Tamoxifen in IVF/FET and Fertility-Preservation Cycles: A Systematic Review of Endometrial Thickness, Clinical Pregnancy, and Live Birth

Background: Tamoxifen, a selective estrogen receptor modulator with partial agonist activity in the endometrium, has been investigated as an alternative for endometrial preparation in assisted reproductive technology (ART) and as a safer stimulation strategy in fertility preservation for breast cancer patients. However, evidence remains fragmented. Objective: This systematic review synthesized available evidence on tamoxifen use in IVF, frozen-thawed embryo transfer (FET), and fertility-preservation cycles, focusing on endometrial thickness (ET), implantation-related outcomes, and live birth. Methods: PubMed, Web of Science, and Scopus were searched for original human studies published within the last 10 years evaluating tamoxifen in IVF/FET or fertility-preservation cycles. Reviews, animal studies, and case reports were excluded. Risk of bias was assessed using ROBINS-I, Newcastle–Ottawa Scale, and JBI checklist. Narrative synthesis was performed due to heterogeneity. Results: Four studies were included. In FET cycles with thin endometrium, tamoxifen significantly increased ET compared with hormone replacement therapy (HRT) (7.32 ± 1.28 mm vs 6.85 ± 0.89 mm; p < 0.05) and was associated with higher live birth (46.9% vs 26.8%; adjusted OR 2.24, p < 0.05) and lower early miscarriage (5.9% vs 26.8%; adjusted OR 0.10, p < 0.05) in one retrospective study. However, a larger randomized controlled trial found no significant difference in implantation or live birth between tamoxifen-HRT and HRT alone. In fertility preservation, tamoxifen-containing protocols showed a trend toward reduced oocyte yield and quality compared with letrozole, though recent cohort data suggest comparable outcomes. In poor ovarian responders, elevated LH before trigger with tamoxifen did not necessarily indicate premature LH surge. Conclusion: Tamoxifen effectively increases endometrial thickness in women with thin endometrium undergoing FET, but does not reliably improve implantation or live birth rates in randomized settings. Its role in fertility preservation appears comparable to letrozole with reassuring long-term safety. Randomized trials with standardized dosing and defined reproductive endpoints are needed.