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.

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.

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.

Elevated day 3 FSH/LH ratio due to low LH concentrations predicts reduced ovarian response.

Adequate ovarian response, essential for successful IVF, cannot be accurately predicted. This study retrospectively reviewed all patients undergoing IVF from 1998 to 2001. Inclusion criteria were age <41 years at treatment onset and a basal day 3 serum FSH concentration <12 IU/l. Women with FSH or=3 in group 1 and <3 in group 2 (controls). Age at treatment initiation, basal serum day 3 FSH and LH concentrations, peak serum oestradiol concentration, number of retrieved and fertilized oocytes and pregnancy rate were analysed. Groups 1 (n = 41, 111 IVF treatment cycles) and 2 (n = 596, 1,434 IVF treatment cycles) were similar in term of woman's mean age. Group 1 had significantly higher mean basal day 3 FSH concentration (P < 0.01) and significantly lower oestradiol concentrations at oocyte retrieval (P < 0.01), mean number of oocytes retrieved and fertilized (P < 0.01) and pregnancy rate (P = 0.016). The same trend persisted after excluding 98 patients with basal FSH concentrations >8 IU/l. In conclusion, elevated day 3 FSH/LH ratio is associated with an inferior outcome in IVF treatment cycles and may be used as an additional predictor for decreased ovarian response.

[Aromatase inhibitors--new applications in gynecology].

P-450 aromatase inhibitors, designed for suppressing estradiol production, were first approved for the treatment of advanced breast cancer. Recent studies have provided evidence that aromatase inhibitors may be effective in the short term for induction of ovulation and in the long-term for treatment of endometriosis. Based on current data, the role of aromatase inhibitors in the management of various gynecological conditions may soon be widely determined.

[Perinatal group B streptococcal disease: a review and revised guidelines for prevention].

Group B Streptococcus (GBS) is a common inhabitant of the maternal genital and gastrointestinal tracts, and colonizes approximately 20% of pregnant women. About 50% of infants born to colonized women will become colonized at birth. Early onset GBS disease affects 5/1000 newborns, and is related to a 5-16% mortality rate and severe morbidity. Selective intra-partum chemoprophylaxis can prevent most cases of GBS early-onset disease. In 1996, the federal Centers for Disease Control and Prevention (CDC), the American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics (AAP) recommended either a culture-based or risk-based approach for prevention of early onset GBS disease. Understanding the epidemiology of the disease and comparing efficacy of the two prevention strategies may elucidate the dispute surrounding this issue. Accordingly, new recommendations from the CDC and the ACOG were published, and their implementation in Israel should now be considered.

[Medical termination of pregnancy with mifepristone--initial experience at the Sheba Medical Center].

OBJECTIVE: To assess the early implementation of medical termination of pregnancy as an alternative treatment option for women in early pregnancy who wish to avoid a surgical procedure. METHODS: The use of mifepristone (RU-486) for medical termination was recently approved in Israel. We performed a prospective follow-up study of the 189 women who underwent medical termination of pregnancy with mifepristone and misoprostol in our center between January 2000 and April 2001. RESULTS: Complete outcome data was obtained for 176 women. Within this group 152 women (86.4%) did not need any surgical procedure to complete the abortion. Uterine curettage was performed in 17 (9.6%) and operative hysteroscopy in 7 (4.0%) of the women because of incomplete abortion or suspected residua of pregnancy. CONCLUSION: Medical abortion offers an efficient and safe treatment option to women who wish to avoid surgical evacuation.

The effect of prolonged cryopreservation on embryo survival.

The purpose of this study was to assess the effects of long-term cryopreservation on the survival and implantation rates of embryos. We performed a matched case-control study comparing 101 women whose embryos were transferred after cryopreservation for 2-9 years, with 101 control women whose embryos were transferred after 6 months or less of cryopreservation. A multiple step-wise logistic regression was performed to determine the independent effect of the duration of cryopreservation, patient age and embryo quality on pregnancy and live birth rates. In the study group, 673 embryos were frozen for 24-108 months and of these 451 were thawed. In the control group, 513 embryos were cryopreserved for up to 6 months and 456 were thawed. The implantation rate was similar (4.5% vs. 5.5%) in both groups. We concluded that the duration of cryopreservation did not adversely affect embryo survival, and prolonged cryopreservation appeared to be a safe treatment option.

