Natural ovulation frozen embryo transfer is just as effective as hormone-based treatment when preparing the uterus for frozen embryo transfer after IVF, according to results from a large randomised clinical trial.

Frozen embryo transfers are now the most common approach worldwide, especially for women who respond well to IVF and produce a higher number of eggs. In these cases, embryos are frozen and transferred in a later cycle to improve overall success rates.

To support implantation, the frozen embryo must be transferred during a precise window when the uterine lining is ready. This can be achieved either through a medicated cycle, using oestrogen and progesterone, or through a natural cycle that follows the body’s own hormone production.

Until now, there has been limited large-scale evidence comparing the safety and outcomes of these two approaches. To address this gap, Daimin Wei at Shandong University in Jinan, China, led a study involving 4,376 women aged 20 to 40 across 24 fertility centres. All participants were planning a single frozen embryo transfer. Half followed a medicated protocol, while the other half used their natural cycle.

“This is the randomised-controlled trial we have been waiting for,” says William Buckett at McGill University in Montreal, Canada, who wasn’t involved in the study.

Live birth rates were nearly identical. Women using their natural cycle had a 41.6% live birth rate, compared with 40.6% in the medicated group. These findings show that natural ovulation frozen embryo transfer delivers comparable success without hormone preparation.

Clear differences appeared when pregnancy complications were analysed. Women who followed their natural cycle had lower rates of pre-eclampsia, early pregnancy loss, placental accreta spectrum, Caesarean delivery, and severe post-partum bleeding.

“These risks not only affect maternal and fetal health during pregnancy, but are also associated with long-term health postpartum,” says Wei. “This is an important new study,” says Tim Child, chair of the UK’s Human Fertilisation and Embryology Authority’s Scientific and Clinical Advances Advisory Committee.

“This very large study confirms and extends previous findings and suspicions, in particular the significantly lower rate of pre-eclampsia, early pregnancy loss, placental accreta, C-section and post-partum haemorrhage [with the natural cycle route],” says Child.

Wei’s team plans further analysis of blood samples from the trial to identify biomarkers that may explain the reduced complication risk.