The role of fertility preservation in patients with endometriosis.

Patients affected with severe endometriosis are at significant risk for ovarian tissue damage, which may lead to infertility, reduced response to ovarian stimulation, and occasionally, premature ovarian failure. The risk for a compromised ovarian reserve in young patients is especially high following repeated surgical intervention and in the presence of bilateral endometriomas. In many cases, enhanced loss of ovarian reserve may also result from the damaging effect of the pathologic process on follicle reservoir even without surgical interventions. Women diagnosed with severe endometriosis and those designated for extensive ovarian surgical intervention are frequently not planning to conceive. In light of recent advances in fertility preservation techniques (FPT), such as oocytes and ovarian tissue freezing, as well as their increasing success rates, we critically evaluate the options for FPT in patients suffering from endometriosis. Personalized counseling should be offered to all patients with endometriosis taking into account age, extent of ovarian involvement, current ovarian reserve, previous and impending surgeries for endometriosis, along with current success rates and possible risks associated with FPT.

Recurrence of empty follicle syndrome with stimulated IVF cycles.

AIM: To determine the incidence of recurrent empty follicle syndrome (EFS) and to analyse the factors associated with this phenomenon. METHODS: Retrospective analysis comparing all EFS cycles with cycles in which oocytes were retrieved in our in vitro fertilization (IVF) unit between 1998 and 2006. RESULTS: Of 8292 IVF cycles, 163 (2.0%) resulted in empty follicles. Risk factors for EFS included advanced age (37.7 ± 6.0 years vs. 34.2 ± 6.0 years, p < 0.001), longer infertility (8.8 ± 10.6 years vs. 6.3 ± 8.4 years, p < 0.05), higher baseline follicle-stimulating hormone levels (8.7 ± 4.7 IU/L vs. 6.7 ± 2.9 IU/L, p < 0.001) and lower E2 levels before the human chorionic gonadotropin injection (499.9 ± 480.9 pg/mL vs. 1516.3 ± 887.5 pg/mL, p < 0.001) compared with cases in which ova were retrieved. Among patients with EFS, recurrent EFSs occurred in 15.8% of subsequent cycles. CONCLUSION: The EFS is a sporadic event in the majority of patients. However, in about 16% of the patients, EFS may recur. These cases may be a variant form of poor response and patients with repetitive EFS syndrome should be counseled concerning their chances to conceive.

Day 5 vitrified blastocyst transfer versus day 6 vitrified blastocyst transfer in oocyte donation program.

The superiority of day 5 blastocysts compared to day 6 blastocysts in fresh cycle transfers was previously demonstrated and attributed mainly to endometrial asynchrony. Data from frozen blastocysts transfers showed conflicting results, possibly due to heterogeneous patient population and embryo quality. The aim of this study was to compare clinical pregnancy rate (CPR) and live birth rate (LBR) between transfers of vitrified day 5 blastocysts and day 6 blastocysts in oocyte donation, blastocyst-only cycles. In a retrospective, multi-center study, with a single oocyte donation program, a total of 1840 frozen embryo transfers (FET's) were analyzed, including 1180 day 5 blastocysts and 660 day 6 blastocysts transfers. Day 5 blastocyst transfers had better embryonic development and significantly higher CPRs (34.24% vs. 20.15%, P < 0.0001), higher LBRs (26.89% vs. 14.77%, P < 0.0001), less cycles to LBR (1.83 ± 0.08 vs. 2.39 ± 0.18, P = 0.003) and shorter time to LBRs (76.32 ± 8.7 vs. 123.24 ± 19.1 days, P = 0.01), compared to day 6 transfers, respectively. A multivariate stepwise logistic regression indicated, that day 5 transfer was an independent factor for CPRs (OR 1.91; 95% CI 1.43-2.54, P < 0.001) and LBRs (OR 2.26; 95% CI 1.19-4.28, P = 0.01), regardless of embryo quality, compared to day 6. In conclusion, day 5 blastocysts in oocyte donation program have significantly higher CPRs and LBRs, and present shorter time to delivery, compared to day 6 blastocysts, regardless of embryo quality.

Severe intraabdominal bleeding caused by endometriotic lesions during the third trimester of pregnancy.

