Serum progesterone concentrations and subcutaneous progesterone supplementation in endometriosis: artificial-cycle frozen embryo transfer

RESEARCH QUESTION: Are there differences between patients with and without endometriosis in progesterone concentrations the day before artificial-cycle frozen embryo transfer (AC-FET) and in live birth rate (LBR) following subcutaneous progesterone when indicated? DESIGN: This retrospective cohort included 985 AC-FET cycles with vaginal progesterone (600 mg/day) from January 2019 to December 2022 at a university-affiliated fertility centre. Among them, 168 cycles (17.05%) were from patients with endometriosis (n = 128) and 817 from controls (n = 649). LBR was evaluated based on progesterone the day before transfer. Subcutaneous progesterone (25 mg/day) was given when <10.6 ng/ml. Cycles were divided into four groups: 1 (endometriosis, reference, 51 cycles) and 3 (controls, 274 cycles) with progesterone <10.6 ng/ml plus supplementation; 2 (endometriosis, 117 cycles) and 4 (controls, 543 cycles) with progesterone ≥10.6 ng/ml. RESULTS: The likelihood of progesterone <10.6 ng/ml before transfer was similar between groups (adjusted odds ratio [aOR] 0.98, 95% CI 0.65-1.47). After adjustment for age, BMI and embryo quality, LBR were comparable between group 1 and groups 2 (aOR 0.79, 95% CI 0.36-1.74), 3 (aOR 0.91, 95% CI 0.45-1.84) and 4 (aOR 1.39, 95% CI 0.71-2.74). Higher progesterone >90th percentile (23.31 ng/ml) on pregnancy test day was associated with higher clinical pregnancy (controls: 73% vs 50.5%, P <0.001; endometriosis: 83.3% vs 46.1%, P = 0.016) and LBR (controls: 63.5% vs 38.2%, P <0.001; endometriosis: 66.7% vs 32.8%, P = 0.027). CONCLUSIONS: Progesterone concentrations before transfer are comparable between endometriosis and control cycles. Vaginal progesterone with subcutaneous supplementation leads to comparable LBR, regardless of endometriosis status.