Polyendocrine metabolic ovarian syndrome and cardiometabolic profile in offspring: a propensity score matched cohort study

Research question Do offspring of women with polycystic ovary syndrome (PCOS) conceived through assisted reproductive technology (ART) exhibit altered cardiometabolic profiles in early childhood? Design Of 2688 singletons born to women with or without PCOS (controls) who were conceived through ART, 2549 were eligible for study analysis. Propensity score matching (PSM) was employed to mitigate confounding variables between groups; 217 maternal-child dyads in PCOS group were matched to 787 maternal-child dyads in the control group. Cardiometabolic profiles at 3- to 6-years of age were assessed. The Benjamini–Hochberg (BH) method was used to control the false discovery rate (FDR). Results Compared to controls, offspring of PCOS mothers showed marginally higher total cholesterol (4.40 vs. 4.23 mmol/L, p=0.013, q=0.046) and a lower proportion had total cholesterol levels in the ideal range (49.3%, 107/217) vs. 59.6% (469/787), p=0.007, q=0.046). Although these differences survived BH-FDR correction, they were small in magnitude and the central tendency of all lipid measures remained within the normal pediatric range. Low-density lipoprotein-C (LDL-C) trended similarly (2.43 vs. 2.33 mmol/L, p=0.049) but did not survive FDR adjustment (q=0.086). No other modules of cardiometabolic profiles differ between PCOS and the controls. In sex-stratified analyses, small but significant lipid differences (PCOS vs. controls: total cholesterol, 4.45 vs. 4.27mmol/L, p=0.024, q=0.042; LDL-C, 2.53 vs. 2.36 mmol/L, p=0.007, q=0.042) were observed exclusively in female offspring, whereas no differences were seen in boys. Conclusion Although total cholesterol was higher in ART-conceived PCOS offspring during early childhood, these minimal lipid differences observed are within normal pediatric ranges, and are not considered clinically actionable. Longitudinal follow-up is warranted to determine whether these subtle deviations have long-term clinical significance.