Objective To investigate the correlation between methylene tetrahydro folate reductase(MTHFR)C677T polymorphism and insulin resistance(IR)in patients with polycystic ovary syndrome(PCOS).Methods A total of 145 PCOS patients and 87 healthy females from the Obstetrics and Gynecology Hospital of Fudan University were enrolled from January 2022 to November 2023.The C677T polymorphism of MTHFR gene,fasting glucose(FPG)and fasting insulin(FINS)levels were determined.Homocysteine(Hcy),total cholesterol(TC),triglyceride(TG),folic acid,vitamin B12(Vit B12)and vitamin D(Vit D)levels were determined.Insulin release test(IRT)was also performed in patients with PCOS.Insulin sensitivity index(ISI),homeostasis model assessment for insulin resistance(HOMA-IR)and the area under insulin curve(AUCINS)were calculated.The research subjects were classified into IR and non-IR groups according to whether IR occurred or not.Results No statistical significance was found between MTHFR C677T and allele frequency distribution and between IR and non-IR groups in healthy control group(P>0.05).The frequencies of CT,TT genotypes and T allele were higher in IR group than those in non-IR group(P<0.05).Differences in FINS,FPG,Hcy,TG,ISI and AUCINS were found between IR and non-IR groups(P<0.05),and the other index differences were not found between the 2 groups(P>0.05).The TC levels of CT and TT genotypes in PCOS group were higher than CC genotype(P<0.05),and the Hcy level of TT genotype were higher than CC and CT genotypes(P<0.05).There was no statistical significance for all the genotypes in IR group(P>0.05).Conclusions MTHFR gene C677T polymorphism is correlated with IR in females with PCOS.In PCOS patients without IR,Hcy and TC levels are increased in patients with TT genotype.