Maternal serum progesterone and BMI are associated with neonatal sex ratios following single frozen embryo transfer

BACKGROUND: The biological mechanisms behind sex ratio variation in assisted reproductive technologies (ART) are not well understood. This study investigated whether maternal serum progesterone (PRG) and body mass index (BMI) are related to neonatal sex after frozen-thawed embryo transfer (FET). METHODS: We conducted a retrospective cohort study of 998 single blastocyst FET cycles performed under a freeze-all strategy from 2019 to 2023. Maternal BMI and serum PRG measured in the peri-transfer period were analyzed in relation to neonatal sex. Receiver operating characteristic (ROC) analyses identified predictive thresholds. Associations were evaluated using multivariable logistic regression models adjusted for potential confounders. RESULTS: ROC analyses identified PRG ≤ 21.11 ng/mL and BMI ≤ 21.30 kg/m² as the optimal cut-offs for predicting male birth. Low PRG was associated with a higher odds of male offspring (OR = 1.61; 95% CI: 1.09-2.36; p = 0.016), as was low BMI (OR = 2.33; 95% CI: 1.61-3.40; p < 0.001). When both factors were present, the likelihood of male birth increased further (OR = 2.30; 95% CI: 1.39-3.80; p = 0.001). A high BMI reduced the association between low PRG and male birth, while an elevated PRG weakened the connection between low BMI and neonatal sex. Female births were correspondingly less common under these conditions (OR = 0.43; 95% CI: 0.26-0.72; p = 0.001). CONCLUSIONS: Maternal progesterone levels and BMI together were associated with neonatal sex ratios after FET. These findings imply that endocrine and metabolic environments influence embryo-endometrium interactions in a sex-specific way and open new pathways for research into developmental programming in ART. These findings do not establish causality and should be interpreted as hypothesis-generating.