P-093 The effect of antioxidant supplementation on sperm quality in infertile men: a randomized placebo-controlled clinical trial
Authors: Ioannidou P , Papanikolaou D , Zegkiniadou T , Mouza A , Savvaidou D , Zepiridis L , Chatzimeletiou A , Lampropoulos A , Grimbizis G , Venetis C , Goulis D , Kolibianakis E 
Published: July 2024

Abstract

Study question
Is sperm quality improved in infertile men after administration for three months of a combination of antioxidants as compared to placebo?

Summary answer
Administration in infertile men for three months of a combination of antioxidants as compared to placebo does not improve sperm quality.

What is known already
In infertile men, limited evidence exists to support treatment with a combination of antioxidants for improving sperm quality. A recent Cochrane meta-analysis suggested that treatment of these patients with combinations of antioxidants as compared to placebo or no treatment results in an increase in sperm motility (MD + 12.71 95%CI +11.33 to + 14.08, 7 studies, 684 patients), while no beneficial effect was observed on DNA fragmentation index (DFI) and on the probability of live birth. Nevertheless, combinations of antioxidants are widely used in clinical practice at present.

Study design, size, duration
This randomized placebo-controlled trial evaluated the effect of a combination of antioxidants on sperm motility (primary outcome). Secondary outcomes were sperm concentration, morphology, DFI and levels of reactive oxygen species (ROS). For this purpose, 79 infertile men, were randomized, using a computer-generated randomization list, between 2019-2022, to receive either a combination of antioxidants (n = 40) or placebo (n = 39) for three months. This was a quadruple-blind trial (participants, clinicians, outcome assessors, data analyst).

Participants/materials, setting, methods
Sperm variables were evaluated according to WHO criteria, ROS levels by the detection of 8-hydroxy-2-deoxy-guanosine peroxidation product on sperm and DFI by flow cytometry. For all outcomes, the changes between treatment initiation and completion were assessed in both the antioxidant and the placebo groups and compared statistically. Values are expressed as mean (95%CI of the mean) and statistical significance was set at p = 0.05.

Main results and the role of chance
Nine patients dropped out from the study, since they did not perform the second sperm analysis for personal reasons and thus did not complete the study process. No differences were observed between the antioxidants and the placebo group regarding male age {mean difference (MD) -1.3 years, 95%CI -1.4 to + 4.1}, smoking (antioxidants: 41.6%, 95%CI 25.5 to 59.2 vs placebo: 43.5%, 95%CI 27.8 to 60.3), exercise (antioxidants: 45.4%, 95%CI 28.1 to 63.6 vs placebo: 16.1%, 95%CI 5.4 to 33.7) and primary infertility (antioxidants: 82.3%, 95%CI 65.4 to 93.2 vs placebo: 85.7%, 95%CI 69.7 to 95.1). No statistically significant differences were observed in infertile men who received a combination of antioxidants or placebo, between the changes of pre and post treatment values, regarding sperm motility (-3.5%, 95%CI: -13 to + 5.9, p = 0.742), concentration (-1.9%, 95%CI: -15.7 to + 11.8, p = 0.0.77), morphology (-0.10%, 95%CI: -0.8 to 0.6, p = 0.793), DFI (0.2%, 95%CI: -3.8 to + 4.4, p = 0.891) and levels of ROS (-1.2%, 95%CI: -3.2 to + 0.8, p = 0.231). No side effects were reported in antioxidants combination treated patients for the duration of follow-up.

Limitations, reasons for caution
The current RCT did not explicitly include men with abnormal DFI, limiting the extrapolation of the results obtained in this group of patients. Moreover, it was not designed to evaluate the probability of pregnancy either spontaneously or after Medically Assisted Reproduction (MAR).

Wider implications of the findings
The current study does not support the use of antioxidants for enhancing male infertility. Future relevant studies should focus on identifying the optimal population and duration of treatment.

Trial registration number
NCT04256278