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.

Reactive Oxygen Species (ROS) occur naturally in pre-implantation embryos as a by-product of ATP generation through oxidative phosphorylation and enzymes such as NADPH oxidase and xanthine oxidase. Biological concentrations of ROS are required for crucial embryonic events such as pronuclear formation, first cleavage and cell proliferation. However, high concentrations of ROS are detrimental to embryo development, resulting in embryo arrest, increased DNA damage and modification of gene expression leading to aberrant fetal growth and health. In vivo embryos are protected against oxidative stress by oxygen scavengers present in follicular and oviductal fluids, while in vitro, embryos rely on their own antioxidant defence mechanisms to protect against oxidative damage including; superoxide dismutase, catalase, GSH and clutamyl cystenine synthestase. Pre-implantation embryonic ROS originate from eggs, sperm and embryos themselves or from the external environment (i.e. in vitro culture system, obesity and aging). This review examines biological and pathological roles of ROS in the pre-implantation embryo, maternal and paternal origins of embryonic ROS and from a clinical perspective we comment on the growing interest for combating increased oxidative damage in the pre-implantation embryo through the addition of antioxidants.

Obesity prevalence worldwide is increasing significantly. Whilst maternal obesity has clear detrimental impacts on fertility, pregnancy and foetal outcomes, more recently there has been an increasing focus on the role of paternal obesity in human fertility. Recent meta‐analyses have indicated that obesity in men negatively affects basic sperm parameters such as sperm count, concentration and motility, increases the incidence of infertility and reduces the chances of conception. Sperm DNA damage, typically characterised by DNA strand breaks and oxidation of DNA nucleotides, is a specialised marker of sperm quality that has been independently associated with recurrent miscarriage, reduced assisted reproduction success and increased mutational loads in subsequent offspring. Whilst, there are still conflicting data in humans as to the association of obesity in men with sperm DNA damage, evidence from rodent models is clear, indicating that male obesity increases sperm DNA damage. Human data are often conflicting because of the large heterogeneity amongst studies, the use of body mass index as the indicator of obesity and the methods used for detection of sperm DNA damage. Furthermore, comorbidities of obesity (i.e., heat stress, adipokines, insulin resistance, changes in lipids, hypogonadism and obstructive sleep apnoea) are also independently associated with increased sperm DNA damage that is not always modified in men with obesity, and as such may provide a causative link to the discrepancies amongst human studies. In this review, we provide an update on the literature regarding the associations between obesity in men and fertility, basic sperm parameters and sperm DNA damage. We further discuss potential reasons for the discrepancies in the literature and outline possible direct and indirect mechanisms of increased sperm DNA damage resulting from obesity. Finally, we summarise intergenerational obesity through the paternal linage and how sperm DNA damage may contribute to the transmission.