OBJECTIVE: Endometriosis is known to be associated with an increased risk for early pregnancy complications, including ectopic pregnancy and miscarriage. However, little has so far been reported on complications linked to severe endometriosis occurring during the third trimester of pregnancy. STUDY DESIGN: A retrospective review of 800 women attending the endometriosis clinic of the Sheba Medical Center during the years 2002-2006 was performed. Cases with severe endometriosis and associated complications during late pregnancy were identified. RESULTS: Three women were found who experienced significant intraabdominal bleeding in the third trimester of pregnancy attributed to a lesion resulting from severe endometriosis. The intraabdominal bleeding occurred between 26-29 weeks of gestation. In all cases the major presenting prenatal symptom was severe lower abdominal pain. The pain was not relieved by the administration of tocolytics or mild analgesics. Explorative laparotomy, performed in all 3 cases, revealed the presence of significant intraabdominal bleeding requiring immediate transfusion of blood products stemming from endometriotic lesions. Fetal complications occurred in all 3 cases. CONCLUSION: The symptoms of endometriosis are often relieved during pregnancy. Yet lesions caused by severe endometriosis can lead to significant intraabdominal bleeding during the third trimester of the pregnancy. Physicians must be aware that close antenatal follow-up and prompt intervention may be required in such cases.

Hospital readmission due to neonatal hyperbilirubinemia.

Severe neonatal hyperbilirubinemia can occur without apparent reason in term healthy breast-fed infants and some develop kernicterus. The aim of our study was to assess the incidence of severe hyperbilirubinemia in term healthy newborns discharged from the hospital. From January 1 through December 31, 1994, 6705 infants were delivered at Bikur-Cholim and Misgav-Ladach Community Hospitals. All 1448 newborns discharged with a serum bilirubin level > 10.0 mg/dL were instructed to return to the hospital within 3 days for follow-up, as well as bilirubin determination. Twenty-one newborns with a bilirubin level > 18.0 mg/dL were identified and readmitted at mean +/- standard deviation (SD) 5.5 +/- 1.8 (range, 5 to 10 days of life). This represents 1.7% of the 1220 infants who returned for follow-up examination. Mean +/- SD serum bilirubin levels at readmission were 19.6 +/- 2.5 mg/dL. All but one of the infants were breast-fed. No cases of ABO incompatibility were found and two newborns were glucose-6-phosphate dehydrogenase (G6PD)-deficient. Sepsis work-up and direct Coomb's tests were negative in all cases. None had hemolysis or were found to have any cause for hyperbilirubinemia other than breast-feeding. Phototherapy was provided in all but two cases, and an exchange transfusion was performed in one case. Three additional infants, with bilirubin levels < 10 mg/dL at discharge, were readmitted due to hyperbilirubinemia. One was diagnosed with neonatal hepatitis. We conclude that, based on our study population, 0.36% of term infants may subsequently develop severe neonatal hyperbilirubinemia in the first postnatal week.(ABSTRACT TRUNCATED AT 250 WORDS)

Neonatal hyperbilirubinemia and physical and cognitive performance at 17 years of age.

To estimate the effect of neonatal hyperbilirubinemia on long-term cognitive ability in full-term newborns with a negative Coombs test, we performed a 17-year historical prospective study of 1948 subjects. Intelligence tests and medical examinations performed at the military draft board were stratified according to serum bilirubin concentration. A logistic regression analysis was used to adjust for the confounding effects of gestational age, birth weight, Apgar score, ethnic origin, socioeconomic class, paternal education, birth order, and the administration of phototherapy and exchange transfusion. No direct linear association was shown between neonatal bilirubin levels and intelligence test scores or school achievement at 17 years of age. However, the risk for low intelligence test scores (IQ score less than 85) was found to be significantly higher (P = .014) among full-term male subjects with serum bilirubin levels above 342 mumol/L (20 mg/dL) (odds ratio, 2.96; 95% confidence interval, 1.29-6.79). This association was not observed among female subjects. We conclude that severe neonatal hyperbilirubinemia, among full-term male newborns with a negative Coombs test, could be associated with lower IQ scores at 17 years of age.

The effect of maternal weight gain in pregnancy on birth weight.

The association between maternal weight gain during pregnancy and the infant's birth weight was studied in 14,121 term singleton births. The parturients were stratified into four body-mass categories, three age groups, four parity groups, and three levels of educational attainment. A separate multiple regression analysis was performed for each category to control for the confounding effect of gestational age, maternal social class, ethnicity, cigarette consumption, marital status, age, parity, education, and weight for height. A significant positive influence of prenatal weight gain on birth weight was found for all subgroups. The effect varied depending on maternal pre-pregnancy body mass, age, parity, and the level of formal education.

Effect of maternal smoking and age on congenital anomalies.

