Serum progesterone levels on fresh blastocyst transfer day: a key determinant of live birth rates

STUDY QUESTION Is there an association between mid-luteal serum progesterone (P) levels on the day of fresh embryo transfer (ET) at the blastocyst stage and the live birth rate (LBR)? SUMMARY ANSWER Serum P levels between 46.6 and 72.3 ng/ml on the day of fresh ET are associated with the highest LBR. WHAT IS KNOWN ALREADY Luteal phase monitoring is a standard practice in frozen ET cycles to personalize luteal phase support. However, the role of serum P levels in fresh ET cycles remains underexplored and inconsistent, with some studies suggesting a link to outcomes while others show no association. STUDY DESIGN, SIZE, DURATION This retrospective, single-center cohort study included all single autologous Day-5 blastocyst fresh ETs performed between June 2020 and March 2023. Serum P levels were measured on the day of ET. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 874 patients underwent ovarian stimulation according to standardized protocols, with ovulation triggered by human chorionic gonadotropin. All patients received the same luteal phase support regimen of vaginal micronized P (800 mg/day). Serum P levels were measured on the morning of ET in a single laboratory, with clinicians blinded to the results. Patients were divided into four quartiles based on their serum P levels: Q1 (10.2–46.5 ng/ml), Q2 (46.6–72.3 ng/ml), Q3 (72.4–106.9 ng/ml), and Q4 (107.0–364.8 ng/ml). The primary outcome was the LBR, with secondary outcomes including clinical pregnancy rates, early miscarriage rates, and neonatal outcomes (birth weight and gestational age at delivery). Univariate and multivariate logistic regression analyses were performed to identify factors associated with LBR. MAIN RESULTS AND THE ROLE OF CHANCE The median serum P level on ET day for the entire study population was 72.3 ng/ml (range: 46.5–106.9), with a minimum value of 10.2 ng/ml and a maximum value of 364.8 ng/ml. The overall LBR was 29.4% (260/874), ranging from 21.0% in Q1 to 38.1% in Q2, 29.5% in Q3, and 30.3% in Q4. A significant association between serum P levels and LBR was observed, with Q1 showing the lowest LBR and Q2 the highest (P < 0.001). Multivariate logistic regression indicated that serum P levels in Q1, Q3, and Q4 were associated with significantly lower LBRs compared to Q2, with adjusted odds ratios of 0.52 (95% CI: 0.32–0.82, P = 0.005), 0.55 (95% CI: 0.36–0.86, P = 0.010), and 0.54 (95% CI: 0.34–0.85, P = 0.010), respectively. For secondary outcomes, clinical pregnancy rates were significantly lower in Q1 (29.2% vs 44.1%, P < 0.001). Early miscarriage rates were higher in Q3 (38.5%) and Q4 (35.6%) compared to Q2 (12.3%, P < 0.001). Preterm birth was significantly more frequent in Q1 than in Q2 (15.2% vs 3.6%, P = 0.010). LIMITATIONS, REASONS FOR CAUTION The study’s retrospective design is a key limitation, introducing potential selection and confounding biases, despite efforts to mitigate these using multivariable analysis. WIDER IMPLICATIONS OF THE FINDINGS These findings highlight the need for prospective studies to validate the association between serum P levels and pregnancy outcomes in fresh ET cycles. Such studies could explore the benefits of personalizing luteal phase support based on serum P levels, including the potential for enhanced P supplementation in low P cases or a freeze-all approach for those with elevated P levels, to improve LBRs and optimize treatment outcomes. STUDY FUNDING/COMPETING INTEREST(S) This study received no external funding. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.