Natural Ovulation in IVF: A Safer and Equally Effective Alternative

A randomized trial found ovulation-timed frozen embryo transfer is as effective as programmed hormone replacement for achieving a healthy live birth. The multicenter trial enrolled 4,376 ovulatory women and used healthy live birth as the primary endpoint, supporting ovulation-timed transfer as an equally efficacious, lower‑drug option for frozen single-embryo transfer.

Historically, most frozen embryo transfer cycles used hormone replacement to program the endometrium and control timing. Ovulation-timed transfer instead relies on the patient’s spontaneous ovulation, reducing exogenous hormone exposure and shifting clinic workflow toward cycle monitoring rather than fixed drug schedules—an operational change that can improve patient-centered timing.

The trial randomized women across 24 fertility centers to natural ovulation or programmed hormone regimens for frozen single embryo transfer. The study found equivalent healthy live birth rates between the two arms and reported similar neonatal outcomes, a large randomized comparison demonstrating parity in efficacy.

The trial also demonstrated lower rates of maternal complications in the natural-ovulation group: reduced pre-eclampsia (2.9% v 4.6%), lower early pregnancy loss (12.1% v 15.2%), and decreased postpartum hemorrhage (2.0% v 6.1%). Rates of placental accreta spectrum and cesarean delivery were also lower, while birthweight outcomes were similar—together suggesting a favorable maternal safety profile with ovulation-timed transfer.