Serum progesterone concentrations at frozen embryo transfer in women with adenomyosis and endometriosis: a retrospective cohort study

BACKGROUND: Endometriosis and adenomyosis are estrogen-dependent inflammatory conditions frequently associated with impaired fertility. Although progesterone resistance at the tissue level is well documented, it remains unclear whether these conditions are associated with altered systemic progesterone exposure during frozen-thawed embryo transfer (FET) cycles and whether higher circulating progesterone levels are required to achieve successful reproductive outcomes. OBJECTIVE: To evaluate mean serum progesterone levels on the day of FET in women with endometriosis and/or adenomyosis compared with unaffected controls, and to explore potential differences according to endometrial preparation protocol and pregnancy outcome. METHODS: This retrospective single-center cohort study included 1,927 women undergoing their first single-blastocyst FET between June 2020 and December 2023. FET cycles were performed using hormone replacement therapy (HRT) or modified natural cycle (mNC) protocols. Serum progesterone was measured on the day of embryo transfer. Women were categorized into three groups: endometriosis, adenomyosis, and unaffected controls. Analyses were stratified by FET protocol. RESULTS: Mean serum progesterone concentrations differed between HRT-FET and mNC-FET cycles and were therefore analyzed separately. In both protocols, progesterone levels were comparable between women with endometriosis or adenomyosis and unaffected controls, and live birth rates did not differ across diagnostic groups or between endometrial preparation strategies within each group. Among women with adenomyosis undergoing HRT-FET, those achieving live birth showed higher mean progesterone levels compared with those who had no live birth (β = 1.76, 95% CI 0.30-3.22, p-value = 0.018), whereas no significant association was observed in mNC-FET cycles. Progesterone concentrations did not differ according to reproductive outcome in women with endometriosis or in unaffected controls. CONCLUSIONS: Women with endometriosis or adenomyosis do not exhibit reduced mean serum progesterone levels at the time of FET compared with unaffected controls, and do not appear to require higher systemic progesterone exposure to achieve live birth. However, lower progesterone levels among women with adenomyosis who did not achieve a live birth, particularly in HRT-FET cycles, suggest that a subset of patients may exhibit different progesterone dynamics, warranting further investigation. Prospective studies are needed to determine whether tailored luteal phase hormonal support strategies may be beneficial in this population.