Antioxidant-Based Therapies in Male Infertility: Do We Have Sufficient Evidence Supporting Their Effectiveness?

Abstract

Under physiological conditions, reactive oxygen species (ROS) play pivotal roles in various processes of human spermatozoa. Indeed, semen requires the intervention of ROS to accomplish different stages of its maturation. However, ROS overproduction is a well-documented phenomenon occurring in the semen of infertile males, potentially causing permanent oxidative damages to a vast number of biological molecules (proteins, nucleic acids, polyunsaturated fatty acids of biological membrane lipids), negatively affecting the functionality and vitality of spermatozoa. ROS overproduction may concomitantly occur to the excess generation of reactive nitrogen species (RNS), leading to oxidative/nitrosative stress and frequently encountered in various human pathologies. Under different conditions of male infertility, very frequently accompanied by morpho-functional anomalies in the sperm analysis, several studies have provided evidence for clear biochemical signs of damages to biomolecules caused by oxidative/nitrosative stress. In the last decades, various studies aimed to verify whether antioxidant-based therapies may be beneficial to treat male infertility have been carried out. This review analyzed the results of the studies published during the last ten years on the administration of low-molecular-weight antioxidants to treat male infertility in order to establish whether there is a sufficient number of data to justify antioxidant administration to infertile males. An analysis of the literature showed that only 30 clinical studies tested the effects of the administration of low-molecular-weight antioxidants (administered as a single antioxidant or as a combination of different antioxidants with the addition of vitamins and/or micronutrients) to infertile males. Of these studies, only 33.3% included pregnancy and/or live birth rates as an outcome measure to determine the effects of the therapy. Of these studies, only 4 were case–control studies, and only 2 of them found improvement of the pregnancy rate in the group of antioxidant-treated patients. Additionally, of the 30 studies considered in this review, only 43.3% were case–control studies, 66.7% enrolled a number of patients higher than 40, and 40% carried out the administration of a single antioxidant. Therefore, it appears that further studies are needed to clearly define the usefulness of antioxidant-based therapies to treat male infertility.

The Role of Seminal Oxidative Stress Scavenging System in the Pathogenesis of Sperm DNA Damage in Men Exposed and Not Exposed to Genital Heat Stress

“…As spermatozoa are characterized by an extremely high susceptibility to oxidative damage, seminal plasma released from accessory glands contains an abundant antioxidant system, which includes both enzymatic and nonenzymatic factors for effectively protecting spermatozoa against ROS attack. In this context, sperm cells are highly dependent on the powerful antioxidant properties of the surrounding environment [ 34 ]. Our previous report demonstrated that a redox imbalance in semen occurred in men exposed to prolonged environmental (professional drivers) or clinically recognized local hyperthermia (varicocele).…”

Oral Antioxidant Treatment of Men Significantly Improves the Reproductive Outcome of IVF Cycles

“…Despite the aforementioned embryological data showing the effectiveness of the antioxidant supplementation taken by males, we chose pregnancy as the primary endpoint, since we believe it is a better marker of improved fertility potential. A recent analysis of the literature of the last ten years concerning the effects of low molecular weight antioxidants (ascorbic acid, N-acetylcysteine, alpha-tocopherol, and CoQ10, administered as a single antioxidant or as a combination of different antioxidants plus vitamins and/or micronutrients) showed that only ten studies included pregnancy and/or live birth rates as an outcome measure to determine the effects of the therapy [ 27 ]. Unfortunately, only two reports found improvement of the pregnancy rate in the group of antioxidant-treated patients in scientifically rigorous case–control studies [ 28 , 29 ].…”

Antioxidant Activity of Opuntia SP. Fruit Extracts on Human Sperm Quality and Cryopreservation Cycle

“…Therefore, oxidative stress could be considered a fundamental parameter of the semen and marker of sperm quality [81]. Indeed, in recent years, numerous studies have found a correlation between ROS overproduction and idiopathic infertility [82,83]. Exposure to antioxidants has positive consequences on all parameters and improves the spermatozoa performance even after the freeze-thaw cycle.…”