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International audience; Purpose: In response to the COVID-19 pandemic, the American Center for Reproductive Medicine (ACRM) transitioned its annual training in assisted reproductive technology (ART) from a hands-on, laboratory-based training course to a fully online training endorsed by the American College of Embryology. Here we describe our experience and assess the quality of an online training format based on participant outcomes for the first three modules of a planned series of online ART training.Materials and methods: These modules included manual semen analysis, sperm morphology and ancillary semen tests (testing for leukocytospermia, sperm vitality, and anti-sperm antibody screening). The virtual format consisted of lecture presentations featuring laboratory protocols with corresponding video demonstrations of routine techniques and best practices. Practical scenarios, troubleshooting, and clinical interpretation of laboratory results were also discussed. At the end of each module, an optional multiple choice question test was held as a prerequisite to obtain certification on the topics presented. Course quality was assessed using participant responses collected via online surveys.Results: The digital delivery methods used were found to have largely or completely met the participants' expectations for all questions (>85%). The majority (>87%) of the participants either strongly agreed or agreed that the course content was well-structured with appropriate depth, and that their overall expectations of the course had been met.Conclusions: This training format appears to be a realistic teaching option to freely share highly specialized expertise and technical knowledge with participants from anywhere in the world with varying levels of competency or experience.

Purpose The objective of this scientometric analysis was to recognize the top 100 cited articles on 'Male infertility and Antioxidants' and analyze its publication characteristics. Materials and methods The Scopus database was used to retrieve related articles and the top 100 identified based on citation rate. Results The articles were published in 56 journals between 1995 and 2019 with a median (interquartile range) citation score of 17 (5-62). Among the top 100 articles, 69 were clinical studies, which included controlled and blinded (33.33%), prospective (27.54%), randomized-controlled trials (26.09%), uncontrolled (11.59%), and retrospective (1.45%) studies. In addition to conventional semen parameters, advanced sperm function tests such as oxidative stress (51%) and sperm DNA damage (23%) were reported. Pregnancy rate (33%) was found to be the most reported reproductive outcome. Antioxidant therapy was mostly investigated in male cohorts with sperm abnormalities such as asthenozoospermia (28%) and clinical conditions such as idiopathic male infertility (20%), varicocele/varicocelectomy (17%) and general male infertility (16%). Conclusions The most influential publications on antioxidants and male infertility were identified for the first time in the literature. This will serve as a reliable source of information for researchers and clinicians alike.

Oxidative stress is a condition due to an imbalance between the concentrations of oxidants and antioxidants, and it is a well-recognized contributor in several male infertility conditions. Varicocele, a common vascular condition, may cause male infertility due to hyperthermia, hypoxia and/or exposure to toxic adrenal and renal metabolites. In this review, the mechanisms by which oxidative stress can affect cellular integrity and functions are described, along with molecular markers of cellular oxidative damage, and the most commonly performed techniques for their detection in seminal fluid. Moreover, we focus on the role of oxidative stress in the pathophysiology of varicocele based on recently published evidence from omics based studies, such as proteomics and genomics. Finally, we discuss strategies for the management of oxidative stress and the clinical guidelines for testing oxidative stress-related sperm DNA fragmentation in this group of patients.