The incidence of congenital anomalies was examined by the level of maternal and paternal smoking during pregnancy for 17,152 infants. A multiple regression analysis was used to control for the possible confounding effects of maternal age, formal education, ethnic origin, religion, marital status, parity, social class, and work outside the home. Neither maternal nor paternal smoking habits were significantly associated with the occurrence of congenital malformations. Maternal age was significantly (P less than .005) related to the incidence of major anomalies. Mothers aged 35 years and older who smoked were found to have a significantly (P less than .002) higher risk for minor malformations and a nonsignificantly increased rate of major malformations. Maternal cigarette smoking may be an important preventable risk factor for congenital anomalies among mothers aged 35 years or older.

Vaginal vault evisceration after total laparoscopic hysterectomy.

BACKGROUND: Vaginal vault rupture with intestinal herniation, although rare, is a recognized postoperative complication of vaginal and abdominal hysterectomies. The incidence after laparoscopic hysterectomy is unknown. CASES: Three women, ages 40-43 years, presented to the emergency room with bleeding and pain 2-5 months after total laparoscopic hysterectomy. The small bowel was visible through the introitus or protruding into the vagina. Inspection of the bowel revealed no evidence of trauma. Two vaginal cuff repairs were completed transvaginally and one laparoscopically, all with interrupted sutures of no. 0 polydioxanone or polyglactin. In follow-up period of 12-17 months, the patients were doing well. CONCLUSION: Total laparoscopic hysterectomy may be associated with an increased risk of vaginal vault evisceration. Because laparoscopy increasingly is used to replace abdominal hysterectomy, it is important to be aware of this complication and its management.

Treatment of pelvic peritoneal cysts by drainage and ethanol instillation.

We performed this study to assess the feasibility and effectiveness of ultrasound-guided drainage and ethanol instillation for the treatment of pelvic peritoneal cysts. Six women had pelvic peritoneal cysts after previous pelvic surgery; when the cysts recurred after simple drainage, the patients underwent transvaginal ultrasound-guided drainage and instillation of 20-30 mL of ethanol into the cyst cavity. All patients except one presented with abdominal pain. All cysts had clinical and ultrasonic benign characteristics. Drainage and ethanol instillation were performed successfully in all patients without severe side effects or complications. After a mean follow-up time of 13.6 months, a recurrence was found in only one patient, who was successfully retreated. These preliminary results indicate that transvaginal ultrasound-guided fluid drainage and ethanol instillation is an effective treatment for pelvic peritoneal cysts.

The cognitive outcome of full-term small for gestational age infants at late adolescence.

OBJECTIVE: To assess the cognitive and academic performance of adolescents who were born small for gestational age (SGA) at term. METHODS: A 17-year historical prospective study was done by matching neonatal data of 1758 infants to the results of the medical and intelligence assessment performed at age 17 years at the army draft board medical examination in Israel. The results of children born SGA (weight at term birth below the third percentile) were compared to those of children who were born appropriate for gestational age (AGA). RESULTS: After adjustment by a multiple linear regression analysis, the mean (+/- standard error of the mean) intelligence test scores were 103.1 +/- 2.9 versus 105.8 +/- 1.5 (P = 0.3) for the males and 100.3 +/- 2.5 versus 104.7 +/- 1.6 (P < .03) for the females. Males born SGA at term were found to have lower educational achievements (having less than 12 years of schooling or attending a vocational school) compared with the AGA group. The odds ratio for this finding after adjustment by a logistic regression analysis was 2.40 (95% confidence interval 1.07-5.39; P < .03). Intranatal events were not found to have an effect on the measured neurodevelopmental outcome. CONCLUSION: Infants born SGA at term have an increased risk for lower cognitive performance and schooling achievements than those born AGA; this result seems to be unrelated to their intranatal course.

Apgar scores and cognitive performance at 17 years of age.

The association between low Apgar scores (7 or less) at 1 and 5 minutes and cognitive performance in late adolescence was assessed. A 17-year follow-up of 1942 subjects was performed. The intelligence test scores at 17 years of age were matched with 1- and 5-minutes Apgar scores. A multiple linear regression analysis was used to control for the possible confounding effect of perinatal factors (birth weight, gestational age, serum bilirubin levels, birth order) and demographic characteristics (ethnic origin, paternal education, social class). The sensitivity and positive predictive value of a low 1-minute Apgar score were 8 and 8% and of a low 5-minute Apgar score 1.5 and 5%, respectively. Low Apgar scores are poorly correlated with long-term intellectual outcome.

