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.

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Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility

Infertility is a global health problem involving about 15% of couples. Approximately half of the infertility cases are related to male factors. The oxidative stress, which refers to an imbalance in levels of reactive oxygen species (ROS) and antioxidants, is one of the main causes of infertility in men. A small amount of ROS is necessary for the physiological function of sperm including the capacitation, hyperactivation and acrosomal reaction. However, high levels of ROS can cause infertility through not only by lipid peroxidation or DNA damage but inactivation of enzymes and oxidation of proteins in spermatozoa. Oxidative stress (OS) is mainly caused by factors associated with lifestyle. Besides, immature spermatozoa, inflammatory factors, genetic mutations and altering levels of sex hormones are other main source of ROS. Since OS occurs due to the lack of antioxidants and its side effects in semen, lifestyle changes and antioxidant regimens can be helpful therapeutic approaches to overcome this problem. The present study aimed to describe physiological ROS production, roles of genetic and epigenetic factors on the OS and male infertility with various mechanisms such as lipid peroxidation, DNA damage, and disorder of male hormone profile, inflammation, and varicocele. Finally, the roles of oral antioxidants and herbs were explained in coping with OS in male infertility.

Oxidative stress and male infertility: current knowledge of pathophysiology and role of antioxidant therapy in disease management

A state of oxidative stress (OS) and the presence of reactive oxygen species (ROS) in the male reproductive tract are strongly correlated with infertility. While physiological levels of ROS are necessary for normal sperm functioning, elevated ROS production can overwhelm the cell's limited antioxidant defenses leading to dysfunction and loss of fertilizing potential. Among the deleterious pleiotropic impacts arising from OS, sperm motility appears to be particularly vulnerable. Here, we present a mechanistic account for how OS contributes to altered sperm motility profiles. In our model, it is suggested that the abundant polyunsaturated fatty acids (PUFAs) residing in the sperm membrane serve to sensitize the male germ cell to ROS attack by virtue of their ability to act as substrates for lipid peroxidation (LPO) cascades. Upon initiation, LPO leads to dramatic remodeling of the composition and biophysical properties of sperm membranes and, in the case of the mitochondria, this manifests in a dissipation of membrane potential, electron leakage, increased ROS production and reduced capacity for energy production. This situation is exacerbated by the production of cytotoxic LPO byproducts such as 4-hydroxynonenal, which dysregulate molecules associated with sperm bioenergetic pathways as well as the structural and signaling components of the motility apparatus. The impact of ROS also extends to lesions in the paternal genome, as is commonly seen in the defective spermatozoa of asthenozoospermic males. Concluding, the presence of OS in the male reproductive tract is strongly and positively correlated with reduced sperm motility and fertilizing potential, thus providing a rational target for the development of new therapeutic interventions.

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Molecular Changes Induced by Oxidative Stress that Impair Human Sperm Motility.

Currently, the world is in the seventh month of the COVID-19 pandemic. Globally, infections with novel SARS-CoV-2 virus are continuously rising with mounting numbers of deaths. International and local public health responses, almost in synchrony, imposed restrictions to minimize spread of the virus, overload of health system capacity, and deficit of personal protective equipment (PPE). Although in most cases the symptoms are mild or absent, SARS-CoV-2 infection can lead to serious acute respiratory disease and multisystem failure. The research community responded to this new disease with a high level of transparency and data sharing; with the aim to better understand the origin, pathophysiology, epidemiology and clinical manifestations. The ultimate goal of this research is to develop vaccines for prevention, mitigation strategies, as well as potential therapeutics.The aim of this review is to summarize current knowledge regarding the novel SARS CoV-2, including its pathophysiology and epidemiology, as well as, what is known about the potential impact of COVID-19 on reproduction, fertility care, pregnancy and neonatal outcome. This summary also evaluates the effects of this pandemic on reproductive care and research, from Canadian perspective, and discusses future implications.In summary, reported data on pregnant women is limited, suggesting that COVID-19 symptoms and severity of the disease during pregnancy are similar to those in non-pregnant women, with pregnancy outcomes closely related to severity of maternal disease. Evidence of SARS-CoV-2 effects on gametes is limited. Human reproduction societies have issued guidelines for practice during COVID-19 pandemic that include implementation of mitigation practices and infection control protocols in fertility care units. In Canada, imposed restrictions at the beginning of the pandemic were successful in containing spread of the infection, allowing for eventual resumption of assisted reproductive treatments under new guidelines for practice. Canada dedicated funds to support COVID-19 research including a surveillance study to monitor outcomes of COVID-19 during pregnancy and assisted reproduction. Continuous evaluation of new evidence must be in place to carefully adjust recommendations on patient management during assisted reproductive technologies (ART) and in pregnancy.

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A comprehensive review of the impact of COVID-19 on human reproductive biology, assisted reproduction care and pregnancy: a Canadian perspective.

The COVID-19 pandemic is an extraordinary global situation, and all countries have adopted their own strategies to diminish and eliminate the spread of the virus. All measures are in line with the recommendations provided by the World Health Organization. Scientific societies, such as the European Society for Human Reproduction and Embryology and American Society for Reproductive Medicine, have provided recommendations and guidance to overcome and flatten the growing curve of infection in patients who undergo IVF treatments. Although there is as yet no evidence that the virus causing COVID-19 might have negative effects on IVF outcomes, fertility treatments have been postponed in order to support healthcare systems by avoiding placing them under additional stress. The possibility of the virus affecting sperm function and egg performance cannot be excluded. In addition, an indirect effect of the virus on gametes and embryos during their manipulation cannot be ruled out. This commentary aims to provide some ideas on the possible effect of the virus on gametes and embryos, as well as how it could affect the normal functioning of the embryology laboratory.

COVID-19 and fertility: a virtual reality.

Oxidative stress (OS), defined as an overabundance of reactive oxygen species (ROS) or a deficiency of antioxidants, has been linked to sperm damage and male infertility. There are many sources of OS and inflammation including varicocele, tobacco usage, alcohol, obesity/metabolic syndrome, leukocytospermia, sexually transmitted disease (i.e., Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum), bacterial prostatitis, microorganism mutations leading to more OS, and viral infections (i.e., human immunodeficiency virus, hepatitis). This review is focusing on infection and inflammation-mediated OS, the inflammatory markers underlying pathology, clinical significance in male infertility, and a brief description of the recommended treatment modalities.

Hashem AlBunni

Papers

Role of oxidative stress, infection and inflammation in male infertility.