Objective The COVID-19 pandemic, caused by the acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), remains an ongoing public health challenge. Although males are affected slightly more than females, the impact of SARS-COV-2 on male reproductive system remains unclear. This systematic review aims to provide a concise update on the effects of COVID-19 on male reproductive health, including the presence of viral RNA in semen, and the impact on semen quality, testicular histology, testicular pain and male reproductive hormones. The global health is fronting an immediate as well as impending threat from the novel coronavirus (SARS-CoV-2) causing coronavirus disease (COVID-19), that inflicts more males than females. Evidence suggest that male reproductive system is susceptible to this viral infection. However, there are still several pertinent queries that remain to be fully explained regarding the mechanism in testicular SARS-CoV-2 dynamics and the exact mode of its actions. Thus, the present systematic review aims to provide a concise update on the effects of coronavirus disease 2019 (COVID-19) on male reproduction.. Methods A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines searching the PubMed database. Eligibility for inclusion were original human studies evaluating the impact of COVID-19 on male reproductive health. Specific outcomes required for inclusion were at least one of the following: i) seminal detection of mRNA virus, or evaluation of ii) semen analysis, iii) testicular histology or ultrasonography, iv) testicular clinical symptoms and/or v) male reproductive hormones in COVID-19-positive patients. Results Of 553 retrieved articles, 25 met the inclusion criteria. This included studies primarily investigating the presence of viral RNA in semen (n = 12), semen quality (n = 2), testicular histology (n = 5), testicular pain (n = 2) and male reproductive hormones (n= 4). Results show little evidence for the presence of viral RNA in semen, although COVID-19 seems to affect seminal parameters, induce orchitis, and cause hypogonadism. Mortality cases suggest severe histological disruption of testicular architecture, probably due to a systemic and local reproductive tract inflammatory response and oxidative stress-induced damage. Conclusions Clinical evaluation of the male reproductive tract, seminal parameters and reproductive hormones is recommended in patients with current or a history of COVID-19, particularly in males undergoing fertility treatment. Any long-term negative impact on male reproduction remains unexplored and an important future consideration.

Background: Computer-aided sperm analyzers (CASA) are currently used worldwide for semen analysis. However, there are doubts about their reliability to fully substitute the human operator. Therefore, this study aimed to systematically review the current literature comparing results from semen evaluation by both CASA-based and manual approaches. Methods: A systematic screening of the literature was performed based on the PRISMA guidelines and by searching on PubMed, Scopus, and Embase databases. Results: A total of 14 studies were included. Our results showed a high degree of correlation for sperm concentration and motility when analysis was performed either manually or by using a CASA system. However, CASA results showed increased variability in low (60 million/mL) concentration specimens, while sperm motility assessment was inaccurate in samples with higher concentration or in the presence of non-sperm cells and debris. Morphology results showed the highest level of difference, due to the high amount of heterogeneity seen between the shapes of the spermatozoa either in one sample or across multiple samples from the same subject. Conclusions: Overall, our study suggests CASA systems as a valid alternative for the evaluation of semen parameters in clinical practice, especially for sperm concentration and motility. However, further technological improvements are required before these devices can one day completely replace the human operator. Artificial intelligence-based CASA devices promise to offer higher efficiency of the analysis and improve the reliability of results. Keywords: Computer-aided sperm analyzers (CASA); computer-assisted sperm analysis; semen analysis; sperm concentration

Objectives: To systematically review and discuss the current evidence from placebo-controlled clinical trials that investigated the use of alternative medicines and herbal remedies in the management of erectile dysfunction (ED). Methods: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-based systematic review using specific keyword combinations was conducted on the PubMed and Scopus databases. Randomised controlled trials investigating herbal medicine in at least one group and using the International Index of Erectile Function (IIEF) as an outcome in patients primarily diagnosed with ED were included for review. Results: Following the literature search, screening and eligibility analysis, a total of 42 articles were included. The 42 articles were categorised as single herb extractions (n = 14), combination herbal formula (n = 5), combination of herbal formula and non-herbal nutraceuticals (n = 7), non-herbal nutraceuticals (n = 5), acupuncture and moxibustion (n = 2), diet and nutrition (n = 3), exercise (n = 5), and topical treatments (n = 1). Based on the results, Korean ginseng, Pygnogenol and Prelox, Tribulus terrestris, Lepidium meyenii, L-arginine, acupuncture and lifestyle interventions were the more predominantly investigated treatments interventions for ED. Conclusions: Panax ginseng, Pygnogenol, Prelox and Tribulus terrestris have promising evidence as herbal products, alongside L-arginine as a nutritional supplement, for ED based on IIEF outcomes, and warrant further clinical investigation. The mechanisms of action remain unclear, but each of these appears to in part increase nitric oxide synthesis. Importantly, improved diet and exercise should be considered, particularly in patients with obesity or diabetes mellitus.

