Preconception Systemic Inflammation Response Index and Time‐to‐Pregnancy

BACKGROUND: Systemic inflammation may affect female reproductive function, but there is relatively little epidemiological evidence regarding the association between pre-pregnancy inflammatory status and fertility. We explore the association between the pre-pregnancy Systemic Inflammation Response Index (SIRI) and the time to pregnancy (TTP) in couples trying to conceive. METHOD: This study included 1739 couples from the National Free Preconception Check-up Project (NFPCP) in Guangzhou. SIRI was calculated as neutrophil count × monocyte count/lymphocyte count from routine complete blood count (CBC) at baseline. Quartile and continuous variable analysis of SIRI was performed, and restricted cubic spline functions were used to evaluate the dose-response relationship. The associations were adjusted for demographic, behavioural, and lifestyle factors. RESULTS: In the NFPCP preconception couple cohort, 1182 pregnancy events were observed. In categorical analyses, women in the highest quartile of SIRI (Q4: 0.99, 5.58) had lower fecundability than those in Q2 (FR, 0.79; 95% CI 0.63, 0.98), indicating a longer TTP. The inverse association became more apparent at SIRI levels above approximately 0.89 in spline-based analyses. Sensitivity analyses yielded comparable effect estimates after restricting the analysis to live birth outcomes and excluding women with chronic inflammatory conditions, fertility-related disorders, or antibiotic use, supporting the robustness of the observed association. CONCLUSIONS: Higher preconception SIRI was associated with longer TTP, and the association remained generally consistent across adjusted and sensitivity analyses. SIRI may have potential value in preconception risk stratification, but further studies are required to confirm its clinical relevance.