Impact of antioxidant treatment on DNA fragmentation index: a double‐blind placebo‐controlled randomized trial

Abstract

Background: Previous reports on effect of antioxidants on sperm DNA integrity were equivocal, and there is a lack of randomized, placebo-controlled studies. Objectives: To evaluate the efficacy of combined antioxidant treatment in subfertile men with normal reproductive hormone levels and high sperm DNA fragmentation index (DFI). Materials and methods: This placebo-controlled, double-blind, randomized study evaluated the effects of combined antioxidant treatment in 77 men from infertile couples, with normal testosterone, LH and FSH levels and DFI ≥25%. All participants were randomly assigned to receive combined antioxidant treatment (vitamins, antioxidants and oligoelements) or placebo for six months. The primary outcome measured was DFI. Secondary outcomes were standard semen parameters. DFI and other semen parameters were, at each time point (pre-treatment, and after three and six months of treatment), compared between the treatment and the placebo group using Mann-Whitney U-test. Results: Antioxidant group had higher sperm concentration after three months of treatment (median: 24.4 9 10 6 /mL vs. 27.2 9 10 6 /mL; P = 0.028) and borderline statistically significant higher concentration after six months of treatment (median: 24.4 9 10 6 / mL vs. 33.3 9 10 6 /mL; P = 0.053) compared to pre-treatment values. The DFI did not change during the 6 months of antioxidant therapy. No statistically significant difference between the antioxidant and placebo group was seen for any of the semen parameters including sperm DFI at any of the three time points. Discussion: The increase in sperm concentration was more pronounced in the antioxidant treated group but not statistically significantly higher than among controls, perhaps due to insufficient statistical power. Previous studies have shown positive effect of antioxidant treatment on DFI and other semen parameters. However, our findings indicate that men with normal reproductive hormone levels may not be the primary target group for such therapy. Conclusion: Six months treatment with antioxidants had no effect on sperm DFI.

Sperm DNA Fragmentation: A New Guideline for Clinicians

“…Antioxidants play an important role in general health by scavenging excess free radicals and thus, preventing oxidative damage to macromolecules. However, the benefits of exogenous antioxidant therapy are less clear [202]. Clinicians commonly utilize antioxidant therapy to maintain redox balance by scavenging ROS [203].…”

An update on the management of male infertility

“…70 In addition, no treatment for high SDF has been proven to have clinical value, despite the proposal of several interventions, including oral antioxidant therapy, folliclestimulating hormone treatment and the use of surgically retrieved testicular sperm. 71,72 Surgically retrieved testicular sperm avoids epididymal transit and this minimises exposure to reactive oxygen species, 73 which could contribute to a high SDF index. However, data regarding treatment outcomes, specifically live birth rate, are not robust.…”

“…Nevertheless, current evidence is insufficient, neither to recommend routine DNA integrity testing for those undergoing ART, nor to predict pregnancy loss 70 . In addition, no treatment for high SDF has been proven to have clinical value, despite the proposal of several interventions, including oral antioxidant therapy, follicle‐stimulating hormone treatment and the use of surgically retrieved testicular sperm 71,72 . Surgically retrieved testicular sperm avoids epididymal transit and this minimises exposure to reactive oxygen species, 73 which could contribute to a high SDF index.…”

Best laboratory practices and therapeutic interventions to reduce sperm DNA damage

“…The effects of vitamin C 30 mg, vitamin E 5 mg, vitamin B12 0.5 µg, l-carnitine 750 mg, coenzyme Q10 10 mg, folic acid 100 µg, zinc 5 mg and selenium 25 µg were evaluated in a placebo-controlled, double-blind, randomised study of 77 infertile men with DFI >25% measured by SCSA (Stenqvist, Oleszczuk, Leijonhufvud, & Giwercman, 2018). There was no statistically significant change in the DFI of antioxidant group compared to placebo group after 3 months (30.0% versus 34.5%, p = .27) and 6 months (34.0% versus 29.5%, p = .18) of treatment.…”