Effects of folic acid on oligozoospermia with MTHFR polymorphisms in term of seminal parameters, DNA fragmentation, and live birth rate: a double-blind, randomized, placebo-controlled trial.

Background: It has been reported that paternal folic acid deficiency is correlated with male infertility and increased birth defects in the offspring. However, there are few data concerning the influence of folic acid supplementation on male-factor infertility with MTHFR gene polymorphisms.
Objectives: To evaluate whether folic acid supplementation has a beneficial effect on oligozoospermia with MTHFR gene polymorphisms in Chinese infertility population.
Materials and Methods: The infertile men suffering oligozoospermia with MTHFR gene polymorphisms were randomly divided into the folic acid treatment groups receiving folic acid 0.8 mg daily for 3 months and the placebo groups receiving placebo for 3 months. Semen parameters, seminal MDA, and DNA fragmentation were measured. Furthermore, spontaneous pregnancy rate and live birth rate were evaluated.
Results: Administration of folic acid for 3 months could significantly improve the seminal parameters in patients with MTHFR 677 TT genotype in comparison with that receiving placebo. Moreover, seminal MDA and sperm DNA fragmentation index in patients with MTHFR 677 TT genotype significantly declined at the end of treatment. Spontaneous pregnancy rate and live birth rate tended to be significantly higher in couples in which the men with MTHFR 677 TT genotype receiving folic acid than that receiving placebo. However, folic acid treatment did not exhibit any advantage in MTHFR 677 CT, 1298 AC, 1298 CC, 1793 GA, or combined 677 CT/1298 AC genotype.
Discussion: The anti-oxidation function of folic acid is one of possible mechanisms invovled in improving seminal parameters and pregnancy outcome.
Conclusions: Folic acid supplementation has a beneficial effect on oligozoospermia with MTHFR 677 TT genotype in term of seminal parameters, seminal MDA, sperm DNA fragmentation, and pregnancy outcome.
(© 2019 American Society of Andrology and European Academy of Andrology.)