No abstract

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.

Sperm DNA integrity is crucial for fertilization and development of healthy offspring. The spermatozoon undergoes extensive molecular remodeling of its nucleus during later phases of spermatogenesis, which imparts compaction and protects the genetic content. Testicular (defective maturation and abortive apoptosis) and post-testicular (oxidative stress) mechanisms are implicated in the etiology of sperm DNA fragmentation (SDF), which affects both natural and assisted reproduction. Several clinical and environmental factors are known to negatively impact sperm DNA integrity. An increasing number of reports emphasizes the direct relationship between sperm DNA damage and male infertility. Currently, several assays are available to assess sperm DNA damage, however, routine assessment of SDF in clinical practice is not recommended by professional organizations. This article provides an overview of SDF types, origin and comparative analysis of various SDF assays while primarily focusing on the clinical indications of SDF testing. Importantly, we report four clinical cases where SDF testing had played a significant role in improving fertility outcome. In light of these clinical case reports and recent scientific evidence, this review provides expert recommendations on SDF testing and examines the advantages and drawbacks of the clinical utility of SDF testing using Strength-Weaknesses-Opportunities-Threats (SWOT) analysis.

Reactive oxygen species (ROS) are short-lived (10-9 s) reactive molecules belonging to the class of free radicals, which are derived from oxygen and characterised by the presence of one or more unpaired electrons in their outer shell. Due to their unstable chemical structure, they attack nearby organic molecules, such as lipids, proteins and DNA, in order to reach a balanced state. The most important ROS include superoxide anion (O −. 2), hydroxyl radical (OH .), peroxyl radicals (ROO .), alkoxyl radicals (RO .), organic hydroperoxides (ROOH) and hydrogen peroxide (H 2 O 2) (Aitken, 2017). Although the latter could be considered as a nonradical oxidant, H 2 O 2 can react with ferrous ions and enhance the synthesis of OH. through the Fenton and the Haber-Weiss reactions. Additionally, nitrogen-based free radicals, such as peroxynitrite (ONOO-) and nitric oxide (NO .), are also a subclass of ROS. The most important source of endogenous free radicals is mitochondria, the organelles responsible for cellular energy production in the form of adenosine triphosphate (ATP). In the inner mitochondrial membrane, different substrates are oxidised and reduced through the electron transport chain complex, generating an electron flux which terminates with ATP synthesis and the reduction of molecular oxygen to water. Although this process is highly efficient, about 1%-2% of oxygen is reduced to superoxide by complex I-and III-mediated single electron transfer (Fukai & Ushio-Fukai, 2011). Non-mitochondrial sources of ROS include peroxisomal β-oxidation,