Placental expression and chromosomal localization of the human Gcm 1 gene.

Although gcm was first recognized for its role in specifying glial cell fate in Drosophila melanogaster, its mammalian counterparts are expressed predominantly in non-neural tissues. Here we demonstrate expression of the mouse and human GCM 1 proteins in placenta. We have prepared a highly specific antibody that recognizes the GCM 1 protein and have used it to assess the temporal and spatial expression profile of the protein. In both mouse and human placenta, the protein is associated with cells that are involved with exchange between maternal and fetal blood supplies: the labyrinthine cells of the mouse placenta and the syncytio- and cytotrophoblasts of the human placenta. Using the full-length hGcm 1 cDNA as a probe, we have mapped the gene on human chromosome 6p12 by fluorescent in situ hybridization.

A case of endometrial cancer following endometrial ablation for dysfunctional uterine bleeding.

BACKGROUND: A concern voiced by critics of endometrial ablation is the possibility that cryptic endometrial adenocarcinoma may develop after such ablation. To date, this concern has been theoretical. CASE: A patient presented with vaginal bleeding and was diagnosed with endometrial carcinoma 5 years after ablation of the superficial endometrium. CONCLUSION: The possibility exists for endometrial carcinoma to develop years after endometrial ablation. Careful patient selection, thorough evaluation of any post-procedure bleeding, careful postoperative surveillance, and continued evaluation of the procedure and its long-term efficacy are indicated.

Severe ovarian hyperstimulation despite prophylactic albumin at the time of oocyte retrieval for in vitro fertilization and embryo transfer.

OBJECTIVE: To report two cases of severe ovarian hyperstimulation syndrome (OHSS) despite the administration of 50 g IV albumin at the time of oocyte retrieval. Two previous published series failed to observe OHSS in patients receiving prophylactic IV albumin. DESIGN: Case reports of two women undergoing controlled ovarian hyperstimulation with E2 > 4,500 pg/mL (conversion factor to SI unit, 3.671) on the day of hCG administration who developed OHSS despite prophylactic albumin administration. SETTING: The division of reproductive endocrinology at the Mount Sinai Medical Center. INTERVENTIONS: Fifty grams IV albumin (200 mL of a 25% albumin solution) were administered over 30 minutes at the time of oocyte retrieval. MAIN OUTCOME MEASURES: Prevention of interstitial fluid accumulation such as ascites, pleural effusions, and generalized edema. The other goals of albumin administration included avoiding hemoconcentration, renal insufficiency, and thrombotic complications. RESULTS: The patients developed sequelae of severe OHSS requiring hospitalization, despite administration of IV albumin. CONCLUSION: Albumin is a promising agent in the prevention of OHSS. However, until the basic pathophysiology of this disorder can be elucidated, the mechanism of its action will remain elusive. Attempts to quantify and report clinical outcomes and the ultimate completion of a prospective randomized study will assist in the prevention and management of this enigmatic disorder.

Does increasing ovum donor compensation lead to differences in donor characteristics?

OBJECTIVE: To evaluate the effects of a compensation increase for anonymous ovum donors on demographic and social characteristics. DESIGN: Retrospective analysis. SETTING: The Mount Sinai Medical Center Ovum Donation Program. PATIENT(S): All program applicants for 2 years preceding (group I, n = 2,934) and 1 year following an increase in donor compensation (group II, n = 1,114; total N = 4,048). INTERVENTION(S): Compensation was increased from $2,500 to $5,000 per cycle. MAIN OUTCOME MEASURE(S): Demographic and social characteristics of applicants and donors. RESULT(S): More group II applicants (65.7%) than group I applicants (49.2%) returned an initial biographical questionnaire. Compensation level did not affect the percentage rejected at any stage in the application process or ultimately selected. There were no differences in donors in age, marital status, education, race, religion, or psychological profile. Group II donors had more previous pregnancies (group II mean = 1.2, group I mean = 0.6) and previous abortions (group II mean = 0.8, group I mean = 0.4). CONCLUSION(S): Increasing compensation may result in a higher percentage of potential donors completing an initial questionnaire but does not alter the demographic and social characteristics of selected donors. Adherence to a rigorous applicant screening ensures that donor characteristics remain independent from compensation.