The development of the fetal vermis: an in-utero sonographic evaluation.

OBJECTIVE: To establish a nomogram for fetal vermis measurements during gestation. METHODS: A prospective cross-sectional study of normal singleton pregnancies. Measurements of the fetal vermis width (in the axial plane) and height (in the sagittal plane) were performed by high-resolution transabdominal ultrasonography between 18 and 38 weeks of gestation in 256 fetuses. RESULTS: Adequate vermis measurements were obtained in 256 fetuses. Vermian width and height as a function of gestational age and biparietal diameter were expressed by regression equations and the correlation coefficients were found to be highly statistically significant (P < 0.0001). The normal mean (+/- SD) for each gestational week was defined. CONCLUSIONS: The present data offer the normal range of the vermian measurements throughout gestation. These values may allow intrauterine assessment of the development of the cerebellar vermis, as well as the posterior fossa.

In vitro fertilization following natural cycles in poor responders.

This prospective study was designed to examine the feasibility of natural cycle in vitro fertilization (IVF) in poor responders, and the clinical factors that may predict successful outcome. Twenty-two poor responders underwent IVF treatment with 44 unstimulated cycles. The results of the natural cycles were compared with those of the 55 low-response stimulated cycles of these patients during the 12 months prior to the study. Eighteen (82%) patients had at least one oocyte retrieved, while nine (41%) had at least one cycle with embryo transfer. Two (9%) patients each gave birth to a healthy term baby. These results are comparable with those of the stimulated cycles. Serum early follicular follicle stimulating hormone (FSH) level was found to be the only reliable predictor of oocyte recovery and overall outcome in each specific natural cycle. However, because of great variability in basal FSH levels among different cycles of the same patient, this is not a reliable predictor of outcome in future cycles. We conclude that poor responders are a unique group of patients who may benefit from natural-cycle IVF treatment.

Comparison of cervical vacuum cup cannula with metal cannula for hysterosalpingography.

OBJECTIVE: The aim of this study was to compare the use of a cervical vacuum cap cannula with the traditional metal cannula. DESIGN: A prospective, randomised, single-blinded comparative study. SAMPLE: Fifty consecutive infertile women undergoing hysterosalpingography for evaluation of infertility METHODS: Hysterosalpingography was performed either with the traditional metal cannula (n = 25) or a cervical vacuum cap cannula (n = 25). MAIN OUTCOME MEASURES: Length of procedure, fluoroscopic time, amount of contrast medium, pain to the patient while applying the cannula and injecting the contrast medium, level of difficulty to the performer, the need to reapply the cannula, complications, and results of the hysterosalpingography. RESULTS: Using the cervical vacuum cap cannula, compared with the metal cannula, the duration of the procedure was significantly shorter (5.3 vs 9.3 minutes; P < 0.001), less fluoroscopic time was needed (0.9 vs 1.8 minutes; P < 0.001), a smaller amount of contrast medium was used (4.6 vs 15.7 mL; P < 0.001), the procedure caused less pain to the patient (3.2 vs 6.8, respectively; on a scale of 1-10; P < 0.001), and was easier for the physician to perform (1.4 vs 3.4; on a scale of 1-10; P < 0.001). No significant differences were encountered between the two groups in the need to reapply the cannula, in the rate of complications or in the results of the hysterosalpingography. CONCLUSIONS: The cervical cap cannula appears to be superior to the traditional metal cannula for performing hysterosalpingography.

The role of laparoscopic-assisted myomectomy (LAM).

