Oxidative stress and male infertility: From research bench to clinical practice

Abstract

Production of very low amounts of ROS in semen appears to play a physiological role in regulating normal sperm functions, whereas high levels of ROS endanger sperm function and viability. Oxidative stress due to excessive production of ROS, impaired antioxidant defense mechanisms, or both precipitates a range of pathologies that are currently believed to negatively affect the male reproductive function. Oxidative stress-induced damage to sperm may be mediated by lipid peroxidation of the sperm plasma membrane, reduction of sperm motility, and damage to the DNA in the sperm nucleus. Despite the established role of OS in the pathogenesis of male infertility, there is a lack of consensus as to the clinical utility of seminal OS testing in an infertility clinic. One important reason for the inability to utilize the OS test in clinical practice is related to the lack of a standard protocol for assessment of seminal OS. Introduction of ROS-TAC score as an accurate measure of seminal OS by our program has helped in our effort to translate the important information gained on OS from the research bench to the clinical practice of andrology. In addition, results of our recent studies indicate the availability of alternate protocols for assessment of seminal OS by measuring ROS directly in the whole (unwashed) ejaculate or assessing the differential contribution of spermatozoa and leukocytes to ROS production in semen using the NBT reduction test. Our results indicate that the diagnostic and prognostic capabilities of the seminal OS test are beyond those of conventional tests of sperm quality and function. The OS test can accurately discriminate between fertile and infertile men and identify patients with a clinical diagnosis of male-factor infertility that are likely to initiate a pregnancy when followed over a period of time. In addition, the test can help select subgroups of infertile men in whom OS is a significant factor and who might benefit from antioxidant supplementation. We strongly believe that incorporating such a test into the routine andrology workup is an important step for the future of the male infertility practice.