 1. Maternal blood screening is originally developed for pregnant women who are at a 'low-risk' for disorders being screened. However, in certain situations maternal serum marker screening can be assayed in women > or =35 years.. 2. Gestational age must be accurately known. First-trimester screening is offered between 10 to 14 weeks of gestation, while second-trimester screening tests are given between 14 and 22 weeks of pregnancy, with 16 to 18 weeks (when the hormone levels are most consistent) being the optimum time. Recently Muller F, et al assessed the diagnostic value of maternal serum marker screening at 18-35 weeks and concluded that biochemical screening is feasible at 18 weeks and later, which may be of interest in selected cases. 3. Multiple gestation screening is not as sensitive as singleton screening with biochemical analysis. 4. Screening utilizing biochemical test, NT and maternal age mainly identifies aneuploidy and some other chromosomal abnormalities only and therefore shall miss majority of other non-Down, non-trisomy 18 chromosome abnormalities, nor does it identify other physical or mental birth defects. 5. A low PAPP-A, low MSAFP, low uE3, and high free beta-hCG, and high inhibin-A levels are associated with higher risk for Down's syndrome while low levels of all hormones suggest an increased risk for trisomy 18. In trisomy 13, PAPP-A and free beta-hCG levels are low but detection rate using second-trimester analytes is poor. 6. Although screening protocol has a 90 % pickup rate of aneuploidy, it is not diagnostic. Hence, suspicious screening results will tell of an increased risk of a problem, but not diagnose the problem as being present or being absent. Therefore, a negative screening result may falsely reassure many women who are carrying an affected fetus. Conversely, a false positive result may culminate in termination of a normal pregnancy. The main aim of screening test is to identify a group of women at significantly high-risk of having an affected child to justify the offer of a diagnostic test. 3. Non-invasive screening using fetal blood cells and fetal DNA. (a)Fetal blood cells: The fetal and maternal circulations are separated by the placental membranes, but this barrier is incomplete to cellular trafficking. Bi-directionality and bimodality (cell and cell-free DNA) of fetomaternal trafficking is an established fact. Fetal nucleated cells such as trophoblasts, erythrocytes and white blood cells are found in maternal blood, and have been widely pursued as potential substrates for noninvasive prenatal diagnosis. However, concentration of these cells in maternal blood is very low (1fetal cell in 103-108 maternal cells) and therefore isolation of these cells for cytogenetic analysis requires expensive euipments and great expertise. Isolation of erythroblasts has attracted most attention because they are abundant in early fetal blood, they are extremely rare in normal adult blood and their half-life in adult blood is only about 30 days. Relatively specific monoclonal anibodies against these cells are also available. Trophoblastic cells and white cells are not used for prenatal screening because trophoblastic cells are cleared by maternal lungs whereas half life of the white cells is very long which may lead to contamination from previous pregnancies. A combination of sophisticated physical and immunological methods are used for the identification, isolation and enrichment of different types of fetal blood cells from maternal blood obtained at 12-16 weeks of gestation. Physical methods include triple density gradient centrifugation and micromanipulation techniques while immunological methods include the use of magnetically labelled or fluorescent monoclonal antibodies such as anti-CD71 (transfferin receptor). Commonly used immunological methods are, magnetic cell sorting (MACS) or fluorescence activated cell sorting (FACS). By these methods the fetal cells can be enriched to about 1 in 10-100 materanl cells. Enriched cells are used for the detection of specific chromosomes by fluorescent in situ hybridization (FISH) and for the analysis of fetal genetic loci by single cell PCR. FISH involves the hybridization of DNA probes representing a specific chromosome or chromosomal region to target DNA such as metaphase chromosomes or interphase nuclei. Fetal trisomy is suspected if some of the enriched cells show three-signal nuclei rather than the normal two. Over the past decade, progress has been made towards the isolation and analysis of fetal blood cells from maternal blood, using various enrichment strategies and analysis by fluorescent in situ hybridization with choromosome-specific probes and PCR. It is now possible to identify simultaneously all major chromosomal abnormalities by the use of multicolor probes directed against chromosomes 21,18,13,Y and X in interphase nuclei. Another method that is currently being explored involves culturing fetal blood cells. The sensitivity for detecting aneuploidy using fetal cells is competitive with first or second-trimester maternal serum screening with the advantage that the invasive testing rate may be as low as 0% rather than 5%. But the current technology precludes application of this concept for mass population. However, fetal cells might be analyzed only after a positive serum or ultrasound finding. If fetal aneuploid cells are not recovered, an invasive diagnostic procedure could be avoided. (b) Fetal DNA Isolation of fetal cells from the cellular fraction of maternal blood needs expensive and advance equipment because of the rarity of such cells. Recently, there has been much interest in the use of the non-cellular portion of blood, namely plasma, for molecular analysis diagnosis. Fetal DNA has been identified in the plasma of pregnant women at concentrations much higher than those present in the cellular fraction. Until recently, it was assumed that fetal DNA detected in maternal plasma was cell free and a definitive diagnosis of fetal chromosomal aneuploidies was not thought possible. Studies now indicate that some fetal DNA originates from intact fetal cells. Trophoblasts may be the predominant cell population involved in the liberation of fetal DNA into the cell-free fraction. It was found that the absolute concentration of fetal DNA in maternal serum increases with gestational age, with a sharp rise near the end of the pregnancy. Fetal DNA is cleared rapidly from maternal blood after delivery with a half-life of minutes. Increase in fetal DNA in maternal plasma has been noticed in pregnancies affected by fetal trisomy, and in premature labour, and preeclampsia. Using fetal DNA in maternal plasma for the screening of fetal chromosome aneuploidies is possible, especially in conjugation with other established serum markers. The median fetal DNA concentration in Down's syndrome cases was found to be 1.7 times higher than in controls. Second-trimester cell-free fetal DNA estimation gave a 21% detection rate at a 5% false-positive rate. When added to quadruple marker screening, fetal DNA estimation modestly increased the screening performance above what is currently available in the second-trimester. The relative ease and reliability with which fetal DNA can be detected have thus opened new possibilities for non-invasive prenatal diagnosis. Invasive diagnostic procedures 1.Chorionic villus sampling CVS is a prenatal test that involves taking a sample of some of the placental tissue. Main complications of CVS include severe transverse limb defects and oromandibular-limb hypogenesis [103]. Possible mechanism of severe transverse limb abnormalities is hypoperfusion, embolization and release of vasoactive substances due to trauma during the procedure. There is strong association between the severity of the defect and the gestation at sampling. Decreasing risk and a trend from proximal to distal limb damage with increasing gestational age at CVS provide biologic plausibility for a true association with limb reduction defects [104,105]. CVS as early as 8 weeks of gestation may lead to amputation of whole limb while sampling at 10 weeks only affects terminal phalanxes. Thus, to avoid severe limb defects, CVS prior to 11 weeks of gestation should be discouraged. The increase in the miscarriage rate following this procedure is about 0.5% above the background risk for miscarriage, which is 2-3% at 10-12 weeks of pregnancy. Various trials compared CVS in first-trimester and amniocentesis in the second-trimester and concluded that both procedures are equally effective and safe with similar rates of procedure-induced fetal loss at experienced centers. The main advantage of CVS over amniocentesis is that prenatal diagnosis is achieved during the first-trimester, which allows a couple the opportunities to consider their options earlier in the pregnancy in the event of an abnormal result. However, screening for ONTDs cannot be achieved through CVS. The main indication for repeat CVS is mosaicism. 2.Amniocentesis Amniocentesis was first used for prenatal diagnosis in the 1950's and the feasibility of culturing and karyotyping amniotic fluid cells was first demonstrated in the late 1960s. Although the exact risk associated with amniocentesis is controversial, it is also not a completely innocuous procedure and can result in various complications such as spontaneous abortion, premature labour, placental abruption, intrauterine death and neonatal death. Other reported procedure-related complications include increased risk of respiratory distress syndrome and pneumonia in neonates, talipes and dislocation of the hip, postprocedural amniotic fluid leakage of amniotic fluid, vaginal bleeding, chorioamnionitis, amniotic band formation and rare needle puncture of the fetus. Amniocentesis may results in future reproductive complications secondary to sensitization to Rh and other rare antigens such as Kell. Amniocentesis can be performed as early as 11-13 weeks of gestation. But at this stage of pregnancy, the procedure is not only technically difficult to perform, it is also associated with increased incidence of total fetal loss, talipes equinovarus and post-procedural amniotic fluid leakage. Incidence of failed culture is also high in early amniocentesis. Thus, the procedure should not be performed before 13 weeks gestation unless there are special circumstances. Potential advantage associated with amniocentesis includes; 1.The amniotic fluid can be tested to measure the amount of AFP, which is a diagnostic test for detecting ONTDs 2. Possibility of an abnormal chromosome result due to chromosomal mosaicism confined to the placenta is reduced.

Chorionic villous sampling

2008-01-08T18:58:00.000-08:00

8 Weeks pregnancy

2008-01-08T18:22:00.001-08:00

2008-01-08T18:17:00.000-08:00

Rupture of the Uterus

2008-01-08T17:56:00.000-08:00

Incidence: About 1:4000, 95% of cases occur in multipara particularly grand multipara. Causes: (A) During pregnancy (I) Spontaneous: 1.Rupture of a uterine scar: e.g. previous C.S. especially upper segment, myomectomy, hysterotomy, uteroplasty or perforation. 2. Abruptio placenta with severe concealed haemorrhage. Anterior sacculation in case of incarcerated retroverted gravid uterus or posterior sacculation due to previous ventrofixation of the uterus. 4. Rupture of a rudimentary horn at the 4th - 5th month. 5. Perforating vesicular mole. (II) Traumatic 1. Perforation during vaginal evacuation. 2. External trauma. (B) During labour: (I) Spontaneous: 1. Obstructed labour. 2. Rupture of a uterine scar. 3.Grand multipara: due to degeneration and overthinning of the uterine muscles. (II) Traumatic : 1. Internal version: particularly after drainage of liquor. 2. Manual separation of the placenta. 3. Destructive operations. 4.Extending cervical tear due to e.g. forceps or ventose applications before full cervical dilatation. (III) Improper use of oxytocins. Weak uterine scar may be a result to: 1. Imperfect suture with improper coaptation of the edges. 2.Bad haemostasis results in blood clot formation which prevents good coaptation and predisposes to wound infection. 3. Wound infection. 4. Subsequent implantation of the placenta over it. 5. Upper segment caesarean section scar is weaker than lower segment scar. 6. Repeated vaginal deliveries after a previous C.S weaken the scar . 7. Types: 1.Complete : involving the whole uterine wall including the peritoneum. 2. Incomplete: not involving the peritoneal coat. Sites: It depends upon the cause of rupture. (1) In obstructed labour: - It is usually in lower uterine segment. - Usually oblique or transverse. - More on the left side due to; i) dextrorotation of the uterus. ii) left occipito-positions are more common. - Extended tear may pass laterally injuring the uterine vessels leading to broad ligament haematoma formation. This rupture may involve the ureter or bladder. (2)In rupture scar: At the site of the scar. Clinical Picture: (A) Impending rupture : before actual rupture the following manifestations may be detected: 1- Lower abdominal pain. 2- Tender uterine scar. 3- Vaginal spotting (minimal bleeding). (B) Actual rupture: i) Symptoms: 1.Sudden severe abdominal pain : It is differentiated from labour pain being continuous . 2.If the patient was in labour there is cessation of uterine contractions. 3.Shoulder pain on lying down due to irritation of the phrenic nerve by accumulating blood under the diaphragm. 4.Silent rupture: minimal symptoms may occur in rupture lower segment scar due to presence of fibrosis and minimal internal haemorrhage. ii) Signs 1- General examination: Variable degrees of collapse is present according to amount of blood loss. This may appear postpartum in case of traumatic rupture uterus. 2- Abdominal examination: - Scar of the previous operation. - Foetal parts are prominent and felt easy. - The presenting part recedes upwards. - Abnormal foetal attitude and lie. - FHS usually not heard. - The uterus is felt separated from the foetus . - In incomplete rupture, the foetus still inside the uterus with suprapubic painful tender swelling which is an accumulated blood in the vesico-uterine pouch. 3- Vaginal examination: - The presenting part recedes upwards. - Vaginal bleeding may be present. - Contracted pelvis may be detected. - A cervical tear may be found extending to the lower uterine segment and a broad ligament haematoma may be present. Differential Diagnosis: 1. Abruptio placentae. 2. Disturbed advanced extrauterine pregnancy. 3. Other causes of acute abdomen. Management: (A) Prophylactic: 1.Early detection of causes of obstructed labour as contracted pelvis and malpresentations. 2. Proper use of oxytocins. 3. Version is not done if liquor amnii is drained. 4.Forceps application and breech extraction should not be done before full cervical dilatation. 5.Elective caesarean section for susceptible scars for rupture as upper segment C.S. 6.Exploration of the genital tract after difficult or instrumental delivery. (B) Curative: 1- Blood transfusion and antishock measures. 2- Immediate laparotomy. 3- Deliver the foetus and placenta. 4- Explore the rupture site: - If it is amenable for repair and the patient did not complete her family ® repair is done. - If it is not amenable for repair® hysterectomy. Subtotal hysterectomy is less time consuming so it is done if there is no cervical tear. 5- Exploration of the other viscera mainly the bladder. 6- Internal iliac artery ligation may be needed in case of broad ligament haematoma as the uterine artery is usually retracted and difficult to be identified. 7- Vaginal repair: may be amenable if there is slight extension of a cervical tear with accessible apex. Complications: (A) Maternal: 1- Shock. 2- Haemorrhage. 3- Paralytic ileus. 4- Bladder, ureter or visceral injuries. 5- Infection. (B) Foetal :Death due to asphyxia from detachment of the placenta.

