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.

A Schematic Overview of the Current Status of Male Infertility Practice

Ashok Agarwal,Ahmad Majzoub,Neel Parekh,Ralf Henkel 대한남성과학회 2020 The World Journal of Men's Health Vol.38 No.3

The practice of male infertility has dramatically evolved over the past few decades. This has been achieved after the realization of the important contribution the male counterpart holds in the couple’s infertility. It is also supported by a number of breakthroughs in the diagnosis and treatment of this medical condition. Several tests to investigate sperm quality and function were introduced along with refinements and/or institution of novel surgical techniques that can correct several causes of infertility. This manuscript is aimed at highlighting the current state of male infertility practice in a robust, schematic method addressing a broader audience involved in the treatment of male infertility.

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.

Metabolic Syndrome and Male Fertility

Ana Dias Martins,Ahmad Majzoub,Ashok Agawal 대한남성과학회 2019 The World Journal of Men's Health Vol.37 No.2

Metabolic syndrome (MetS) represents a cluster of conditions that have a negative impact on human health overall. Its preva-lence has been rapidly increasing worldwide and has coincided with a global decrease in birth rates and fertility potential. This review aims to address this observation through studying the relationship between MetS and male reproductive health. The effects of obesity, dyslipidemia, hypertension, and insulin resistance on male fertility were examined and supporting evi-dence explaining the pathophysiology of sperm dysfunction with each MetS component were described. Adopting a healthy lifestyle appears to be the single most important intervention to prevent the unwanted effects of MetS on men’s health and fertility. Further studies addressing the components of MetS and their impact on male reproduction are required to enhance our understanding of the underlying pathophysiology and to propose new methods for therapeutic intervention.

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.

The Use of Testicular Sperm for Intracytoplasmic Sperm Injection in Patients with High Sperm DNA Damage: A Systematic Review

Ambar Rafael F.,Agarwal Ashok,Majzoub Ahmad,Vij Sarah,Tadros Nicholas N.,Cho Chak-Lam,Parekh Neel,Borges Edson,Glina Sidney 대한남성과학회 2021 The World Journal of Men's Health Vol.39 No.3

The advent of intracytoplasmic sperm injection (ICSI) has changed the human reproduction landscape by overcoming several limitations related to both male and female infertility factors. However, despite the development of new technologies, the live-birth rate with ICSI has not exceeded 30%. In order to improve assisted reproductive technology outcomes, advanced sperm function analysis have gained increased attention and the effects of sperm DNA fragmentation (SDF) on assisted repro-duction success are being extensively studied. Utilizing ejaculated sperm with an elevated SDF has been found to result in poor ICSI outcomes. Furthermore, studies have reported that testicular sperm has lower SDF level, when compared to ejacu-lated sperm. This has led a number of clinicians world-wide to offer testicular sperm retrieval for ICSI in non-azoospermic males with high SDF. This practice has remained controversial due to lack of high quality evidence.

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

Ashok Agarwal,Neel Parekh,Manesh Kumar Panner Selvam,Ralf Henkel,Rupin Shah,Sheryl T. Homa,Ranjith Ramasamy,Edmund Ko,Kelton Tremellen,Sandro Esteves,Ahmad Majzoub,Juan G. Alvarez,David K. Gardner,Cha 대한남성과학회 2019 The World Journal of Men's Health Vol.37 No.3

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.