It is widely accepted that oxidative stress plays an important role in the pathophysiology of male infertility and that antioxidants could have a significant role in the treatment of male infertility. The main objectives of this study are: 1) to systematically review the current evidence for the utility of antioxidants in the treatment of male infertility; and 2) propose evidence-based clinical guidelines for the use of antioxidants in the treatment of male infertility. A systematic review of the available clinical evidence was performed, with articles published on Scopus being manually screened. Data extracted included the type of antioxidant used, the clinical conditions under investigation, the evaluation of semen parameters and reproductive outcomes. The adherence to the Cambridge Quality Checklist, Cochrane Risk of Bias for randomized controlled trials (RCTs), CONSORT guidelines and JADAD score were analyzed for each included study. Further, we provided a Strength Weakness Opportunity Threat (SWOT) analysis to analyze the current and future value of antioxidants in male infertility. Of the 1,978 articles identified, 97 articles were included in the study. Of these, 52 (53.6%) were uncontrolled (open label), 12 (12.4%) unblinded RCTs, and 33 (34.0%) blinded RCTs, whereas 44 (45.4%) articles tested individual antioxidants, 31 (32.0%) a combination of several products in variable dosages, and 22 (22.6%) registered antioxidant products. Based on the published evidence, we 1) critically examined the necessity of additional double-blind, randomized, placebo-controlled trials, and 2) proposed updated evidence-based clinical guidelines for antioxidant therapy in male infertility. The current systematic review on antioxidants and male infertility clearly shows that antioxidant supplementation improves semen parameters. In addition, it provides the indications for antioxidant treatment in specific clinical conditions, including varicocele, unexplained and idiopathic male infertility, as well as in cases of altered semen quality.

Purpose: The use of antioxidants is common practice in the management of infertile patients. However, there are no estab-lished guidelines by professional societies on antioxidant use for male infertility. Materials and Materials and Methods:Methods: Using an online survey, this study aimed to evaluate the practice pattern of reproductive specialists to determine the clinical utility of oxidative stress (OS) testing and antioxidant prescriptions to treat male infertility. Results:Results: Responses from 1,327 participants representing 6 continents, showed the largest participant representation being from Asia (46.8%). The majority of participants were attending physicians (59.6%), with 61.3% having more than 10 years of experience in the field of male infertility. Approximately two-thirds of clinicians (65.7%) participated in this survey did not order any diagnostic tests for OS. Sperm DNA fragmentation was the most common infertility test beyond a semen analysis that was prescribed to study oxidative stress-related dysfunctions (53.4%). OS was mainly tested in the presence of lifestyle risk factors (24.6%) or sperm abnormalities (16.3%). Interestingly, antioxidants were prescribed by 85.6% of clinicians, for a duration of 3 (43.7%) or 3?? months (38.6%). A large variety of antioxidants and dietary supplements were prescribed, and scientific evidence were mostly considered to be modest to support their clinical use. Results were not influenced by the physician?셲 age, geographic origin, experience or training in male infertility. Conclusions:Conclusions: This study is the largest online survey performed to date on this topic and demonstrates 1) a worldwide under-standing of the importance of this therapeutic option, and 2) a widely prevalent use of antioxidants to treat male infertility. Finally, the necessity of evidence-based clinical practice guidelines from professional societies is highlighted.

Background The use of herbal medicine and alternative medicine is reported to be in up to 50% of prescriptions for benign prostate hyperplasia (BPH) in Europe, along with an increased global interest for holistic medicinal approaches. This study aimed to systematically review the published evidence investigating the use of herbal medicines as a treatment for BPH in clinical trials based on PRISMA guidelines. Methods A literature search was conducted using PubMed, Cochrane, Medline, and Scopus databases, including English language clinical trials (Jadad score of ≥ 4) that investigated herbal medicine as a sole intervention, reporting at least one of the following outcomes: International Prostate Symptom Score (IPSS); American Urological Association Symptom Index (AUASI); Maximum Urinary Flow Rate (Qmax); Post-void residual volume (PRV); Prostate volume (PV); Serum Prostatic Specific Antigen (PSA); Quality of Life (QoL) Scores. Results Following article screening, 28 articles were included. The most frequently studied herbs in isolation or in combination were Serenoa repens (54%), Urtica dioica (14%), Cucurbita pepo (14%), lycopene (14%), Pygeum africanum (14%) and Linum usitatissimum (7%). These herbal-based formulations mostly improved the symptoms associated with BPH (IPSS/AUASI, Qmax, PSA, QoL scores, PRV and PV). This review further discusses these herbs and the outcomes, with a focus on the potential mechanisms of action. Conclusions There are limited high quality clinical trials investigating herbal medicine on BPH, where S. repens is significantly more represented than other popular herbs for BPH, such as C. pepo, U. dioica, P. africanum, and lycopene. Although the included studies broadly found positive positive results for standardised outcomes for LUTS and urinary flow, there was great variability in the study designs requires caution in interpretation. As these herbs are supported by in vivo and in vitro studies on potential mechanisms of actions, comparison of efficacy of mono-herbal and poly-herbal approaches, standardized extracts based on identification of active constituents, as well as dosage and long-term safety studies are warrented.

