ApoB and LDL partially explain the association between family history of diabetes and lower clinical pregnancy in women who conceived with PCOS

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Purpose To investigate whether family history of diabetes (FHD) is associated with reproductive outcomes in women with polycystic ovary syndrome (PCOS), and to explore whether baseline metabolic biomarkers statistically explain part of this association. Materials and methods We performed a secondary analysis of the PCOSAct trial. Outcomes were first summarized in the full trial cohort, and the primary post-conception analysis was then restricted to the 320 women who conceived. Modified Poisson regression with robust standard errors was used to estimate risk ratios (RRs) for the association between FHD and clinical pregnancy. E-values were calculated to assess the potential influence of unmeasured confounding. Predictive mediation analyses were performed to evaluate whether baseline lipid parameters statistically explained part of this association. Restricted cubic splines (RCS) were used to examine the dose–response relationships. Results Among women who conceived, those with a positive FHD had a lower clinical pregnancy rate than those without FHD (57.8% vs. 70.7%, p = 0.048), whereas conception rates were similar in the full cohort. Live birth was also numerically lower in the FHD-positive group among women who conceived, but this difference did not reach statistical significance. Positive FHD was also associated with a less favorable metabolic features, including higher body mass index, waist-to-height ratio, LDL, triglycerides, and ApoB, and lower HDL (all p < 0.05). In modified Poisson models, the association between positive FHD and clinical pregnancy was directionally negative (Model 1: RR = 0.82, 95% CI: 0.65–1.02; Model 5: RR = 0.85, 95% CI: 0.66–1.08). Predictive mediation analyses revealed that LDL and ApoB statistically explained part of this association, accounting for 21.1 and 25.3%, respectively. RCS analyses further showed inverse dose-dependent associations of ApoB and LDL with clinical pregnancy. Conclusion A positive FHD was associated with lower clinical pregnancy rates among women with PCOS who conceived. This association might be partly explained by elevated ApoB and LDL levels, although the modified Poisson models and E-value analyses support a cautious interpretation. These findings suggest that elevated ApoB and LDL are associated with poorer post-conception reproductive outcomes and may statistically explain part of the observed association.

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