Obstructed Labour

2008-01-08T17:50:00.000-08:00

Definition: It is arrest of vaginal delivery of the foetus due to mechanical obstruction. Aetiology: (I) Maternal causes: 1-Bony obstruction : e.g. - Contracted pelvis. - Tumours of pelvic bones. 2-Soft tissue obstruction: i) Uterus: - Impacted subserous pedunculated fibroid. - Constriction ring opposite the neck of the foetus. ii) Cervix: cervical dystocia. iii) Vagina: - Septa. - Stenosis. - Tumours. iv) Ovaries : Impacted ovarian tumours. (II) Foetal causes: 1- Malpresentations and malpositions : e.g. - Persistent occipito- posterior and deep transverse arrest, - Persistent mento-posterior and transverse arrest of the face presentation. - Brow, - Shoulder, - Impacted frank breech. 2- Large sized foetus ( macrosomia). 3- Congenital anomalies : e.g. - Hydrocephalus. - Foetal ascitis. - Foetal tumours. 4- Locked and conjoined twins. Diagnosis: It is the clinical picture of obstructed labour with impending rupture uterus (excessive uterine contraction and retraction). (A) History: of - prolonged labour, - frequent and strong uterine contractions, - rupture membranes. (B) General examination : shows signs of maternal distress as: - exhaustion, - high temperature (³ 38oC), - rapid pulse, - signs of dehydration : dry tongue and cracked lips. (C) Abdominal examination: 1- The uterus : - is hard and tender, - frequent strong uterine contractions with no relaxation in between (tetanic contractions). - rising retraction ring is seen and felt as an oblique groove across the abdomen. 2- The foetus : - foetal parts cannot be felt easily. - FHS are absent or show foetal distress due to interference with the utero-placental blood flow. (D) Vaginal examination: 1- Vulva: is oedematous. 2- Vagina : is dry and hot. 3- Cervix: is fully or partially dilated, oedematous and hanging. 4- The membranes : are ruptured. 5- The presenting part: is high and not engaged or impacted in the pelvis. If it is the head it shows excessive moulding and large caput. 6- The cause of obstruction can be detected. (E) Differential diagnosis: 1- Constriction ring. 2- Full bladder. 3- Fundal myoma. Complications: (I) Maternal : 1- Maternal distress and ketoacidosis. 2- Rupture uterus. 3- Necrotic vesico -vaginal fistula. 4- Infections as chorioamnionitis and puerperal sepsis. 5- Postpartum haemorrhage due to injuries or uterine atony. (II) Foetal: 1- Asphyxia. 2- Intracranial haemorrhage from excessive moulding. 3- Birth injuries. 4- Infections. Management: (A) Preventive measures: Careful observation , proper assessment, early detection and management of the causes of obstruction. (B) Curative measures: Caesarean section is the safest method even if the baby is dead as labour must be immediately terminated and any manipulations may lead to rupture uterus.

Obstetric Terms

2008-01-08T17:34:00.000-08:00

Presentation: The part of the foetus related to the pelvic brim and first felt during vaginal examination. The presentation may be: (a) Cephalic (96%): i) Vertex: when the head is flexed. ii) Face: when the head is extended. iii) Brow: when it is midway between flexion and extension. (b) Breech (3.5%). (c) Shoulder (0.5%). Cephalic presentation is the commonest as this makes the foetus more adapted to the pyriform-shaped uterus with the larger buttock in the wider fundus and the smaller head in the narrower lower part of the uterus. Position: The relation of the foetal back to the right or left side of the mother and whether it is directed anteriorly or posteriorly. The denominator: is a bony landmark on the presenting part used to denote the position. In vertex it is the occiput. In face it is the mentum (chin). In breech it is the sacrum. In shoulder it is the scapula. Occipito-anterior positions are more common than occipito - posterior positions because in occipito - anterior positions the concavity of the anterior aspect of the foetus due to its flexion fits with the convexity of the vertebral column of the mother due to its lumbar lordosis. * In each presentation, except the shoulder , there are 8 positions. In vertex presentation they are: - Left occipito -anterior (LOA) 60%. - Right occipito-anterior (ROA) 20%. - Right occipito - posterior (ROP) 15%. - Left occipito-posterior (LOP)5%. - Left occipito-transverse (LOT). - Right occipito - transverse (ROT). - Direct occipito -anterior (DOA). - Direct occipito - posterior (DOP). LOA is more common than ROA, and ROP is more common than LOP as in LOA and ROP the head enters the pelvis in the right oblique diameter which is more favourable than the left oblique because: i) anatomically, the right oblique is slightly longer than the left, ii) the pelvic colon reduces the length of the left oblique. Lie: It is the relation between the long axis of the foetus and that of the mother. - Longitudinal in cephalic and breech presentations. - Transverse or oblique in shoulder presentation. Attitude: The relation of foetal parts to each other. - Flexion in the majority of cases. - Extension in face presentation. Synclitism: The posture in which the 2 parietal bones are at the same level. Asynclitism: - The posture in which one parietal bone is at a lower level than the other due to lateral inclination of the head. - Asynclitism is beneficial in bringing the shorter subparietal supraparietal diameter (9 cm) to enter the pelvis instead of the longer biparietal (9.5 cm). - Slight degree of asynclitism may occur in normal labour. (1) Anterior parietal bone presentation: - The anterior parietal bone is lower and the sagittal suture is near to the promontory. - It occurs more in multigravidas due to laxity of the abdominal wall. - It occurs also in contracted flat pelvis. (2) Posterior parietal bone presentation: - The posterior parietal bone is lower and the sagittal suture is near to the symphysis. - It occurs more in the primigravidas due to tense abdominal wall. Anterior parietal bone presentation is more favarouble because; 1. The head lies more in the direction of the axis of the pelvic inlet. During correction of asynclitism, the head meets only the resistance of the sacral promontory while in posterior parietal bone presentation the head meets the resistance of the whole length of the symphysis pubis. 2. In posterior parietal bone presentation the head stretches the anterior wall of the lower uterine segment with liability to rupture. 3. Engagement: - It is the passage of the widest transverse diameter of the presenting part, which is the biparietal in vertex presentation, through the pelvic inlet. - The engaged head cannot be easily grasped by the first pelvic grip, but it can be palpated by the second pelvic grip. - Rule of fifths: 2/5 or less of the foetal head is felt abdominally above the symphysis pubis. - Vaginally : the vertex is felt vaginally at or below the level of ischial spines. - Stations: -Station 0 the vertex at the level of ischial spines. -Stations -1,-2 and -3 represents 1,2 and 3 cm respectively above the level of ischial spines. -Stations +1, +2 and +3 represents 1,2 and 3 cm respectively below the level of ischial spines. - In the primigravidas, engagement of the head occurs in the last 3-4 weeks of pregnancy due to the tonicity of the abdominal and uterine muscles. - In the multipara, the head is usually engaged at the onset of labour or even at the beginning of the second stage due to less tonicity. Causes of non-engagement: (I) Faults in the passenger: 1- Large head. 2- Hydrocephalus. 3- Occipito-posterior positions. 4- Malpresentations. 5- Multiple pregnancy. 6- Placenta praevia. 7- Short cord. 8- Polyhydramnios. (II) Faults in the passages: 1- Contracted pelvis. 2- Pelvic tumours. 3- Full bladder or rectum. (III) Faults in the power: Atony of the abdominal muscles.

