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.