News | New Evidence on Frozen Embryo Transfer: Comparable Success Without Hormones
With advances in assisted reproduction, frozen-thawed embryo transfer (FET) after in vitro fertilization (IVF) has become standard worldwide and now accounts for more than 60% of all embryo transfers. Whether to prepare the endometrium using a woman’s natural ovulatory cycle or an artificial estrogen-and-progesterone regimen remains a central debate in reproductive medicine.
A large randomized clinical trial from China, recently published in The BMJ, found that natural ovulation and programmed hormone regimens achieved similar rates of healthy live birth, while the natural approach was associated with significantly lower risks of several maternal pregnancy complications.
The study enrolled 4,376 regularly ovulating women aged 20–40 at 24 reproductive centers in China who planned a single frozen-thawed embryo transfer. Participants were randomly assigned to natural ovulation (2,185) or programmed hormone treatment (2,191), with endometrial preparation based on either their own cycle or exogenous hormones and careful monitoring of transfer timing.
Healthy live birth occurred in 910 women (42%) in the natural ovulation group and 890 (41%) in the programmed hormone group, with no significant difference in live birth rates. The result challenges the longstanding assumption that hormone regimens improve success.
Safety outcomes were more notable. Among women with a clinical pregnancy, preeclampsia was less common with natural ovulation than with programmed hormones (2.9% vs 4.6%). The natural group also had lower rates of early pregnancy loss (12.1% vs 15.2%), placenta accreta spectrum (1.8% vs 3.6%), cesarean delivery (69.5% vs 75.6%), and postpartum hemorrhage (2.0% vs 6.1%).
No significant differences were seen in birth weight or neonatal complications, suggesting that the natural ovulation regimen did not increase perinatal risk.
The treatment cancellation rate was slightly higher with natural ovulation (16.2% vs 11.5%), reflecting the greater need for precise ovulation monitoring and timing and a somewhat higher likelihood of cycle cancellation.
The researchers noted potential limitations and bias, but the large, multicenter randomized design, systematic assessment of maternal and neonatal safety, and consistent supplementary analyses strengthened the findings.
The authors wrote: “For endometrial preparation before frozen embryo transfer, a natural ovulation regimen was non-inferior to a programmed hormone regimen for healthy live birth and reduced the risk of maternal pregnancy complications.” They added that the study may inform future trials of preconception interventions to reduce maternal morbidity and mortality.
News | New Evidence on Frozen Embryo Transfer: Comparable Success Without Hormones
News | New Evidence on Frozen Embryo Transfer: Comparable Success Without Hormones
With advances in assisted reproduction, frozen-thawed embryo transfer (FET) after in vitro fertilization (IVF) has become standard worldwide and now accounts for more than 60% of all embryo transfers. Whether to prepare the endometrium using a woman’s natural ovulatory cycle or an artificial estrogen-and-progesterone regimen remains a central debate in reproductive medicine.
A large randomized clinical trial from China, recently published in The BMJ, found that natural ovulation and programmed hormone regimens achieved similar rates of healthy live birth, while the natural approach was associated with significantly lower risks of several maternal pregnancy complications.
The study enrolled 4,376 regularly ovulating women aged 20–40 at 24 reproductive centers in China who planned a single frozen-thawed embryo transfer. Participants were randomly assigned to natural ovulation (2,185) or programmed hormone treatment (2,191), with endometrial preparation based on either their own cycle or exogenous hormones and careful monitoring of transfer timing.
Healthy live birth occurred in 910 women (42%) in the natural ovulation group and 890 (41%) in the programmed hormone group, with no significant difference in live birth rates. The result challenges the longstanding assumption that hormone regimens improve success.
Safety outcomes were more notable. Among women with a clinical pregnancy, preeclampsia was less common with natural ovulation than with programmed hormones (2.9% vs 4.6%). The natural group also had lower rates of early pregnancy loss (12.1% vs 15.2%), placenta accreta spectrum (1.8% vs 3.6%), cesarean delivery (69.5% vs 75.6%), and postpartum hemorrhage (2.0% vs 6.1%).
No significant differences were seen in birth weight or neonatal complications, suggesting that the natural ovulation regimen did not increase perinatal risk.
The treatment cancellation rate was slightly higher with natural ovulation (16.2% vs 11.5%), reflecting the greater need for precise ovulation monitoring and timing and a somewhat higher likelihood of cycle cancellation.
The researchers noted potential limitations and bias, but the large, multicenter randomized design, systematic assessment of maternal and neonatal safety, and consistent supplementary analyses strengthened the findings.
The authors wrote: “For endometrial preparation before frozen embryo transfer, a natural ovulation regimen was non-inferior to a programmed hormone regimen for healthy live birth and reduced the risk of maternal pregnancy complications.” They added that the study may inform future trials of preconception interventions to reduce maternal morbidity and mortality.
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