Hydrosalpinx fluid has embryotoxic effects on murine embryogenesis: a case for prophylactic salpingectomy.

OBJECTIVE: To ascertain if hydrosalpinges are associated with reduced pregnancy rates and increased pregnancy loss after IVF-ET. Increased volume and leakage of hydrosalpinx fluid may exert negative effects on follicular development and embryo quality and/or render the uterine environment hostile to embryogenesis. We undertook this study to examine the effect of hydrosalpinx fluid on murine embryogenesis in vitro. DESIGN: Descriptive study. SETTING: Tertiary care facility. PATIENT(S): Premenopausal females undergoing salpingectomy or salpingostomy for hydrosalpinges. INTERVENTION(S): Collection of discarded hydrosalpinx fluid and development of a dose response curve for the effect of hydrosalpinx fluid on murine embryogenesis. MAIN OUTCOME MEASURE(S): Development of single cell mouse embryos in vitro. RESULT(S): All samples of tubal fluid obtained from hydrosalpinges demonstrated a significant embryo toxic effect at either the 100% or 10% concentration. Hydrosalpinx fluid demonstrated pH values (8.45 to 8.65) significantly higher than the physiologic range. Correction of pH to that of media did not affect cavitation rate. CONCLUSION(S): There is a well-defined and significant toxic effect of hydrosalpinx fluid. Procedures such as salpingectomy or proximal tubal occlusion to circumvent the passage of hydrosalpinx fluid into the uterine cavity may have beneficial effects on the developmental environment for embryos in vivo.

Cumulative number and morphological score of embryos resulting in success: realistic expectations from in vitro fertilization-embryo transfer.

OBJECTIVE: To define statistical thresholds for the number and morphological score of embryos transferred that would be predictive of reproductive success in an IVF program. DESIGN: A retrospective review of patient records. SETTING: The Mount Sinai Medical Center Assisted Reproductive Technologies Program. PARTICIPANTS: One hundred women who underwent IVF-ET for a diagnosis of tubal occlusion and later delivered viable infants. RESULTS: The mean number of embryos transferred before achieving live birth was 10.7 +/- 7.9 (mean +/- SD), with one half of patients achieving success within the first seven embryos transferred, and 95% achieving success within 25 embryos. For high quality embryos, the numbers were 7.5 +/- 6.3, 5, and 17, respectively, and, for the cumulative embryo score, a measure of both embryo morphology and metabolic activity, were 114.2 +/- 86.0, 83, and 280, respectively. Greater than 50% of live births occurred within the first two ET attempts. CONCLUSIONS: Although more than half of patients achieved reproductive success within the first two ETs and the first five high quality embryos transferred, after this threshold, fecundity declined rapidly. The calculation of cumulative embryo scores offered additional prognostic information. While all prior attempts to define IVF-ET failure have done so by including patients who did not become pregnant, we have found an analysis of our successes to be a useful adjunct in counseling patients.

Relationship between circulating human chorionic gonadotropin levels and premature luteinization in cycles of controlled ovarian hyperstimulation.

OBJECTIVE: To determine if premature luteinization (serum P levels > 1.1 ng/mL on or before the day of hCG administration) during controlled ovarian hyperstimulation (COH) is associated with elevated levels of serum hCG. SETTING: Tertiary fertility center. DESIGN: Retrospective evaluation of ovum donors undergoing COH. PATIENTS: Forty-four women underwent COH. Comparisons of serum hCG levels and hormonal and cycle characteristics were made between cycles with premature luteinization (group I) and without premature luteinization (group II). RESULTS: Group I (16 women) were similar to women in group II in age, amount of hMG, and the ratio of FSH:hMG received. Both groups received hCG on similar days, but women in group I had higher peak E2 levels. Serum hCG levels increased and correlated with serum P levels in group I only and were higher on the day of hCG administration (group I 1.8 +/- 0.9 mIU/mL versus group II 1.2 +/- 0.45 mIU/mL; conversion factor to SI unit, 1.00). Peak E2 and LH levels, ampules of hMG and the FSH:LH ratio, and day of hCG administration did not correlate with hCG levels. Human chorionic gonadotropin exposure, as measured by area under the curve, was significantly higher in group I compared with group II. CONCLUSION: Higher serum levels of hCG and integrated hCG exposure are found in COH cycles with premature luteinization compared with cycles without premature luteinization. Higher hCG levels may be due to decreased clearance of hCG from the circulation and/or the hCG content of hMG.