Ovulation induction

2008-01-07T17:59:00.000-08:00

Introduction: Ovulation induction includes medical induction by ovulatory agents and surgical induction. Ovulatory agents were introduced in 1960, expanded considerably in the last years. Each drug has specific indication, mechanism of action & clinical monitoring. Surgical induction of ovualtion is resorted to when the medical methods of induction fail. It entails making a port through which the ovum is released in cases of polycystic ovarian disease ( PCOD). Pre-therapy work up: 1- Document anovulation (BBT, endometrial biopsy) 2- Rule out and treat reversible pathology (e.g. pituitary tumor). 3- Rule out ovarian failure ( FSH > 40mIU/ml). 4- Ensure that other elements of fertility are intact (good male and tubal factor). 5- Document the couple’s psychological readiness for - Prolonged therapy - Possible failure - Method risk Indication of ovulation induction: 1- Anovulatory infertility. 2- Timing of ovulation for artificial insemination-husband (AIH), artificial insemination- donor (AID). 3- Oocyte maturation for IVF, ICSI,……… Clomiphene Citrate Pharmacology: -Is an orally active non-steroidal compound which is structurally related to ( di-ethyl-stilbosterol (DES). -Exhibits both estrogenic and anti-estrogenic effects. Mode of action: 1- Central action ( hypothalamic): -It occupies estrogen receptors in the hypothalamus (because of its structural similarity to estrogen). -Its dissociation from chromatin is impaired and remains in the nucleus for a longer period blocking the interaction of receptors with estrogen. So, it causes a state of estrogen insensitivity of the target cells i.e. blinding them to the endogenous estrogen level ® inhibition of uptake of estrogen into the hypothalamus and pituitary. ® ¯ –ve feed back effect of estrogen ® GnRH and gonadotropin release ® stimulate follicular activity. 2- Peripheral action ( ovarian): Clomiphene may also act by 2 mechanisms on the ovary; • Direct stimulating effect. • ovarian sensitivity to gonadotropins. Selection of patients: 1- Should have intact hypothalamo – pituitary- ovarian axis. • Intact hypothalamus: capable of producing GnRH. • Intact pituitary gland: capable to respond to GnRH. • Ovary with certain degree of follicular activity (i.e endogenous estrogen present). 2- Should have normal prolactin value. 3- Should have good liver function. So, Clomiphene is used to treat patients with group II WHO which include; 1- Hypothalamic –pituitary dysfunction. 2- PCOD. Clomiphene citrate is ineffective in: 1- Severe hypothalamo-pituitary failure (Group I WHO) 2- Hypo-estrogenic patient. Success of Clomiphene depend on: 1- Sufficient stage of follicular maturation. 2- Body wt. not < 80% of the ideal body weight. Regimens of Clomiphene: [1]. Conventional regimen -Begin by 50mg/day (one tablet) beginning in the 5th day of a spontaneous or progesterone-induced bleeding for 5 days. -However, Clomiphene can be started in 2nd, 3rd, 4th or 5th day of onset of menses. The outcome in terms of ovulation rate, luteal phase defect or pregnancy rate is optimum for day 5. -The pre-ovulatory LH surge is expected to occur 5-10 days after the last tablet (average 7 days) and couples are advised to have intercourse on alternate days for 1w starting 5day after the last Clomiphene tablet. Monitoring of therapy: to document ovulation (a) FSH, LH on day 5 and 9 (b) Estradiol on day 14 (c) Progesterone on day 23 ( > 3ng/ml) However these assays are expensive and time consuming (d) Cervical mucus score and postcoital test (PCT) on day 14 (score 8 or more with BBT indicate ovulation). (e) Ultrasound folliculometry daily from day 9 until ovulation (18 – 22mm followed by collapse and fluid in cul-de-sac). (f) Timed endometrial biopsy (document ovulation if endometrial response appropriate). (g) Basal body temperature (BBT); thermogenic shift. -If ovulation is not documented and pregnancy does not occur ® continue another cycle after increasing the dose by 50mg (maximum 250mg/day) till ovulation. -If ovulation documented and pregnancy does not occur ® continue the same dose for other cycle(s). - If menstrual bleeding does not occur within 4 weeks after the last clomiphene tablet and the cycle was ovulatory, a pelvic examination or pregnancy test is done. - Another treatment is withheld if overstimulation is noted (ovarian cyst). - Once an ovulatory dose is reached, treatment should be continued on a regular basis until: 1- Conception occur 2- Other infertility factors are discovered which would prevent preg. 3- Serious side effects occurred 4- The couple wishes to discontinue therapy NB. However, because only 5% of all couples conceive after 6months of therapy, empiric use of other modalities should be considered at that time. - Another treatment cycle begins when: 1- Return of BBT to normal. 2- Intensity and duration of last menses is normal. 3- No signs and symptoms of ovarian enlargement. 4- Rule out preg. by HCG assay. Of all patients who conceive during therapy, 75% of them will do so within the first 3 ovulatory cycles. [2] Incremental or extended regimen: -For patients who did not respond to conventional C.C. therapy larger doses of Clomiphene are used; 50 mg for 5days then increase dose every 5 days by 50mg but maximum dose never exceed 250mg/day. -The treatment period of more than 3weeks does not improve the result. During therapy, monitoring of E2 and U/S until the largest diameter reaches 18-19mm when HCG is injected. [3] Combined Clomiphene therapy: - Used in cases of Clomiphene failure. - The combinations include the following: (A). Clomiphene + human chorionic gonadotropin (HCG): Patients who fail to ovulate with CC alone may ovulate after injection of HCG 5-7 days after CC. Idea: - 80% of anovulatory patients respond to cc by folliculogenesis, endogenous LH peak and ovulation. - 20% fail to ovulate by demonstration of persistent follicles by means of U/S but will do so after 35hr. after injection of HCG 10,000 I.U. -When 100mg Clomiphene fail to induce ovulation, inject 5000-10,000 IU 7 days after the last dose of cc this is followed by another injection 5 days later to stimulate the function of corpus luteum (CL). -Proper timing best with U/S folliculometry is important because HCG when given before follicular maturation favor atresia and inhibition of ovulation. A dose of 5000 I.U is usually sufficient and larger dose increase the risk of hyper-stimulation and multiple pregnancy. -The couple is advised to have intercourse in the same day of injection and in the following 2 days. (B) Clomiphene and HMG: (sequential fashion) -Clomiphene increase the reactivity of the ovary to HMG. This reduce the dose and duration of treatment. The dose of HMG is decreased by 50%. Begin by CC 50mg – 200mg/day for 5 days followed by HMG usually starting with 2 ampoules daily then the dose depend on urinary and serum E2. (C) Clomiphene + GnRH: 1- 100mg CC on days 5-9 plus, GnRH 0.6 – 1.2mg three times daily as nasal drops from day 11-14. 2- GnRH 25 mg 3 times daily on days 5-7 then 100mg CC on days 10-14. 3- GnRH 100 mg daily for 4weeks, followed by CC. (D) Clomiphene + Estrogen: -Estrogen increases the quantity and quality of cervical mucus. • Ethinyl estradiole 20-40 mg for 5 days after the last CC pill. • Estradiol benzoate 1mg for 7 days after 100mg cc • Sequential preparation: estrogen – progestogen; [2mg Estradiol valerate for 21 days & 50 mg Levonorgestrel for 10 days] gives some favorable results. (E) Clomiphene and Corticosteroids: -If there is androgen excess (androgen profile should be obtained), CC is effective if androgen excess is ovarian in origin, but if androgen excess is of adrenal or adrenal/ovarian origin, glucocorticoid should be given. 1- Continuos use: Dexamethzone 0.5mg started 2 weeks before inducing menses and continued while giving Clomiphene and until pregnancy test becomes positive. 2- Interval use: is better than continuos use CC on days 5-9 & dexamethazone on days 5-14 -The effect of glucocorticoid is attributed to its reduction of androgen of adrenal origin and consequently enhances the pituitary gonadotorpin release and ovarian follicle reactivity. (F) Clomiphene and Bromocriptine: -The suppression of prolactin increases the responsiveness of the hypothalamo-pituitary- ovarian axis to CC. -It may be due to direct effect on the ovary or secretion of GnRH and gonadtropin. N.B.: Obese patients has high level of endogenous estrogen (E1) and ¯ SHBG so needs larger dose of Clomiphene to compete with estrogen for hypothalamic receptors. The anti-fecundity effect of Clomiphene: [= disparity between ovulation and pregnancy] There is discrepancy between ovulation rate and pregnancy rate & this is due to the anti-estrogenic effect of CC which interfere with conception by: 1- Impeding ascent of sperm through the cx mucus by altering its quantity. 2- Inhibition of implantation of the blastocyst by interfering with the proper development of the endometrium. 3- Impairing implantation by direct action on fertilized ovum 4- It causes luteal phase defect by • Inadequate stimulation of the endomet. during luteal phase • Direct negative effect of the ovary • Improper development of the ovary Also Clomiphene may cause luteinized unruptured follicle. Results of CC therapy: 1- Ovulation rate 70% 2- Pregnancy rate 40% 3- Multiple pregnancy 8% 4- Congenital malformations are not increased. 5- Abortion rate high 30-40% due to CL insufficiency & antiestrogenic effect on the endometrium. Clomiphene citrate treatment in ovulatory women: • IVF • GIFT • IUI Ovulation is initiated with CC then followed by HMG or FSH then HCG Side effects of Clomiphene: (not dose related and occur with 50mg dose) 1- Vasomotor flushes. 2- Abdominal pain or distention. 3- Breast discomfort. 4- Nausea and vomiting. 5- Visual spots or flashes. 6- Ovarian hyperstimulation syndrome (OHSS): -There is mild but significant ovarian enlargement (14%). - Moderate & severe OHSS is rare. *If the patient is symptomatic, pelvic examination, intercourse and undue exercise should be avoided because the enlarged ovaries are very fragile *Ovarian enlargement regresses rapidly and rarely delays subsequent treatment cycle. 7- Multiple pregnancy (4-9%). 8- Luteal phase defect (LPD): - Due to direct effect on the ovary & endometrium. Also it may be caused by non-physiologic circulation of gonadotropins & E2. - Treatment by: • increasing dose of CC (i.e. CC causes LPD & is used in its treatment). • HCG & progesterone. 9- Abortion (30-40%); due to LPD. 10- Dysmucorrhea: CC fails to produce pre-ovulatory cervical mucus peak despite increased estrogen, due to increased sensitivity of the endocervical glands to the anti-estrogenic effect of CC. N.B.: There is no evidence that the effect of clomid is long lasting & the response is limited to that cycle in which the drug is used. Cyclofenil (Ondogyn) - Chemically related to CC. and is similar to CC in biologic activity. - It is weak estrogenic activity (1/1000). Mode of action: as CC (i.e. acts on hypothalamo – pituitary axis & on ovary). Indications: as Clomiphene Regimen: • 200mg 3 times daily for 5 starting on day 3 or 5 • It may be combined with HMG. And may be combined with bromocriptine Results: ovulation and pregnancy rates are less than with CC: • Ovulation rate 50% • Less multiple pregnancy. • Pregnancy rate 20%. Tamoxifen (Nolvadex) Non steroidal anti-estrogen, structurally related to CC. Advantages over CC: 1- Lack of anti-estrogenic side effects on cervical mucus. 2- Lack of hyper-stimulation syndrome. 