Antioxidants do not improve semen parameters or DNA integrity in men with male factor infertility, according to randomized controlled study results published in Fertility and Sterility.
As oxidative stress has been shown to interfere with sperm health, antioxidants are currently being marketed to treat male factor infertility. Although a meta-analysis has shown antioxidant supplementation may increase the chance of live births in subfertile men, large randomized placebo-controlled trials have not been performed.
To examine this, men of 144 heterosexual couples were randomly assigned to treatment groups that would receive either a daily placebo or an antioxidant formulation for 3 to 6 months. Couples who experienced at least 12 months of male factor fertility; had a male partner aged ≥18 years with ≥1 abnormal semen parameter on a semen analysis in the preceding 6 months; and had a female partner between age 18 and 40 years with regular menstrual cycles, evidence of ovulation, and a normal uterine cavity with ≥1 patent fallopian tube were included in the study. Women age >35 years were required to have a normal ovarian reserve based on hormone levels and follicle counts and men’s sperm concentrations were required to be between >5 and ≤15 million/mL. In addition, men could not take fertility medication or testosterone and had to refrain from taking any vitamins for 4 weeks prior to treatment assignment.
The antioxidant treatment consisted of 500 mg of vitamin C, 400 mg of vitamin E, 0.20 mg of selenium, 1000 mg of L-carnitine, 20 mg of zinc, 1000 µg of folic acid, 10 mg of lycopene, and 2000 U of vitamin D each day. Blood and semen analysis were conducted on samples provided by the men on the day of randomization and after 90 days of treatment. Couples were provided with free ovulation predictor tests and instructed on timing their sexual intercourse during the first 3 months of treatment. Couples who had not conceived in the first 3 months received up to 3 cycles of ovarian stimulation with intrauterine insemination. Women who conceived were observed throughout pregnancy and delivery.
Significant differences in the changes of sperm concentration and total sperm count from baseline and month 3 of treatment between the experimental and placebo groups were observed. Change in sperm concentration in men who received the antioxidants was -4.0 million/mL (interquartile range [IQR]: -12.0, 5.7) vs 2.4 million/mL (IQR: -9.0, 15.5) in men in the placebo group (P =.029). Change in total motile sperm count in men who received antioxidants was -10.6 million (IQR: -32.5, 12.6) vs 1.6 million (IQR: -21.8, 42.9) in men in the placebo group (P =.021). Changes in morphology, motility, and DNA fragmentation did not differ significantly between the 2 groups. With regard to the live-birth rate, 15% of the couples with a man who had received antioxidants had a live birth compared with 24% of the men receiving placebo (P =.14).
Overall, this study showed no improvement in semen parameters after 3 months of antioxidant therapy.
However, the investigators noted that because this study had a relatively limited sample size, larger trials are needed to confirm this finding.
Steiner AZ, Hansen KR, Barnhart KT, et al. The effect of antioxidants on male factor infertility: the Males, Antioxidants, and Infertility (MOXI) randomized clinical trial [published online February 25, 2020]. Fertil Steril. doi:10.1016/j.fertnstert.2019.11.008