Oxidative Stress: A Comprehensive Review of Biochemical, Molecular, and Genetic Aspects in the Pathogenesis and Management of Varicocele

Finelli Renata,Leisegang Kristian,Kandil Hussein,Agarwal Ashok 대한남성과학회 2022 The World Journal of Men's Health Vol.40 No.1

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 in-fertility 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 clini-cal guidelines for testing oxidative stress-related sperm DNA fragmentation in this group of patients.

Utility of Antioxidants in the Treatment of Male Infertility: Clinical Guidelines Based on a Systematic Review and Analysis of Evidence

Agarwal Ashok,Leisegang Kristian,Majzoub Ahmad,Henkel Ralf,Finelli Renata,Panner Selvam Manesh Kumar,Tadros Nicholas,Parekh Neel,Ko Edmund Y.,Cho Chak-Lam,Arafa Mohamed,Alves Marco G.,Oliveira Pedro F 대한남성과학회 2021 The World Journal of Men's Health Vol.39 No.2

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.

Male Fertility and the COVID-19 Pandemic: Systematic Review of the Literature

Mohammad Ali Khalili,Kristian Leisegang,Ahmad Majzoub,Renata Finelli,Manesh Kumar Panner Selvam,Ralf Henkel,Moshrefi Mojgan,Ashok Agarwal 대한남성과학회 2020 The World Journal of Men's Health Vol.38 No.4

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.

An In-Depth Bibliometric Analysis and Current Perspective on Male infertility Research

Baskaran Saradha,Agarwal Ashok,Leisegang Kristian,Pushparaj Peter Natesan,Panner Selvam Manesh Kumar,Henkel Ralf 대한남성과학회 2021 The World Journal of Men's Health Vol.39 No.2

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.

A Web-Based Global Educational Model for Training in Semen Analysis during the COVID-19 Pandemic

Agarwal Ashok,Finelli Renata,Durairajanayagam Damayanthi,Leisegang Kristian,Sharma Rakesh,Gupta Sajal,Singh Neha,Belo Andrea,Darbandi Mahsa,Madani Sarah,Covarrubias Simryn,Darbandi Sara,Sadeghi Raha,P 대한남성과학회 2021 The World Journal of Men's Health Vol.39 No.4

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.

Highly Cited Articles in the Field of Male Infertility and Antioxidants: A Scientometric Analysis

Agarwal Ashok,Selvam Manesh Kumar Panner,Baskaran Saradha,Finelli Renata,Leisegang Kristian,Barbăroșie Cătălina,Pushparaj Peter Natesan,Robert Kathy Amy,Ambar Rafael F.,Iovine Concetta,Durairajanayaga 대한남성과학회 2021 The World Journal of Men's Health Vol.39 No.4

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.

Sperm DNA Fragmentation: A New Guideline for Clinicians

Ashok Agarwal,Ahmad Majzoub,Saradha Baskaran,Manesh Kumar Panner Selvam,Chak Lam Cho,Ralf Henkel,Renata Finelli,Kristian Leisegang,Pallav Sengupta,Catalina Barbarosie,Neel Parekh,Marco G. Alves,Edmund 대한남성과학회 2020 The World Journal of Men's Health Vol.38 No.4

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.