Birth order and birth weight reexamined.

We studied the longitudinal association of birth order and birth weight in two series of very large sibships, each consisting of at least seven children, and compared the findings with those based on analysis of cross-sectional data from a large population-based survey, the Jerusalem Perinatal Study. The birth weights of the cross-sectional sample were adjusted by multiple linear regression for a number of factors known to confound cross-sectional studies, including maternal age, education, marital status, religion, smoking, height and prepregnant weight, gestational age, and sex of the newborn. Birth weight increased with increasing birth order in both adjusted cross-sectional and socioeconomically homogeneous longitudinal data.

Use of magnetic resonance imaging in pregnancy to diagnose intussusception induced by colonic cancer.

Intussusception of the colon initiated by a malignant tumor is an extremely rare occurrence during pregnancy. The nonspecific presenting symptoms may be attributed to the pregnancy itself, making diagnosis difficult. We report a case in which the use of magnetic resonance imaging led to prompt diagnosis.

Birth weight and intellectual performance in late adolescence.

The impact of birth weight on cognitive performance in late adolescence was assessed in a study of 20,567 male infants born in Jerusalem between 1964-1970. The 17-year follow-up was performed by matching computerized data base records. Stepwise multiple regression analysis was used to estimate the effect of birth weight on intelligence test scores, adjusting for the influence of ethnic origin, maternal and paternal education, social class (determined by area of residence), maternal age, and birth order. These confounders explained 22% of the variance in intelligence test scores. The adjusted differences in intelligence test scores were significantly lower for groups with birth weight less than 2000 g (-6.5 points), 2000-2499 g (-3.6 points), and 2500-2999 g (-1.6 points) compared with the group weighing 3000-3499 g. Most low birth weight infants achieved intellectual performance within the normal range. However, despite this reassuring finding, low weight at birth in male subjects was found to have a statistically significant independent association with inferior intelligence test achievements in late adolescence.

The risk of carbon monoxide poisoning after prolonged laparoscopic surgery.

OBJECTIVE: To evaluate whether thermal energy produced by laser and bipolar electrosurgery during laparoscopic procedures significantly elevates blood carboxyhemoglobin levels. METHODS: We prospectively studied 27 healthy nonsmoking patients, mean +/- standard deviation (SD) age 39.1 +/- 8.0 years (range 22-56), scheduled for laparoscopic procedures in which smoke was generated. Prolonged operative laparoscopy involved high-flow carbon dioxide insufflation, intensive evacuation of intra-abdominal smoke, and controlled hyperventilation with 50-100% oxygen. Laser and bipolar electrosurgery were used in all cases. Blood samples were drawn before and after surgery. Carboxyhemoglobin concentrations were measured using a highly accurate gas chromatography method. RESULTS: The mean +/- SD duration of surgery was 141 +/- 72 minutes (range 45-300). The mean +/- SD carboxyhemoglobin levels were 0.70 +/- 0.15% (range 0.44-1.20%) before surgery and 0.58 +/- 0.20% (range 0.30-1.33%) after surgery. A significant decrease (P < .001) in carboxyhemoglobin concentrations occurred during surgery (mean +/- SD, 20 +/- 11%; range 3-46%). The carboxyhemoglobin level was increased at the end of surgery in only one woman. In only one patient did the levels exceed 1% (1.33%), still well below the human threshold tolerance level of 2%. The Spearman correlation coefficient between carboxyhemoglobin concentrations and duration of surgery was r = 0.308 (P = .12). CONCLUSION: Carbon monoxide (CO) poisoning is not associated with even prolonged laparoscopic surgical procedures. This may be attributed to aggressive smoke evacuation that minimizes exposure to CO, and to active elimination of CO by ventilation with high oxygen concentrations.

Effect of very advanced maternal age on pregnancy outcome and rate of cesarean delivery.

