Association of MTHFR C677T and A1298C Polymorphisms with Ovarian Reserve in Infertile Women with Thyroid Autoimmunity.

Background/

Objectives

Variability in the methylenetetrahydrofolate reductase (MTHFR) gene has been implicated in reproductive dysfunction and may influence ovarian physiology in women with thyroid autoimmunity (TAI). This prospective study aimed to investigate the association of the MTHFR C677T and A1298C polymorphisms with ovarian reserve and controlled ovarian hyperstimulation (COH) outcomes in infertile women with TAI.

Methods

Genomic DNA was extracted from peripheral blood samples of 145 euthyroid infertile women with TAI undergoing assisted reproductive treatment and 100 fertile controls. The TAI cohort was divided into women with preserved ovarian reserve (TAI1) and diminished ovarian reserve (TAI2). MTHFR C677T and A1298C polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Genotype and allele frequencies were compared between groups, and associations with COH outcomes were evaluated.

Results

Significant differences in MTHFR C677T genotype and allele distributions were observed between the TAI1 and TAI2 subgroups. Genotype distributions also differed significantly between the overall TAI cohort and fertile controls, with significant differences observed between the TAI1 subgroup and controls, but not between the TAI2 subgroup and controls. No significant associations were found for the MTHFR A1298C polymorphism, while associations between MTHFR polymorphisms and COH outcomes were limited and inconsistent.

Conclusions

The MTHFR C677T, but not A1298C, polymorphism is associated with ovarian reserve in infertile women with TAI. These findings suggest that genetic variation in MTHFR may contribute to the heterogeneity of ovarian reserve in this population, while its influence on ovarian response to stimulation appears limited.