Mildly Stimulated Cycle with Letrozole Compared with Natural Cycle and HRT Cycle in Patients undergoing FET with Normal Ovulation

Background: The number of frozen embryo transfer (FET) is increasing, however, an optimal protocol for FET is undetermined. Our study was to evaluate the letrozole use on the patients with normal menstrual cycles (MC) compared with HRT cycle and natural cycle. Methods: It is a large retrospective study involved 2932 patients. Inverse probability of treatment weighting (IPTW) approach aimed to equate each group with respect to measured baseline covariates to achieve a comparison with reduced selection bias. Patients matched by algorithm were divided into 3 groups: hormone replacement therapy (HRT) cycle (n=2877), letrozole cycle (n=2637) and natural cycle (NC) (n=2475). The primary outcome measure was live birth rate, the secondary outcome measures were positive hCG rate, biochemical pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, early miscarriage rate, late miscarriage rate, preterm delivery rate and full-term pregnancy rate. Results: In our crude analysis, letrozole group had a higher live birth rate compared with HRT cycle (OR 1.2, 95% CI 1.07–1.35) and natural cycle (OR 1.31, 95% CI 1.16–1.47) and after adjusting for confounding factors, live birth rate was consistently higher in letrozole group. Moreover, the biochemical pregnancy, clinical pregnancy, ongoing pregnancy and full-term delivery rate were higher in letrozole group. Conclusion: For infertile women with normal menstrual cycle undergoing frozen-thawed embryo transfers, mildly stimulated cycle with letrozole present relatively large advantage compared with HRT cycle and natural cycle with higher live birth pregnancy indicating that letrozole use could improve pregnancy outcomes in patients with normal ovulation during FET. Trial registration Retrospectively registered.