Are intracytoplasmic sperm injection and high serum estradiol compounding risk factors for adverse obstetric outcomes in assisted reproductive technology?

Objective: To evaluate whether intracytoplasmic sperm injection (ICSI) use and E-2 on the final day of assisted reproductive technology (ART) stimulation are associated with adverse obstetric complications related to placentation. Design: Retrospective cohort study. Setting: Large private ART practice. Patient(s): A total of 383 women who underwent ART resulting in a singleton live birth. Intervention(s): None. Main Outcome Measure(s): Adverse placental outcomes composed of placenta accreta, placental abruption, placenta previa, intrauterine growth restriction, preeclampsia, gestational hypertension, and small for gestational age infants. Result(s): Patients with adverse placental outcomes had higher peak serum E-2 levels and were three times more likely to have used ICSI. Adverse placental outcomes were associated with increasing E-2 (odds ratio 1.36, 95% confidence interval 1.13-1.65) and ICSI (odds ratio 3.86, 95% confidence interval 1.61-9.27). Adverse outcomes increased when E-2 was >3,000 pg/mL and continued to increase in a linear fashion until E-2 was >5,000 pg/mL. The association of ICSI with adverse outcomes was independent of male factor infertility. Interaction testing suggested the adverse effect of E-2 was primarily seen in ICSI cycles, but not in conventional IVF cycles. Estradiol >5,000 pg/mL was associated with adverse placental events in 36% of all ART cycles and 52% of ICSI cycles. Conclusion(s): ICSI and elevated E-2 on the day of hCG trigger were associated with adverse obstetric outcomes related to placentation. The finding of a potential interaction of E-2 and ICSI with adverse placental events is novel and warrants further investigation. (C) 2016 by American Society for Reproductive Medicine.