The dual trigger study: Rationale and study design of a prospective double-blind randomized clinical trial comparing pregnancy rates after co-administration of low dose hCG at the time of GnRH agonist trigger or 35 h later for the prevention of OHSS.

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of controlled ovarian stimulation. The use of gonadotropin releasing hormone (GnRH) agonist for the trigger of oocyte maturation is effective in the prevention of OHSS although it may result in a lower pregnancy rate. The use of adjuvant low dose human chorionic gonadotropin (hCG) at the time of trigger or at the time of oocyte retrieval may improve pregnancy rates. The goal of this dual trigger study is to evaluate the safety and efficacy of the use of low dose hCG administered at the time of GnRH agonist trigger or 35 h later as well as the potential impact on pregnancy rates. The population will consist of 82 women undergoing IVF treatment who are at risk of developing OHSS. This study will be a single center prospective randomized double-blind placebo controlled trial. The randomization schedule will be administered by the Investigational Drug Services of the University. After controlled ovarian stimulation, induction of oocyte maturation will be achieved using a GnRH agonist and patients will be randomized to receive either low dose hCG 1000 IU at the time of trigger and placebo at oocyte retrieval (Study group) or placebo at the time of trigger and hCG 1500 IU at the time of oocyte retrieval (Control group). The main outcomes will be live birth rates and incidence of OHSS. Two ancillary studies will include a quality of life survey and serum assessment of independent corpus luteum function.

Occult abnormal pregnancies after first post-embryo transfer serum beta-human chorionic gonadotropin levels of 1.0-5.0 mIU/mL.

OBJECTIVE: To assess the occult pregnancy rate after "negative" first post-embryo transfer (ET) serum ß-hCG results. DESIGN: Two-part retrospective cohort study and nested case series. SETTING: University-based fertility center. PATIENT(S): A total of 1,571 negative first post-ET serum ß-hCG results were included in the study; 1,326 results (primary cohort, June 2009-December 2013) were initially reported as <5 mIU/mL and 245 results (secondary cohort, January 2014-March 2015) were reported as discrete values from 1.0 to 5.0 mIU/mL. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Rates of occult pregnancy, ectopic pregnancy, and complications after negative first post-ET serum ß-hCG results. RESULT(S): A total of 88.8% (1,178/1,326) of the negative first post-ET results reported as <5 were actually <1.0 mIU/mL. Occult pregnancy was incidentally identified in 1.2% (12/1,041) of subjects with follow-up. Six had ectopic pregnancies, and seven experienced serious complications; 11 (91.7%) of the 12 occult pregnancies had a first post-ET serum ß-hCG level of 1.0-5.0 mIU/mL and 1 (8.3%) <1.0 mIU/mL. All pregnancies with serious complications had initial ß-hCG levels of 1.0-5.0 mIU/mL. Of the 245 results reported as discreet values, occult pregnancies were diagnosed in 5.5% (9/163) of subjects with follow-up. One had an ectopic pregnancy, which was treated with methotrexate. There were no serious complications in the secondary cohort. CONCLUSION(S): The majority of negative first post-ET serum ß-hCG levels are <1.0 mIU/mL. Results from 1.0 to 5.0 mIU/mL may fail to exclude abnormal pregnancy and are associated with poor outcomes compared with ß-hCG levels <1.0 mIU/mL. Serial serum ß-hCG may be warranted in this population.

Survey assessing obesity policies for assisted reproductive technology in the United States.

OBJECTIVE: To determine what assisted reproductive technologies (ART) policies, if any, have been instituted in response to an increasingly overweight and obese patient population. DESIGN: Cross-sectional survey. SETTING: University-affiliated IVF clinic. PATIENT(S): Women in the overweight and obese body mass index (BMI) categories seeking ART treatments. INTERVENTION(S): Anonymous survey sent to medical directors at 395 IVF centers listed in Society for Assisted Reproductive Technology database. MAIN OUTCOME MEASURE(S): Assessment of recommendations, policies, and restrictions for patients who are overweight/obese and who desire treatment for infertility, including in IVF, IUI, and donor egg cycles. RESULT(S): Seventy-seven anonymous responses were received (19.5% response rate): 64.9% of centers have a formal policy for obesity, and 84% of those have a maximum BMI at which they will perform IVF, while 38% of those have a maximum BMI for performing IUI; 64.6% of respondents reported anesthesia requirements/concerns as the primary criteria for patient exclusion. Other primary considerations included safety during ongoing pregnancy and ART outcomes. CONCLUSION(S): Centers that have policies regarding obesity and access to ART consider efficacy, procedural safety, safety in pregnancy, and overall health status. Policies vary widely. The patient's autonomy must be balanced with nonmaleficence and the avoidance of interventions that may be unsafe both immediately and long term.

Single-Nucleotide Polymorphism-Microarray Ploidy Analysis of Paraffin-Embedded Products of Conception in Recurrent Pregnancy Loss Evaluations.

