Why Natural Ovulation is the Optimal Choice Before IVF Frozen Embryo Transfer

Recent findings from a comprehensive randomized trial indicate that natural ovulation methods for preparing the uterus for frozen embryo transfer after in vitro fertilization (IVF) are equally effective and come with fewer risks compared to traditional hormone therapy.

Emerging data suggests that for women with strong responses to IVF treatment (which can yield multiple eggs), freezing embryos and transferring them in a later cycle can enhance success rates. Consequently, frozen embryos now represent the majority of embryo transfers conducted globally.

Post-IVF, the crucial timing for transferring frozen embryos into the uterus occurs during the menstrual cycle when the endometrium (the uterine lining) is adequately thick to facilitate implantation.

Women can opt for either a medicated cycle, which involves administering estrogen and progesterone for uterine preparation, or a natural cycle, where the body’s natural hormone production is monitored, assuming regular cycles.

Determining the optimal choice remains complex due to a lack of substantial trials evaluating the complications linked to these varying methods.

To address this uncertainty, Daimin Wei and a team from Shandong University in Jinan, China, conducted a large-scale clinical trial involving 4,376 women across 24 fertility treatment centers. All participants were aged 20 to 40 and were slated for a single frozen embryo transfer. Participants were divided equally between the medicated and natural cycle groups.

“This is the randomized controlled trial we’ve been waiting for,” remarks William Bucket from McGill University in Montreal, Canada, who was not involved in the study.

Live birth rates were comparable between both methods, with 41.6% in the natural cycle group and 40.6% in the medicated group. This suggests that natural ovulation is as effective as hormone therapy for preparing the uterus for embryo implantation.

However, an analysis of maternal complications during and after pregnancy revealed notable distinctions.

Women utilizing natural cycles exhibited a lower likelihood of preeclampsia, a severe condition marked by elevated blood pressure, along with fewer incidences of early pregnancy loss. They were also less prone to develop placenta accreta spectrum, a condition that makes the placenta difficult to detach following childbirth. Additionally, this group had reduced rates of cesarean sections and severe postnatal hemorrhage.

“These risks impact both maternal and fetal health during pregnancy and hold significance for long-term postpartum health,” states Wei.

“This research is vital,” notes Tim Child, Chair of the Scientific and Clinical Progress Advisory Committee of the UK Human Fertilization and Embryology Authority. The clinic now advises individuals with regular menstrual cycles that both natural and medicated methods yield similar success rates.

However, Child points out that there is evidence suggesting natural cycles may lower the risk of preeclampsia. This reduction may be attributed to the presence of the corpus luteum, which regulates hormones necessary for preparing the uterus for pregnancy.

“This extensive study corroborates and expands on previous findings, especially concerning significantly lower rates of preeclampsia, early miscarriage, placenta accreta, cesarean sections, and postpartum hemorrhage linked to the natural cycle approach,” Child asserts.

Wei’s team is set to analyze blood samples gathered during the trial to identify potential biomarkers that could shed light on the differences observed in pregnancy complications.