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.


METHODS
Prospective cohort study.


METHODS
Academic medical center.


METHODS
Two hundred twenty-three women undergoing ovarian stimulation.


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


METHODS
Day 3 FSH, E(2), antral follicle count, amount of gonadotropin used, the number of follicles >13 mm, E(2) on the day of hCG administration, and oocyte number.


RESULTS
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 E(2) 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.


CONCLUSIONS
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.
Rosen
Mitchell P
MP
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, California 94115, USA.
Shen
Shehua
S
McCulloch
Charles E
CE
Rinaudo
Paolo F
PF
Cedars
Marcelle I
MI
Dobson
Anthony T
AT
D015415:Biomarkers / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D005307:Fertilization in Vitro; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D009865:Oocytes; D006080:Ovarian Follicle / Q000502:physiology*; D010062:Ovulation Induction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D017384:Sequence Deletion; D020858:Tissue and Organ Harvesting
D015415:Biomarkers; D042965:Methylenetetrahydrofolate Reductase (NADPH2)