Letrozole-stimulated cycles versus hormone replacement treatment cycles for frozen embryo transfer in women with polycystic ovary syndrome: a prospective randomized controlled trial

PurposeThis study aimed to compare the pregnancy outcomes of letrozole (LE)-induced ovulation and hormone replacement treatment (HRT) in endometrial preparation for frozen embryo transfer (FET) in women with polycystic ovary syndrome (PCOS).MethodsA randomized controlled trial involved 200 patients with PCOS from December 2017 to December 2022. Participants, who underwent FET with one or two good-quality blastocysts or cleavage-stage embryos, were randomly assigned to the LE group or HRT group in a 1:1 ratio. The primary outcome was the clinical pregnancy rate. Secondary outcomes included biochemical pregnancy, implantation, ectopic pregnancy, miscarriage, multiple pregnancy, and live birth rates.ResultsThe clinical pregnancy rate was 66.0% in the LE group compared to 53.0% in the HRT group (absolute difference, 13.0% [95% CI, - 0.5 to 26.5%]; RR, 1.25 [95% CI, 0.98 to 1.57]; P = 0.061). The biochemical pregnancy rate was higher in the LE group (71.0% vs 57.0%; absolute difference, 14.0% [95% CI, 0.8 to 27.2%]; RR, 1.25 [95% CI, 1.01 to 1.54]; P = 0.039). No significant differences were observed for the other secondary outcomes. The LE group showed higher biochemical pregnancy and live birth rates in the normal weight and normal androgen subgroups. Pregnancy outcomes were similar in the overweight and hyperandrogenic subgroups.ConclusionThere were no statistically significant differences in clinical pregnancy rates between the LE and HRT cycles for FET in women with PCOS. However, the LE protocol may be a preferable option to HRT for women with normal weight or normal androgen levels.Clinical trial registrationThis study was registered at Chinese Clinical Trial Registry (http://www.chictr.org.cn/; ChiCTR-IOR-17014124).