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

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%, 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.