High Peak Estradiol/Mature Oocyte Ratio Predicts Lower Clinical Pregnancy, Ongoing Pregnancy, and Live Birth Rates in GnRH Antagonist Intracytoplasmic Sperm Injection Cycles.

OBJECTIVE: To define the relationship between peak estradiol (E2)/mature oocyte ratio and pregnancy outcomes in gonadotropin-releasing hormone (GnRH) antagonist intracytoplasmic sperm injection (ICSI) cycles. STUDY DESIGN: Retrospective cohort study in the setting of an academic reproductive medicine practice. Records from 162 fresh, autologous, GnRH antagonist ICSI cycles performed between 2009 and 2012 .were analyzed. The main outcome measures were rates of clinical pregnancy (CPR), ongoing pregnancy (OPR), and live birth (LBR). RESULTS: For the primary analysis, 4 groups were created based on peak E2/mature oocyte ratio (group 1: <200, group 2: 200-300, group 3: 300-400, and group 4: >400 pg/mL/oocyte). After adjusting for age, basal FSH, and the number of mature oocytes, a significantly lower OPR was seen in group 4 as compared to group I (OR 0.15, 95% CI 0.03-0.86; p=0.032) and group 3 (OR 0.17, 95% CI 0.03-0.98; p=0.048), respectively. The adjusted LBR was also significantly lower in group 4 as compared to group 1 (OR 0.15, 95% CI 0.03-0.83; p=0.030). In a secondary analysis, 3 ranges of peak E2/ mature oocyte ratio (<200, 200-400, and >400 pg/ mL/oocyte) were compared between low, normal, and high responders (<6, 6-15, and >15 mature oocytes, respectively). Clinical pregnancy rate, OPR, and LBR were all lower in normal responders when the E2/oocyte ratio exceeded 400 pg/mL/oocyte as compared to <200 pg/mL/oocyte and 200-300 pg/mL/oocyte (CPR 1% vs. 16% and 32%, respectively, p=0.017; OPR 0 vs. 15% and 27%, respectively, p=0.011; and LBR 0 vs. 13% and 26%, respectively, p=0.018). CONCLUSION: Very elevated peak E2/mature oocyte ratio is associated with a lower CPR, OPR, and LBR in fresh, autologous, GnRH antagonist ICSI cycles.

The impact of short-term depot-medroxyprogesterone acetate treatment on resting metabolic rate.

OBJECTIVE: This study examines the effect of a progestogen (depot-medroxyprogesterone acetate, DMPA) on resting metabolic rate (RMR) in a cohort of young, normal-weight healthy women. We hypothesize an increase in RMR and nonshivering thermogenesis (NST) resulting in increased body temperature by DMPA. STUDY DESIGN: We performed a prospective cohort study in 13 subjects tested at baseline, 3 weeks and 9 weeks after 150 mg intramuscular DMPA administration. RMR was determined with indirect calorimetry. Secondary endpoints included changes in body mass index (BMI), body composition, temperature and serum levels of estradiol (E2), luteinizing hormone (LH), progesterone and MPA. RESULTS: The percent change in RMR from baseline to week 3 (9%) was significantly higher than the percent change from baseline to week 9 (1.6%) (p=.045). The greatest percent change from baseline to week 3 compared to baseline to week 9 was seen in women initiating DMPA in the luteal phase of the cycle. Hypothalamic-pituitary-ovarian axis was evident by decreases in E2, LH and progesterone. DMPA resulted in increased body temperature with a significant correlation between the change in body temperature and the change in RMR. No change in body composition was seen. CONCLUSIONS: RMR and NST increased in young healthy women with normal BMI 3 weeks after receiving the initial dose of 150 mg DMPA for contraception. The effect was augmented when the drug was administered during the luteal phase of the menstrual cycle. IMPLICATION: DMPA increases RMR and thermogenesis independent of changes in body mass. An increase in weight with chronic DMPA may result from a combination of hyperphagia and abnormal NST in predisposed individuals.

Pregnancy outcomes decline with increasing body mass index: analysis of 239,127 fresh autologous in vitro fertilization cycles from the 2008-2010 Society for Assisted Reproductive Technology registry.