Pycnogenol, produced from Pinus pinaster (French maritime pine) extractions, is a significant source of medicinal procyanidins with OS and immune-modulating properties. Limited studies suggest a role in protection against induced spermatotoxicity through improved OS markers, and may improve fertility outcomes of subfertile males. However, the most significant clinical indication of this combination has been demonstrated for erectile dysfunction. Urtica dioica (stinging nettle) contains numerous molecules relevant to human health, including various polyphenols, triterpenoids, sterols, flavonoids, lectins, and fatty acids. Mechanisms of action relevant to the clinical indications include antioxidant and anti-inflammatory activity, alongside 5α-reductase and aromatase inhibition, and antiproliferative and cell cycle arrest in cancers. Preclinical studies have shown benefit in both BPH and prostate cancer cell lines, and the prevention of diabetes-induced reproductive dysfunction. Clinical studies predominantly combine U. dioica with Sabel serrulata (saw palmetto) in BPH-induced LUTS. This combination has shown benefit in numerous clinical trials particularly in IPSS scores, improved residual volume, peak, and maximal urinary flow rates. This chapter reviews the current preclinical and clinical evidence for these herbal medicines in andrology.

International audience; Sperm vitality testing is a basic semen examination that has been described in the World Health Organization (WHO) Laboratory Manual for the Examination and Processing of Human Semen from its primary edition, 40 years ago. Several methods can be used to test sperm vitality, such as the eosin-nigrosin (E-N) stain or the hypoosmotic swelling (HOS) test. In the 6th (2021) edition of the WHO Laboratory Manual, sperm vitality assessment is mainly recommended if the total motility is less than 40%. Hence, a motile spermatozoon is considered alive, however, in certain conditions an immotile spermatozoon can also be alive. Therefore, the differentiation between asthenozoospermia (pathological decrease in sperm motility) and necrozoospermia (pathological decrease in sperm vitality) is important in directing further investigation and management of infertile patients. The causes leading to necrozoospermia are diverse and can either be local or general, testicular or extra-testicular. The andrological management of necrozoospermia depends on its etiology. However, there is no standardized treatment available presently and practice varies among clinicians. In this study, we report the results of a global survey to understand current practices regarding the physician order of sperm vitality tests as well as the management practices for necrozoospermia. Laboratory and clinical scenarios are presented to guide the reader in the management of necrozoospermia with the overall objective of establishing a benchmark ranging from the diagnosis of necrozoospermia by sperm vitality testing to its clinical management.

Autoimmune disorders currently affect 5%-8% of the global population, characterized by an aberrant chronic inflammatory response to self-antigens. The aim of this study was to systematically review the current available evidence investigating the impact of systemic autoimmune diseases and associated immunosuppressive treatment on fertility parameters of adult men. Clinical trials, observational studies, and case reports written in English and reporting semen analysis, evaluation of seminal oxidative stress, and/or sperm DNA fragmentation in patients affected by psoriasis and psoriatic arthritis, celiac disease, inflammatory bowel diseases, systemic lupus erythematosus, ankylosing spondylitis, hidradenitis suppurativa, uveitis, dermatomyositis, and rheumatoid arthritis were collected by searching on PubMed, EMBASE, OVID, Scopus, and Cochrane Library databases, with no limit of time. The study quality and the extent of bias in design, methods, and outcome assessment were evaluated by applying the Joanna Briggs Institute Critical Appraisal tools. Evidence suggested that various autoimmune diseases or relevant medications can adversely affect male fertility parameters and that patients may benefit of counseling and sperm cryopreservation. Clinical trials further investigating any adverse effect of autoimmunity and related thereby on male infertility are warranted, to develop appropriate guidelines for males diagnosed and treated for autoimmune disorders.

