Association Between Serum Progesterone Levels on the Day of Frozen–Thawed Embryo Transfer and Pregnancy and Neonatal Outcomes

Background/Objectives: Serum progesterone (P) levels on the day of frozen–thawed embryo transfer (FET) appear to influence treatment success. Some studies suggest that low P levels may negatively affect pregnancy outcomes, whereas others report a detrimental impact of elevated p values. Although a threshold of 10 ng/mL is frequently cited as indicative of adequate luteal support, the optimal P cut-off on the FET day remains unclear. This study aims to identify a predictive serum p value above which pregnancy rates do not decline in artificial FET cycles. Methods: A retrospective cohort study comprising 236 women who underwent FET between November 2021 and July 2023 was conducted at the Center of Assisted Medical Procreation of Centro Materno-Infantil do Norte. Serum P levels were measured on the day of FET. Three analytical approaches were used in assessing the association between P levels and FET outcomes: (1) fixed threshold of 10 ng/mL; (2) stratification into quartiles (Q1 < 7.30; Q2: 7.30–10.26; Q3: 10.27–13.42; Q4 > 13.42 ng/mL); (3) optimal P cut-off derived from ROC analysis (9.34 ng/mL). Continuous variables were compared using T-test or One-Way ANOVA. Categorical variables were analyzed using Chi-square test or Fisher’s exact test. Associations between P levels and pregnancy outcomes were further examined using logistic regression. Results: Using the P threshold of 10 ng/mL, women with p < 10 ng/mL showed significantly lower positive β-hCG rates (p = 0.020), implantation rates (p = 0.002), and clinical pregnancy rates (CPRs) (p = 0.019). Quartile-based comparisons revealed no significant differences. Regarding the ROC-derived cut-off, women with p ≥ 9.34 ng/mL had significantly higher positive β-hCG rates (38.5% vs. 52.8%, p = 0.012), implantation rates (30.0% vs. 45.5%, p = 0.002), CPR (36.3% vs. 50.0%, p = 0.016), ongoing pregnancy rates (24.4% vs. 37.6%, p = 0.013), and live birth rates (24.4% vs. 37.6%, p = 0.013). p ≥ 9.34 ng/mL remained an independent predictor of improved pregnancy outcomes in multivariate analysis. Conclusions: Serum P levels ≥ 9.34 ng/mL on the day of FET were associated with significantly higher pregnancy success, supporting the relevance of center-specific P thresholds and suggesting potential benefit in individualized luteal phase support strategies.