Progesterone levels on the day of the β-hCG test predict pregnancy outcomes in FET cycles

Abstract

Abstract Serum progesterone (P) levels are critical for endometrial receptivity and implantation in frozen-thawed embryo transfer (FET) cycles. However, the prognostic role of P levels measured on the day of the β-human chorionic gonadotropin (β-hCG) pregnancy test has not been fully elucidated. This study aimed to evaluate the association between β-hCG day serum P levels and pregnancy outcomes in FET cycles. This retrospective cohort study included 621 FET cycles performed between January 2023 and December 2024, of which 79.5% were conducted using hormone replacement therapy (HRT) protocols and 20.5% using natural cycle (NC) protocols. Serum P levels were measured on the day of the β-hCG pregnancy test. Receiver operating characteristic (ROC) curve analysis was used to determine protocol-specific P thresholds for predicting ongoing pregnancy (OPR). Ongoing pregnancy was defined as a viable intrauterine pregnancy confirmed by ultrasound at or beyond 12 weeks of gestation. Multivariable logistic regression was applied to identify independent predictors of OPR. ROC analysis identified optimal P thresholds of 15.5 ng/mL in NC cycles (AUC 0.821) and 14.15 ng/mL in HRT cycles (AUC 0.595). Overall, 44% of patients had serum P levels below the protocol-specific threshold. OPR was significantly higher in patients with P levels above the threshold (NC: 63.0% vs. 12.8%; HRT: 48.1% vs. 31.9%; p  < 0.001). Multivariable regression demonstrated that younger maternal age and higher β-hCG day P levels independently predicted OPR. In HRT cycles, blastocyst-stage transfer was also significantly associated with improved outcomes (OR = 0.27, 95% CI 0.13–0.59; p  < 0.05). Serum P levels measured on the day of the β-hCG test are significantly associated with pregnancy outcomes in both HRT and NC FET cycles. Routine monitoring of late luteal P levels and individualized luteal phase support strategies may enhance clinical success rates.