OBJECTIVE: To examine the effect of body mass index (BMI) on IVF outcomes in fresh autologous cycles. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 239,127 fresh IVF cycles from the 2008-2010 Society for Assisted Reproductive Technology registry were stratified into cohorts based on World Health Organization BMI guidelines. Cycles reporting normal BMI (18.5-24.9 kg/m(2)) were used as the reference group (REF). Subanalyses were performed on cycles reporting purely polycystic ovary syndrome (PCOS)-related infertility and those with purely male-factor infertility (34,137 and 89,354 cycles, respectively). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation rate, clinical pregnancy rate, pregnancy loss rate, and live birth rate. RESULT(S): Success rates and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for all pregnancy outcomes were most favorable in cohorts with low and normal BMIs and progressively worsened as BMI increased. Obesity also had a negative impact on IVF outcomes in cycles performed for PCOS and male-factor infertility, although it did not always reach statistical significance. CONCLUSION(S): Success rates in fresh autologous cycles, including those done for specifically PCOS or male-factor infertility, are highest in those with low and normal BMIs. Furthermore, there is a progressive and statistically significant worsening of outcomes in groups with higher BMIs. More research is needed to determine the causes and extent of the influence of BMI on IVF success rates in other patient populations.

Pregnancy outcomes decline with increasing recipient body mass index: an analysis of 22,317 fresh donor/recipient cycles from the 2008-2010 Society for Assisted Reproductive Technology Clinic Outcome Reporting System registry.

OBJECTIVE: To examine the effect of recipient body mass index (BMI) on IVF outcomes in fresh donor oocyte cycles. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 22,317 donor oocyte cycles from the 2008-2010 Society for Assisted Reproductive Technology Clinic Outcome Reporting System registry were stratified into cohorts based on World Health Organization BMI guidelines. Cycles reporting normal recipient BMI (18.5-24.9) were used as the reference group. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation rate, clinical pregnancy rate (PR), pregnancy loss rate, live birth rate. RESULT(S): Success rates and adjusted odds ratios with 95% confidence intervals for all pregnancy outcomes were most favorable in cohorts of recipients with low and normal BMI, but progressively worsened as BMI increased. CONCLUSION(S): Success rates in recipient cycles are highest in those with low and normal BMI. Furthermore, there is a progressive and statistically significant worsening of outcomes in groups with higher BMI with respect to clinical pregnancy and live birth rate.

Ectopic pregnancy rate increases with the number of retrieved oocytes in autologous in vitro fertilization with non-tubal infertility but not donor/recipient cycles: an analysis of 109,140 clinical pregnancies from the Society for Assisted Reproductive Technology registry.

OBJECTIVE: To study the impact of controlled ovarian stimulation on ectopic pregnancy (EP) rate as a function of the number of oocytes retrieved, using donor IVF cycles as a control. DESIGN: Retrospective cohort study using a large national database. SETTING: Not applicable. PATIENT(S): Data from 109,140 cycles from the 2008-2010 SART registry, including 91,504 autologous cycles and 17,636 donor cycles in patients with non-tubal infertility. INTERVENTION(S): Varying amounts of oocytes retrieved in autologous and donor IVF. MAIN OUTCOME MEASURE(S): Ectopic pregnancy rates. RESULT(S): In autologous cycles, the EP rate significantly increased as oocyte yield increased. This association was not found in oocyte recipients. CONCLUSION(S): In autologous IVF cycles, increasing oocyte yield is correlated with a significantly increased EP rate. This association is not found in oocyte recipients, indicating that the increased EP rate may be due to the supraphysiologic hormone levels achieved with controlled ovarian hyperstimulation.

High Peak Estradiol Predicts Higher Miscarriage and Lower Live Birth Rates in High Responders Triggered with a GnRH Agonist in IVF/ICSI Cycles.

