Association between serum complement C3 and polycystic ovary syndrome: a systematic review and meta-analysis.

Complement C3 is a key effector molecule of the innate complement system, which participates in inflammatory responses, immune regulation and the maintenance of metabolic homeostasis. Consistency and evidence grade regarding the association between serum C3 levels and polycystic ovary syndrome (PCOS) remain controversial. This systematic meta-analysis aims to assess changes of C3 levels in PCOS patients. We systematically searched PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), VIP Chinese Science and Technology Journal Database (VIP) and Wanfang Database for studies concerning PCOS and C3, from database inception to December 31, 2025. Literature screening, data extraction and risk of bias assessment using the Newcastle-Ottawa Scale (NOS) were independently performed by two investigators. Sensitivity analysis was performed by sequentially omitting each individual study to verify the robustness of the pooled results. Funnel plots were adopted for preliminary evaluation of publication bias. Subgroup analysis was used to explore potential effect modifiers. All statistical analyses were conducted using R software (version 4.6.0) to guarantee the scientific validity and reliability of the findings. A total of 6 studies meeting the predefined inclusion criteria were included, enrolling 915 individuals. C3 levels were higher in PCOS patients than controls (SMD = 0.73, 95% CI: 0.54-0.93), with moderate heterogeneity (I²=47.1%, P = 0.092). No significant difference was observed between subgroups. Sensitivity analysis confirmed the robustness of the overall association. This meta-analysis suggests that circulating C3 levels are elevated in PCOS. However, due to the observational design and limited evidence, these findings are exploratory. Prospective studies are needed to validate this association. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251121390.