Oxidative stress and elevated levels of seminal and sperm reactive oxygen species (ROS) may contribute to up to 80% of male infertility diagnosis, with sperm ROS concentrations at fertilization important in the development of a healthy fetus and child. The evaluation of ROS in semen seems promising as a potential diagnostic tool for male infertility and male preconception care with a number of clinically available tests on the market (MiOXSYS, luminol chemiluminescence and OxiSperm). While some of these tests show promise for clinical use, discrepancies in documented decision limits and lack of cohort studies/clinical trials assessing their benefits on fertilization rates, embryo development, pregnancy and live birth rates limit their current clinical utility. In this review, we provide an update on the current techniques used for analyzing semen ROS concentrations clinically, the potential to use of ROS research tools for improving clinical ROS detection in sperm and describe why we believe we are likely still a long way away before semen ROS concentrations might become a mainstream preconception diagnostic test in men.

BackgroundOxidative stress in semen contributes up to 80% of all infertility diagnosis. Diagnostics to measure oxidative stress in semen was recently added to the 6th edition WHO methods manual, although diagnostic predictive values need to be interpreted with caution as there are still several research questions yet to be answered.ObjectivesTo determine the natural fluctuations in semen redox indicators (MiOXSYS® and OxiSperm® II) within and between men and their association with markers of sperm oxidative stress.Materials and methodsTotal, 118 repeat semen samples from 31 generally healthy men aged 18–45 years, over 6 months. Standard semen analysis as per 5th WHO manual. Semen redox levels measured via MiOXSYS® and OxiSperm® II. Additional attributes of sperm quality; HBA® binding assay and sperm hyperactivation and oxidative stress; DNA fragmentation (Halo® Sperm) and lipid peroxidation (BODIPY™ 581/591 C11) were assessed.ResultsSamples with high redox‐potential (MiOXSYS® ≥1.47 sORP/106 sperm/ml) had lower sperm, motility, morphology and higher DNA fragmentation (P < 0.05). Upon further analysis, these associations were driven solely by the adjustment of sperm concentration (106/ml) in normalised redox‐potential. No significant associations between NBT‐reactivity (OxiSperm® II) and measures of the sperm function or oxidative stress were observed (P > 0.05). Fluctuations in semen redox levels varied greater between men than within men over the study period.DiscussionNeither MiOXSYS® nor OxiSperm® II assays were predictive of sperm function or sperm oxidative stress. This was likely due at least in part to limited understanding of their biochemistry and clinical application. As a result, these assays seem to provide no additional clinical utility beyond that of a standard semen analysis, highlighting the imperative for the development of new robust point‐of‐care devices for accurately determining sperm oxidative stress.ConclusionThese findings suggest that MiOXSYS® and OxiSperm® II systems for the measurement of sperm oxidative stress may have limited diagnostic potential.