OBJECTIVE: To compare the analysis of chromosome number from paraffin-embedded products of conception using single-nucleotide polymorphism (SNP) microarray with the recommended screening for the evaluation of couples presenting with recurrent pregnancy loss who do not have previous fetal cytogenetic data. METHODS: We performed a retrospective cohort study including all women who presented for a new evaluation of recurrent pregnancy loss over a 2-year period (January 1, 2012, to December 31, 2013). All participants had at least two documented first-trimester losses and both the recommended screening tests and SNP microarray performed on at least one paraffin-embedded products of conception sample. Single-nucleotide polymorphism microarray identifies all 24 chromosomes (22 autosomes, X, and Y). RESULTS: Forty-two women with a total of 178 losses were included in the study. Paraffin-embedded products of conception from 62 losses were sent for SNP microarray. Single-nucleotide polymorphism microarray successfully diagnosed fetal chromosome number in 71% (44/62) of samples, of which 43% (19/44) were euploid and 57% (25/44) were noneuploid. Seven of 42 (17%) participants had abnormalities on recurrent pregnancy loss screening. The per-person detection rate for a cause of pregnancy loss was significantly higher in the SNP microarray (0.50; 95% confidence interval [CI] 0.36-0.64) compared with recurrent pregnancy loss evaluation (0.17; 95% CI 0.08-0.31) (P=.002). Participants with one or more euploid loss identified on paraffin-embedded products of conception were significantly more likely to have an abnormality on recurrent pregnancy loss screening than those with only noneuploid results (P=.028). The significance remained when controlling for age, number of losses, number of samples, and total pregnancies. CONCLUSION: These results suggest that SNP microarray testing of paraffin-embedded products of conception is a valuable tool for the evaluation of recurrent pregnancy loss in patients without prior fetal cytogenetic results. Recommended recurrent pregnancy loss screening was unnecessary in almost half the patients in our study. LEVEL OF EVIDENCE: II.

Progestin and AdipoQ Receptor 7, Progesterone Membrane Receptor Component 1 (PGRMC1), and PGRMC2 and Their Role in Regulating Progesterone's Ability to Suppress Human Granulosa/Luteal Cells from Entering into the Cell Cycle.

The present studies were designed to determine the role of progesterone receptor membrane component 1 (PGRMC1), PGRMC2, progestin and adipoQ receptor 7 (PAQR7), and progesterone receptor (PGR) in mediating the antimitotic action of progesterone (P4) in human granulosa/luteal cells. For these studies granulosa/luteal cells of 10 women undergoing controlled ovarian hyperstimulation were isolated, maintained in culture, and depleted of PGRMC1, PGRMC2, PAQR7, or PGR by siRNA treatment. The rate of entry into the cell cycle was assessed using the FUCCI cell cycle sensor to determine the percentage of cells in the G1/S stage of the cell cycle. PGRMC1, PGRMC2, PAQR7, and PGR mRNA levels were assessed by real-time PCR and their interactions monitored by in situ proximity ligation assays (PLAs). These studies revealed that PGRMC1, PGRMC2, PAQR7, and PGR were expressed by granulosa/luteal cells from all patients, with PGRMC1 mRNA being most abundant, followed by PAQR7, PGRMC2, and PGR. However, their mRNA levels showed considerable patient variation. P4's ability to suppress entry into the cell cycle was dependent on PGRMC1, PGRMC2, and PAQR7 but not PGR. Moreover, PLAs indicated that PGRMC1, PGRMC2, and PAQR7 formed a complex within the cytoplasm. Based on these studies, it is proposed that these three P4 mediators form a complex within the cytoplasm that is required for P4's action. Moreover, P4's ability to regulate human follicle development may be dependent in part on the expression levels of each of these P4 mediators.

Successful frozen blastocyst transfers after failed fresh transfers in assisted reproductive technologies patients with hydrosalpinx.

Untreated hydrosalpinx is known to decrease in vitro fertilization success. We report on 4 patients with hydrosalpinx for whom fresh transfers of 11 good quality embryos did not produce a pregnancy; however, frozen blastocyst transfers in natural cycles resulted in several successful pregnancies, with an implantation rate of 60% (9/15 blastocysts implanted).

Virtual hysterosalpingography in the diagnosis of bicornuate versus septate uterus.

OBJECTIVE: To study the value of virtual hysterosalpingography (VHSG) in the diagnosis of bicornuate vs. septate uterus. DESIGN: Retrospective study of all cases with bicornuate or septate uterus that had VHSG during the last 3 years at our center. SETTING: Private fertility center and radiology institute with university affiliations. PATIENT(S): A total of 47 patients (from more than 1,000 studies) with bicornuate uterus (n = 15) or septate uterus (n = 32) were analyzed to determine the ability of VHSG to distinguish both entities. INTERVENTION(S): Virtual hysterosalpingography was performed in patients with bicornuate or septate uterus. MAIN OUTCOME MEASURE(S): Procedure length, discomfort, amount of radiation, and ability to outline the uterine fundus. RESULT(S): We were able to clearly distinguish bicornuate from septate uterus. In all patients who underwent septoplasty the VHSG diagnosis of septate uterus was confirmed. Virtual hysterosalpingography was well tolerated by all patients; scanning took 5 seconds per patient, and the average radiation was very low (0.9 ± 0.7 mSv). CONCLUSION(S): Virtual hysterosalpingography seems to be a valuable tool in the diagnosis of common uterine anomalies.