J.O. Doyle

Peak serum estradiol level during controlled ovarian hyperstimulation is associated with increased risk of small for gestational age and preeclampsia in singleton pregnancies after in vitro fertilization.

OBJECTIVE To assess the impact of elevated peak serum E(2) levels (EPE(2); defined as levels >90th percentile) on the day of hCG administration during controlled ovarian hyperstimulation (COH) for IVF on the likelihood for small for gestational age (SGA), preeclampsia (PreE), and preterm delivery (PTD) in singleton pregnancies. DESIGN Retrospective cohort study. SETTING Tertiary-care academic medical center. PATIENT(S) Singleton live-birth pregnancies conceived after fresh IVF-ET. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) The delivery rate of SGA infants and the development of PreE and PTD in patients with and without EPE(2). RESULT(S) Patients with EPE(2) during COH were more likely to deliver SGA infants (7 [26.9%] vs. 10 [3.8%]; odds ratio [OR], 95% confidence interval [CI] {9.40, 3.22-27.46}) and develop PreE (5 [18.5%] vs. 12 [4.5%]; adjusted OR, 95% CI {4.79, 1.55-14.84}). No association was found between EPE(2) and the likelihood for delivery before 37 weeks, 35 weeks, or 32 weeks of gestation. Receiver operating characteristic analysis revealed that EPE(2) level predicted adverse obstetrical outcome (SGA + PreE) with 38.5% and 91.7% sensitivity and specificity, respectively. Using a serum peak E(2) cutoff value of 3,450 pg/mL (>90th percentile level), the positive predictive value was 37%, while the negative predictive value was 92%. CONCLUSION(S) EPE(2) level (>3,450 pg/mL) on the day of hCG administration during COH is associated with greater odds of developing PreE and delivery of an SGA infant in singleton pregnancies resulting from IVF cycles.

Metformin Therapy in a Hyperandrogenic Anovulatory Mutant Murine Model with Polycystic Ovarian Syndrome Characteristics Improves Oocyte Maturity during Superovulation

BackgroundMetformin, an oral biguanide traditionally used for the treatment of type 2 diabetes, is widely used for the management of polycystic ovary syndrome (PCOS)-related anovulation. Because of the significant prevalence of insulin resistance and glucose intolerance in PCOS patients, and their putative role in ovulatory dysfunction, the use of metformin was touted as a means to improve ovulatory function and reproductive outcomes in PCOS patients. To date, there has been inconsistent evidence to demonstrate a favorable effect of metformin on oocyte quality and competence in women with PCOS. Given the heterogeneous nature of this disorder, we hypothesized that metformin may be beneficial in mice with aberrant metabolic characteristics similar to a significant number of PCOS patients. The aim of this study was to gain insight into the in vitro and in vivo effects of metformin on oocyte development and ovulatory function.MethodsWe utilized metformin treatment in the transgenic ob/ob and db/db mutant murine models which demonstrate metabolic and reproductive characteristics similar to women with PCOS. Results: Metformin did not improve in vitro oocyte maturation nor did it have an appreciable effect on in vitro granulosa cell luteinization ( progesterone production) in any genotype studied. Although both mutant strains have evidence of hyperandrogenemia, anovulation, and hyperinsulinemia, only db/db mice treated with metformin had a greater number of mature oocytes and total overall oocytes compared to control. There was no observed impact on body mass, or serum glucose and androgens in any genotype.ConclusionsOur data provide evidence to suggest that metformin may optimize ovulatory performance in mice with a specific reproductive and metabolic phenotype shared by women with PCOS. The only obvious difference between the mutant murine models is that the db/db mice have elevated leptin levels raising the questions of whether their response to metformin is related to elevated leptin levels and/or if a subset of PCOS women with hyperleptinemia may be responsive to metformin therapy. Further study is needed to better define a subset of women with PCOS that may be responsive to metformin.

Rescue human chorionic gonadotropin for false empty follicle syndrome: optimism for successful pregnancy outcome

OBJECTIVE To describe two cases of successful pregnancy after a rescue course of hCG in the setting of false empty follicle syndrome. DESIGN Case report. SETTING Academic medical center. PATIENT(S) Two patients undergoing ultrasound-guided oocyte retrieval with failure to obtain oocytes during oocyte retrieval. INTERVENTION(S) Rescue course of hCG with second oocyte retrieval 35 hours later. MAIN OUTCOME MEASURE(S) Live birth. RESULT(S) Two live-birth pregnancies. CONCLUSION(S) Live-birth pregnancies are a realistic possibility after administration of a rescue course of hCG and repeat oocyte retrieval in the setting of false empty follicle syndrome.

Medical egg freezing: How cost and lack of insurance cover impact women and their families

Medical egg freezing (MEF) is being recommended increasingly for women at risk of losing their reproductive ability due to cancer chemotherapy or other fertility-threatening medical conditions. This first, binational, ethnographic study of women who had undergone MEF sought to explore womens experiences under two different funding systems: (i) the USA, where the cost of MEF is rarely covered by private or state health insurance; and (ii) Israel, where the cost of MEF is covered by national health insurance. Women were recruited from four American and two Israeli in-vitro fertilization clinics where MEF is offered. In-depth, semi-structured interviews were conducted with 45 women (33 Americans, 12 Israelis) who had completed at least one cycle of MEF. All of the Israeli women had cancer diagnoses, but were not faced with the additional burden of funding an MEF cycle. In marked contrast, the American women – 23 with cancer diagnoses and 10 with other fertility-threatening medical conditions – struggled, along with their families, to ‘piece together’ MEF funding, which added significant financial pressure to an already stressful situation. Given the high priority that both American and Israeli women in this study placed on survival and future motherhood, it is suggested that insurance funding for MEF should be mandated in the USA, as it is in Israel. This article concludes by describing new state legislative efforts in this regard.