Plasma metabolite levels before pregnancy and pregnancy outcomes in couples of reproductive age: prospective evidence from the PREBIC cohort in Chongqing, China

Infertility represents a major global reproductive health challenge. Metabolite levels in both partners are highly correlated and may serve as potential confounders for each other. However, how the overall preconception plasma metabolic profiles of both partners jointly influence natural conception outcomes remains unclear. Based on the Chongqing Preconception Reproductive Health and Birth Outcomes Cohort (PREBIC), this study aims to explore the association between preconception plasma metabolite levels in couples of reproductive age and conception outcomes.

The Chongqing PREBIC was launched in January 2019 at the Chongqing Health Center for Women and Children, recruiting couples of reproductive age undergoing preconception health examinations to establish baseline cohorts and collect blood samples. Follow-up was then performed every 3 months for clinical pregnancy outcomes following 24 months of unprotected intercourse. The study ultimately included 1292 couples of reproductive age for analysis. According to natural conception status, participants were assigned into a pregnant group (n=967) and a non-pregnant group (n=325). Baseline plasma samples were subjected to standardized metabolomic testing using the Bruker IVDR NMR platform, yielding 167 metabolic parameters. Elastic network regression was employed to screen key metabolites, and logistic regression models were constructed to evaluate the association between metabolites and 2-year pregnancy outcomes, and confounding factors such as age, body mass index (BMI), smoking and alcohol consumption were adjusted.

Among the 1292 couples of reproductive age, the 2-year pregnancy rate was 74.85%. Eighty-two metabolites showed positive correlations between partners, with a mean correlation coefficient of 0.15. After controlling for inter-variable correlations using elastic network model, 14 male metabolites and 20 female metabolites were found to be associated with conception outcomes. Logistic regression revealed gender-specific associations between plasma metabolite levels in both partners and conception outcomes: in males, triglycerides in low-density lipoprotein were positively associated with conception outcomes (Q4 vs Q1: RR=1.12, 95%CI: 1.03 to 1.19, P adjust=0.047). In females, low-density lipoprotein, apolipoprotein A in high-density lipoprotein, apolipoprotein B in low-density lipoprotein, creatinine, and leucine were negatively associated with conception outcomes. Acetic acid in in both partners was positively correlated with conception outcomes (Q4 vs Q1: male RR=1.13, 95%CI: 1.04 to 1.21, P adjust=0.047; female RR=1.18, 95%CI: 1.05 to 1.28, P adjust=0.007).

Preconception metabolite levels in couples of reproductive age may act on future reproductive potential in a gender-specific manner, with common key metabolites identified.

Based on these findings, it is recommended that the health policy-making departments accelerate the transition of preconception care services from focusing solely on women toward a dual-partner co-management model. Incorporate the pre-pregnancy metabolism of both males and females of reproductive age into routine preconception eugenics health services, with priority monitoring of metabolic indicators, including lipid homeostasis and energy metabolism; develop precision intervention measures according to metabolic differences between genders; improve the urban-rural integrated preconception health management system covering both partners; and enhance reproductive health at the public health source level, providing policy basis and technical support for optimizing birth population quality.