3- Lower cost. Dose: 10mg/day for 5 days may up to 40mg/day Side effects: No toxicity but hot flushes are more with tamoxifen. Human Menopausal Gonadotropins -HMG are extracted from urine of postmenopausal women. -It has been in clinical use since 30 years. -It contains FSH and LH (75 or 150 IU of each) • HMG is available in 3 preparations FSH: LH with 1:1 ratio as in pregonal, Humegon FSH: LH with 3:1 ratio as in normegon Pure FSH as in metrodin This pure FSH contains negligible amount (< 1 IU) of LH and was initially developed as a product that might be used in conditions of LH excess such as polycystic ovaries. • A new preparation of genetically engineered recombinant FSH ( r FSH) is now available which has the advantage of being free from any extraneous proteins which are invariably present in most urinary extracted compounds Principles of gonadotropin therapy FSH LH Responsible for recruitment, selection growth and ripening of the dominant follicle • Final maturation of G. follicle • Ovulation • Formation of C.L Indications: (selection of patients): 1- Patients with hypothalamo-pituitary failure (WHO group I) 2- Patients with hypothalamo-pituitary dysfunction (WHO group II) who failed to conceive with C.C. Regimen -No fixed dose -HMG is given by I.M. injection and purified FSH by S.C injection . -The patient is started on day 2 of the cycle with 150 m daily and seen on cycle day 8 and every 1-3 days thereafter for monitoring. -Daily dose depend upon ovarian response. Monitoring of therapy Is done by: 1- Pelvic U/S for the size and no of follicles 2- Estrogen level: • Urinary and blood levels • Effect on cervical mucus The aim of monitoring 1- Assess the effective dose that causes ovarian response 2- Assess the length of time required for follicular maturation 3- Assess the appropriate time for induction with HCG 4- To ¯ the possibility of multiple pregnancy and ovarian hyperstimulation On the day of satisfactory follicular growth (Diameter 18-19mm) and acceptable E2 level ® HCG is given 5000 – 10,000 IU and the patient is instructed to have intercourse in the same day of injection and in the following 2 days The cycle is cancelled and the HCG is withheld and the couple advised to abstain from intercourse if: 1- More than 3 dominant follicles are present 2- E2 level exceeded 2000ng/ml In order to avoid multiple pregnancy and hyperstimulation syndrome. N.B.: Group II: more sensitive to HMG than group I ® more cancelled cycles. Less response to HMG than group I. Results: • Ovulation rate 90% • Preg. rate 50-70% preg. is less in group II due to age factor (advanced age) premature luteinization) • Multiple preg 10-30% • Abortion rate 20% Side effects 1- Hyperstimulation syndrome 2- Multiple preg. 3- Local reaction at the injection site perhaps due to prot. content (patients are switched to purified preparation FSH). Combination HMG therapy [1] Clomiphene citrate + HMG CC 100mg from day 2-6 for follicular recruitment then followed by HMG daily or on alternate days. This ¯ the amount of HMG need However, this regimen is only of use for anovulatory patients of group II who have endogenous gonadotropins and hence endogenous E2 [2] GnRH agonist and HMG combination Principle • Group I patients (hypogonadotropic) have better response and outcome than group II patients (normogonadotropic) • Patients with elevated levels of LH as in PCO are particularly prone to lower success rate after HMG and higher abortion rate this led to the suggestion that converting group II patients into a hypogonadotropic state may improve the results. This is done by giving Gn-Rh agonist before starting HMG, the so called medical menopause, induced by down regulation caused by the agonist. Regimen Complete down regulation (serum estradiol < 50 pgm/ml) takes about 3w if started in the follicular phase and 10-14 days if started in midluteal phase as flare up is accentuated by the natural rise in FSH if the agonist is given in the follicular phase, where the action of the agonist is prolonged. Following downregulation, HMG is started in the usual way but patients may need higher doses with higher costs N.B.: Down regulation may persist for some time after stoppage of the agonist. So, luteal phase support should be given to replace the ¯ed endogenous LH we can give: • HCG 2000 u twice in the 3rd and 6th day following ovulating dose • Progesterone I.M. (50-100mg daily) • Progesterone supp. (100-200mg daily) for 14 days HCG has the Advantage of less frequent administration but it has the disadvantage of - risk of hyperstimulation - Give false +ve preg. test [3] HMG co-treatment with growth hormone This co-treatment with GH serum and follicular fluid IGF, level when compared with standard HMG. Regimen without GH. Although this regimen ¯ amount of HMG needed, it does not appear to improve the clinical response in normal women the ultimate role for cotreatment may be in women who have previously responded very poorly to standard HMG regimen Gonadotropin – Releasing hormone GnRH is a 10 aa protein synthesized and released from the arcuate nucleus of the hypothalamus and released in discrete secretory bursts into the portal circulation and acts to release both LH and FSH . When delivered in pulses, exogenous GnRH acts in physiologic manner to stimulate gonadotropin release. In contrast, when delivered in a continuous fashion, GnRH ttt results in downregulation of pit. Gonadotropin release and suppression of gonadal function Indications: Used in patients lacking endogenous GTH but having intact pit. gland . 1- Hypothalamic amenorrhea 2- Hypothalamic infertility 3- Also used in cases of resistant PCOD Regimen Pulsatile GnRH is delivered by means of small infusion pump that can be programmed to deliver small bolus (1-20 mg) every 60-90 minutes . It can be delivered either subcutaneously or I.V. however the I.V. route of administration appears to be more effective Ovulation usually occurs after 14 days of ttt (10-21 days) when the leading follicle is 14mm or over, the women is instructed to use the urinary LH kit and when the surge is detected, the couple is advised to have intercourse on the following 3 days. Luteal support is needed and done either by: • Continuing GnRH • or using HCG • or Progesterone Advantages 1- More physiologic and safer then GTH 2- Used alone or with cc or HMG 3- Less OHSS. 4- Less multiple preg. Results • Group I : 30% conception rate/cycle and 5% multiple preg. • Group II: lower preg. rate Side effect 1- Formation of anti GnRH antibodies 2- Allergic reaction 3- Infection at catheter site 4- Pump failure Bromocriptine 2 bromo a ergocriptine is a semisynthetic product derived from the family of ergot alkaloids . Indications 1) Anovulation in cases of : • Pit. microadenoma • Hypothyroidism ( TSH ) • Following steroid contraceptives • Following drugs • Following electroconvulsive therapy 2) Inhibition of postpartum lactation 3) Acromegaly 4) Parkinsonism Action : ¯ RRL (dopaminergic on hypoth – direct on pit) Dose : 2.5mg twice daily for 21 days with building of the dose Side effects 1- Nausea and dyspepsia 2- Constipation 3- Postural hypotension 4- Nasal congestion 5- Muscle cramps Superovulation: Induction of multiple ovulation in patients who are ovulatory Used in: - Long unexplained infertility with IUI - Assisted reproductive technology ART (IVF – GIFT) * Unexplained infertility Induction of ovulation is used as an empirical therapy either alone or with IUI CC ® 3-5% preg. rate/ cycle And higher with IUI combination HMG ® 18-15% preg. rate/cycle * IVF – GIFT Superovulation is used as preg. rate is related to the no. of embryos replaced Surgical induction of ovulation [1] Multiple ovarian puncture: ovarian drilling: Laparoscopic multiple ovarian puncture (15-20 sites) using cautery diathermy or laser vaporization lead to a response similar to that with HMG in CC resistant PCO patient Also, patients who don’t ovulate spontaneously following the procedure become more responsive to medical therapy and up to 60% of them will ovulate when cc is recommended The advantage of ovarian puncture over HMG are 1- One step ttt 2- No monitoring is required 3- The risk of iatrogenic multiple preg. is eliminated Disadvantages 1- Operative procedure with general anaethesia 2- Postoperative adhesions: however it is less than ov. wedge resection which is now obsolete Mechanism: removing part of hormone producing ovarian tissue ® ¯ androgen and inhibin levels ® ¯ FSH, LH ¯ and resumption of spont. ovulation The choice between ovarian puncture and HMG in cc – resistant patients will depend on: 1- Local availability of facilities 2- Experience 3- Patent wishes [2] Ovarian wedge resection: Removing part of the ovary now obsolete as it ® post op. Adhesions

Diagnosis of Pregnancy

2007-12-31T16:36:00.000-08:00

(I) THE FIRST TRIMESTER (0-12 WEEKS) (A) Symptoms: 1.Amenorrhoea : sudden cessation of a previously regular menstruation is the most common symptom denoting pregnancy. However, pregnancy may occur during lactational amenorrhoea. On the other hand, bleeding may occur early in pregnancy as in threatened abortion. Slight bleeding may occur also at the expected time of menstruation in the first 12 weeks of pregnancy but never afterwards due to separation of parts of the decidua vera. 2.Morning sickness: nausea with or without vomiting commences in the morning. It usually appears about 6 weeks after onset of the last menstrual period and usually disappears 6-12 weeks later. 3.Frequency of micturition: due to congestion and pressure on the bladder and disappear after the first trimester to reappear again near the end of pregnancy when the foetal head descends into the maternal pelvis. 4.Breast 4. symptoms: as enlargement, sensation of fullness, tingling and tenderness. 5. Appetite changes and sleepiness. (B) Signs: (I)Breast signs: 1. Increase in size and vascularity. 2. Increase pigmentation of the nipple and primary areola. 3. Appearance of the secondary areola. 4. Montgomery’s follicles. 5. Expression of colostrum. 6. Breast signs are diagnostic only in primigravidae. In multigravidae , it may be due to the previous pregnancies . (II) Uterine signs: 1. The uterus becomes enlarged, globular and soft. 2. Palmer's sign: uterine contractions felt during bimanual examination. 3. Hegar's sign: during bimanual examination, the two fingers in the anterior fornix can be approximated to fingers of the abdominal hand behind the uterus due to softening of the lower part of the uterus and its emptiness. This sign can be elicited between 6-10weeks but not after as the growing conception will fill the whole uterine cavity. (III) Cervix : soft, hypertrophied and violet. (IV) Vagina: violet, moist, warm with increased acidity. (C) Investigations: (I) Pregnancy tests: These depend on presence of human chorionic gonadotrophin (hCG) in maternal serum and urine. 1- Urine pregnancy tests : i- Agglutination Test: Latex particles, or sheep erythrocyte (tube) coated with anti-hCG. ii- Agglutination Inhibition Tests iii- Dip stick Rapid and simple tests based on enzyme-labelled monoclonal antibodies assay can detect low level of hCG in urine. Causes of false positive results: 1. Proteinuria. 2. Haematuria. 3. At time of ovulation (cross reaction with LH). 4. HCG injection for infertility treatment within the previous 30 days. 5. Thyrotoxicosis (high TSH). 6. Premature menopause (high LH & FSH). 7. Early days after delivery or abortion. 8. Trophoblastic diseases. 9. hCG secreting tumours. Causes of false negative results: 1. Missed abortion. 2. Ectopic pregnancy. 3. Too early pregnancy. 4. Urine stored too long in room temperature. 5. Interfering medications. 2- Serum pregnancy tests: (i) Radioimmunoassay of b -subunit of hCG. (ii) Radio receptor assay. 3- Enzyme- linked immunosorbent assay (ELISA). can be used for urine and serum. The pregnancy test becomes negative about: l one week after labour, l 2 weeks after abortion, and l 4 weeks after evacuation of vesicular mole. Uses of pregnancy test: 1. Diagnosis of pregnancy. 2. Diagnosis of foetal death. 3. Diagnosis of ectopic pregnancy. 4. Diagnosis and follow up of gestational trophoblastic diseases. (II) Ultrasonography: Gestational sac can be detected after 4-5 weeks of amenorrhoea. Foetal heart pulsation can be detected as early as 7 weeks. (II) THE SECOND TRIMESTER (13-28 WEEKS) (A) Symptoms: 1. Amenorrhoea. 2. Morning sickness and urinary symptoms decrease. 3.Quickening : The first sensation of the foetal movement by the mother, occurs at 18-20 weeks in primigravida and at 16-18 weeks in multiparas. 4. Abdominal enlargement. (B) Signs: 1. Breast signs: become more manifested. 2. Skin signs : Cloasma, linea nigra and striae gravidarum appear. 3. Uterine signs: i-The uterus is felt abdominally. ii-Braxton Hick's contractions: intermittent painless contractions can be felt by abdominal examination. 4-Foetal signs: i- Internal ballottement: can be elicited at 16 weeks by a push to the foetal parts with the two fingers through the anterior fornix. ii- External ballottement: can be elicited at 20 weeks by a push to the foetal parts with one hand abdominally and the other hand receiving the impulse. iii- Palpation of foetal parts and movement: by the obstetrician at 20 weeks. iv- Foetal heart sound: can be auscultated at 20-24 weeks by the Pinard's stethoscope. v- Umbilical (funic) souffle: A murmur with the same rate of FHS due to rush of blood in the umbilical arteries. It is occasionally detected when a loop of the cord lies below the stethoscope. (C) Investigations in doubtful cases. 1. Pregnancy tests. 2. Ultrasonography. X-ray: It shows the foetal skeleton starting from the 16th week of pregnancy. It has 3.been replaced by ultrasonography due to the following hazards: i- Teratogenic effects particularly before 10 weeks. ii- Chromosomal changes in the foetal gonads leading to genetic disorders in the following generations. iii- Subsequent leukaemia in childhood. (III) THE THIRD TRIMESTER (29-40 WEEKS) All signs of pregnancy become more evident. Pregnancy tests are positive, sonar and X-ray are diagnostic. Sure Signs of Pregnancy: 1. Palpation of foetal parts. 2. Palpation of foetal movements. 3. Auscultation of foetal heart sounds. 4. The occasional auscultation of the umbilical (funic) souffle. 5. Detection of foetal skeleton by X-ray. 6. Ultrasonographic detection of foetal parts, movements and /or heart movements. Differential Diagnosis of Pregnancy: (A) Early pregnancy: (I) Causes of amenorrhoea. (II) Causes of symmetrically enlarged uterus: 1- Myoma. 2- Adenomyosis. 3- Pyometra. 4- Haematometra. 5-Metropathia haemorrhagica. (III) Pelvi-abdominal swellings: 1- Ovarian swellings. 2- Tubal swellings. 3- Pelvic haematocele. 4- Full bladder. (B) Late pregnancy: 1- Myomas. 2- Ovarian neoplasm. 3- Ascitis. 4- Pseudocyesis. 5- Other causes of pelvi-abdominal mass.