Assisted reproductive technologies (ART) are considered as one of the primary management options to address severe male factor infertility. The purpose of this study was to identify the research trends in the field of male infertility and ART over the past 20 years (2000-2019) by analysing scientometric data (the number of publications per year, authors, author affiliations, journals, countries, type of documents, subject area and number of citations) retrieved using the Scopus database. We used VOS viewer software to generate a network map on international collaborations as well as a heat map of the top scientists in this field. Our results revealed a total of 2,148 publications during this period with Cleveland Clinic Foundation contributing the most (n = 69). The current scientometric analysis showed that the research trend on ART has been stable over the past two decades. Further in-depth analysis revealed that density gradient centrifugation (46%) and intracytoplasmic sperm injection (59.2%) are the most reported techniques for sperm separation and ART, respectively. Additionally, azoospermia was the most studied clinical scenario (60.6%), with majority of articles reporting pregnancy rate (47.25%) as the primary reproductive outcome for ART. This study provides insight into the current focus of research in the area of male infertility and ART as well as the areas that require further research in future.

Obesity is a significant global health and socio-economic challenge, and considered an important risk factor for poor health outcomes including male reproductive dysfunction and infertility. As excess adiposity causes testicular dysfunction and infertility, novel therapeutic strategies require investigation. Nigella sativa (Ns) seed oil and metformin have both demonstrated a potential positive effect on obesity, although both remain poorly investigated in male fertility. Therefore, this study aimed to determine the effect of Ns oil and metformin on total body weight (TBW), mitochondrial membrane potential (MMP), serum testosterone and semen parameters in an obese animal model. Wistar rats (n = 54) were divided into six groups: normal chow (NC), high sugar diet (HSD) only, HSD and saline, HSD and metformin (75 mg/Kg/day), HSD and Ns (200 mg/Kg/day) (NS200), HSD and Ns (400 mg/Kg/day) (NS400). Intervention was force fed for the last 8 weeks of the 14 weeks dietary exposures. Results showed that the HSD increased TBW (P = 0.001) and reduced sperm concentration (P = 0.013) and progressive motility (P = 0.009) compared to the NC group. Metformin, NS200 and NS400 improved TBW (P = 0.035, P = 0.006 and P = 0.005, respectively) and testosterone (P < 0.001) compared to the HSD saline group, where metformin and NS400 improved sperm concentration (P < 0.001 and P = 0.049, respectively) and MMP (P < 0.001). There were no changes in sperm motility and viability for all experimental exposures, although NS400 (P = 0.047) negatively affected sperm viability. Metformin and Ns may be novel treatment options in obesity-induced infertility, although a potential negative impact on viability is cautioned for high dose Ns. These results warrant further investigation of Ns and Metformin for the management of obese infertile males.

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.

Obesity is considered a global health problem affecting more than a third of the population. Complications of obesity include cardiovascular diseases, type 2 diabetes mellitus, malignancy (including prostatic cancer), neurodegeneration and accelerated ageing. In males, these further include erectile dysfunction, poor semen quality and subclinical prostatitis. Although poorly understood, important mediators of obesity that may influence the male reproductive system include hyperinsulinemia, hyperleptinemia, chronic inflammation and oxidative stress. Obesity is known to disrupt male fertility and the reproduction potential, particularly through alteration in the hypothalamic-pituitary-gonadal axis, disruption of testicular steroidogenesis and metabolic dysregulation, including insulin, cytokines and adipokines. Importantly, obesity and its underlying mediators result in a negative impact on semen parameters, including sperm concentration, motility, viability and normal morphology. Moreover, obesity inhibits chromatin condensation, DNA fragmentation, increases apoptosis and epigenetic changes that can be transferred to the offspring. This review discusses the impact of obesity on the male reproductive system and fertility, including associated mechanisms. Furthermore, weight management strategies, lifestyle changes, prescription medication, and complementary and alternative medicine in the management of obesity-induced subfertility is discussed.

