Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2020 Mar;113(3):552-560.e3.
doi: 10.1016/j.fertnstert.2019.11.008. Epub 2020 Feb 25.

The effect of antioxidants on male factor infertility: the Males, Antioxidants, and Infertility (MOXI) randomized clinical trial

Anne Z Steiner  1 , Karl R Hansen  2 , Kurt T Barnhart  3 , Marcelle I Cedars  4 , Richard S Legro  5 , Michael P Diamond  6 , Stephen A Krawetz  7 , Rebecca Usadi  8 , Valerie L Baker  9 , R Matthew Coward  10 , Hao Huang  11 , Robert Wild  2 , Puneet Masson  12 , James F Smith  13 , Nanette Santoro  14 , Esther Eisenberg  15 , Heping Zhang  11 ; Reproductive Medicine Network
Affiliations
Randomized Controlled Trial

The effect of antioxidants on male factor infertility: the Males, Antioxidants, and Infertility (MOXI) randomized clinical trial

Anne Z Steiner et al. Fertil Steril. 2020 Mar.

Abstract

Objective: To determine whether antioxidants improve male fertility, as measured by semen parameters and DNA fragmentation at 3 months and pregnancy resulting in live birth after up to 6 months of treatment, among couples with male factor infertility.

Design: Multicenter, double-blind, randomized, placebo-controlled trial with an internal pilot study.

Setting: Nine fertility centers in the United States from December 2015 to December 2018.

Patient(s): Men (N = 174) with sperm concentration ≤15 million/mL, motility ≤40%, normal morphology ≤4%, or DNA fragmentation >25%, and female partners who were ovulatory, ≤40 years old, and had documented tubal patency.

Intervention(s): Males randomly assigned to receive an antioxidant formulation (n = 85) containing 500 mg of vitamin C, 400 mg of vitamin E, 0.20 mg of selenium, 1,000 mg of l-carnitine, 20 mg of zinc, 1,000 μg of folic acid, 10 mg of lycopene daily, or placebo (n = 86). Treatment lasted for a minimum of 3 months and maximum of 6 months, and couples attempted to conceive naturally during the first 3 months and with clomiphene citrate with intrauterine insemination of the female partner in months 4 through 6.

Main outcome measure(s): Primary outcome was live birth; secondary outcomes included pregnancy within 6 months of treatment. For the internal pilot, the primary outcomes were semen parameters and sperm DNA fragmentation index after 3 months of treatment.

Result(s): In the Males, Antioxidants, and Infertility (MOXI) study, after 3 months of treatment, the change in sperm concentration differed between the antioxidant group (median -4.0 [interquartile range-12.0, 5.7] million/mL) and placebo group (+2.4 [-9.0, 15.5] million/mL). However, there were no statistically significant differences between the two groups for changes in sperm morphology, motility, or DNA fragmentation. Among the 66 oligospermic men at randomization, sperm concentration did not differ at 3 months between the antioxidant and control groups: 8.5 (4.8, 15.0) million/mL versus 15.0 (6.0, 24.0) million/mL. Of the 75 asthenospermic men, motility did not differ at 3 months: 34% ± 16.3% versus 36.4% ± 15.8%. Among the 44 men with high DNA fragmentation, DNA fragmentation did not differ at 3 months: 29.5% (21.6%, 36.5%) versus 28.0% (20.6%, 36.4%). In the entire cohort, cumulative live birth did not differ at 6 months between the antioxidant and placebo groups: 15% versus 24%.

Conclusion(s): Antioxidants do not improve semen parameters or DNA integrity among men with male factor infertility. Although limited by sample size, this study suggests that antioxidant treatment of the male partner does not improve in vivo pregnancy or live-birth rates.

Clinical trial registration number: NCT02421887.

Keywords: Antioxidants; male factor infertility; randomized controlled trial.

PubMed Disclaimer

Conflict of interest statement

CONFLICT OF INTEREST

All authors had financial support from NICHD/NIH for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Dr. Diamond reports other support from Advanced Reproductive Care, LLC outside the submitted work; Dr. Legro reports other support from Bayer, Kindex, Odega, Ferring, Millendo, and AbbVie outside the submitted work; Dr. Hansen reports other support from Roche Diagnostics and Ferring International Pharmascience Center, US outside the submitted work; Dr. Steiner reports support from Prima-Temp outside the submitted work.

Comment in

References

    1. Wang A, Fanning L, Anderson DJ, Loughlin KR. Generation of reactive oxygen species by leukocytes and sperm following exposure to urogenital tract infection. Arch Androl 1997;39:11–7. - PubMed
    1. Agarwal A, Prabakaran S, Allamaneni SS. Relationship between oxidative stress, varicocele and infertility: a meta-analysis. Reprod Biomed Online 2006;12:630–3. - PubMed
    1. Saleh RA, Agarwal A, Sharma RK, Nelson DR, Thomas AJ Jr. Effect of cigarette smoking on levels of seminal oxidative stress in infertile men: a prospective study. Fertil Steril 2002;78:491–9. - PubMed
    1. Aitken RJ. Generation of reactive oxygen species, lipid peroxidation, and human sperm function. Biology of reproduction 1989;41:183–97. - PubMed
    1. Gharagozloo P, Aitken RJ. The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. Human Reproduction;26:1628–40. - PubMed

Publication types

Associated data