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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.

Reactive oxygen species (ROS) are physiologically involved in functions like sperm maturation, capacitation and acrosome reaction, but their excess is involved in male infertility. Antioxidants in seminal plasma (SP) are an important factor balancing physiologic and harmful ROS activities. In this study, we determined and compared the full profiles of the water- and fat-soluble antioxidants in SP and serum of 15 healthy fertile subjects (ranging between the ages of 35 and 42 years). Ejaculates were obtained after 2⁻5 days of sexual abstinence. After liquefaction and withdrawal of an aliquot for the sperm count, samples were centrifuged to obtain SP. Thirty min after semen donation, a venous blood sample was collected from each subject. Donors with lower SP concentrations of ascorbic acid ( n = 5) or α-tocopherol ( n = 5) received a 4 week oral administration of either vitamin C (100 mg/day) or vitamin E (30 mg/day). They were then re-assayed to determine the SP and serum levels of ascorbic acid and α-tocopherol. SP and serum samples were properly processed and analyzed by HPLC methods suitable to determine water (ascorbic acid, glutathione (GSH) and uric acid) and fat-soluble (all- trans -retinoic acid, all- trans -retinol, α-tocopherol, carotenoids and coenzyme Q 10 ) antioxidants. Data demonstrate that only ascorbic acid is higher in SP than in serum (SP/serum ratio = 4.97 ± 0.88). The other water-soluble antioxidants are equally distributed in the two fluids (GSH SP/serum ratio = 1.14 ± 0.34; uric acid SP/serum ratio = 0.82 ± 0.12). All fat-soluble antioxidants are about 10 times less concentrated in SP than in serum. In donors treated with vitamin C or vitamin E, ascorbic acid and α-tocopherol significantly increased in both fluids. However, the SP/serum ratio of ascorbic acid was 4.15 ± 0.45 before and 3.27 ± 0.39 after treatment, whilst those of α-tocopherol were 0.11 ± 0.03 before and 0.10 ± 0.02 after treatment. The results of this study, by showing the peculiar composition in water- and fat-soluble antioxidants SP, indicate that it is likely that still-unknown mechanisms allow ascorbic acid accumulation in SP against a concentration gradient. SP mainly relies its defenses on water- rather than fat-soluble antioxidants and on the mechanisms ensuring their transfer from serum.