Letrozole co-treatment in IVF achieves estrogen suppression without compromising IVF outcomes in endometrial cancer and atypical endometrial hyperplasia: a retrospective study

Elevated estrogen levels during controlled ovarian stimulation (COS) pose a theoretical risk for women with endometrial cancer (EC) or atypical endometrial hyperplasia (AEH) undergoing fertility-sparing treatment. This study aimed to evaluate whether letrozole (LET) co-treatment could reduce estrogen exposure without compromising in vitro fertilization (IVF) outcomes. A retrospective cohort study included 102 patients with EC/AEH who underwent IVF after fertility-sparing treatment between January 2016 and June 2024 at a tertiary hospital. Each COS cycle was classified as non-LET, half-term LET, or full-term LET according to the duration of LET administration. Clinical characteristics and IVF outcomes were compared. Generalized estimating equation models with patient identification number as the clustering variable were used to account for repeated cycles within patients and to adjust for relevant clinical characteristics. The analysis included 193 COS cycles and 147 ET cycles, comprising 28 fresh ET cycles and 119 frozen ET cycles. Compared with no LET, trigger-day estradiol concentrations were lower with both half-term LET (adjusted geometric mean ratio, 0.53; 95% confidence interval [CI], 0.40–0.71) and full-term LET (adjusted geometric mean ratio, 0.32; 95% CI, 0.25–0.42; both P< 0.001). Full-term LET was associated with a thinner endometrium on the trigger day (adjusted mean difference, −2.10 mm; 95% CI, −3.28 to −0.92), whereas no significant difference was observed between half-term LET and no LET. No significant overall differences were observed in oocyte yield, metaphase II oocytes, two-pronuclear embryos, available embryos, or high-quality embryos. Adjusted pregnancy outcomes following frozen ET and across all 147 ET cycles did not differ significantly overall among the three groups. Six patients had documented recurrence after COS, including two with a second recurrence, and one additional patient experienced loss of complete response. LET co-treatment reduced E2 levels during COS without affecting IVF outcomes for women with EC/AEH. Half-term LET co-treatment may benefit patients undergoing fresh embryo transfer and full-term LET may be advantageous for frozen embryo transfer.