Natural ovulation as effective as hormones before IVF embryo transfer

Natural ovulation before frozen embryo transfer is as effective as hormone treatment for achieving a healthy baby by in vitro fertilisation (IVF), finds a clinical trial from China published by The BMJ today.

Natural ovulation is also linked to a lower risk of several complications for the mother, such as pre-eclampsia (abnormally high blood pressure), the results show.

Globally, the use of frozen embryo transfer after IVF has increased substantially and accounts for more than 60% of all embryo transfers.

Doctors prepare the womb lining (endometrium) for frozen embryo transfer most often by either a natural ovulation regimen, which relies on the patient's own ovulation cycle, or a programmed regimen, which uses hormone drugs (oestrogen and progesterone).

A big question in fertility treatment is which of these methods works best and is safest, but previous trials have been unable to draw firm conclusions.

To address this knowledge gap, researchers drew on data for 4,376 ovulatory women (aged 20-40 years) at 24 fertility centres in China who were planning to undergo a frozen single embryo transfer.

Women were randomised to either a natural ovulation regimen (2,185 patients) or a programmed regimen (2,191 patients) for endometrial preparation and were monitored to determine the ideal timing for embryo transfer.

The results show that 910 (42%) of patients in the natural ovulation regimen group and 890 (41%) in the programmed regimen group achieved a healthy live birth.

The risk of pre-eclampsia was also lower in the natural ovulation regimen group among patients who achieved clinical pregnancy compared with the programmed regimen group (2.9% v 4.6%).

And rates of early pregnancy loss (12.1% v 15.2%), placental accreta spectrum - when the placenta fails to detach easily after birth (1.8% v 3.6%), caesarean section (69.5% v 75.6%), and postpartum haemorrhage - severe bleeding after childbirth (2.0% v 6.1%) were all lower in the natural ovulation regimen group.

No differences between the two groups were seen for birth weight or complications in newborns. The rate of cycle cancellation (stopping treatment) was, however, higher in the natural ovulation group (16.2% v 11.5%).

The researchers acknowledge some limitations that may have biased their results, but say this was a large, multicentre study that considered both the effectiveness and safety of mothers and babies, and results were consistent after additional analyses, suggesting that they withstand scrutiny.

As such, they conclude: “The findings of this study suggest that a natural ovulation regimen for endometrial preparation before frozen embryo transfer is as effective as a programmed regimen in terms of a healthy live birth and results in a lower risk of maternal complications during pregnancy.”

They add: “The findings of this trial may serve as a model for other preconception intervention trials to prevent maternal morbidity and mortality.”

Reference:

Wei D, Qin Y, Sun Y, Yan J, Zhao H, Guan Y et al. Natural ovulation versus programmed regimens before frozen embryo transfer in ovulatory women: multicentre, randomised clinical trial BMJ 2026; 392 :e087045 doi:10.1136/bmj-2025-087045