Alongside an increasing prevalence of couple and male infertility, evidence suggests there is a global declining trend in male fertility parameters over the past few decades. This may, at least in part, be explained through detrimental lifestyle practices and exposures. These include alcohol and tobacco consumption, use of recreational drugs (e.g., cannabis, opioids and anabolic steroids), poor nutritional habits, obesity and metabolic syndrome, genital heat stress (e.g., radiation exposure through cell phones and laptops, prolonged periods of sitting, tight-fitting underwear and recurrent hot baths or saunas), exposure to endocrine-disrupting chemicals (e.g., pesticide residue, bisphenol A, phthalates and dioxins) and psychological stress. This review discusses these lifestyle practices and the current evidence associated with male infertility. Furthermore, known mechanisms of action are also discussed for each of these. Common mechanisms associated with a reduction in spermatogenesis and/or steroidogenesis due to unfavourable lifestyle practices include inflammation and oxidative stress locally or systemically. It is recommended that relevant lifestyle practices are investigated in clinical history of male infertility cases, particularly in unexplained or idiopathic male infertility. Appropriate modification of detrimental lifestyle practices is further suggested and recommended in the management of male infertility.

Androgens have diverse functions in muscle physiology, lean body mass, the regulation of adipose tissue, bone density, neurocognitive regulation, and spermatogenesis, the male repro- ductive and sexual function. Male hypogonadism, characterized by reduced testosterone, is com- monly seen in ageing males, and has a complex relationship as a risk factor and a comorbidity in age-related noncommunicable chronic diseases (NCDs), such as obesity, metabolic syndrome, type 2 diabetes, and malignancy. Oxidative stress, as a significant contributor to the ageing process, is a common feature between ageing and NCDs, and the related comorbidities, including hypertension, dyslipidemia, hyperglycemia, hyperinsulinemia, and chronic inflammation. Oxidative stress may also be a mediator of hypogonadism in males. Consequently, the management of oxidative stress may represent a novel therapeutic approach in this context. Therefore, this narrative review aims to discuss the mechanisms of age-related oxidative stress in male hypogonadism associated with NCDs and discusses current and potential approaches for the clinical management of these patients, which may include conventional hormone replacement therapy, nutrition and lifestyle changes, ad-herence to the optimal body mass index, and dietary antioxidant supplementation and/or phyto-medicines. info:eu-repo/semantics/openAccess

The declining trend of male fertility parameters from global perspectives and the ambiguity of its diagnosis make it inevitable to find potent management and prevention strategies. Improper lifestyle factors are gradually deviating overall human systems from normal homeostasis and leading to numerous pathological conditions. The male reproductive system is vulnerable to adverse effects of unhealthy lifestyle and environmental factors because of its superficial anatomical location, intricate structure, high sensitivity to various physical conditions (like temperature and pressure), and being immunologically privileged sites. Several poor habits and morbid lifestyle factors either impose direct adverse effects on male reproductive tissues or indirectly disrupt male reproductive functions by affecting the endocrine regulatory axes. This chapter discusses (a) the lifestyle factors that are potentially deteriorating male fertility parameters; (b) the mechanisms by which they affect male reproductive functions; and (c) the modifiable lifestyle measures to ameliorate male fecundity.

