Treatment of primary infertility in McCune-Albright syndrome: a case report of a successful in vitro fertilization cycle.

OBJECTIVE: To report a case in which pregnancy and live birth were achieved in an infertile patient with McCune-Albright syndrome via in vitro fertilization (IVF). DESIGN: Case report. SETTING: University hospital. PATIENTS: A 29-year-old woman with McCune-Albright syndrome who presented with primary infertility due to ovulatory dysfunction and bilateral tubal blockage. INTERVENTIONS: In vitro fertilization without unilateral oophorectomy. MAIN OUTCOME MEASURES: Live birth after IVF treatment. RESULTS: Fresh IVF stimulation and bilateral oocyte retrieval yielded 12 oocytes and 4 top quality embryos. Fresh single embryo transfer did not result in pregnancy. Live birth occurred after the second frozen embryo transfer cycle. CONCLUSIONS: In vitro fertilization can lead to ongoing pregnancy in infertile patients with McCune-Albright syndrome without requiring unilateral oophorectomy.

Infection precautions for severe acute respiratory syndrome coronavirus 2 in assisted reproduction centers: dodging an invisible bullet.

The coronavirus disease 2019 pandemic has resulted in many changes in how we interact in society, requiring that we protect ourselves and others from an invisible, airborne enemy called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Until a vaccine is developed, and it reaches high levels of distribution, everyone must continue to be diligent to limit the viral spread. The practice of assisted reproduction during this pandemic presents unique challenges in addition to the risks identified in general clinical care. The established good tissue practices employed in laboratories are not designed to protect gametes and embryos from an airborne virus, particularly one that may be shed by an asymptomatic staff member. Armed with theoretical risks but lacking direct evidence, assisted-reproduction teams must examine every aspect of their practice, identify areas at a risk of exposure to SARS-CoV-2, and develop a mitigation plan. Several professional fertility societies have created guidelines for the best practices in patient care during the coronavirus disease 2019 pandemic. As we learn more about SARS-CoV-2, updates have been issued to help adapt infection-control and -prevention protocols. This review discusses what is currently known about SARS-CoV-2 infection risks in assisted reproductive centers and recommends the implementation of specific mitigation strategies.

A randomized controlled trial of combination letrozole and clomiphene citrate or letrozole alone for ovulation induction in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate whether a combination of letrozole and clomiphene citrate (CC) results in higher ovulation rates than letrozole alone in infertile women with polycystic ovary syndrome (PCOS). DESIGN: Open-label randomized controlled trial. SETTING: Academic medical center using two clinic sites. PATIENT(S): Women 18-40 years of age with a diagnosis of infertility and PCOS as defined by the Rotterdam criteria and no other known cause of infertility. INTERVENTIONS(S): Participants were randomized in a 1:1 ratio, stratified by age and body mass index, to either 2.5 mg letrozole alone or the combination of 2.5 mg letrozole and 50 mg CC daily on cycle days 3-7 for one treatment cycle. MAIN OUTCOME MEASURE(S): Ovulation defined as mid-luteal serum progesterone concentration ≥3 ng/mL. RESULT(S): Seventy patients were randomized: 35 to letrozole alone and 35 to letrozole and CC. Results were analyzed according to the intention-to-treat principle. Women who received the combination of letrozole and CC had a statistically higher ovulation rate compared with those who received letrozole alone (27 of 35 women [77%] vs. 15 of 35 women [43%]). There were no serious adverse events or multiple-gestation pregnancies in either group. The side-effects profile was similar in the two treatment groups. CONCLUSION(S): The combination of letrozole and CC was associated with a higher ovulation rate compared with letrozole alone in women with infertility and PCOS. Further studies are needed to evaluate the effect on live birth rate. CLINICAL TRIAL REGISTRATION NUMBER: NCT02802865.

MicroRNA-31 is significantly elevated in both human endometrium and serum during the window of implantation: a potential biomarker for optimum receptivity.

The window of implantation of human embryos into the endometrium spans Cycle Days 20-24 of the 28-day menstrual cycle. However, uterine receptivity may not be reliably replicated in infertile patients throughout this span. Thus, it is of importance to be able to determine optimal receptivity through a minimally invasive measure. We screened expression of a number of candidate micro-RNAs (miRNAs) in endometrial tissues and serum collected from a panel of fertile women during both the proliferative phase and the secretory phase of a normal menstrual cycle. We found that several miRNAs were significantly elevated in endometrial tissues in the secretory phase versus the proliferative phase. One of these, miR-31, was found to be not only detectable in serum samples but also significantly elevated in the secretory phase versus the proliferative phase. MiR-31 is known to target several immunomodulatory factors, such as FOXP3 and CXCL12. We find that both of these factors are significantly downregulated in endometrial tissues during the secretory phase. Our data suggest that miR-31 is a potential biomarker for optimal endometrial receptivity, possibly operating through an immunosuppressive mechanism.

Human papillomavirus vaccination and sexual behavior in young women.

