C677T methylenetetrahydrofolate reductase polymorphism interferes with the effects of folic acid and zinc sulfate on sperm concentration.
OBJECTIVE
To determine the frequency of C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism in fertile and subfertile males, and the MTHFR-dependent response of sperm concentration after folic acid and/or zinc sulfate intervention.


METHODS
Double-blind, placebo-controlled intervention study. Two outpatient fertility clinics and nine midwifery practices in The Netherlands.


METHODS
One hundred thirteen fertile and 77 subfertile males. Daily capsules of folic acid (5 mg) and/or zinc sulfate (66 mg), or placebo for 26 weeks.


METHODS
Prevalence of C677T MTHFR polymorphism and the response of sperm concentration related to MTHFR carriership after intervention treatment.


RESULTS
The C677T methylenetetrahydrofolate reductase genotypes were comparable in fertile and subfertile males. Independent of fertility state, sperm concentration significantly increased in wild-types after folic acid and zinc sulfate treatment only. Heterozygotes and homozygotes did not significantly benefit from either treatment.


CONCLUSIONS
C677T methylenetetrahydrofolate reductase polymorphism is not a risk factor for male factor subfertility. In contrast to heterozygotes and homozygotes for C677T MTHFR polymorphism, sperm concentration in wild-types significantly improved after folic acid and zinc sulfate intervention. A stronger role of other folate genes on spermatogenesis is suggested.
Ebisch
Inge M W
IM
Department of Obstetrics and Gynecology, University Medical Centre Nijmegen, Nijmegen, The Netherlands.
van Heerde
Waander L
WL
Thomas
Chris M G
CM
van der Put
Nathalie
N
Wong
Wai Yee
WY
Steegers-Theunissen
Régine P M
RP
D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000494:pharmacology*; D005787:Gene Frequency; D006801:Humans; D007248:Infertility, Male / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009154:Mutation / Q000502:physiology*; D010919:Placebos; D013076:Sperm Count; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D019287:Zinc Sulfate / Q000494:pharmacology*
D010919:Placebos; D019287:Zinc Sulfate; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)