Summary: In an open-label multicentre randomised controlled trial of 155 women with polycystic ovary syndrome (PCOS) undergoing frozen-thawed embryo transfer (FET), a letrozole ovulation regimen achieved a clinical pregnancy rate comparable to a programmed regimen (62.96% vs 60.81%, P>0.05). No difference was found in live birth or abortion rates; 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 FET; open-label, multicentre randomised controlled trial across six hospitals in China (September 2022 to February 2024). |
| Intervention | Letrozole ovulation regimen for endometrial preparation, paired with simple luteal support (n=81). |
| Comparison | Programmed (hormonal) 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 live birth, abortion, hypertensive disorders of pregnancy, gestational diabetes, preterm birth or neonatal birth weight. Single-drug luteal support was more frequent in the letrozole arm (53.16% vs 16.67%, P0.05); live birth 58.73% vs 55.56% (P>0.05). Effect sizes, 95% confidence intervals and NNT were not reported in the abstract. |
Letrozole vs programmed FET in PCOS
RCT · PCOS · frozen-thawed embryo transfer
Letrozole endometrial preparation gave clinical pregnancy and live birth rates comparable to a programmed regimen, while more often needing only single-drug luteal support. The trial is underpowered to confirm true equivalence.
Expert Commentary
This trial is best read as a comparability study rather than a demonstration that letrozole is superior. The primary outcome, clinical pregnancy rate, did not differ between arms, and no signal of benefit emerged for live birth or obstetric and neonatal outcomes, including in the single-blastocyst subgroup. The one statistically robust finding is procedural: women prepared with letrozole more often needed only single-drug luteal support, which may simplify protocols, reduce medication burden and lower cost. That is a reasonable, if modest, argument for the regimen, but it should not be reframed as improved fertility. The principal limitation is power. With 155 participants and an event-driven primary endpoint, the study is underpowered to exclude clinically meaningful differences, so a null result here is reassuring rather than definitive, and the wide play of chance must be kept in mind. The open-label design is a further caveat, since unblinded clinicians and patients can influence luteal-support decisions, the very outcome that reached significance. Can I use this with my patients? Cautiously yes, for an ovulatory-capable PCOS patient who prefers a less medicalised preparation, framing it as comparable rather than better. No industry or manufacturer sponsorship was evident from the abstract, and no implausibly large effects were claimed. Larger, adequately powered trials reporting live birth with confidence intervals are needed before letrozole displaces programmed preparation as a default.
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