STUDY OBJECTIVE: To compare sexual attitudes and behaviors of young women who have received or declined the HPV vaccine. DESIGN: Cross-sectional survey. SETTING: Obstetrics and gynecology and pediatrics clinics at a large, Midwestern, academic health center. PARTICIPANTS: 223 young women (ages 13-24): 153 who had received HPV vaccination and 70 with no prior HPV vaccination. MAIN OUTCOME MEASURES: Sexual behaviors; attitudes toward sexual activity. RESULTS: Vaccinated young women were slightly but significantly younger than unvaccinated (mean age 19.2 vs 20.0). Both groups showed a large percentage of participants engaging in high-risk sexual behavior (75% vs 77%). The mean age at sexual debut was not significantly different between the groups (16.8 vs 17.0) nor was the average number of sexual partners (6.6 for both). Unvaccinated participants were more likely to have been pregnant (20% vs 8.6%, P = .016), although this difference was not significant in multivariate analysis CI [0.902-5.177]. Specific questions regarding high-risk sexual behaviors and attitudes revealed no significant differences between the groups. CONCLUSION: We found that sexual behaviors, including high-risk behaviors, were similar between young women who had and had not received HPV vaccination. Our findings provide no support for suggestions that the vaccine is associated with increased sexual activity. Importantly, we found that young women in our population are sexually active at a young age and are engaged in high-risk behaviors, affirming the importance of early vaccination.

Clinical factors associated with live birth after single embryo transfer.

OBJECTIVE: To identify patient, cycle, and retrieval characteristics associated with embryo implantation and live birth in patients undergoing single embryo transfer (SET). DESIGN: Analysis of prospectively collected IVF database. SETTING: Academic IVF program. PATIENT(S): All patient cycles meeting criteria for SET between June 2004 and September 2010. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy and live birth. RESULT(S): Single embryo transfer was performed in 438 cycles, resulting in a clinical pregnancy rate of 76.2% and a live birth rate of 66.8% per transfer. Clinical pregnancy was associated with younger female age, ≥ 58% mature (metaphase II) oocytes at the time of retrieval, and increasing blastocyst expansion. Ongoing pregnancy was associated with younger female age and more advanced blastocysts. A diagnosis of uterine factor was negatively associated with live birth. CONCLUSION(S): Even in a favorable prognosis population, younger female age is associated with clinical pregnancy and live birth. Although all patients underwent blastocyst transfer, expanded and hatching blastocysts were strongly associated with pregnancy and live birth. A diagnosis of uterine factor was the only infertility diagnosis found to affect live birth after SET. Obesity did not negatively affect SET outcome. These findings may assist physicians in determining the best candidates for SET.

Five-years of a mandatory single-embryo transfer (mSET) policy dramatically reduces twinning rate without lowering pregnancy rates.

OBJECTIVE: To report the outcomes of a program policy instituted in 2004 mandating single-embryo transfer (mSET) for all women aged <38 years, with at least seven zygotes, no prior failed fresh cycle at our center, and at least one good-quality blastocyst. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENT(S): All women <38 years old undergoing a fresh cycle with autologous oocytes and all women undergoing a fresh cycle with donor oocytes from June 1, 1999, to May 31, 2004 (before mSET) and from June 1, 2004, to May 31, 2009 (after mSET). INTERVENTION(S): mSET policy implementation. MAIN OUTCOME MEASURE(S): Live-birth rate, multiple pregnancy rate, clinical volume, and outcomes of all mSET fresh IVF transfers were analyzed. RESULT(S): Clinical volume was unchanged between the two time groups. After implementation of mSET, live-birth rates improved from 51.1% to 55.9% and multiple-birth rates dropped from 34.8% to 17.5%. A total of 364 mSET fresh transfers were performed with a live-birth rate of 64.6% and a multiple-birth rate of 3.4%. CONCLUSION(S): A mandatory SET policy based on prognostic factors can be instituted with no drop in clinical volume and no negative effect on delivery rates. Multiple gestation rates can be dramatically lowered.

Overexpression of SK3 channels dampens uterine contractility to prevent preterm labor in mice.

The mechanisms that control the timing of labor have yet to be fully characterized. In a previous study, the overexpression of small conductance calcium-activated K(+) channel isoform 3 in transgenic mice, Kcnn3(tm1Jpad)/Kcnn3(tm1Jpad) (also known as SK3(T/T)), led to compromised parturition, which indicates that KCNN3 (also known as SK3) plays an important role in the delivery process. Based on these findings, we hypothesized that SK3 channel expression must be downregulated late in pregnancy to enable the uterus to produce the forceful contractions required for parturition. Thus, we investigated the effects of SK3 channel expression on gestation and parturition, comparing SK3(T/T) mice to wild type (WT) mice. Here, we show in WT mice that SK3 transcript and protein are significantly reduced during pregnancy. We also found the force produced by uterine strips from Pregnancy Day 19 (P19) SK3(T/T) mice was significantly less than that measured in WT or SK3 knockout control (SK3(DOX)) uterine strips, and this effect was reversed by application of the SK3 channel inhibitor apamin. Moreover, two treatments that induce labor in mice failed to result in complete delivery in SK3(T/T) mice within 48 h after injection. Thus, stimuli that initiate parturition under normal circumstances are insufficient to coordinate the uterine contractions needed for the completion of delivery when SK3 channel activity is in excess. Our data indicate that SK3 channels must be downregulated for the gravid uterus to generate labor contractions sufficient for delivery in both term and preterm mice.