Obesity and metabolic syndrome (MetS) are global epidemics, driven by an obesogenic environment. This is mediated by complex underlying pathophysiology, in which chronic inflammation is an important aetiological and mechanistic phenomenon. A shift towards a subclinical TH 1-lymphocyte mediated innate and chronic inflammatory response is well defined in obesity and MetS, demonstrated in multiple systems including visceral adiposity, brain (hypothalamus), muscles, vasculature, liver, pancreas, testes, epididymis, prostate and seminal fluid. Inflammatory cytokines disrupt the hypothalamic-pituitary-testes axis and steroidogenesis cascades (hypogonadotropic hypogonadism), spermatogenesis (poor semen parameters, including DNA fragmentation and detrimental epigenetic modification) and results in subclinical prostatitis and prostate hyperplasia. This review aims to highlight the role of chronic inflammation in obesity and MetS, cytokines in male reproductive physiology and pathophysiology, the impact on steroidogenesis and spermatogenesis, prostate pathology and erectile dysfunction. Currently, it is recommended that clinical assessment of male infertility and reproductive dysfunction in obese and MetS patients includes inflammation assessment (highly sensitive C-reactive protein), and appropriate advice and therapeutic options are incorporated in the management options. However, the mechanisms and therapeutic options remain poorly understood and require significant interdisciplinary research to identify potential novel therapeutic strategies.

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.

Malnutrition is classified as either excess consumption (overnutrition) or inadequate consumption (undernutrition) of nutrients, and a clear association between nutritional status, body mass index, and male reproductive potential has been established. Both over- and undernutrition is associated with increased oxidative stress (OS) systemically and in the male reproductive tract, hypothesized to cause infertility in malnourished males. Obesity is a disease of pandemic proportions, developing from the interaction of genetic, environmental, socio-economic, and psychological factors, mediated by complex metabolic cellular and molecular mediators. OS and poor semen quality in obese males is mediated at least in part by micronutrient deficiencies, particularly antioxidants. The pathophysiology of obesity and related male infertility is discussed in the context of malnutrition and OS, including the use of nutritional modifications and antioxidant supplementation as potential therapeutic options.

Purpose: Since its discovery in December 2019, the novel coronavirus SARS-CoV-2 has spread globally, causing the current COVID-19 (coronavirus disease-19) pandemic. As there is an increase of infections in the male population, concerns have emerged about the potential impact of COVID-19 on male reproductive organs and male fertility. Therefore, this study systematically investigates the current evidence of SARS-CoV-2 impact on male reproduction and pregnancy outcomes, discussing them in light of the evidence published on other coronaviruses. Materials and Methods: Literature search was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 24 original articles were included for the analysis, investigating the effects of the infection on semen parameters, male reproductive hormones, and pregnancy outcomes. Further, a Strengths-Weaknesses- Opportunities-Threats (SWOT) analysis was conducted based on the available evidence linking the virus with male reproduction and conception. Results: Although there is limited data, viral mRNA has been identified in semen of infected men, with some evidence of altered seminal parameters. Low testosterone and dihydrotestosterone with raised luteinizing hormone has been reported as well as preterm delivery in pregnant women; however, data regarding vertical transmission remains contradictory and inconclusive. Conclusions: The recent literature provides evidence that male gonads may be potentially vulnerable to SARS-CoV-2 infection, recommending caution to pregnant women and couples planning natural pregnancy or assisted reproduction.

PURPOSE: Male infertility is emerging as a major, escalating global health problem that imposes the need to investigate research trends in male infertility. The purpose of this study is to analyze male infertility research trends in the past 20 years using the bibliometric database from Scopus. MATERIALS AND METHODS: In order to perform an in-depth bibliometric analysis, we propose a 'Funnel Model', which includes several layers representing different sub-areas of male infertility research. Adopting this Funnel Model, using Scopus, we retrieved relevant bibliometric data (articles per year, authors, affiliations, journals, and countries) for various areas of male infertility research and performed descriptive statistics. RESULTS: The bibliometric analysis showed an exponential increase in male infertility research in the last 20 years. USA dominated in research output, with Agarwal, A. as the most prolific researcher. Testicular cancer, obesity and metabolic syndrome, and azoospermia were found to dominate male infertility research, whereas erectile dysfunction and unexplained male infertility had lesser attention. Interestingly, prognostic/diagnostic and mechanistic studies have significantly increased in parallel over the last 20 years. Furthermore, our bibliometric analysis revealed fewer publications in proteomics, transcriptomics and metabolomics when compared to genomics. Also, an increasing trend in publication was seen in assisted reproductive technology (ART) research. CONCLUSIONS: An integrated and steep escalation in the field of omics and ART research appears to be a prerequisite for further development of future diagnostic and therapeutic strategies for male infertility.