Optimal range of serum progesterone on endometrial transformation day predicts clinical pregnancy in down-regulated HRT-FET cycles: a retrospective cohort study

Background The predictive value of serum progesterone on the day of endometrial transformation in hormone replacement therapy-frozen embryo transfer (HRT-FET) cycles remains unclear, and its effect may vary by protocol. This study aimed to evaluate its impact and compare it between standard and down-regulated HRT protocols. Methods This retrospective study of 1,073 cycles defined a progesterone cutoff of 0.56 ng/mL via ROC analysis. Cycles were categorized into low (< 0.56 ng/mL) and high (≥ 0.56 ng/mL) subgroups, with multivariate logistic regression identifying predictors of clinical pregnancy. A secondary three-tier stratification (< 0.56, 0.56–1.0, ≥ 1.0 ng/mL) was performed to define the optimal therapeutic window. Results Clinical pregnancy rates did not differ significantly between progesterone subgroups in the overall cohort or the standard HRT group. However, in down-regulated HRT cycles, the high progesterone level (≥ 0.56 ng/mL) was associated with higher clinical pregnancy rate (62.4% vs. 48.9%, P = 0.012) and was an independent predictor of clinical pregnancy exclusively in down-regulated cycles (OR = 3.682, 95% CI: 1.575–8.612, P = 0.003). Three-tier analysis showed a non-linear relationship, with rates lowest at < 0.56 ng/mL (48.92%), peaking at 0.56–1.0 ng/mL (63.55%), and declining at ≥ 1.0 ng/mL (55.56%, P = 0.035), identifying 0.56–1.0 ng/mL as the optimal range. Conclusion The predictive value of serum progesterone is protocol-specific. In down-regulated HRT-FET cycles, a level of 0.56–1.0 ng/mL on transformation day is optimal, suggesting routine monitoring may guide individualized luteal support.