Systematic review of antioxidant types and doses in male infertility: Benefits on semen parameters, advanced sperm function, assisted reproduction and live-birth rate

Cellular protection against the deleterious effects of reactive oxidants generated in aerobic metabolism, called oxidative stress, is organized at multiple levels. Defense strategies include three levels of protection; prevention, interception, and repair. Regulation of the antioxidant capacity includes the maintenance of adequate levels of antioxidant and the localization of antioxidant compounds and enzymes. Short-term and long-term adaptation and cell specialisation in these functions are new areas of interest. Control over the activity of prooxidant enzymes, such as NADPH oxidase and NO synthases, is crucial. Synthetic antioxidants mimic biological strategies.

Sperm DNA fragmentation (SDF) has been generally acknowledged as a valuable tool for male fertility evaluation. While its detrimental implications on sperm function were extensively investigated, little is known about the actual indications for performing SDF analysis. This review delivers practice based recommendations on commonly encountered scenarios in the clinic. An illustrative description of the different SDF measurement techniques is presented. SDF testing is recommended in patients with clinical varicocele and borderline to normal semen parameters as it can better select varicocelectomy candidates. High SDF is also linked with recurrent spontaneous abortion (RSA) and can influence outcomes of different assisted reproductive techniques. Several studies have shown some benefit in using testicular sperm rather than ejaculated sperm in men with high SDF, oligozoospermia or recurrent in vitro fertilization (IVF) failure. Infertile men with evidence of exposure to pollutants can benefit from sperm DNA testing as it can help reinforce the importance of lifestyle modification (e.g., cessation of cigarette smoking, antioxidant therapy), predict fertility and monitor the patient’s response to intervention.

The ability of zinc to retard oxidative processes has been recognized for many years. In general, the mechanism of antioxidation can be divided into acute and chronic effects. Chronic effects involve exposure of an organism to zinc on a long-term basis, resulting in induction of some other substance that is the ultimate antioxidant, such as the metallothioneins. Chronic zinc deprivation generally results in increased sensitivity to some oxidative stress. The acute effects involve two mechanisms: protection of protein sulfhydryls or reduction of (*)OH formation from H(2)O(2) through the antagonism of redox-active transition metals, such as iron and copper. Protection of protein sulfhydryl groups is thought to involve reduction of sulfhydryl reactivity through one of three mechanisms: (1) direct binding of zinc to the sulfhydryl, (2) steric hindrance as a result of binding to some other protein site in close proximity to the sulfhydryl group or (3) a conformational change from binding to some other site on the protein. Antagonism of redox-active, transition metal-catalyzed, site-specific reactions has led to the theory that zinc may be capable of reducing cellular injury that might have a component of site-specific oxidative damage, such as postischemic tissue damage. Zinc is capable of reducing postischemic injury to a variety of tissues and organs through a mechanism that might involve the antagonism of copper reactivity. Although the evidence for the antioxidant properties of zinc is compelling, the mechanisms are still unclear. Future research that probes these mechanisms could potentially develop new antioxidant functions and uses for zinc.