OBJECTIVE: To determine outcomes of pregnancies in women at least 44 years of age and to determine factors predicting cesarean delivery in these patients. METHODS: Between January 1988 and December 1995, 109 women at least 44 years old delivered in our medical center. These women were matched to a group of 309 women 20-29 years of age. Multiple logistic regression analysis was used to evaluate the association between maternal age and outcome variables, controlling for possible confounding factors. Based on the logistic regression, a predictive model was calculated for cesarean delivery and validated prospectively in a separate group of 30 consecutive women at least 44 years old, who delivered during the first 8 months of 1996. RESULTS: Very advanced maternal age, compared with younger age, was associated with a significantly higher rate of medical complications (hypertensive disorder and diabetes) (odds ratio [OR] 2.5; 95% confidence interval [CI] 1.5, 4.1; P < .001), instrument-assisted vaginal delivery (OR 7.5; 95% CI 2.2, 25.0; P < .004), and cesarean delivery (OR 7.3; 95% CI 2.2, 16.7; P < .001). The incidences of preterm labor, premature rupture of membranes, emergency cesarean delivery, meconium-stained amniotic fluid, small for gestational age newborns, and 5-minute Apgar scores of 7 or lower were not influenced by maternal age. The regression model showed an increased risk for cesarean delivery associated with age of at least 44 years (OR 7.3; 95% CI 2.2, 16.7), primiparity (OR 3.5; 95% CI 1.3, 9.8), infertility treatment (OR 3.6; 95% CI 1.5, 8.8), and egg donation (OR 19.5; 95% CI 6.1, 62.2), with positive and negative predictive values of 94 and 86%, respectively. CONCLUSION: Maternal age of at least 44 years is associated with medical complications in pregnancy and more interventions during labor. However, overall pregnancy outcomes are favorable. Cesarean delivery can be predicted accurately based on maternal age, parity, and infertility treatment.

Long-term outcome of laparoscopic presacral neurectomy for the treatment of central pelvic pain attributed to endometriosis.

OBJECTIVE: To evaluate the long-term pain reduction achieved by laparoscopic presacral neurectomy. METHODS: One hundred seventy-six women with median (range) age 30 (18-45) years underwent presacral neurectomy combined with excision and vaporization of endometriotic lesions and were observed, using structured questionnaires, for up to 72 months postoperatively. The study included a convenience sample of the first 100 questionnaires returned. Forty of the women were studied for 12-23 months, and 60 for 24-72 months. The main outcome measures were reduction of pelvic pain, dysmenorrhea, and dyspareunia after surgery. RESULTS: Pelvic pain, dysmenorrhea, and dyspareunia were reportedly reduced by more than 50% in 74, 61, and 55 patients, respectively, more than 12 months after laparoscopic presacral neurectomy. More than 50% reduction in pelvic pain was reported by 69.8%, 77.3%, 71.4%, and 84.6% of the patients, respectively, with endometriosis stages I-IV, using the revised classification of the American Fertility Society. Comparatively, more than 50% reduction in dysmenorrhea was reported by 52.8% of the patients with stage I endometriosis, 68.2% with stage II, 71.4% with stage III, and 69.2% with stage IV. Reduction of dyspareunia by more than 50% was reported by 54.7% of the patients with stage I endometriosis, 50.0% with stage II, 28.6% with stage III, and 61.5% with stage IV. CONCLUSION: Long-term outcome of laparoscopic presacral neurectomy is satisfactory in the majority of patients. The stage of endometriosis is not related directly to the degree of pain improvement achieved.

Hyperechogenic fetal bowel and elevated serum alpha-fetoprotein: a poor fetal prognosis.

OBJECTIVE: To evaluate the clinical significance of increased fetal bowel echogenicity in women with elevated maternal serum alpha-fetoprotein (MSAFP) during the second trimester. METHODS: The study group comprised six pregnant women with elevated second-trimester MSAFP (greater than 2.5 multiples of the median), whose ultrasonographic evaluations indicated hyperechogenic fetal bowel. They were compared with six pregnant women whose fetuses, during routine second-trimester ultrasonographic screening for fetal anomalies, were found to have a hyperechogenic bowel without elevated MSAFP, according to natural history, pregnancy outcome, and associated features. RESULTS: All six fetuses with the combination of elevated MSAFP and echogenic bowel were growth-restricted; four died in utero and one of the two live-born infants died during the neonatal period. The single survivor in this group was born prematurely; necrotizing enterocolitis was diagnosed at 30 days of life and surgery was performed. None of the cases had associated congenital anomalies. Only one of the six controls had associated anomalies (trisomy 21), and this pregnancy was terminated. The pregnancy course of the remaining five fetuses was normal; all were appropriate for gestational age and were delivered at term. No perinatal mortality occurred in this group; however, in one infant, cerebral palsy was diagnosed at 10 months of age. CONCLUSION: Fetal bowel hyperechogenicity found in women with elevated second-trimester MSAFP levels is associated with poor fetal outcome, particularly fetal growth restriction with fetal and neonatal death, and should be considered an ominous prenatal finding.