diagnostic laparoscopy , DR. Alaa Mosbah ,M.D OBS&GYN

2007-12-29T15:19:00.000-08:00

Introduction : Diagnostic laparoscopy is indicated in any situation when inspection of the abdomen will help establish a diagnosis and to define subsequent treatment. Patients that are to undergo endoscopic surgery should have a complete pre-operative evaluation prior to scheduling the surgery. The preoperative evaluation often includes laboratory and echographic exams in order to determine the clear indication for surgery. The following text describes the usual operating room set up and procedures for a diagnostic laparoscopy. Positioning of the patient / Anesthesia : The patient is transported to the operating room and general anesthesia performed. Following this, place the patient in modified dorsolithotomy position. This position is most practical for operating and allows easy mobilization of the uterus as well as access for hysteroscopy. Some operating tables may be repositioned intraoperatively, allowing the surgeon to change the angle of the legs. Special care should be taken to avoid nerve injury by mal positioning the patient, particularly along the popliteal fossa and brachial plexus. If any part of the patient is in contact with a metal object, she may be at risk of electrosurgical burns. General anesthesia is preferred for laparoscopy as it provides adequate muscle relaxation and assisted respiration particularly as the patient is in Trendelenburg position. Disinfect the vagina, paying special attention to the umbilicus. Empty the urinary bladder. Some surgeons prefer to leave a Foley catheter in place throughout the procedure. We maintain continuous Foley drainage in selected operations, such as a Burch procedure or hysterectomy. These procedures often require longer operating times and are more likely to result in injury to the bladder. For simpler procedures, we simply empty the bladder at the beginning of the operation. Place a tenaculum on the cervix and insert the uterine cannula. This cannula will allow the uterus to be manipulated and should have the capability to perform chromopertubation. Position of the operating team and equipment : The surgeon must be familiar with the mechanics and operation of each piece of equipment. Prior to anesthetizing the patient the operating team must check that the insufflator is functioning and has an adequate supply of gas, the light source is functioning, and the video equipment is in working order. This will prevent avoidable malfunctions which may result in serious complications and surgical delays. Mobile racks for camera and TV monitor, video-recorder, light-source and insufflator are available and help organize the operating room equipment. The surgeon stands on the left side of the patient, the nurse next to him and the assistant on the opposite side. From here, the surgeon is able to continuously monitor all of the equipment (insufflator, light-source, irrigation system, electric generator). Alternatively, the surgeon and his assistant may both stand to the left of the patient with the video monitor on the opposite side. The TV monitor (1 or 2) should be located so that each member of the operating team may follow the procedure. If there is only one monitor, it is best placed at the feet of the patient. Instruments : To perform a basic diagnostic laparoscopy one must have equipment to create a pneumoperitoneum, light source, video, a cable and telescope, and instruments to manipulate the uterus and adnexea. Distention media : The peritoneal cavity is a potential space which only allows visualization of the pelvic organs with adequate distention. The gases commonly used for laparoscopy are carbon dioxide (CO2) and nitrous oxide (NO2). Carbon dioxide is more readily absorbed, non-toxic, and does not support combustion. The only serious risk is that of hypercarbia which only develops at an absorption rate of greater than 100ml/min. For this reason, patients are generally hyperventilated during surgery. The intra-abdominal pressure should not rise above 15mm Hg, higher pressures will increase the absorption rate and risk of gas embolism. Carbon dioxide embolism has been reported at a rate of 1:10,000 to 1:60,000. Early diagnosis may be made by auscultating the characteristic "mill wheel" murmur. Nitrogen is less readily absorbed by body fluids and may lead to subphrenic discomfort. It is also not flammable and does not support combustion. The risk of embolism is similar to that for carbon dioxide. The surgeon must also choose between a large array of gas insufflating systems, both mechanical and electronic. The electronic system maintains the intra-peritoneal pressure at a constant pre set level. Thus the surgeon may perform the procedure without having to constantly monitor the pressures and volumes. Basic instruments · Veress' needle. · One 10-12 mm trocar to pass the laparoscope. · Two to three 5 mm trocars (through which to pass instruments). · One 10-12 mm trocar for larger instruments. · Uterine manipulator. · Laparoscopic scissors. · Atraumatic grasping forceps. · Smooth forceps designed for grasping the tubes. · Bipolar electrocoagulator. · Mobilizer (if possible with graduations). · High flow irrigation-aspiration system. · CO2 laser coupler (optional) and adequate back-stop device. Instruments for more advanced procedures · Unipolar electrocoagulator. · Two needle holders. · Clip forceps. Minimal equipment required to perform laparoscopy · High luminosity laparoscope with 10 mm trocar. · 400 W light source. · CO2 insufflator automatically regulated for pressure and flow rate. It should enable a high rate of CO2 (at least 6 l/min.). · Video camera and screen. · Irrigation-aspiration system with high flow. · Equipment for bipolar and unipolar electrosurgery. · Endoscopic instruments: scissors, 2 forceps (one atraumatic), bipolar coagulating forceps, clip forceps. · Three secondary trocars 5 mm. · One secondary trocar 10-12 mm. Operating Procedure Pneumoperitoneum Insert the Veress'' needle through a vertical, 1 cm intraumbilical incision. In general a 7cm length is sufficient although a 15cm needle is also available for very obese patients. Prior to insertion the spring mechanism is checked on the needle to help avoid visceral puncture. At this intraumbilical site the abdominal wall is thinnest with no intervening fat and the peritoneum closely underlying the fascia. To insert the Veress' needle the abdominal wall is lifted with one hand and the needle passed through the incision. Intraperitoneal placement is confirmed by injecting 5 ml of saline through the Veress' needle. The solution should flow without resistance and should not return when trying to aspirate. Next, deposit a drop of saline on the external os of the needle. It should fall into the needle hub when negative pressure is created by lifting the anterior abdominal wall. Next, insuffltate carbon dioxide at a low flow rate of 2 liters/minute, allowing the patient to adapt gradually to the pneumoperitoneum. When a pressure of 14 mm of mercury is obtained, place the machine should on automatic flow in order to maintain this pressure. Most machines will automatically adjust the flow rate (usually at a maximum flow of 6 l/min.). In rare cases adhesions or extreme obesity may limit the surgeons ability to use the Veress' needle intraumbilically. If these situations arise, the surgeon may either perform and open laparoscopy or insert the Veress' needle through the posterior vaginal fornix. Placement of trocars After attaining a sufficient pneumoperitoneum, place one 10-12 mm umbilical trocar through the Veress' needle incision. The distal tip of the trocar must be sharp. During insertion of the trocar, compress the upper abdominal wall with the free hand to make the lower abdominal wall tense, giving a firm platform against which to insert the trocar and cannula. Direct the trocar towards the pelvis to avoid injury to major vessels.The trocar should pierce the peritoneal cavity as high as possible to assure a panoramic view. Occasionally, the trocar must be placed above the umbilicus (this must be done under direct laparoscopic visualization through an initial umbilical site). Pass the laparoscope through the trocar sleeve and immediately confirm correct intraperitoneal placement. Standard diagnostic laparoscopes vary in diameter from 5-11mm. The 5mm laparoscope is adequate for inspection but is not sufficient for more complex procedures. The light source is also an essential element. In general the standard 150 watt light source is sufficient only for diagnostic laparoscopy. Complex procedures requires a more powerful light (250-400 watt halogen lamp). Next, place the patient in Trendelenburg position in order to allow for the gravitational effect to move the bowel out of the pelvic cavity. Then insert two or three 5 mm trocars under direct vision at ancillary puncture sites for instruments. These secondary trocars are inserted suprapubically, taking care to avoid the epigastric vessels laterally and the bladder medially. While inserting these ancillary trocars, angle toward the pouch of Douglas while the uterus is held in ante-version. Secondary 8-12 mm, rather than 5 mm trocars, may be useful for some procedures. Collaboration with the anesthetist The pressure of the pneumoperitoneum and the extent of the Trendelenburg position must be adapted to the hemodynamic and respiratory demands of each individual patient. Continued communication and collaboration with the anesthetist throughout the procedure is mandatory. This is extremely important because it may be necessary to reduce the Trendelenburg position, lower the intraabdominal pressure, or even convert to laparotomy at any time during the procedure. Inspection of the abdomen and pelvis It is important to approach the evaluation of the pelvis in a systematic and thorough manner. Upper abdomen Begin the inspection with the upper abdomen. Rotate the laparoscope to view the caecum and appendix, using a probe if necessary. Examine the course of the ascending colon to the hepatic flexure. Examine the right lobe of the liver and gall bladder. Sub-diaphragmatic adhesions may indicate prior pelvic inflammatory disease (Fitz-Hugh-Curtis Syndrome). Avoiding the ligamentum falciparum, the laparoscope is rotated to view the left lobe of the liver and stomach. And finally, rotate the laparoscope around to view the descending colon. Uterus, fallopian tubes Next, examine the pelvic organs starting with the uterus. Note its shape, size, position, and mobility. Noting these characteristics may guide in making the diagnosis of either uterine myomas, adenomyosis, or aberrant Mullerian duct fusion. Look at the anterior cul-de-sac and round ligaments for evidence of endometriosis. Inspect the fallopian tubes entirely with the aid of a probe or forceps. Follow the length of the tube looking for evidence of prior infection or endometriosis. Note the thickness of the wall and mobility of the ampulla. Note all peritubal adhesions, or hydrosalpinxes. In cases of infertility, after completing the inspection of the pelvic organs, proceed with chromopertubation to evaluate tubal patency (see below). A more sophisticated technique for evaluating the fallopian tube is salpingoscopy, for a more detailed examination of the tubal mucosa. Ovaries Complete the inspection of one round ligament, fallopian tube and ovary before continuing on with the opposite side. The ovary is manipulated with a probe or forceps in order to examine its entire surface and evaluate its mobility. Again note any signs of endometriosis or adhesion formation. Uterosacral ligaments Finally, examine both uterosacral ligaments and the pouch of Douglas. For a clear view it may be necessary to aspirate the free fluid. Again, this is a common site for endometriosis and adhesion formation. Chromopertubation Chromopertubation is a basic element of a diagnostic laparoscopy for infertility to assess tubal patency. Inject a dilute solution of methylene blue (1:20 solution) through the cervical cannula. Follow the passage of the liquid through the fallopian tube a verify passage of dye through the fimbria. Closure of abdominal incisions After completing the evaluation of the pelvis or endoscopic procedure, in more advanced cases, the laparoscopy is completed as follows. Remove the ancillary ports, examining the incisions internally for bleeding. Then remove the laparoscope and allow the intra-abdominal gas to escape through the sleeve. Take the patient out of Trendelenburg position in order to optimize the decompression of the pneumoperitoneum. Close the small lower abdominal incisions with non-absorbable suture to be removed in 5-7 days. It is wise to place an absorbable fascial suture in the larger >10 mm umbilical incisions followed by a cutaneous non-absorbable suture. Indication for diagnostic laparoscopy 1. Infertility. This is one of the most common indications for diagnostic laparoscopy. A variety of pertinent diagnosis my be determined at laparoscopy these include: adhesions- evidence of prior pelvic infection Structural abnormalities of the uterus, including congenital developmental abnormalities (such as a bicornuate or unicornuate uterus), and fibroids. Endometriosis Fallopian tube occlusion. A diagnostic laparoscopy may clarify the diagnosis and treatment prior to reconstructive surgery. 2. Chronic pelvic pain. The systematic evaluation of the abdomen and pelvis provided by this relatively benign surgery can provide key diagnostic information in the evaluation of a woman with chronic pelvic pain. In particular, the laparoscopy my reveal adhesions or endometriosis not visible by other diagnostic techniques. 3. Chronic Pelvic Inflammatory Disease (PID). It is essential to carefully inspect the liver and diaphragm when considering this diagnosis. 4. Endometriosis. The appearance of endometriosis varies and it is important that the laparoscopist is aware of the spectrum that one might see during a laparoscopy. Early endometriosis may appear as clear vesicles before progressing to red plaques and eventually black plaques. An intra-operative biopsy will confirm the diagnosis. Indications for an urgent diagnostic laparoscopy 1. Acute Pelvic Inflammatory Disease. If the diagnosis cannot be clearly made by the clinical presentation, a diagnostic laparoscopy may be useful the confirm this diagnosis. 2. Ectopic Pregnancy. Today, a laparoscopy for ectopic pregnancy often not only provides the diagnosis, but also allows for the immediate surgical treatment. 3. Torsion of a tube or ovary. This is often a difficult diagnosis to establish. Echography rarely provides a clear diagnosis. Again laparoscopy can both diagnose and treat this condition. Contra-indications to laparoscopy Absolute contraindications A large abdominal mass such as a fibroid or ovarian cyst An irreducible external hernia. A laparoscopy in this situation could enlarge the hernia sac and make the condition worse. Hypovolemic shock. Medical problems such as cardio-respiratory failure, obstructive airway disease, or a recent myocardial infarction. An inexperienced surgeon or a lack of proper equipment. Relative contraindications Multiple prior abdominal incisions Morbid obesity. The difficulty in creating the pneumoperitoneum may be overcome by introducing the Veress'' needle through the posterior vaginal fornix. Local skin infections may require that the locations for the abdominal incisions be altered. Generalized peritonitis Intestinal obstruction or ileus. This is a relative contra-indication because of the increased risk of bowel perforation upon entry of the Veress'' needle or trocars. Coincidental medical conditions such as ischemic heart disease, blood dyscrasias or coagulopathies. Ancillary instruments Forceps A wide range of forceps are available for laparoscopic use. It is less important to have a wide range of forceps than to have perfected the use of one or two. It is important to have at least one of each, an atraumatic forceps and a forceps with teeth for stronger traction. Scissors Scissors which pass through a 5 mm port are sufficient for general dissection. Microscissors may be preferable for adhesiolysis close to the fimbriae or in other delicate locations. It is important that one of the blades is fixed to allow gentle traction to be applied before cutting. Laser The laser will precisely destroy tissue. Both rigid and flexible systems are available. Sutures and clips Sutures Techniques for tying and applying will be discussed in later chapters. In general there are two suturing techniques that are used in laparoscopic surgery. In the first the knot is tied within the abdomen. In the second the knot is tied extracorporeally. Suturing equipment includes: a needle holder, grasping forceps, knot pusher, and needles which can be passed through a 5 mm port. Ligatures Ligatures are most easily applied by using a prepacked modified Roeder loop introduced through the standard 5mm cannula. Clips and Staples Clips and staples my be invaluable for obtaining hemostasis. Instruments are also available which will apply up to three rows of staples on either side of the line where an incision is to be made. A blade contained within the instrument makes the incision. These instruments are disposable and expensive. Although a wide range of equipment exists for performing laparoscopic surgery, it is important to master the use of the basic instruments and appreciate their full potential before expanding to the use of more complicated devices.