Laparoscopic myomectomy has recently gained wide acceptance. However, this procedure remains technically highly demanding and concerns have been raised regarding the prolonged time of anesthesia, increased blood loss, and possibly a higher risk of postoperative adhesion formation. Laparoscopic-assisted myomectomy (LAM) is advocated as a technique that may lessen these concerns regarding laparoscopic myomectomy while retaining the benefits of laparoscopic surgery, namely, short hospital stay, lower costs, and rapid recovery. By decreasing the technical demands, and thereby the operative time, LAM may be more widely offered to patients. In carefully selected cases, LAM is a safe and efficient alternative to both laparoscopic myomectomy and myomectomy by laparotomy. These cases include patients with numerous large or deep intramural myomas. LAM allows easier repair of the uterus and rapid morcellation of the myomas. In women who desire a future pregnancy, LAM may be a better approach because it allows meticulous suturing of the uterine defect in layers and thereby eliminates excessive electrocoagulation.

The accuracy of serum interleukin-6 and tumour necrosis factor as markers for ovarian torsion.

BACKGROUND: The aim of this study was to investigate a possible role for interleukin-6 (IL-6) and tumour necrosis factor (TNF-alpha) as pre-operative markers for the diagnosis of ovarian torsion. METHODS: Twenty consecutive patients admitted to the gynaecological emergency room with suspected clinical diagnosis of ovarian torsion were prospectively assigned to the study. Blood samples were drawn pre-operatively and examined for serum concentrations of IL-6 and TNF-alpha. Surgeons were blinded to laboratory results prior to laparoscopy. RESULTS: The pre-operative diagnosis of ovarian torsion was confirmed during an urgent diagnostic laparoscopy in 8 (40%) patients. The surgical diagnosis among the remaining 12 patients was a large ovarian cyst not in torsion. In six out of eight (75.0%) patients with ovarian torsion serum IL-6 concentrations were elevated. None of the 12 patients without torsion had elevated serum IL-6 concentrations. This difference was statistically significant (P < 0.001). There was no significant difference in the proportion of women with elevated serum TNF-alpha concentrations, two of eight (25.0%) patients with torsion and four of 12 (33.3%) control cases. CONCLUSIONS: Elevated serum IL-6 concentrations, but not serum TNF-alpha concentrations, were significantly associated with the occurrence of ovarian torsion. In patients with vague clinical signs of ovarian torsion, serum IL-6 might help to distinguish which patients should undergo diagnostic laparoscopy.

A comparative study of multifetal pregnancy reduction from triplets to twins in the first versus early second trimesters after detailed fetal screening.

OBJECTIVES: To compare the outcome of multifetal pregnancy reduction from triplets to twins performed either early (at 11-12 weeks' gestation) or late (at 13-14 weeks). METHODS: Ninety-five high-order pregnancies following assisted conception were studied. Transabdominal sonographically guided multifetal pregnancy reduction was performed early in 46 women, while 49 women first underwent a sonographic fetal anomaly scan before undergoing selective reduction. RESULTS: Sonographic screening led to selective termination of a specific fetus in nine cases due to increased nuchal translucency and relative intrauterine growth restriction in three cases each, and meningomyelocele, abdominal cyst and cystic hygroma in one case each. In the early reduction group a diagnosis of hypoplastic left heart in the two remaining twins was subsequently made, and one pair of twins suffers from cerebral palsy. The rate of pregnancy loss was not statistically different between the early (4.3%; 2/46) and late (4.0%; 2/49) termination groups. The birth weight and gestational age at birth were not statistically different between the early ( n = 85) and late ( n = 94) groups (2110 +/- 580 vs. 2140 +/- 490 g, and 35.8 +/- 3.0 vs. 35.7 +/- 3.5 weeks). Similarly there was no statistically significant difference between early and late groups in the incidence of very premature (24-32 weeks; 9.3 vs. 8.3%) and premature (33-36 weeks; 46.5 vs. 47.9%) births. CONCLUSIONS: Early second-trimester multifetal pregnancy reduction from triplets to twins may allow more selective termination of abnormal fetuses without an adverse effect on the outcome of pregnancy. However, further studies are needed in order to confirm our observations in a larger series.

Sonohysterography for the diagnosis of residual trophoblastic tissue.

