Impact of time interval from cesarean delivery to frozen embryo transfer on reproductive and neonatal outcomes.

OBJECTIVE: To evaluate differences in reproductive and neonatal outcomes on the basis of the time interval from cesarean delivery to subsequent frozen embryo transfer (FET). DESIGN: Retrospective cohort. SETTING: Multicenter fertility practice. PATIENTS: Women undergoing autologous elective single embryo transfer FET after prior cesarean delivery. INTERVENTION: Time from prior cesarean delivery to subsequent FET. MAIN OUTCOME MEASURES: live birth (LB). RESULTS: A total of 6,556 autologous elective single embryo transfer FET cycles were included. Frozen embryo transfer cycles were divided into eight groups on the basis of the time interval from prior cesarean delivery to subsequent FET in months. A secondary analysis was then performed with time as a continuous variable. The proportion of LBs did not differ significantly across all time interval groups and over continuous time (range: 40.0%-45.6%). The mean gestational age at the time of delivery did not significantly differ as the time between prior cesarean delivery and subsequent FET increased (range: 37.3-38.4). When time was evaluated continuously, the proportion of preterm births was higher with a shorter time between cesarean delivery and subsequent FET. The mean birth weight ranged from 3,181-3,470g, with a statistically significant increase over time. However, the proportions of extremely low birth weight, very low birth weight, and low birth weight did not significantly differ. CONCLUSION: There were no significant differences in reproductive outcomes on the basis of the time interval from cesarean delivery to FET, including LB. The proportion of preterm deliveries decreased with a longer time between cesarean delivery and FET. Differences in mean neonatal birth weight were not clinically significant because the proportion of low birth weight neonates was not significantly different over time. Although large, this sample cannot address all outcomes associated with short interpregnancy intervals, particularly rarer outcomes such as uterine rupture. When counseling patients, the timing of FET after cesarean delivery must be balanced against the risks of increasing maternal age on reproductive and neonatal outcomes.

Prevalence of Polycystic Ovary Syndrome in Patients With McCune Albright Syndrome.

STUDY OBJECTIVE: To identify polycystic ovarian syndrome (PCOS) in a population of female patients with McCune-Albright syndrome (MAS) by retrospective chart review. DESIGN: Retrospective study. SETTING: Academic setting. PARTICIPANTS: All female patients with a prior diagnosis of MAS who were more than 12 years of age at the time of chart review. Only complete medical records from January 2009 to January 2020 were included in the analysis. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Diagnosis of PCOS based on the Rotterdam 2003 criteria. RESULTS: Seventeen female patients with MAS were included in the analysis. PCOS appeared to be more prevalent in MAS patients than expected based on population estimates (exact binomial test = 0.353; CI = 0.142-0.617, P = .01). The average body mass index was not significantly different between MAS patients with and without PCOS (23.38 kg/m2 vs 23.44 kg/m2, 2-sample Wilcoxon rank-sum test with continuity correction, W = 29, P = 0.733). The majority of patients (71%) were treated with an aromatase inhibitor and/or a gonadotropin-releasing hormone (GnRH) agonist. CONCLUSIONS: The results of this study suggest that female individuals with MAS have a statistically higher prevalence of PCOS. These findings warrant further studies to determine whether the increased risk of PCOS may be associated with precocious puberty, treatment of precocious puberty, or other factors.

Fetal programming of polycystic ovary syndrome: Effects of androgen exposure on prenatal ovarian development.

Polycystic ovary syndrome (PCOS) is a common form of anovulatory infertility with a strong hereditary component but no candidate genes have been found. The inheritance pattern may be due to in utero androgen programming on gene expression and mitochondria. Mitochondria are maternally inherited and alterations to mitochondria after fetal androgen exposure may explain one of the mechanisms of fetal programming in PCOS. Our aim was to investigate the role of excessive prenatal androgens in ovarian development by identifying how hyperandrogenemia affects gene expression and mitochondria in neonatal ovary. Pregnant dams were injected with dihydrotestosterone on days 16-18 of pregnancy. Day 0 ovaries were collected for gene expression and mitochondrial studies. RNAseq showed differential gene expressions which were related to mitochondrial dysfunction, fetal gonadal development, oocyte maturation, metabolism, angiogenesis, and PCOS. Top 20 up and downregulated genes were validated with qPCR and Western Blot. Transcriptional pathways involved in folliculogenesis and genes involved in ovarian and mitochondrial function were dysregulated. Further, DHT exposure altered mitochondrial ultrastructure and function by increasing mitochondrial oxygen consumption and decreasing mitochondrial efficiency with increased proton leak within the first day of life. Our data indicates that one path that leads to PCOS begins at birth and is programmed in utero by androgens.

The importance of estradiol measurement in patients undergoing in vitro fertilization.

Successful outcomes of in vitro fertilization (IVF) are dependent in part on successful oocyte maturation and retrieval during a controlled ovarian stimulation process, which is guided by serial ultrasound and estradiol measurements. Yet, laboratory analysis of estradiol poses challenges due to the need for accuracy and specificity across concentrations that span multiple orders of magnitude. The Endocrine Society released a 2013 position statement that called for improvements in methods to analyze estradiol, and while some progress has been made in standardization and assay specificity, further work is needed to meet the needs of patients in both the IVF setting and in other clinical contexts. This review highlights the capabilities and challenges of current laboratory methods for the analysis of estradiol in the IVF setting, including automated immunoassays and liquid chromatography-tandem mass spectrometry, and discusses current efforts to improve the analytical sensitivity and standardization of estradiol assays. Clinical laboratorians should be aware of the limitations of current estradiol assays and select appropriate methods for the measurement of estradiol in their patient population.

Clomiphene Stair-Step Protocol for Women With Polycystic Ovary Syndrome.

OBJECTIVE: To compare time to ovulation, ovulation rates, and side effect profile of traditional and the stair-step protocol for ovulation induction using clomiphene citrate in women with polycystic ovary syndrome (PCOS). METHODS: We performed a retrospective study of women seeking care for infertility with a diagnosis of PCOS at a university-based infertility clinic from July 2012 to July 2014. We included patients who were resistant to the initial starting dose of 50 mg clomiphene. The primary outcome was time to ovulation. Secondary outcomes included ovulation rates, clinical pregnancy rates, and mild and moderate-to-severe side effects based on dose. For the traditional protocol, higher doses of clomiphene were used each subsequent month if no ovulation occurred. For the stair-step protocol, higher doses of clomiphene were given 7 days after the last dose if no dominant follicles were seen on ultrasonography. Our study had 80% power to detect a 20% difference in ovulation. RESULTS: One hundred nine patients were included in the analysis with 66 (60.6%) in the traditional and 43 (39.4%) in the stair-step protocol. Age and body mass index were similar between groups. The time to ovulation was decreased in the stair-step protocol group compared with the traditional protocol group (23.1±0.9 days vs 47.5±6.3 days). Ovulation rates were increased in the stair-step group compared with the traditional group at 150 mg (16 [37%] vs 8 [12%], P=.004) and at 200 mg (9 [21%] vs 3 [5%], P=.01). Pregnancy rates were similar between groups once ovulation was achieved (12 [18.1%] vs 7 [16.3%], P=.08). The stair-step protocol had an increased incidence of mild side effects (vasomotor flushes, headaches, gastrointestinal disturbance, mastalgia, changes in mood; 18 [41%] vs 8 [12%]), but there was no difference in the incidence of severe side effects (headaches, visual disturbances). CONCLUSION: For women with PCOS, the stair-step clomiphene protocol is associated with decreased time to ovulation and increased ovulation rates at higher doses when compared with the traditional protocol.