Investigating the association between systemic immune-inflammation index and female fertility: a retrospective cohort study

BACKGROUND: Inflammation has been linked to female fertility, yet its impact on ovarian reserve and response remains unclear. This study investigates the associations between systemic inflammatory markers, ovarian reserve—assessed by anti-Müllerian hormone (AMH) and antral follicle count (AFC)—and ovarian response, measured by the number of oocytes retrieved, in women undergoing assisted reproductive treatment (ART). METHODS: A retrospective cohort study of 19,282 women evaluated systemic inflammatory markers, including systemic immune-inflammation index (SII), platelet-neutrophil product (PPN), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR), derived from neutrophil, platelet, and lymphocyte counts. Blood samples were collected on menstrual cycle days 2–4 for complete blood count analysis. Linear regression assessed associations between inflammatory markers and ovarian reserve (AMH, AFC) or ovarian response (oocytes retrieved). Restricted cubic splines tested nonlinear relationships, and stratified analyses identified sensitive subpopulations. RESULTS: Elevated first-trimester systemic inflammatory markers, including SII, PPN, PLR, and NLR, were significantly associated with reduced ovarian reserve and ovarian response. Adjusted models confirmed dose-response declines: highest vs. lowest quartiles showed significant reductions in AMH (e.g., SII β=-0.037, 95% CI -0.055, -0.018), AFC (e.g., NLR β=-0.116, 95% CI -0.150, -0.082), and oocytes retrieved (e.g., PPN β=-0.072, 95% CI -0.106, -0.039) (all P < 0.05). Nonlinear relationships were observed for PLR and NLR with AFC (inflection points at PLR = 123.53, NLR = 2.22; P nonlinear < 0.05). Stratified analyses indicated greater susceptibility in women on antagonist protocols (P interaction < 0.05), but not by age or BMI. Sensitivity analyses corroborated robustness. CONCLUSION: Elevated systemic inflammatory markers are associated with diminished ovarian reserve and response. These findings suggest that inflammatory markers may serve as potential predictors of ovarian function and treatment outcomes, emphasizing the need to address systemic inflammation in fertility care.