OBJECTIVE: To investigate parameters predictive of pregnancy outcomes in high responders undergoing fresh, autologous, GnRH antagonist IVF/ICSI cycles using a GnRH agonist trigger. STUDY DESIGN: Retrospective cohort study of all patients deemed high-risk for ovarian hyperstimulation syndrome who underwent fresh, autologous IVF/ICSI using a GnRH agonist trigger at an academic fertility center from 2010-2012. RESULTS: A total of 71 first cycles were analyzed. Rates of clinical pregnancy, live birth (LB), and total (clinical plus biochemical) miscarriage (MC) were 52%, 38%, and 25%, respectively. Mean peak estradiol (E2) and the number of oocytes retrieved were 3,701 pg/mL and 15.2, respectively. Peak E2 was significantly higher in those cycles resulting in clinical MC (p = 0.003). After adjusting for age, basal follicle stimulating hormone, and the number of oocytes retrieved, elevated peak E2 remained associated with increased clinical MC (p = 0.029) and trended towards a relationship with higher total MC (p = 0.062). When peak E2 was treated as a binary variable based on the threshold value of > 5,000 pg/mL, peak E2 above this value was associated with a higher rate of clinical MC (OR = 16.14 with 95% CI 1.25-209.35, p = 0.033) and total MC (OR = 6.81 with 95% CI 1.12-41.54, p = 0.037), as well as a lower LB rate (OR = 0.095 with 95% CI 0.01-0.90, p = 0.041). CONCLUSION: Clinicians should recognize most IVF/ICSI patients triggered with a GnRH agonist as inherently in danger of excessively high serum E2 and avoid peak levels > 5,000 pg/mL in order to avoid higher MC and lower LB rates.

Pregnancy rates in donor oocyte cycles compared to similar autologous in vitro fertilization cycles: an analysis of 26,457 fresh cycles from the Society for Assisted Reproductive Technology.

OBJECTIVE: To use a large US IVF database and compare pregnancy outcomes in fresh donor oocyte versus autologous IVF cycles in women age 20-30 years. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): Women undergoing fresh autologous ovarian stimulation, and oocyte donors and recipients in the United States between 2008 and 2010. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation, clinical pregnancy (CP), and live birth (LB) rates. RESULT(S): Despite similar demographics, stimulation, and embryo parameters, donor oocyte recipients had significantly higher rates of implantation, CP, and LB compared to those undergoing fresh autologous cycles. Odds ratios for implantation, CP, and LB significantly favored the donor oocyte group in all comparisons, including those limited to intracytoplasmic sperm injection cycles, intracytoplasmic sperm injection with male factor, unexplained infertility, cleavage stage embryo transfer, blastocyst transfer, elective single blastocyst transfer, and autologous patients with prior tubal ligation. CONCLUSION(S): Recent US data suggest that the hormonal environment resulting from autologous ovarian stimulation lowers IVF success rates. Further research is needed to determine when to avoid fresh embryo transfer in autologous patients.

Pregnancy outcomes decline in recipients over age 44: an analysis of 27,959 fresh donor oocyte in vitro fertilization cycles from the Society for Assisted Reproductive Technology.

OBJECTIVE: To use a large and recent national registry to provide an updated report on the effect of recipient age on the outcome of donor oocyte in vitro fertilization (IVF) cycles. DESIGN: Retrospective cohort study. SETTING: United States national registry for assisted reproductive technology. PATIENT(S): Recipients of donor oocyte treatment cycles between 2008 and 2010, with cycles segregated into five age cohorts: ≤34, 35 to 39, 40 to 44, 45 to 49, and ≥50 years. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation, clinical pregnancy, live-birth, and miscarriage rates. RESULT(S): In donor oocyte IVF cycles, all age cohorts ≤39 years had similar rates of implantation, clinical pregnancy, and live birth when compared with the 40- to 44-year-old reference group. Patients in the two oldest age groups (45 to 49, ≥50 years) experienced statistically significantly lower rates of implantation, clinical pregnancy, and live birth compared with the reference group. Additionally, all outcomes in the ≥50-year-old group were statistically significantly worse than the 45- to 49-year-old group, demonstrating progressive decline with advancing age. CONCLUSION(S): Recent national registry data suggest that donor oocyte recipients have stable rates of pregnancy outcomes before age 45, after which there is a small but steady and significant decline.

Oocyte number as a predictor for ovarian hyperstimulation syndrome and live birth: an analysis of 256,381 in vitro fertilization cycles.