Failed fertilization in vitro: second day micromanipulation of oocytes versus reinsemination.

OBJECTIVE: To compare routine reinsemination with 2nd day micromanipulation in patients with poor day 1 fertilization. DESIGN: A retrospective review of patient records. SETTING: The Mount Sinai Medical Center Assisted Reproductive Technologies Program. PARTICIPANTS: Patients undergoing IVF-ET who had poor fertilization (< 35%) with standard insemination and underwent second day reinsemination of oocytes (group I, n = 84) compared with patients who underwent 2nd day micromanipulation with subzonal insemination (group II, n = 12). MAIN OUTCOME MEASURES: Fertilization rate, cleavage rate, number of embryo transfers, and pregnancy rate. RESULTS: Fertilization rate and cleavage rate were significantly higher in group II patients. Pregnancies per transfer were similar between groups I (3/21, 14.3%) and II (0/9, 0%). Second day fertilization was possible in 9 of 12 group II patients, and fertilization rate was higher than day 1 in all nine, however, only 50% achieved cleavage, and none achieved pregnancy. CONCLUSIONS: Although micromanipulating oocytes that fail to fertilize may identify occult male factor infertility, may help the clinician plan future cycles, and may result in fertilization and even transfer of embryos in some cycles, there were no pregnancies in our series, and, for now, the clinical efficacy of this procedure remains in question.

Sisters of women with premature ovarian failure may not be ideal ovum donors.

OBJECTIVES: To determine whether the sisters of women with premature ovarian failure (POF) showed a response to gonadotropin stimulation comparable to that of anonymous ovum donors. DESIGN: Historical cohort study. SETTING: Records of 228 consecutive ovum recipients in an academic assisted reproductive technology program. PATIENT(S): Criteria for inclusion were oocyte recipients age < or = 40 years, FSH > 18 mIU/mL (conversion factor to SI unit, 1.00), and/or failure to respond appropriately to controlled ovarian hyperstimulation (COH). Seventy-nine recipients were classified on the basis of whether they received oocytes from anonymous donors (group I, n = 66) or sister donors (group II, n = 13). MAIN OUTCOME MEASURE(S): Controlled ovarian hyperstimulation response, pregnancy rates (PRs), and implantation rates. RESULT(S): The ages of the donors to groups I and II were comparable (31.1 +/- 16.7 versus 29.8 +/- 7.2 years), but those in group II exhibited a higher baseline FSH level (12.8 +/- 2.1 versus 8.6 +/- 5.8 mIU/mL). Group II versus I had a relative risk of 5.1 for cancellation (4 of 13 [30.8%] versus 4 of 66 [6.1%], respectively). In completed cycles of groups I and II, respectively, there was no difference in serum E2 on the day of hCG administration (2,356 +/- 826 versus 1,847 +/- 843 pg/mL; conversion factor to SI unit, 3,671), number of oocytes retrieved (25 +/- 14 versus 22 +/- 13), number of embryos transferred (4.4 +/- 2.1 versus 4.0 +/- 1.0), spontaneous abortion rate (22.7% versus 25.0%), PR (35.5% versus 36.4%), and implantation rate (16.2% versus 16.4%). CONCLUSION(S): There is an increased cancellation rate and, consequently, an overall trend toward decreased ovarian response to gonadotropin stimulation in the sisters of patients with POF. Despite these factors, the implantation rates and PRs of embryos derived from patients reaching retrieval were similar to those from anonymous donors. We recommend counseling women with POF that their sisters may not be ideal ovum donors.

An elevated day three follicle-stimulating hormone:luteinizing hormone ratio (FSH:LH) in the presence of a normal day 3 FSH predicts a poor response to controlled ovarian hyperstimulation.