OBJECTIVE: To assess the efficacy, safety, and associated complications of sonohysterography for the diagnosis of residual trophoblastic tissue. METHODS: We conducted a prospective study of 23 consecutive patients admitted to our ultrasonography unit with clinical and ultrasonographic signs of retained intrauterine tissue. RESULTS: Twelve patients had hydrosonographic features suggestive of residual trophoblastic tissue (i.e., an intrauterine lesion not detachable from the uterine wall after instillation of saline), whereas in 11 cases the hydrosonographic findings were negative for retained tissue. Blood flow was detected within abnormal intrauterine masses in 4 of 12 patients with trophoblastic tissue, whereas it was not detected in any patient without retained tissue (P = .093). No complications were encountered during the procedure or the postprocedure period. None of the patients had anesthetic complications, perforation of the uterus, fluid overload, or any other surgical complication. All 12 patients underwent hysteroscopic removal of the suspected residual trophoblastic tissue, and histologic confirmation of residual trophoblastic tissue was obtained in all cases. CONCLUSIONS: Sonohysterography for detection and diagnosis of residual trophoblastic tissue is an accurate and safe procedure. Further studies comparing the efficacy of sonohysterography with that of diagnostic hysteroscopy are warranted.

Prediction of hyperbilirubinemia in near-term and term infants.

OBJECTIVE: The purpose of this study was to determine whether end-tidal carbon monoxide (CO) corrected for ambient CO (ETCOc), as a single measurement or in combination with serum total bilirubin (STB) measurements, can predict the development of hyperbilirubinemia during the first 7 days of life. METHODS: From 9 multinational clinical sites, 1370 neonates completed this cohort study from February 20, 1998, through February 22, 1999. Measurements of both ETCOc and STB were performed at 30 +/- 6 hours of life; STB also was measured at 96 +/- 12 hours and subsequently following a flow diagram based on a table of hours of age-specific STB. An infant was defined as hyperbilirubinemic if the hours of age-specific STB was greater than or equal to the 95th percentile as defined by the table at any time during the study. RESULTS: A total of 120 (8.8%) of the enrolled infants became hyperbilirubinemic. Mean STB in breastfed infants was 8.92 +/- 4.37 mg/dL at 96 hours versus 7.63 +/- 3.58 mg/dL in those fed formula only. The mean ETCOc at 30 +/- 6 hours for the total population was 1.48 +/- 0.49 ppm, whereas those of nonhyperbilirubinemic and hyperbilirubinemic infants were 1.45 +/- 0.47 ppm and 1.81 +/- 0.59 ppm, respectively. Seventy-six percent (92 of 120) of hyperbilirubinemic infants had ETCOc greater than the population mean. An ETCOc greater than the population mean at 30 +/- 6 hours yielded a 13.0% positive predictive value (PPV) and a 95.8% negative predictive value (NPV) for STB >/=95th percentile. When infants with STB >95th percentile at <36 hours of age were excluded, the STB at 30 +/- 6 hours yielded a 16.7% PPV and a 98.1% NPV for STB >75th percentile. The combination of these 2 measurements at 30 +/- 6 hours (either ETCOc more than the population mean or STB >75th percentile) had a 6.4% PPV with a 99.0% NPV. Conclusions. This prospective cohort study supports previous observations that measuring STB before discharge may provide some assistance in predicting an infant's risk for developing hyperbilirubinemia. The addition of an ETCOc measurement provides insight into the processes that contribute to the condition but does not materially improve the predictive ability of an hours of age-specific STB in this study population. The combination of STB and ETCOc as early as 30 +/- 6 hours may identify infants with increased bilirubin production (eg, hemolysis) or decreased elimination (conjugation defects) as well as infants who require early follow-up after discharge for jaundice or other clinical problems such as late anemia. Depending on the incidence of hyperbilirubinemia within an institution, the criteria for decision making should vary according to its unique population.

Management of a triplet pregnancy with two anencephalic fetuses and polyhydramnios.

The occurrence of a triplet pregnancy discordant for anencephaly is rare and its management presents a clinical dilemma. We report what appears to be the first case of a triplet pregnancy with two anencephalic fetuses complicated by premature contractions and severe polyhydramnios. Its management, which results a healthy newborn weighing 1385 g is discussed.