Summary: In a small, open-label, multi-centre randomised trial of 155 women with polycystic ovary syndrome (PCOS) undergoing frozen-thawed embryo transfer (FET), no statistically significant difference in clinical pregnancy rate was detected between a letrozole ovulation regimen (62.96%) and a programmed regimen (60.81%, P>0.05). The letrozole arm more often needed only single-drug luteal support (53.16% vs 16.67%, P<0.05).
PICO Summary
| Element | Detail |
|---|---|
| Population | 155 women with PCOS undergoing frozen-thawed embryo transfer; open-label multi-centre RCT across six hospitals in China (September 2022 to February 2024). |
| Intervention | Letrozole ovulation regimen for endometrial preparation (n=81). |
| Comparison | Programmed (hormone-replacement) endometrial preparation regimen (n=74). |
| Outcome | Primary outcome clinical pregnancy rate: 62.96% (letrozole) vs 60.81% (programmed), P>0.05, no significant difference. No significant differences in abortion rate, live birth rate, hypertensive disorders of pregnancy, gestational diabetes, preterm birth, or neonatal birth weight. Single-blastocyst subgroup (n=108): clinical pregnancy 66.67% vs 73.33% and live birth 58.73% vs 55.56%, both P>0.05. Single-drug luteal support more frequent with letrozole (53.16% vs 16.67%, P<0.05). No 95% confidence intervals, absolute risk reduction, or NNT were reported; the trial was not designed or powered as a formal non-inferiority study. |
Letrozole vs programmed FET in PCOS
RCT · PCOS · frozen embryo transfer
No significant difference in clinical pregnancy rate between letrozole and programmed endometrial preparation. Letrozole cycles more often needed only single-drug luteal support, a practical rather than reproductive advantage.
Expert Commentary
This trial is best read as a null result rather than a demonstration of equivalence. Across 155 women with PCOS, no significant difference in clinical pregnancy rate was detected between the letrozole ovulation regimen and a programmed regimen, and secondary outcomes including live birth, miscarriage, and obstetric and neonatal endpoints were similarly non-significant. The figures should not be reframed as proof that the regimens are equal. The study was open-label and modest in size, was not powered as a formal non-inferiority trial, and reported no confidence intervals, so a clinically meaningful gap in either direction cannot be excluded. The principal weighed limitation is therefore statistical power: with roughly 80 women per arm, a trial of this size can readily miss real differences in pregnancy outcomes, and the wide possible margin around a roughly 2-percentage-point gap leaves the question genuinely open. The one robust signal is practical rather than reproductive, namely that letrozole cycles more often required only single-drug luteal support, which may reduce treatment burden and cost. Can I use this with my patients? Reasonably yes as an existing option for a PCOS patient who prefers a lighter luteal-support protocol, but not as evidence that letrozole improves the chance of a baby. Larger adequately powered trials reporting live birth with confidence intervals are needed before any superiority claim is made.
References
Xie Y, Li P, Hao G, Deng W, Zhao J, Gao S, et al. Letrozole ovulation regimen for frozen-thawed embryo transfer in women with polycystic ovary syndrome: a multi-centre randomised controlled trial. Reprod Biol Endocrinol. 2025;23(1):103. doi:10.1186/s12958-025-01432-w