Contracted pelvis and cephalopelvic disproportion

2007-12-28T09:36:00.000-08:00

Contracted pelvis and cephaopelvic disproportion Definition: a contracted pelvis is a pelvis whose shape and size are sufficiently abnormal to cause difficulty in vaginal delivery of normal (average size body ) This may occurs when : 1- One or more of the pelvic diameters is reduced enough to cause dystochia (Obstetric definition) 2- One or more of the pelvic diameters is reduced below the average by on or more centimeters (antatomical definition) CPD: or fetopelvic disproportion in presentations other than cephalic) can arise from either : 1- Diminished pelvic capacity 2- Excessive fetal size or abnormal fetal development Or more usually a combination of both In contemporary obstetric practice dystochia literally means difficult labour and is characterized by abnormal progress by labour Generally this can occurs as a result of 3 distinct causes that may exist singly in combination 1- Abnormalities in the power: a. Uterine contractility (uterine dysfunction in significantly strong or inappropriately coordinated to affect the dilate the cervix = dysfunctional labour) b. Inadequately voluntary maternal expulsive effort during the 2nd stage of labour 2- Abnormalities in the passenger: a. Abnormal presentation and / or position b. Abnormal fetal development (congenitally malformed baby) 3- Abnormalities in the passage : a. Abnormalities in size or shape of the bony pelvis (contracted pelvis) b. Abnormalities of soft tissues of the reproduction tract and other pelvic organs (soft tissue obstruction) Classification of contracted pelvis A - Pelvic inlet contraction : when the shortest onteroposterioer diameter of the inlet < 10cm or when the greatest transverse diameter is < 12cm or when the brim idea Anteroposterior diameter x 100) is < 85 Transverse diameter The Anteroposterior diameter of the pelvic inlet is commonly approximated by manually measuring the diagonal conjugate which is about 1.5cm greater therefore inlet contraction id dysnied as a diagonal conjugate < 11.5cm Contracted inlet can cause: 1- delayed desert of the fetal head or primigravida until after the onset of labour if at all. (usually the head is engaging or already engaged in the least 2 weeks of pregnancy in normal nullipara before the onset of labour 2- face and shoulder presentation (3 times more frequent) 3- cord prolpase (4-6 times more frequent) NB: contracted pelvis has no relation to breach presentation 4- in contracted pelvis, rupture of membranes the absnce of preserve of the head against the cervix and the lower uterine segment predisposes to less effective uterine contractions (inertia) B- Midpelvic contraction: 1- More common that inlet contraction 2- It usually causes transverse arrest of the head resulting in difficulty or failed midforceps and increased CS rate 3- Average midpelvic measurements are: a. Transverse (interspinous) = 10.5cm b. Anteroposterior 9from the lower border of the symphysis pubis to the junction of 54- ) = 11.5cm posterioer sagittal (from midpoint of interspinous line namely the previous point of the sacrum to the junction of S4-S5= 5cm c. The definition of midpelvic contraction is not prescise as in inlet contraction d. Midpelvic is called contracted of the sum of interspinous and posterior sagittal < 13.5cm (normally 15.5cm) e. Although these is no precise manual method for measuring medpelvic diameters its suggested to be contracted if : i. The spines are prominent (under projection) ii. The pelvic side walls are convergent iii. The sacroscietic notch is narrow normally the sacrospinopus ligament should measure at least 2 fingers breath (if < 2 fingers the notch is suggested to be narrow) iv. The intertuberous diameter is narrow. Normally the relation between ineter spinous and inter tuberous diameter is constant. However a normal intertuberous interspinous diameter C- Pelvic outlet contraction: Usually defined as an interischil tuberous diameter < 8cm with consequent narrow subpubic angle Its incidence is usually about 1% Outlet contraction without concomitant midplane contraction is rare Diminution of the intertuberous diameter with consequent narrowing of the anterior saggital triangle of the outlet forces the fetal head posterioely resulting in increased incidence of perineal lacerations A contracted outlet may constitute dystocia not so much by itself as through the after associated midpelvic contraction D- Combination of both inlet and outlet contractions generally contracted pelvis (just-minor pelvis) Etiology of pelvic contraction I-Congenital : 1- Naegel's pelvis = asymmetric or obliquely contracted pelvis due to absence of one of the sacrum 2- Robert's pelvis: transversly contracted pelvis due to absence of 2 sacral 3- High assimilation pelvis: the sacrum is made of 6 dused segments 4- Low assimilation pelvis: the sacrum is made of 4 fused segments 5- Split pelvis: absent pubic bone usually associated with extopia vesica 6- Dislocation of the hip joint II- Acquired: 1- Metabolic disease : a. Rickets in which the following types of pelvis are found: i. Flat rachitic pelvis ii. Generally contracted rachitic pelvis iii. Generally contracted flat rachitic pelvis (rachitic stigmata on top of generally contracted pelvis) b. Osteomalcia : causing trirdiate or rosette shaped or peaked pelvis 2- Vertebral column disease : a. kyphasis b. scoliosis c. spondylolthesis 3- Lower limb disease : a. Resulting inmissing or shortening of one limb during childhood or adolescence before ossification of the pelvis b. This results in pelvis obliquity (coxolgic pelvis) froctuers (accidents inflammatory TB ostcomylitis) 4- Disease of the pelvic bones: a. Fractures b. Tumours of pelvic bones MECHANISM OF LABOUR IN SOME COMMON TYPES OF CONTRACTED PELVIS I- Generally contracted pelvic (justo minor) Features: 1- Commonest type of contracted pelvic usually in short women 2- It shows gynaecoid chometers but these is propotional dimination of all diameters with funneling in 20% of cases Mechanism of labour: 1- Delayed descent and engagement 2- Marked moulding and formation 3- Extreme felxsion of the head (roader obliquity) 4- Deep transverse arrest (failure of long anterior rotation ) in OP if associated with outlet contracted (20% of cases) NB: Cord proplase is rare due to narrow spaces and fitting of the presenting parts at the pelvic brim II- Flat rachitic pelvis: Features : 1- Forward of the sacral promontory resulting in reduction of the true conjugate 2- Hyperplasia at the junction between sacral vertebra may result in false promontory 3- Divergence of the ischial tubersity and aceteabulum resulting in wide subpubic angle and increased bituveros diameter 4- Contractions occur only at the level of the inlet so if the head possed the inlet there will be more difficulty (single dimensionally contracted pelvis) Mechanism of labour: 1- Head engagement in the transverse diameter 2- Asynclitism with anterioer porful bone presentment 3- Lateral displacement of the head to bring the short biterporal diameter in the short true conjugate 4- Deflection occurs with descent 5- With further descent both asynclitism and deflection are corrected 6- rotation (2/3 circles) interiorly because the outlet is wide III- Simple flat pelvis: Features : reduced AP diameter of the inlet cavirty and outlet without rachitic stigmata Mechanism of labour: 1- At the pelvis inlet: like flat rachitic pelvis 2- At the outlet there will be: a. Extreme flexsion and moulding (reduced AP diameter at the outlet) b. Increased incidence of perineal lacerations due to backwards dispalecment of the fetal head (narrow) subpubic angle ) c. In OP: deep transverse arrest or face to pubis (short posterior rotation) IV – Funnel pelvis (contracted outlet) Causes: 1- 20% if generally contracted pelvis 2- Android pelvis 3- High assimilation pelvis 4- Spreadylo lithesis: sublaxation of the 5the labour in front of the sacral promontory resulting in downwards and backward displacement of the sacrum deep, cavity and increased inclination of the plane of the inlet and some cases may show outlet contraction resulting in funneling 5- Lunbodacrel kyphasis 6- Obliquely contracted pelvis 7- Some cases of richets & asteomalacia Mechanism of labour : 1- Extreme flexion & moulding at the outlet 2- Backwards displacement of the head due to narrow subpubic angle resulting in increased incidence of perineal laceration 3- In OP: deep transverse arrest or face to pubis Diagnosis of CP I- History 1- post history of trauma or disease that cause pelvic contractions eg Rickets osteamalacia, poliomyelitis TB fractures or thopedic surgery 2- Bad obstetric history Malpresentation repeated fetal losses and operative deliveries II- Examination: 1- General: a. Short stature b. Rachitic manifestation c. Abnormal gait (eg limbing waddling) 2- Abdominal (during pregnancy) a. Pendulous abdomen b. Scar of CS c. Malpresntation face brow shoulder presentation d. Non engaged head in last 2w of pregnancy in primigravida III- Investigation: 1- Pelvimetry : a. Clinical pelvimetry b. MRI c. Radiographic pelvimetry (x-ray CT) d. Sonographic cephalometry Cephalopelvic disproportion test Pelvimetry I- Clinical Pelvimetry 1- External Pelvimetry of the inlet 2- External Pelvimetry of the outlet - Subpubic angle (normalley 90) - measured by fingers or morris disc - normally the angle can accommodate two fingers near the apex - Bituberous diameter (normally 11Cm) : - measured by pushing the knuckles of the 4 fingers or closed first between ischil tuberosities or by pelvimeter (Thom's crossing pelvimeter) - normally this diameter can accommodates the closed first or the knuckles of the 4 fingers easily 3- Anteroposterior diameter of the outlet normally 13cm - Measured by 2 fingers in the vagina by the same method used fordiagnal conjugate 4- Posterior and anterior sagittal diameter of the outlet (normalley 102 cm) measured by Thom's pelvimeter Thom's diction: for spontaneous vaginal delivery to occur the sum of the transverse and posterior diameter of the outlet must be > 15cm NB: pelvic outlet is accessible clinically so obstetrician must not be surprised by outlet contraction during labour outlet contraction must be diagnosed during pregnancy or very early in labour in the first exam. Internal pelvimetry : - Usually done after 36 weeks - Patient in lithotomy position without anesthesia by the gloved rt hand 1- Diagnosed conjugate (normally 12-15cm) - tip of rt middle finger reaching the sacral promontory mark the point that impringes on the lower border of the symphsis pubis on the radial border of the rt index - withdraw the rt 2 fingers and measure the distance between the tip of the middle finger and that point by a ruler NB: the same method is used to measure the anetroposteriorer diameter of the outlet but tip of middle finger touches the tip of sacrum 2- palpatic the shape of the sacrum normally it is broad with cancer or flat anterior surface 3- palpable the two ischial spines and approximate distance between them : normalley it is felt not prominent or undeuley projecting with the distance between them > 10.5cm 4- palpable the coccyx: normally is mobile and can recedes back wards easily 5- palpable the sacroscpinous ligaments normally it is 2 fingers breadth (3.5cm) 6- palpable side walls of the pelvis and sacroscietic notch - normalley parallel or divergent walls with wide notch 7- the anteroposterior diameter of the pelvic outlet - Measured by the same manner as diagonal conjugate Radiological pelvimetry A- Plain x-ray: - for borderline cases of pelvic contraction 1- lateral pelvimetry is the best to be done during labour look for the following an lateral fibm - Pelvic inclination (angle between the true conjugate and anterior surface of lunbar ureterbea ) - sacral promontory (jutting or not ) - length and shape of the sacrum - sacroscitic notch (wide or narrow) - level of the head in rotation to the ischial spine - true conjugate and posterior sagital measured by a ruller after putting a scale on the film 2- inlet and outlet radiological pelvimetry is of less importance x-ray pelvimetry is of little value in cephalic presentation (clinical cephalopelvic disproportion tests are more valuable ) CT : Advantages : 1- reduced radiation exposure 2- greater accuracy and easier technique MRI : Advantages : 1- no ionizing radiation 2- accurate measurement 3- complete fetal and placental imaging 4- evaluation of soft tissue dystocia Disadvantages: 1- cost 2- time factor 3- equipments availability Cephalopelvic disproportion tests If the head is not engaged in the last 2 weeks of pregnancy CPD is suspected and can be tested by the following maneuovers in which the fetal head is used as a pelvimeter 1- Pinard's maneuver: a. The women is examined in the seminstting position to coorect pelvic inclination (the oasis of the fetus and the uterus becomes perpendicular to the brim b. The head is grasped by the left head and pushed steadily in the pelvis c. The fingers of the rt hand is in front of the symphesis pubis to determine whether the head is engaged or not and degree overlap of the head on the symphsis pubis 2- Pinard's –Muller – Kerr's bimanual maneuver: a. The women on her back with the head and shoulder slightly abducted b. The left hand described in pinard's maneuver . the idea and middle fingers of the rt hand inside the vagina to note the degree of descent of the fetal head in relation to the ischial spine and the angle between the head and posterior surface of the symphesis pubis c. If the head is not engaged the throuth of the rt hand is placed on the sympysis pubis to note any overlap of the head over it d. Gentle fundle pressure by an assistant may be helpful e. If no CPD exists the head readily enters the pelvis and vaginal delivery can be predicted f. Inability to push the head into the pelvis doesn’t necessarily indicate that vaginal delivery is impossible g. if the head flexed head overrides the symphysis pubis this will be a presumptive widen of disproportion Degrees of CP and CPD CP CPD Minor degree Minor AP diameter 9-10cm No actual CPD because uterine contractions and pelvic reserve compensate this minor degree of contraction and vaginal delivery is the rule if no associated complication The a anterior surface of the head is in line with the posterior surface of the symphysis pubis flushing of the head with the S-pubis) with contraction during labour the head is engaged Moderate degree 1st degree CPD (moderate disproportion) - AP diameter 8-9cm - Resulting I CPD - Great majority of cases of CP - Difficult to predict its outcome so managed by trial labour and CS if failed - The anterior surface of the head is in line with the anterior surface of the symp pubis (overriding of the head with symphsysis pubis) - During labour sufficient moulding and uterine contraction may allow vaginal delivery (trial of labour if failed CS) Major degree 2nd degree CPD (severe disproportion) - AP diameter 6-8cm - Results in 2nd degree CPD - With living fetus CS is absolutely indicated - With dead fetus craniotomy can be tried if experienced obstetrician is available Extreme degree - AP diameter<6cm - Correspond also to 2nd degree CPD but CS is done even with dead fetus because the AP diameter is less than the smallest diameter of the head (Bimostoid which equal 7.5cm) so the problem cant's be solved by any destructive opeartiation (even the cronioclost and cephalo tribe) - The head is projecting beyond the anterior surface of the symphesis pubis (overriding head) - Vaginal delivery of living baby is impossible and CS is the rule - Corresponds to both major and extreme degree of CP but with dead fetus craniotomy is tried in major degree and CS is the only line in extreme degree Summary : - Mild (minor ) degree CPD corresponds to minor degree of CP : spontaneous vaginal delivery is the rule forceps may be needed for short ening of the 2nd stage of labour - Moderate degree (1st degree) CPD corresponds to moderate degree CP : trial labour if failed CS - Severe degree CPD (2nd degree) corresponds to major and extreme of CP : CS is the rule for living babies. For dead babies craniotomy is trial in major degree only if trained obstetrician is available and CS is done in extreme degree even with dead baby