OBJECTIVE: To determine if an elevated FSH:LH ratio predicts response in infertile patients undergoing controlled ovarian hyperstimulation (COH) for IVF-ET. DESIGN: Retrospective study. SETTING: The Division of Reproductive Endocrinology at the Mount Sinai Medical Center, New York, New York. PARTICIPANTS: Seventy-four patients undergoing IVF-ET using similar protocols for COH with day 3 FSH, LH, and E2 testing available for analysis. All patients were < 41 years of age and had day 3 serum FSH < 15 mIU/mL (conversion to SI unit, 1.00). MAIN OUTCOME MEASURES: Follicle-stimulating hormone:LH ratio, day 8 serum E2, peak serum E2, cancellation rate, pregnancy rate, and number and size of follicles. RESULTS: An FSH:LH ratio > or = 3.6 (group I) predicted a poor response to COH (sensitivity 85.7% and specificity 95%). There were no significant differences regarding day 3 serum FSH and ampules of gonadotropins used for COH. Group I (ratio > or = 3.6) patients responded to COH with lower day 8 E2 (97 +/- 18 versus 319 +/- 36 pg/mL; conversion factor to SI unit, 3.671), peak E2 (422 +/- 115 versus 2,368 +/- 183 pg/mL), and fewer follicles > 15 mm (1.3 +/- 0.5 versus 17.1 +/- 1.0). In group I the cycle cancellation rate (12/14) was significantly higher than the group II cycle cancellation rate (2/60) and pregnancy rate in group II (ratio < 3.6) was 25%. CONCLUSIONS: The FSH:LH ratio may increase before a dramatic increase in serum FSH is observed and appears to be a useful marker of ovarian reserve.

Elevated day 3 serum follicle stimulating hormone and/or estradiol may predict fetal aneuploidy.

OBJECTIVE: To determine whether baseline serum FSH and/or E2 concentrations can predict the risk for fetal chromosomal abnormalities. DESIGN: Case control study. SETTING: Reproductive technology program at a university hospital. PATIENT(S): Patients who underwent dilation and curettage (D + C), and whose products of conception were karyotyped. INTERVENTION(S): Patients underwent natural conception or controlled ovarian hyperstimulation followed by intrauterine insemination, in vitro fertilization and embryo transfer, gamete intrafallopian transfer, or zygote intrafallopian transfer. MAIN OUTCOME MEASURE(S): Baseline serum FSH and E2 concentrations and fetal karyotype. RESULT(S): Genetic evaluation of 78 D + C specimens revealed 34 normal and 44 abnormal fetal karyotypes. A significantly greater proportion of women with abnormal fetal karyotype had elevated baseline serum FSH (> or =15 mIU/mL [RIA] or 10 mIU/mL [Immulite]) and/or E2 > or = 50 pg/mL [Immulite]) compared with women of normal fetal karyotype. Among karyotypically abnormal abortuses, autosomal trisomy was the most common abnormality noted (79.5%), followed by mosaicism (6.8%), triploidy (6.8%), monosomy XO (4.5%), and balanced translocation (2.3%). CONCLUSION(S): Baseline serum FSH and/or E2 concentrations may be valuable as predictors of fetal aneuploidy.

Diagnosing amnionicity at 6 weeks of pregnancy with transvaginal three-dimensional ultrasonography: case report.

OBJECTIVE: To report a case of monochorionic, diamniotic twin pregnancy diagnosed at 6 weeks of pregnancy with three-dimensional (3D) transvaginal sonography and to discuss the use of this diagnostic method in the evaluation of multifetal pregnancy in the first trimester. DESIGN: Case report. SETTING: University-based IVF program. PATIENT(S): A 30-year-old ovum recipient underwent ultrasonographic evaluation of a first-trimester twin pregnancy. INTERVENTION(S): Two-dimensional (2D) and 3D transvaginal sonography. MAIN OUTCOME MEASURE(S): Accurate diagnosis of chorionicity and amnionicity. RESULT(S): Monoamniotic pregnancy and conjoined twinning could not be ruled out by using 2D transvaginal sonography at 6 weeks, because only one yolk sac (YS) and no membranes could be visualized, and the two embryos were closely positioned within one gestational sac. Applying 3D technique, two YSs and two separate embryos could clearly be observed, establishing the correct diagnosis of a monochorionic, diamniotic pregnancy. CONCLUSION(S): The 3D transvaginal ultrasonography provides a quick and accurate diagnostic modality for the evaluation of a first-trimester multiple gestation.

