To identify preconception clinical and multi-omics factors associated with conception and early pregnancy loss in women with unexplained recurrent pregnancy loss (URPL).
Approach:
Study Design: A prospective cohort study involving 149 women with URPL, followed for 12 months.
Data Collection: Preconception fasting plasma analyzed for clinical biomarkers, untargeted metabolomics, and proteomics.
Statistical Analysis: Multivariable logistic regression used to evaluate associations with reproductive outcomes.
Key Findings:
66.4% of women conceived during follow-up (99 out of 149).
Higher testosterone levels associated with lower probability of conception (aOR 0.50, 95% CI 0.28–0.89, p = 0.019).
Women who conceived had higher levels of progesterone-related metabolites, including 17-hydroxyprogesterone (FC = 3.89), pregnanediol 3-O-glucuronide (FC = 2.37), and pregnanetriol 3α-O-β-D-glucuronide (FC = 2.39).
Higher prolactin levels associated with increased odds of early pregnancy loss (aOR 1.09, 95% CI 1.01–1.18, p = 0.036).
Early pregnancy loss characterized by lower bile acid-related metabolites and higher caffeine and methylxanthine metabolites.
Interpretation:
Associations were observed between androgen-related biology, prolactin, non-criteria antiphospholipid antibodies, and bile acid metabolism with reproductive outcomes in URPL.
Limitations:
Study limited to a single cohort and requires validation in independent cohorts.
Potential confounding factors, such as maternal age and body mass index, were not fully accounted for in the analysis.
Conclusion:
The study identifies potential biomarkers and factors associated with reproductive outcomes in women with URPL, warranting further investigation.
A large BRFSS analysis points to persistent screening disparities among sexual orientation and gender identity minority respondents, with particularly large gaps in some gender identity minority groups.