Agarwal A, et al. World J Mens Health. 2019 Sep;37(3):296-312. https://doi.org/10.5534/wjmh.190055

Agarwal A, et al. World J Mens Health. 2020 Jan;38:e44. https://doi.org/10.5534/wjmh.200128

Varicocele has been associated with reduced male reproductive potential. With the advances in biomolecular techniques, it has been possible to better understand the mechanisms involved in testicular damage provoked by varicocele. Current evidence suggests the central role of reactive oxygen species (ROS) and the resultant oxidative stress (OS) in the pathogenesis of varicocele-associated male subfertility although the mechanisms have not yet been fully described and it is likely to be multifactorial. Excessive ROS is associated with sperm DNA fragmentation, which may mediate the clinical manifestation of poor sperm function and fertilization outcome related to varicocele. Testing of ROS/OS and DNA fragmentation has the potential to provide additional diagnostic and prognostic information compared to conventional semen analysis and may guide therapeutic management strategies in individual patient.

The diagnosis of male infertility relies largely on conventional semen analysis, and its interpretation has a profound influence on subsequent management of patients. Despite poor correlation between conventional semen parameters and male fertility potential, inclusion of advanced semen quality tests to routine male infertility workup algorithms has not been widely accepted. Oxidative stress is one of the major mediators in various etiologies of male infertility; it has deleterious effects on spermatozoa, including DNA damage. Alleviation of oxidative stress constitutes a potential treatment strategy for male infertility. Measurement of seminal oxidative stress is of crucial role in the identification and monitoring of patients who may benefit from treatments. Various tests including reactive oxygen species (ROS) assay, total antioxidant capacity (TAC) assay or malondialdehyde (MDA) assay used by different laboratories have their own drawbacks. Oxidation-reduction potential (ORP) is a measure of overall balance between oxidants and antioxidants, providing a comprehensive measure of oxidative stress. The MiOXSYS™ System is a novel technology based on a galvanostatic measure of electrons; it presents static ORP (sORP) measures with static referring to the passive or current state of activity between oxidants and antioxidants. Preliminary studies have correlated sORP to poor semen qualities. It is potentially useful in prognostication of assisted reproductive techniques outcomes, screening of antioxidants either in vivo or during IVF cycles, identification of infertile men who may benefit from treatment of oxidative stress, and monitoring of treatment success. The simplified laboratory test requiring a small amount of semen would facilitate clinical application and research in the field. In this paper, we discuss the measurement of ORP by the MiOXSYS System as a real-time assessment of seminal oxidative stress, and argue that it is a potential valuable clinical test that should be incorporated into the male infertility workup and become an important guide to the treatment of oxidative stress-induced male infertility.

The clinical utility of sperm DNA fragmentation tests needs to be revisited in light of increasing evidence of detrimental effect of sperm DNA damage on reproductive outcomes. Current evidence supports the association between high sperm DNA fragmentation and poor outcomes with regards to natural conception and intrauterine insemination. The relationship between high sperm DNA fragmentation and impaired outcomes after in-vitro fertilization and intracytoplasmic sperm injection are more equivocal. However, recent studies indicate that poor sperm chromatin content is associated with an increased risk of early pregnancy loss after in-vitro fertilization and intracytoplasmic sperm injection. Several strategies are proposed to alleviate sperm DNA fragmentation and/or select sperm with higher quality chromatin content for assisted reproductive techniques. The intake of oral antioxidants, varicocele repair, use of recurrent ejaculations alone or combined with micromanipulation-based sperm selection techniques, and the use of testicular sperm for intracytoplasmic sperm injection have been attempted with promising results. Sperm DNA fragmentation tests provide clinically relevant information for natural conception and artificial reproduction independent of those derived from conventional semen parameters. The increasing knowledge of paternal factors on pregnancy outcome and the improvement in treatment strategies should prompt routine evaluation of sperm DNA fragmentation in infertile couples.