Perinatal outcome after embryo transfer in ovum recipients. A comparison with standard in vitro fertilization.

OBJECTIVE: To compare perinatal outcome after embryo transfer vs. standard in vitro fertilization (IVF) in ovum recipients. STUDY DESIGN: We reviewed 22 consecutive ovum donor pregnancies delivered at Mount Sinai Hospital between July 1989 and November 1992 and matched them for age, parity and order of gestation to a control group who underwent standard IVF-embryo transfer (ET) during that period. RESULTS: The two groups showed similar rates of maternal complications, including hypertensive disorders, gestational diabetes and puerperal complications. When compared to patients undergoing autologous IVF-ET, ovum recipients had a lower rate of preterm labor (22.7% vs. 54.6%, P < .05), a higher mean gestational age at delivery (38.7 vs. 36.1 weeks, P < .01) and increased mean birth weight of neonates (2,924 vs. 2,374 g, P < .005). Though infants born through traditional IVF-ET were more likely to be preterm, Apgar scores were similar at one and five minutes. Our data support the generally favorable outcome seen in pregnancies conceived through ovum donation despite the fact that many of these patients had prior poor prenatal outcomes, long intervals until conception, and coexisting medical conditions. CONCLUSION: Ovum donation in women of comparable ages has obstetric outcomes equal to or better than patients undergoing traditional IVF-ET. Obstetric and perinatal outcome do not seem to be impaired in patients receiving donated oocytes.

Is the risk of perinatal transmission of human immunodeficiency virus increased by the intrapartum use of spiral electrodes or fetal scalp pH sampling?

OBJECTIVE: Our aim was to determine whether the intrapartum use of fetal scalp electrodes or fetal scalp pH sampling increases the rate of perinatal transmission of human immunodeficiency virus. STUDY DESIGN: The rate of perinatal transmission of human immunodeficiency virus in 31 monitored pregnancies was determined, and those pregnancies were compared with a control group of 117 pregnancies. RESULTS: The monitored group was comparable to the control group with respect to maternal age, race, human immunodeficiency virus risk behavior, CD4+ cell count, p24 antigen status, and stage of human immunodeficiency virus disease. The mean gestational age at delivery and the mean birth weight were similar in the monitored group and the control group. The perinatal transmission rate for the monitored group (29.0%) was not statistically different from that of the control group (25.6%). CONCLUSIONS: If confirmed by larger studies, our findings suggest that the intrapartum use of fetal scalp electrodes or fetal scalp pH sampling does not appear to increase the perinatal transmission of human immunodeficiency virus.

Endometriosis is not detrimental to embryo implantation in oocyte recipients.

PURPOSE: Our purpose was to determine the effects of endometriosis on implantation and pregnancy rates in ovum recipients. METHODS: The medical records of 239 consecutive oocyte recipient patients who were treated between January 1, 1991, and June 30, 1995, were analyzed retrospectively. Recipients with endometriosis (group 1; n = 55) were compared to recipients without endometriosis (group II; n = 184). Patients in group I had active endometriotic disease confirmed by laparoscopy and were subdivided into mild (Stages I and II; n = 18) and moderate to severe (Stages III and IV; n = 37) endometriosis. RESULTS: No difference was found in recipient age, endometrial thickness, donor age, and embryos transferred. The pregnancy rates (28 versus 29%) and implantation rates (12 and 13%) were also comparable between group I and group II, as well as between patients with mild and patients with moderate to severe endometriosis. CONCLUSIONS: The presence of endometriosis in oocyte recipients does not lower implantation or pregnancy rates. We conclude that the adverse effect of endometriosis on reproductive outcome is not related to implantation but, in fact, is most likely an effect on oocyte or embryo quality.

Early first-trimester ultrasound provides a window through which the chorionicity of twins can be diagnosed in an in vitro fertilization (IVF) population.