OBJECTIVE: To investigate the association between oocyte number and the rates of ovarian hyperstimulation syndrome (OHSS) and live birth (LB) in fresh autologous in vitro fertilization (IVF) cycles. DESIGN: Retrospective cohort study. SETTING: An academic reproductive medicine practice. PATIENT(S): We analyzed data from 256,381 IVF cycles using the 2008-2010 Society for Assisted Reproductive Technology national registry. Patients were divided into five groups based on retrieved oocyte number. MAIN OUTCOME MEASURE(S): Rates of OHSS and LB were calculated for each group. A generalized estimating equation (GEE) was used to assess differences in OHSS and LB between groups. Receiver operating characteristic (ROC) curves were used to evaluate oocyte number as a predictor of OHSS and LB. INTERVENTION(S): None. RESULT(S): The LB rate increased up to 15 oocytes, then plateaued (0-5: 17%, 6-10: 31.7%; 11-15: 39.3%; 16-20: 42.7%; 21-25: 43.8%; and >25 oocytes: 41.8%). However, the rate of OHSS became much more clinically significant after 15 oocytes (0-5: 0.09%; 6-10: 0.37%; 11-15: 0.93%; 16-20: 1.67%; 21-25: 3.03%; and >25 oocytes: 6.34%). These trends remained after adjustment with the use of GEE. ROC curves revealed that although oocyte number is not useful in the prediction of LB, 15 retrieved oocytes is the number that best predicts OHSS risk. CONCLUSION(S): Retrieval of >15 oocytes significantly increases OHSS risk without improving LB rate in fresh autologous IVF cycles. In general, less aggressive stimulation protocols should be considered, especially in high-responders, to optimize outcomes.

Management of gynecologic surgery in the patient with factor XI deficiency: a review of the literature.

UNLABELLED: Factor XI deficiency is a rare bleeding disorder that is more commonly found in Ashkenazi Jews. Bleeding manifestations of this disorder are varied and poorly correlate with factor XI levels. Spontaneous bleeding is uncommon, whereas delayed postoperative bleeding is often the presentation of factor XI deficiency. To date, there are no standard recommendations for prophylactic treatment in women undergoing gynecologic surgery. Here, we review published cases of gynecological surgery in women with factor XI deficiency and discuss the risks and benefits of various therapeutic options. TARGET AUDIENCE: Obstetricians And Gynecologists. LEARNING OBJECTIVES: After participating in this activity, physicians should be better able to identify the pathophysiology of factor XI deficiency. Compare previous outcomes of prophylactic treatment in patients with factor XI deficiency undergoing gynecological surgery. Implement possible prophylactic therapies for patients with factor XI deficiency undergoing gynecological surgery.

Giant uterine leiomyomata.

OBJECTIVE: To present the case of a patient with giant uterine leiomyomata and review literature pertinent to the subject. DESIGN: Case report and literature review. SETTING: A major university, tertiary-care hospital. PATIENT(S): One patient, with said pathology, who gave informed consent for exploratory laparotomy, total abdominal hysterectomy, and bilateral salpingo-ophorectomy. INTERVENTION(S): Exploratory laparotomy, total abdominal hysterectomy, bilateral salpingo-ophorectomy, reoperation with abdominal washout, and hemostasis for hemoperitoneum. MAIN OUTCOME MEASURE(S): Not applicable. RESULT(S): Not applicable. CONCLUSION(S): Those with giant uterine leiomyomata are a very unique and tiny subset of the millions of women with fibroids. They should be treated similarly to older, more critically ill patients. Their optimal surgical management requires the careful attention to considerations and techniques not common to the typical myomectomy or hysterectomy.

Cetrorelix lowers premature luteinization rate in gonadotropin ovulation induction-intrauterine insemination cycles: a randomized-controlled clinical trial.

Attempting to compare the rates of premature luteinization (PL), clinical pregnancy, and cycle cancellation in ovulation induction-intrauterine insemination (OI-IUI) cycles with and without the GnRH antagonist, cetrorelix, a randomized-controlled trial was undertaken in which patients were randomized to one of two OI-IUI protocols. Those in the cetrorelix arm showed a significantly reduced rate of PL and no change in clinical pregnancy or cycle cancellation rate, leading to the conclusion that GnRH antagonists can decrease the rate of PL, but appear to have no effect on pregnancy or cycle cancellation in gonadotropin OI-IUI cycles.