Tamoxifen Combined with Hormone Replacement in Women with Thin Endometrium Receiving Frozen-Thawed Embryo Transfer for Promoting Endometrial Growth: A Double-Blinded, Randomized Controlled Trial

Background: Thin endometrium continues to pose a significant challenge in assisted reproductive technology (ART) cycles, necessitating further exploration of therapeutic approaches. Tamoxifen (TMXF) has been primarily used in ovarian stimulation therapy and can also be implemented as an endometrial preparation protocol, potentially improving endometrial thickness. Does TMXF combined with hormone replacement therapy (HRT) in women with thin endometrium receiving frozen-thawed embryo transfer (FET) improve the endometrial thickness and pregnancy outcome compared to hormone replacement alone? Methods: This single-centre prospective double-blind randomized controlled trial ran between March 2020 and October 2022. In it, 120 patients with thin endometrium were randomized to TMXF-HRT and control HRT groups at a 1:1 ratio. The primary outcome was endometrium thickness. The secondary outcomes include embryo implantation rate, miscarriage rate and live birth rate. This trial is registered at the ClinicalTrials.gov, number NCT04292886 (Registration Date: March 1, 2020). Results: Endometrial thickness was significantly greater in the TMXF-HRT group than in the HRT alone group (7.80 ± 0.93 vs 6.93 ± 0.80 mm, P < 0.001), and multivariate analysis confirmed a positive effect of TMXF supplementation on endometrial thickness. However, no significant differences were observed between the two groups in embryo implantation rate or live birth rate. Conclusion: TMXF combined with HRT can significantly increase endometrial thickness and has the potential to improve clinical pregnancy outcomes (the difference was not statistically significant).