Objective · To investigate the characteristics of leptin secretion and DNA methylation of leptin gene of ovarian granulosa cells in patients with polycystic ovary syndrome (PCOS) associated with metabolic syndrome (MS). Methods · Twenty patients underwent in vitro fertilization for fallopian tube factor at the Reproductive Medical Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine September to December 2016 were selected. They were divided into two groups, i.e. PCOS group (n10) and PCOS-MS group (n10). Chemiluminescence method was used to detect serum sex hormones and glucose metabolism indexes. Glycerol phosphate oxidase-peroxidase-4-aminoantipyrine and phenolic method was used to detect lipid metabolism indexes. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration of leptin in serum and follicular fluid. Combined bisulfite restriction analysis was used to test methylation level of the leptin DNA promoter in ovarian granulosa cells. Wilcoxon rank and χ2 test were used for statistical analysis. Results · There was no difference in age and basic hormone levels between two groups. Compared with the PCOS group, the insulin resistance index and triglyceride level in patients with PCOS-MS group were significantly higher (P0.045, P0.044), high density lipoprotein level was decreased significantly (P0.048), the level of leptin in serum and follicular fluid was increased significantly (P0.031, P0.042), the methylation sites of CpG island in leptin DNA promoter upstream 299-556 sequence of luteinized granulosa cells were reduced significantly (P0.026), and the good quality embryo rate was significantly lower (P0.043). Conclusion · The leptin levels in the serum and follicular fluid of patients with PCOS-MS are elevated, accompanieda decrease in the methylation level of the leptin DNA promoter in luteinized granulosa cells and in the proportion of high-quality embryos, which may be one of the reasons leading to the decline of PCOS-MS female fertility.