Placenta Praevia

2007-12-28T09:19:00.000-08:00

*Definition: In placenta previa, the placenta is located over or very near the internal os. *Four degrees have been recognized: 1. Total placenta previa: The internal cervical os is covered completely by placenta. 2. Partial placenta previa: The internal os is partially covered by placenta. 3. Marginal placenta previa: The edge of the placenta is at the margin of the internal os. 4. Low lying placenta: The placenta is implanted in the lower uterine segment such that the placental edge actuallly does not reach the internal os but is in close proximity to it. -In vasa previa, the fetal vessels course through membranes and present at the cervical os. This is an uncommon cause of antepartum hemorrhage and is associated with a high rate of fetal death. -The degree of placenta previa will depend on the cervical dilatation at the time of examination. *Frequency -The zygote that implants very low in the uterine cavity is likely to form a placenta that lies in very close proximity to the internal cervical os. -In most cases, it does not become symptomatic until the late 2nd or 3rd trimester -It is about 1 in 200 deliveries, or 0.5 % *Etiology 1-Multiparity and advancing age increase the risk of placenta previa, the incidence of previa in women over 35 is 1 in 100 and for those over 40 it was 1 in 50. Conversely, the incidence was 1 in 300 for women aged 20 to 29 2-Prior cesarean delivery or induced abortion increases the placenta previa, it is about 3.9 % in women who had previously cesarean delivery. It is 3- 5fold increase. -The incidence increased with the number of previous cesarean sections; it was 1.9 % with two prior cesarean and 4.1 % with three or more prior cesarean deliveries. 3-Defective decidual vascularization, a possible result of inflammatory or atrophic changes, has been implicated in the development of placenta previa. 4-The relative risk of placenta previa to be increased 2-fold related to smoking. The CO hypoxemia caused compensatory placental hypertrophy. 5-A large placenta, which spreads over a larger area of the uterus, as seen with erythroblastosis and with multiple fetuses, predisposes to previa. 6-It may be associated with placenta accreta or placenta increta or percreta. Such abnormally firm attachment of the placenta might be because of poorly developed decidua in the lower uterine segment. - 5 % of women with a placenta previa had a clinically significant placenta accreta. For women with a prior cesarean section, the incidence was almost 25 %. Clinical Findings -The most characteristic event is painless hemorrhage, which usually does not appear until near the end of the second trimester or after. -Some abortions, however, may result from such an abnormal location of the developing placenta. -Frequently, bleeding has onset without warning, presenting without pain. The initial bleeding is rarely profuse. Usually it ceases spontaneously, only to recur. -In some cases, particularly those with a placenta implanted near but not over the cervical os, bleeding does not appear until the onset of labor. -The cause of hemorrhage the placenta is located over the internal os, the formation of the lower uterine segment and the dilatation of the internal os result inevitably in tearing of placental attachments. The bleeding is increased by the inability of the myometrial fibers of the lower uterine segment to contract and constrict the torn vessels. -Coagulation Defects, coagulopathy is rare with placenta previa, even when extensive separation from the implantation site has occurred. Diagnosis 1-The diagnosis can seldom be established firmly by clinical examination unless a finger is passed through the cervix and the placenta is palpated. Such examination of the cervix is done in operating room .Today, a "double set up" examination is rarely necessary. 2-Sonography ,the simplest, most precise, and safest method of placental localization is provided by (1) Transabdominal sonography, the average accuracy is about 95 %, false positive results are often a result of bladder distention. Therefore, ultrasonic scans in apparently positive cases should be repeated after emptying the bladder. (2) The use of transvaginal ultrasonograpby improved diagnostic accuracy to visualize the internal os in all cases, in contrast to only 70 % using transabdominal equipment. 93 % positive predictive value and 98 % negative predictive value for TVS. (3) Transperineal sonograrphy allow visualization of the internal os in all cases examined. (4) Magnetic Resonance Imaging to visualize placental abnormalities including placenta previa It is unlikely that this will replace ultrasonic scanning routine evaluation in the near future. Placental "Migration" - Placentas that lie close to the internal cervical os, but not over it, during the second trimester, or even early in the third trimester; are very unlikely to persist as previa. 1-Low lying placenta not covering the internal os, previa did not persist and hemorrhage was not encountered. 2-Of those placenta covering the os at midpregnancy, about 40 % persisted as a previa. -The mechanism of placental movement is not completely understood. The term migration is clearly a misnomer -The apparent movement of the low lying placenta relative to the internal os probably results from inability to precisely define this relationship in a 3 -dimensional manner using 2 dimensional sonography in early pregnancy. This difficulty is coupled with differential growth of lower and upper myometrial segments. Management -Women with a placenta previa may be considered as follows: (1) Those in whom the fetus is preterm but there is no pressing need for delivery, (2) Those in whom the fetus is reasonably mature, (3) Those in labor, and (4) Those in whom hemorrhage is so severe as to mandate delivery despite fetal immaturity. (1) Management of the pregnancy complicated by placenta previa and a preterm fetus, but with no active bleeding, consists of hospitalization. The mother and her family must be prepared to transport her to the hospital immediately. Delivery - Cesarean section is the accepted method of delivery in all cases of placenta previa. In most cases a transverse uterine incision is made. Occasionally a vertical incision is recommended in some circumstances. -When placenta previa is complicated by degrees of placenta accreta, control bleeding from the placental bed by: 1 -Oversewing the implantation site with 0 chromic sutures. -Cho and colleagues (1991) described placing circular interrupted 0 chromic sutures around the lower segment, above and below the transverse incision. -Druzin (1989) described four cases in which the lower uterine segment was tightly packed with gauze that successfully arrested hemorrhage. The pack was removed transvaginally 12 hours later. 2 -In some cases, bilateral uterine artery ligation is helpful, 3 -In others, internal iliac artery ligation. 4- If these methods fail, hysterectomy is necessary. Prognosis -In 1927 Bill advocated adequate transfusion and cesarean section, this results in a marked reduction in maternal mortality from placenta previa -In1945, Macafee and Johnson independently suggested expectant therapy for patients remote from term, -Preterm delivery is a major cause of perinatal death. -The fetal growth retardation is increased with placenta previa.

Physiology of Reproduction

2007-12-28T08:35:00.000-08:00

1-Hypothalamus -It lies at the base of the brain just above the junction of optic nerves -It contains many nuclei including (Supraoptic, paraventricular & arcuate nuclei) -It secrets both releasing & inhibiting hormones *Hypothalamic releasing factors 1-Gonadotrophin releasing hormone (LHRH or Gn RH), it consists of 10 amino acids 2-Thyrotophin releasing hormone (TRH), it consists of 3 amino acids 3-Corticotrophin releasing hormone (CRH), it consists of 41 amino acids 4-Growth hormone releasing hormone, it consists of 40 amino acids *Hypothalamic inhibiting factors 1-Growth hormone inhibiting hormone, it consists of 14 amino acids 2-Prolactin inhibiting factor (Dopamine) Functions of the hypothalamus 1-Regulation of the primitive functions needed for survival as (Appetite control, temperature control, salt & water retention, metabolism & growth) 2-Control of reproduction, it acts as a transducer to convert neuronal pulses into release of GnRH Gonadotrophin releasing hormone -It is a decapeptide (10 amino acids) -Secreted by the preoptic & arcuate nuclei in pulses every 60-90 minutes -Passes in the hypophyseal portal circulation to reach the anterior pituitary ----- secretion of FSH & LH -Half life ---- 2-4 minutes -Decreased GnRH pulse frequency is associated with oligomenorrhea or amenorrhea -Increased GnRH pulse frequency is associated with PCOD Control of GnRH Pulses 1-Dopamine ---- decrease the pulse frequency 2-Endogenous opioid ---- inhibit the pulse frequency 3-Neuropeptide Y ----- stimulate the pulse frequency 4-Noreoinephrine ------ stimulate the pulse frequency II-Pitutary gland -It consists of anterior lobe (adenohypophysis) & the posterior lobe (neurohypothesis) -The adult pituitary measure 13 x 10 x 6 mm & weighs 0.5 gm -The anterior pituitary secretes: gonadotronhins (FSH & LH), & prolactin 1-Follicle stimulating hormone (FSH) -It is a water soluble glycoproteins, consists of α-subunit (92 amino acids) & β- subunit (118 amino acids) -Secreted by the basophilic cells -Begins to be secreted at the end of the previous cycle, reaching a peak at day 3 o the new cycle, then the level falls & again it rises to reach a second peak at the 13th day just before ovulation -Half life --- 3-4 hours -Actions of FSH 1-Stimulate growth, ripening & maturation of the ovarian follicles 2-Stimulate aromatase activity in the granulosa cells 3-In combination with LH, it results in ovulation 4-Stimulate the formation of LH receptors 2-Luteinizing hormone (LH) -It is a water soluble glycoprotein, consists of α- subunit (92 amino acids) & β- subunit (121 amino acids) -Secreted by the basophilic cells -LH level: It is fairly constant throughout the cycle & reaches a peak about the 13th day -Half life --- 20 minutes Actions of LH -In combination with FSH it promotes ripening of the follicles -The LH surge ----- rupture of the mature follicle & ovulation -Stimulate corpus luteum to secrete estrogen & progesterone 3-Prolactin -Polypeptide hormone (191 amino acids) -Secreted by the lactotrophs (acidophilic cells) -It is the only anterior anterior pitutary hormone controlled by hypothalamic inhibiting factor (Dopamine) Actions of prolactin 1-Lactation 2-High levels inhibit estrogen secretion by the ovary 3-Essential for corpus luteum function 4-Control of ovulation by preventing further ovulation after fertilization Hypothalamic-Pituitary-Ovarian Axis -Hypothalamus releases GnRH to & passes via the hypophyseal portal circulation & act on gonadotrophin receptors in the anterior pituitary cells resulting in cyclic release of FSH & LH -Secretions of the hypothalamic GnRH is influenced by negative feed- back effect of estrogen & progesterone -FSH stimulate the growth of primary follicles & only one predominate to form mature follicle & secrete increasing amounts of estrogen ----- estrogen peak----- stimulate the anterior pituitary to secrete LH (positive feed back) -LH surge will lead to ovulation & formation of corpus luteum that secretes estrogen & progesterone -This high estrogen level will lead to suppression of Gn.RH (negative feed back) ----- low LH levels & degeneration of corpus luteum resulting in menstruation Types of feed back mechanisms 1-Long loop feed back (may be positive or negative) -The effect of the target organ hormones (estrogens & progesterone) on the hypothalamus & pituitary 2-Short loop feed back -The pituitary trophic hormones ---- suppression of the hypothalamic releasing factors 3-Ultra short loop feed back -Autocrine & paracrine effects of GnRH on the gonadotropin secreting cells in the hypothalamic nuclei Ovaries The ovaries has two functions: 1-Production of ova (ovarian cycle) 2-Endocrine function ----- production of estrogens & progesterone -The length of the ovarian cycle range from 21-35 days -The ovarian cycle is composed of (follicular & luteal) separated by ovulation 1- Follicular phase -The phase of ripening of the ovum -Begins on the first day of menstruation & occupies the first 14 days -Under the effect of FSH, 50 or more follicles start to ripen, one of these ova outstrips the rest and matures, dominant follicle), while the others undergo atresia -During the process of ripening, the mature Graffian follicle makes its way towards the ovarian surface to bring the discus proligerus with the ovum under the peritoneum The mature Graffian follicle -Size ---- 12-24 mm -Structure ---- composed of: 1-Ovum 2-Perivitelline space surrounds the ovum 3-Zona pellucida surrounds the perivitelline space. 4-Corona radiata: granulosa cells arranged in rows surrounding the ovum and attached to the zona by fine cytoplasmic processes 5-Cumulus oophorus (discus proligerus): Group of granulosa cells that attach the corona radiata to the wall of the follicle 6-Granulosa cells that lines the inner wall of the follicle & surround the follicular space that is filled with liquor folliculi 7-Theca interna cells spindle shaped cells 8-Theca externa cells --- Stroma cells that are compressed & modified to from a false capsule Ovulation Definition ----- rupture of the mature Graffian follicle with escape of the ovum surrounded by corona radiata through a stigma in the follicular wall into the peritoneal cavity & is picked up by the fimbrae of the fallopian tube Mechanism of ovulation *Central mechanism due to LH surge *Peripheral mechanisms 1-Thinning & degeneration of the cyst wall due to the action of proteases 2-Contraction of micromuscle cells in the theca externa & the stroma (due to PG in the follicular fluid) 3-Increased intrafollicular tension due to increase in the fluid content 2- Luteal phase -The phase of formation, function & early degeneration of the corpus luteum -Duration of the luteal phase is more constant than the follicular phase -Duration is said to be 14 + 2 day *Stages of corpus luteum formation 1- Stage of Proliferation 2-Vascularization: new blood vessels invade the follicle through the site of rupture 3-Maturity: the corpus luteum is functioning with maximum activity after 5 days for 3-4 days 4-Degeneration: occur 4-6 days before the next menstrual period ---- corpus albicans & results in low estrogen and progesterone levels & menstruation Corpus luteum of pregnancy The troplablast secrete human chorionic gonadotrophins within 7 days that prevents degeneration of corpus luteum & continues to produce estrogen & progesterone ---- suppression of anterior pituitary gland & the ovarian cycle Corpus fibrosum or atreticum The primary oocytes that do not mature will disappear at menopause or soon after 1-If the oocyte is blighted at an early stage the primordial follicle is obliterated & replaced by connective tissue 2-If there is some ripening -The oocyte will disintegrate by pyknosis & chromatolysis -A small cyst is formed lined with granulosa cells surrounded by theca lutein cells Causes of follicular atresia 1-Secretion of inhibitory peptide that impairs the binding of LH receptors 2-Inhibition of FSH by negative feed back from: (Estrogen & inhibin hormone) Ovarian Hormones I- Estrogens Sources --- produced by: 1-Ovary from (Graffian follicle & Corpus luteum) 2-Adrenal cortex (small amounts) 3-Placenta Metabolism: in the liver by conjugation with glucouronide or sulphate group, excreted in feces & urine Synthesis of estrogen (Two cell theory) 1-LH acts on the theca cells to produce androgens (androstendione & testosterone ) 2-Androgens diffuses from the theca cells to the granulosa cells 3-FSH stimulates aromatase enzyme to estrogens (estradiol E2 & estriol E3) Levels (2 peaks) -First peak before ovulation (about 300 pg/ml), then it falls -Second peak in the midluteal phase (about 200 pg/ml). then decrease when corpus luteum degenerates Biological actions of estrogen 1-General effects -Appearance of secondary sex characters at puberty -On the breast: it increase the duct system & vascularity -On bones stimulates osteoblastic activity & union of epiphysis -Salt & water retention 2-Central effects (On hypothalamus & pituitary), large dose inhibits FSH release 3-Actions on the genital tract @-On the uterus -Increased vascularity -Endometrium undergo proliferation & hyperplasia -Myometrium undergo hypertrophy & increased sensitivity to oxytocin @-On the cervix -Increase the volume of cervical mucus (water & salt content) -Positive spinabarkeit -Positive Fern test @-On the vagina -Epithelial lining: proliferation & increased glycogen deposition -Increased vaginal acidity due to conversion of glycogen into lactic acid 2-Progesterone Sources 1-Ovary ( corpus luteum), 2-Placenta Metabolism in the liver & 20% is excreted in urine as pregnanediol Levels -Progesterone level starts to rise just before ovulation -Reaches a peak in the mid luteal phase (15 ng/ml) & then drops gradually before menstruation Biological effects of progesterone 1- General actions 1-Increases the basal body temperature (thermogenic) 2-Salt & water retention 3-Relaxes smooth muscles 4-On the breast: development of alveolar system 2- Central action -Large doses inhibit LH secretion 3-On the genital tract *On the uterus 1- Endometrium: induces secretory changes in an estrogen primed endometrium 2-Myometrium -- uterine contractions become frequent but of high amplitude 3-Isthmus ----- Constriction *On the Cervix -The mucus becomes more viscid with negative sptinnbarkeit & negative fern test Menstrual Cycle 1-Menstrual phase Duration ----- 3-7 days -Scattered small areas of the endometrium are necrosed & are shed off at alternative times. then the whole endometrium is cast off except the deep compact layer -At the end of menstruation, the basal part of the glands start to grow and form new glands 2-Resting phase -Duration: 1-2 days following menstruation -Thickness of endometrium: 1-2 mm -Glands: simple tubular scattered widely in the stroma -Epithelium: cubical ciliated epithelium which dips down to from glands. -Stroma: small spindle shaped connective times cells with little cytoplasm 3-Proliferative phase -Duration: 9-10 days -Glands: tubular, increase in length & dilatation more numerous -Epithelium: more columnar with central nuclei. -Stroma cells are more globular & increase in size & vascularity 4-Secretory phase (Under the effects of progesterone & estrogens) -Duration: 12-14 day (from ovulation till menstruation) -Thickness: 5-7 mm -Glands: more tortous corkscrew, distended with secretions -Stroma: shows dense leucocytic infiltration 2-3 day before menstruation. The stroma cells become more polygonal & increase in size -Differentiated into 3 layers: (superficial compact zone, Middle spongy layer & Deep compact layer)

