Methylenetetrahydrofolate reductase (MTHFR) is associated with ovarian follicular activity

Objective

Polymorphisms in the MTHFR gene have been associated with decreased cell division and apoptosis. This finding led us to evaluate whether MTHFR polymorphisms were associated with follicular growth within the ovary. More specifically, we investigated the effect of the two common polymorphisms C677T and A1298C in our population of women undergoing ovarian stimulation.

Design

Prospective cohort study.

Setting

Academic medical center.

Patient(s)

Two hundred twenty-three women undergoing ovarian stimulation.

Intervention(s)

The DNA from patients was genotyped at the MTHFR C677T and A1298C polymorphisms.

Main Outcome Measure(s)

Day 3 FSH, E₂, antral follicle count, amount of gonadotropin used, the number of follicles >13 mm, E₂ on the day of hCG administration, and oocyte number.

Result(s)

Women with the variant MTHFR 1298 C allele had significantly higher basal FSH levels, and after ovarian stimulation, produced fewer follicles >13 mm, had lower E₂ levels on the day of hCG administration, and required more ampules of gonadotropin hormone during treatment. Women with the variant MTHFR 677 T allele demonstrated no significant differences.

Conclusion(s)

The MTHFR A1298C polymorphism, but not the C677T polymorphism, is associated with higher basal FSH levels and may be a determinant of response to ovarian stimulation. These findings make a compelling case for the MTHFR A1298C polymorphism to modulate folliculogenesis.

Key Words: In vitro fertilization (IVF), MTHFR, folic acid, ovarian reserve, follicle development, ovarian stimulation