PURPOSE: Early and accurate diagnosis of placentation alerts the obstetrician to potential clinical sequelae. The reproductive endocrinologist has a unique opportunity to sonographically evaluate the very early intrauterine pregnancy. We undertook this study to determine whether chorionicity could accurately be predicted using early first-trimester transvaginal ultrasound. RESULTS: Of 47 sets of twins conceived through our IVF-ET program, all underwent detailed transvaginal sonography. These findings were then compared with results of placental pathology examination, after birth. Transvaginal sonography was performed 41 days following embryo transfer. All 3 monochorionic placentas were correctly predicted by ultrasound, while the remaining 44 placentas were dichorionic. CONCLUSIONS: The significance of our findings lies both in our 100% accuracy in diagnosis and in the extremely early gestational age at which we were able to establish correctly the diagnosis of chorionicity. The errors in diagnosis made by previous investigators were often the result of not recognizing single placentae which were later histologically shown to be the result of placental fusion. The infertility specialist has a unique window of opportunity to evaluate placentation and should provide useful information regarding chorionicity to the obstetrical team.

Three-dimensional measurement of gestational and yolk sac volumes as predictors of pregnancy outcome in the first trimester.

Along with crown-rump length (CRL), the size (diameter) of embryonic structures such as gestational sac (GS) and yolk sac (YS) may have prognostic value for embryonic development. We proposed that first-trimester volume calculations of these structures using transvaginal three-dimensional ultrasound technique may have value as predictors of adverse reproductive outcome. Forty-nine consecutive patients (treated for infertility) with singleton pregnancies were included in this prospective study. Seventy-three examinations were performed in case of pregnancies with normal, and 12 with abnormal outcome. GS and YS volumes were plotted against gestational age (GA) (25-65 days post ovulation) to create nomograms for normal outcome and the same procedure was carried out with CRL measurements as well. Measurements of abnormal pregnancies were compared with these nomograms. Specificity, sensitivity, positive and negative predictive values were also calculated. Regression analysis revealed a power correlation between GS volumes and GA, logarithmic relationship was observed when YS volumes were plotted against GA. CRL showed logarithmic correlation with GA as well. Both GS volumetry and CRL measurements proved to have statistically significant predictive value for adverse outcome (p<0.05). However, no statistically significant difference was found when YS volumes of normal and abnormal pregnancies were compared. Specificity, sensitivity, positive and negative predictive values of GS volumes and CRL were similar. Mean YS/GS ratios also had good predictive values (p<0.05). Volume determination of YS and GS can be performed quickly and simply applying three-dimensional sonography. Volumetry of GS proved to be a sensitive predictor for pregnancy outcome and can be a good supplement to CRL measurements.

Embryo quality and pregnancy potential of fresh compared with frozen embryos--is freezing detrimental to high quality embryos?

To determine the effect of cryopreservation on embryo quality and the pregnancy potential of embryos, donated oocytes from the same donor (n = 24) were randomly allocated, with subsequent transfer to two or more different ovum recipients resulting in at least one fresh and one frozen embryo transfer cycle from the same cohort of oocytes. Endometrial receptivity was controlled in all ovum recipients, and male factor patients were excluded. The number of embryos transferred, mean embryo grade transferred, number of high quality embryos (grade < or = 2.5, grade 1 being best) transferred and embryo implantation and live birth rates are reported. Significantly more embryos (4.4 +/- 1.2 versus 3.3 +/- 1.2, P < 0.00003) of higher quality (1.9 +/- 0.5 versus 2.1 +/- 0.5, P < 0.013) and of a more advanced cell stage (3.0 +/- 0.6 versus 2.6 +/- 0.7, P < 0.019) were transferred fresh than after cryopreservation respectively. Implantation rates/embryo [19/151 (12.6%) and 9/111 (8.1%)] and live birth rates/transfer [11/42 (26.2%) and 6/45 (13.3%)], from fresh and frozen transfers respectively, were not significantly different despite the larger number of high quality embryos transferred fresh. Embryo cryopreservation adversely affects embryo quality, but does not have detrimental effects on the implantation or pregnancy potential of high quality embryos. Because of the loss of embryos during freeze-thawing during frozen embryo cycles, every effort should be made to attempt a fresh transfer.