Role of Caudal, Pudendal and Paracervical blocks : DR. Alaa Mosbah M.D OBS&GYN ,Egypt ,Mansoura

2007-12-27T17:50:00.000-08:00

CAUDAL BLOCK Caudal epidurals in labour have become less popular because better perineal analgesia can be achieved by the use of epidural infusions and primigravidae are more likely to receive an epidural block. Also, there have been recent concerns about the risks of inadvertent intravenous and fetal injection. A modified caudal epidural technique can provide rapid onset perineal anaesthesia without cardiovascular disturbance and with relatively little loss of expulsive power. If used for perineal anaesthesia only, caudal block is a useful, safe technique for experienced anaesthetists provided that the volume of local anaesthetic is limited to a maximum of 10 mls, injected slowly (with multiple aspirations). It should be noted that this dose is less than half that which is required to achieve full labour analgesia. The block should be inserted before the head is on the perineum . Since it has been shown that pencil point spinal needles have a low incidence of headache (0 to 0.66% with 27G and 25G Whitacre needles) spinal anaesthesia is often more appropriate than lumbar or caudal epidural anaesthesia for rotational forceps, manual removal of placenta and, at times, low forceps delivery. INDICATIONS1. Unrelieved perineal pain.2. Premature urge to push.3. Low forceps delivery.4. When lumbar epidural analgesia is contraindicated. INCIDENCEIn most Australian hospitals, caudal blocks are being used less frequently in labour as the number of spinals has increased. The major indications for caudals are perineal pain, labour pain, forceps delivery, and manual removal of placenta. Less commonly, caudals can provide anaesthesia for artificial rupture of the membranes, suturing of episiotomies and repair of vaginal lacerations. CAUDAL ANALGESIA IN COMBINATION WITH OTHER MAJOR REGIONAL BLOCKS At the Royal Women's Hospital, of those women who had a caudal, at least 62% also had a lumbar epidural. The lumbar epidural was either already in situ or was inserted at the same time as the caudal. It has been shown that for the lumbar epidural route, increasing the volume of anaesthetic is more likely to secure good sacral blockade than injection in the sitting position. However, in our experience sacral blockade can occasionally only be achieved with a caudal or spinal block. COMPLICATIONSl. Vascular tap and intravascular injection of local anaesthetic .2. Failed block (8%) - the sacral hiatus is absent in 5% of adults. 3. Subarachnoid injection - the dural sac reaches S2 .4. Infection.5. Fetal injection . Modified caudal block is a safe technique with a limited specific place in modern obstetric anaesthesia. PARACERVICAL BLOCK The risk of complications, particularly fetal bradycardia, generally make this technique an unsuitable form of anaesthesia for obstetric patients. However, if used, it should be avoided in the presence of fetal distress or uteroplacental insufficiency and the fetal heart rate should be monitored continuously during and after insertion of the paracervical block . COMPLICATIONS1. Vaginal trauma.2. Systemic local anaesthetic toxicity due to excessive dosage or intravenous injection .3. Parametrial haematoma.4. Sacral plexus trauma.5. Infection and deep abscess formation.6. Fetal scalp injection of local anaesthetic.7. Fetal bradycardia probably caused by decreased uteroplacental perfusion.8. Needle stick injury. PUDENDAL NERVE BLOCK Pudendal nerve block provides anaesthesia for spontaneous vaginal delivery or low forceps delivery. The pudendal nerve (S2 - S4) is the major sensory innervation of the lower vagina, vulva and perineum and provides motor fibres to the external anal sphincter and the perineal muscles. Pudendal nerve block was first reported for vaginal delivery in 1916 . It is inadequate for rotational forceps delivery and manual removal of the placenta. Either a transvaginal or transperineal approach can be used. The bilateral success rate has been reported as 50% after the transvaginal approach and 25% after the transperineal approach. INDICATIONS.1. Low forceps delivery.2. Vaginal and perineal pain when lumbar or caudal epidural or spinal analgesia is unavailable, contraindicated or declined. COMPLICATIONS 1. Vaginal trauma.2. Systemic local anaesthetic toxicity due to excessive dosage or intravenous injection.3. Vaginal or ischio-rectal haematoma. 4. Infection and deep abscess formation.5. Fetal trauma or direct local anaesthetic injection.6. Needle stick injury. Caudal Analgesia Although the caudal route was the first widely used approach to the epidural space for continuous block in labour (Hingson and Edwards, 1942), and remained in frequent use in a few centres until the late 1970's (McCaul), its present role is very limited. Apart from providing good analgesia for low instrumental deliveries and perineal repair, the use of caudal block is usually restricted to a very few enthusiasts and to those cases in which a lumbar epidural is anatomically impossible or contraindicated by local infection . (However, local sepsis may also preclude the use of caudal block) . The patient should be prepared according to the guidelines shown in . Following the provision of secure venous access and preloading with crystalloid, the patient is either turned into the left lateral position with both knees flexed and forward tilt of the upper hip, or (occasionally) the knee-elbow position according to patient or operator preference. The skin of the lumbosacral area is prepared with a bactericidal solution and sterile drapes are applied. A bleb of local anaesthetic is raised in the skin overlying the sacral hiatus, between the sacral cornua, at a site deep to the proximal extremity of the natal cleft. A 21- gauge needle may then used to infiltrate the deeper tissues, but this is not essential. A variety of needles and cannulae may be used for the block itself, including a:1. 7.6 cm 19-gauge caudal needle,2. disposable 3.8 cm 19-23g hypodermic needle,3. 20-24-g intravenous catheter for a "single-shot" technique, or4. Tuohy needle (17 or 18g) and catheter for a continuous technique. Whichever needle is used, it is gently inserted at an angle of 70-80degrees to the skin and slowly advanced until the bony resistance of the sacrum is detected . The needle is withdrawn slightly, the entry angle reduced by about half, and then reinserted until the resistance of the sacrococcygeal ligament is felt at a depth of 1.5-3.8 cm. The ligament is then penetrated and the needle or catheter inserted to a depth of 2-3 cm, bearing in mind that the dural sac terminates at the S2 level, and that dural puncture should be avoided . Test aspiration for blood or CSF is performed. If the test is negative, this is followed by the injection of a 3ml test dose of local anaesthetic, with a hand positioned over the sacrum to detect any tissue swelling, resulting from malposition of the needle or catheter either subperiosteally or along the dorsal surface of the sacrum. Following a negative test dose and in the absence of pain on injection, the definitive dose may be injected slowly in small, repeated increments . If CSF is aspirated or if blood continues to be aspirated after repositioning of the needle or catheter the block should be abandoned. Single-shot needles or cannulae are withdrawn following injection. Catheters are affixed to their connectors and filters and strapped in position. Lignocaine is preferred to bupivacaine in view of the potential for large doses of bupivacaine to produce cardiovascular collapse and intractable ventricular dysrhythmias . should intravascular injection occur into one of the abundant epidural veins . The dose and concentration of lignocaine depends on the indication for the block. A recommended dose for outlet forceps delivery would be 15 to 20mls of 1.5% lignocaine with adrenaline. For perineal analgesia, a dose of 10 to 15mls of 1.0% lignocaine with adrenaline would suffice . Pudendal Nerve Block During the second stage of labour, pain largely results from distension of the lower vagina, vulva and perineum. In addition, the musculature of the anterior compartment of the pelvis must be negotiated by the descending presenting part. These structures obtain most of their sensory and motor innervation from the second to fourth sacral nerve roots via the pudendal nerve. Pudendal nerve blocks are of value in providing analgesia for the second stage when contraindications to neuraxial blockade exist and for the provision of pelvic floor relaxation when forceps delivery is required. They may also be used to provide anaesthesia of the perineum in order to create or repair an episiotomy. Pudendal nerve blocks have been utilized in the past as an alternative to epidurals in assisted twin and breech deliveries . Increasing evidence supporting the safety of epidurals in these situations has contributed to a diminished use of pudendal nerve blocks . The anatomy of the pudendal nerve should be considered when performing the block. The block is performed with the patient in the lithotomy position. Two approaches have been described: transvaginal and transcutaneous or perineal. The basis of both approaches is to block the nerve before it gives off its terminal branches. Its most reliable landmarks are exploited - the ischial spine in the transvaginal, and the ischial tuberosity, in the perineal approach. Transvaginal approach:In the transvaginal approach, the ischial spine can be palpated either transvaginally or per rectum. It is important to use a needle with a guide in order to limit the depth of submucosal penetration ("Huber" security point ). When a left sided block is performed, the ischial spine is palpated with the index finger of the left hand, the syringe is held in the right hand and the needle is guided between the index and middle fingers of the left hand towards the ischial spine. The sacrospinous ligament lies 1 cm medial and posterior to the spine. The needle is passed through the ligament for a distance of 1 cm until a loss of resistance is appreciated. The tip now lies in the area of the pudendal nerve. The pudendal vessels are closely associated. After aspiration, 10 mls of local anaesthetic solution are injected. The block is repeated on the other side. Perineal approach:The perineal approach is considered valuable when the engaged head makes vaginal palpation difficult. The ischial tuberosity is located by palpation . The needle is introduced slightly medial to this point, for a distance of 2.5 cm. The nerve is usually encountered without eliciting paraesthesia. Up to 8 mls of solution is infiltrated at this point. The needle is then withdrawn and directed into the deep and superficial tissue of the vulva along its anterior margin in order to block the the ilioinguinal and genitofemoral component . The block is repeated on the other side. The limitations of this block include:- Failure to provide adequate analgesia. It has been reported that up to half of all bilateral pudendal blocks are ineffective on one or both sides . A pudendal nerve block will not abolish sensation to the anterior part of the perineum because this region is supplied by branches of the ilioinguinal and genitofemoral nerves. Subcutaneous infiltration anteriorly along the vulva is therefore described as a component of this technique. Failure to wait sufficient time is a commonly cited reason for failure of a pudendal block. Pudendal nerve blocks do not abolish the pain of uterine contraction and cervical dilation which is transmitted via sympathetic nerve fibres derived from spinal levels T10 - L2 . It does not cause relaxation of the uterus. - Intravascular injection with subsequent local anaesthetic toxicity is a risk imposed by the close proximity of the pudendal vessels . - Fetal complications are uncommon. Exposure of the fetus to a high plasma level of local anaesthetic is a possibility that should be considered. Delivery usually occurs within a short period of time which may not allow for clearance of local anaesthetic from fetus via the placenta. 1% lignocaine is the most commonly used agent. Peak concentrations occur within 10 - 20 minutes. The maternal plasma concentrations which occur after this block are much lower than after either epidural or paracervical blocks. This block has been reported to prolong the second stage of labour as a result of loss of the bearing-down reflex. The addition of adrenaline may further prolong the second stage of labour . Paracervical Block Paracervical blockade may be used as a means of reducing pain during the first stage of labour. Pain associated with uterine contraction and cervical stretching and dilatation is transmitted from these structures on visceral afferents which accompany sympathetic fibres. These pass sequentially through the uterine, cervical, inferior hypogastric and superior hypogastric plexuses to the lumbar and lower thoracic sympathetic chains. During early labour, the bulk of these enter the spinal cord at the T11 - T12 segments. As pain becomes more severe, the two adjacent segments, T10 and L1 become involved . The block is performed bilaterally with the patient in the lithotomy position. The proximity of the broad ligaments just deep to the lateral fornices of the vagina is exploited with the aim of interrupting pain transmission at the level of the uterine and pelvic plexuses . An 18.5 cm needle with a security tip (Iowa trumpet, Kobak) is used to limit the injection to within 1.5 - 2 cm of the epithelium. The needle is connected to a 20 ml Luer-Lok syringe. Measures to avoid intravascular injection are vital. After careful aspiration non-adrenaline containing local anaesthetic solution is infiltrated. The specific injection sites have been variously described: 3 and 9 oclock; 4 and 8 oclock; or alternatively all sites . The distribution of radio-opaque dyes observed in X-ray studies is similar . An interval of 15 minutes should be observed between injections during which time signs of maternal and fetal toxicity should be excluded. Paracervical blockade can be used to provide analgesia during the first stage of labour when contraindications of epidural analgesia are present. The optimal time for institution of this block is the accelerated phase of the first stage when the severity of pain increases. The presenting part is typically engaged. The cervix is thin and effaced and has a tendency to be drawn up during uterine contractions . Paracervical blockade does not provide analgesia of the perineum during the second stage during which pain is transmitted primarily via the pudendal nerves to the S2 - 4 spinal cord segments . The technique has several limitations. The failure rate is reported to be as high as 18% . The proximity of uterine blood vessels in the vaginal fornices creates maternal and fetal risks. Fetal bradycardia occurs in 10-50% of cases . This is attributed to asphyxia which is believed to result from transient uterine artery vasospasm due to high concentrations of local anaesthetic in the paracervical region. The technique has a duration of action limited to 90 minutes with plain lignocaine. The use of adrenaline or bupivacaine in an attempt to increase the duration of the block should be avoided as both increase the incidence of fetal bradycardia . Preparation and Monitoring for Regional Blockade Adequate preparation of the obstetric patient is vital in order to minimise the complications of regional anaesthesia. This will be achieved by obtaining a history, performing a physical examination, and, if indicated, performing preliminary investigations. Of particular relevance in the history is the presence of cardiac disease, pre-eclampsia, coagulopathy, or any maternal condition which may present a relative contraindication to neuraxial blockade. The presence of any of these conditions may preclude the selection of the spinal and/or epidural route for analgesia or anaesthesia. Informed consent must be obtained. Fasting and acid-aspiration prophylaxis should be observed in patients undergoing caesarean section. The presence of a skilled assistant is essential. During the performance of the block and subsequently, careful attention to positioning will increase the likelihood of a succesful block. Large bore intravenous access and adequate prehydration will be required to minimise hypotension. Either reusable or disposable Tuohy needles and syringes may be used. Tuohy needles feature blunt cutting tips whose ends are curved. This assists in identification of the epidural space without dural puncture. The commonly used sizes for obstetric analgesia are 16g and 18g. These needles accept 18 and 20 gauge catheters respectively. Epidural catheters are typically made from PVC. The tip features either three helically-arranged lateral injection holes, or a single end hole . Three holed designs have been criticised for their potential to result in a malpositioned catheter such that individual holes may lie between different meningeal layers or in an epidural vein. This can result in a multi-compartment block or inadvertent intravascular injection of local anaesthetic . Single ended catheters have a higher incidence of false negative aspiration for blood and missed segments. Appropriate monitoring should be instituted. This should include monitoring of:1. The maternal circulation (pulse rate and blood pressure).Hypotension may complicate neuraxial blockade despite careful attention to prehydration and avoidance of aortocaval compression. A baseline pulse rate and blood pressure must be obtained before initiating the block. Blood pressure should be measured at intervals of not more than 5 minutes during establishment of the block and thereafter hourly whilst the block is being maintained. During caesarean section the blood pressure should be measured at 5 minute intervals. A qualified person should be responsible for hemodynamic monitoring. Appropriate management of hypotension should be instituted early. 2. The level of the block.The level of the block should be monitored 3. The fetus. Methods of monitoring fetal wellbeing include:a. Auscultation of heart rate with pinnards or doppler.b. Graphical display of the cardiotocograph .c. The use of scalp electrodes.d. Measurement of fetal scalp pH. The fetus should be monitored whenever an epidural is being utilised. In uncomplicated labours this is usually accomplished with a cardiotocograph. Scalp electrodes are used when the cardiotocograph fails to generate a reliable trace or when fetal distress is present. This requires a sufficiently dilated cervix. Scalp pH is used to gain more information on fetal wellbeing when other signs of fetal distress are present. 4. Bladder function.Painless bladder distension as the result of neural blockade may contribute to postpartum stress incontinence. This has been observed to occur in association with concentrations of bupivacaine of 0.5% .The bladder should be emptied intermittently. Prevention of local anaesthetic toxicity How do we Prevent the Development of Local Anaesthetic Toxicity? The use of local anesthetics (LA) may be accompanied by systemic and Iocalised adverse reactions, usually secondary to:1. accidental intravascular injection,2. inadvertent intrathecal injection, or3. administration of an excessive dose. Intravenous injection of 20-25 mg of bupivacaine has been reported to induce fatal cardiovascular collapse . Factors which can diminish the incidence of toxic reactions are:1. fractionation of the injected dose, 2. aspiration before injection, 3. selection of less toxic LAs . 4. reduction in the concentration of LA, and 5. test-dosing before injection of the main dose. The diagnosis of inadvertent intravascular placement of an epidural needle or catheter can be made by using either air or a sympathomimetic amine as the 'marker' agent. Unintended intrathecal placement can be diagnosed by the injection of an appropriately small dose of a rapid onset LA. Injection of 1 ml of air into an epidural catheter can be a highly specific and sensitive marker of intravascular catheter Iocalisation, but the safety of the doppler test has yet to be proven and, moreover, a precordial doppler and an extra person have to be available . Epinephrine, the catecholamine currently used in most test-doses, has several disadvantages. This mixed alpha- and beta-adrenergic agent does not consistently produce maternal tachycardia in laboring women. Cyclic maternal heart rate changes, due to painful uterine contractions, occur normally in unanesthetised parturients. The effect of epinephrine superimposed on these physiological changes in heart rate is not always discernible. Moreover, a major adverse effect of systemic epinephrine is its inhibition of uterine blood flow (UBF). This reduction of UBF has been demonstrated in gravid ewes and lasts for 2-5 minutes . Although the chronotropic response in term pregnant women is reduced, a test dose containing 5 mcg of isoproterenol (isoprenaline) might be a safer and more effective alternative .Isoproterenol produces a superior increase in maternal heart rate with minor effects on uterine blood flow in the chronic maternal fetal sheep preparation . In this animal model, incorporation of isoproterenol as a test dose does not produce neurotoxicty . These results suggest that isoproterenol may be safe for use as an epidural test dose in pregnant women. Some contradictory results exist concerning the increased sensitivity, during pregnancy, to the toxicity of local anesthetics. Santos et al. compared the systemic toxicity of ropivacaine and bupivacaine in non-pregnant and pregnant ewes and concluded that..."The systemic toxicity of ropivacaine or bupivacaine is not enhanced by gestation in sheep. This is in contrast to an earlier study in which cardiotoxicity of bupivacaine was enhanced during ovine pregnancy." A major concern in pregnancy is the trans-placental distribution of local anesthetics . Differences in the cord-to-maternal plasma drug concentration ratio essentially reflect trans-placental differences in the extent of plasma binding . When this ratio is high there should be a delay in the equilibration of drug in fetal tissues. Conversely, similar umbilical artery and umbilical vein concentration ratios observed for the various agents argue against large differences in their equilibration rates in the fetus. Thus, the impact, if any, of plasma binding on the risks of fetal toxicity is unclear . The prevention of toxicity of local anesthetics in the mother and the fetus is of utmost importance but, in this field, many questions remain to be answered. Regional techniques compared The use of subarachnoid local anaesthetic agents and narcotics for labour and delivery varies between institutions and individual anaesthetists. While practices may vary, the role of subarachnoid anaesthesia in comparison with other regional techniques can be defined in terms of the relative advantages and disadvantages of this method of anaesthesia. Efficacy and application of blockade:Local anaesthetics may be used intrathecally to accomplish sacral anaesthesia for instrumental vaginal deliveries and for other obstetric procedures. Subarachnoid blockade to a level above T7 may also be employed for cesarean section. Under these circumstances, subarachnoid blockade provides reliable, dense surgical anaesthesia. Epidural anaesthesia is also suitable for both labour and delivery but, sometimes, sacral segments may be difficult to block (with a lumbar epidural) and the blocks may occasionally be patchy or asymmetrical . In comparison to subarachnoid blockade, caudal blockade is only suitable for sacral anaesthesia . Opiates may also be administered by the subarachnoid route and provide good analgesia for labour but not for delivery . Furthermore, intrathecal opiates provide superior analgesia when compared to opiates administered via the epidural route . Side effects such as pruritus may be higher in patients receiving intrathecal opiates. Speed of onset:When compared to epidural or caudal anaesthesia, subarachnoid anaesthesia offers a rapid onset of action which is often of benefit to the patient, anaesthetist and surgeon. Unfortunately, an increased speed of onset of anaesthesia is only purchased at the price of a greater degree of hypotension . Postdural puncture headache:Postdural puncture headache may occur in up to 20% of patients when a 25-gauge spinal needle is used . This miserable complication occurs more frequently in young females and is responsible for the reluctance of many anaesthetists to use this technique in the parturient. Except in cases of inadvertent dural puncture with the needle, this problem is not seen with epidural or caudal anaesthesia. The use of 26-gauge spinal needles has been shown to lower the incidence of postdural puncture headache . The use of 29-gauge needles has been associated with little risk of postdural puncture headache, even in young patients . The low incidence of headache with these small needles increases the acceptability of subarachnoid blockade in obstetric anaesthesia . Titratable level of blockade and continuous infusions:The use of epidural catheters to provide a means by which the level of anaesthesia can titrated, topped up, or continuously infused for labour and delivery has been well established. The routine use of subarachnoid catheters for uncomplicated vaginal delivery has not gained wide acceptance in obstetric anaesthesia for several reasons. It has been stated that the large bore needles usually employed to introduce catheters would be associated with a high incidence of postdural puncture headache but this does not appear to occur in clinical practice . These catheters may increase the risk of infection, although again, there is very little supporting evidence for this concern. In an attempt to address these issues, microcatheters (32-gauge) which can be passed through a standard 25 or 26-gauge spinal needle have been used. Continuous spinal anaesthesia is obtained with negligible risk of local anaesthetic toxicity to the mother and fetus. Significant problems have been reported with these microcatheters and include cauda equina syndrome, kinking, difficulty in threading and catheter fracture. The more recent use of combined spinal epidural techniques allows for continuous and titratable anaesthesia with the advantage of a rapid and dense subarachnoid block. The potential disadvantages of an intrathecal catheter are avoided and, with a small spinal needle, the risk of postdural puncture is minimal . Overall, because of its advantages spinal anaesthesia (especially with the use of smaller spinal needles) continues to challenge the pre-eminent role of epidural anaesthesia in obstetrics. CHARACTERISTICS OF LOCAL ANESTHETIC TOXICITY (I) CNS toxicity:a) Excitation Phase: tinnitus, confusion, restlesness, perioral numbness or tingling, metallic taste, lightheadness, sense of dread and impending doom.b) Convulsive Phase: grand-mal clonic-tonic seizurec) Depression Phase: CNS depression with drowsiness and unconsciousness.d) Repiratory depression and apnea. (II) CVS Toxicity:a) Excitation Phase: - hypertension, tachycardia (with convulsions) b) Depression Phase:(i) Negative inotropic effect with decreased blood pressure, cardiac output and stroke volume.(ii) Peripheral vasodilation with further hypotension. c) Cardiovascular Collapse KEY FEATURES OF BUPIVACAINE TOXICITY (i) More likely to result in cardiovascular collapse (CV collapse dose / dose for convulsions = 3.7 for bupivacaine and 7.1 for lidocaine). (ii) Ventricular arrhythmias are more likely to accompany cardiac toxicity (use bretylium). (iii) Pregnant women are more sensitive to cardiac toxicity from bupivacaine. (iv) Resuscitation is usually legthy. (v) Toxicity is enhanced by acidosis and hypercarbia. PossibleEffects of Major Regional Blockade on Cardiotocographic Patterns. Uterine Contractions Mechanism Increased Frequency and intensity Analgesia decreases catechol amine leels Decreased Frequency and intensity Decreased blood supply to uterus. ?Inhibition of motor nerve supply to uterus?Direct effect of Local Anaesthetic on smooth muscle Fetal heart rate: beat to beat variability Increase Acute fetal hypoxia due to placental hypoperfusion Decrease Direct effect of local anaesthetic agents.Chronic hypoxia and acidosis from placental hypoperfusion Fetal heart rate:Long term deceleations Early Head compression from increased uterine tone. Late Placental insufficiency worsened by placental hypoperfusion Variable/td> Cord compression aggravated by maternal hypotension and increased intensityof uterine contractions. RECOMMENDED MAXIMUM DOSES OF LOCAL ANAESTHETICS -Illustrated in the case of a 60Kg woman Drug Dose Dose/Kg AMIDES Lidocaine with epi 420 (7mg/kg) Lidocaine plain 300 (5mg/kg) Bupivacaine with epi 180 (3mg/kg) Bupivacaine plain 120 (2mg/kg) Etidocaine 240 (4mg/kg) Mepivacaine 420 (7mg/kg) Prilocaine 720 (12mg/kg) ESTERS Cocaine 180 (3mg/kg) Procaine 840 (14mg/kg) Chloroprocaine 840 (14mg/kg) Tetracaine 180 (3mg/kg)