Micronized Vaginal Progesterone Dose and Serum Progesterone Thresholds Determine Reproductive Outcomes in Frozen–Thawed Embryo Transfer With Hormone Replacement Therapy

Purpose: To evaluate the combined effects of micronized vaginal progesterone (P4) dose and achieved serum P4 levels on reproductive outcomes in hormone replacement therapy-frozen embryo transfer (HRT-FET) cycles by classifying patients according to both parameters. Methods: This retrospective cohort study analyzed 1137 single good-quality blastocyst transfers performed between 2017 and 2022. Patients received OneCrinone 90 mg/day, Lutinus 300 mg/day, or Luteum 800 mg/day. Serum P4 levels on the day of embryo transfer (ET) and assisted reproductive technology (ART) outcomes were compared, including dose-serum P4-based subgroup analyses. Receiver operating characteristic analysis was used to explore a serum P4 cutoff for clinical pregnancy. Results: Higher daily doses were associated with increased serum P4 levels and higher implantation, clinical pregnancy, and live birth rates. An exploratory serum P4 cutoff of 13.1 ng/mL on the day of ET was associated with clinical pregnancy, with significantly better outcomes observed in patients with P4 ≥ 13.1 ng/mL. Dose-serum P4-based subgroup analyses showed that both parameters jointly influenced ART outcomes. Conclusion: In HRT-FET cycles, achieving adequate micronized vaginal P4 dosage together with sufficient serum P4 levels on the ET day is associated with improved ART outcomes. Monitoring serum P4 may help support individualized luteal phase management.