Displaying publications 1 - 20 of 56 in total

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  1. Agarwal A, Finelli R, Selvam MKP, Leisegang K, Majzoub A, Tadros N, et al.
    World J Mens Health, 2021 Jul;39(3):470-488.
    PMID: 33831977 DOI: 10.5534/wjmh.210025
    PURPOSE: The use of antioxidants is common practice in the management of infertile patients. However, there are no established guidelines by professional societies on antioxidant use for male infertility.

    MATERIALS AND 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: 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 3-6 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's age, geographic origin, experience or training in male infertility.

    CONCLUSIONS: This study is the largest online survey performed to date on this topic and demonstrates 1) a worldwide understanding 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.

  2. Agarwal A, Finelli R, Durairajanayagam D, Leisegang K, Sharma R, Gupta S, et al.
    World J Mens Health, 2021 Oct;39(4):804-817.
    PMID: 34169688 DOI: 10.5534/wjmh.210075
    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.

  3. Agarwal A, Panner Selvam MK, Baskaran S, Finelli R, Leisegang K, Barbăroșie C, et al.
    Andrologia, 2021 Feb;53(1):e13842.
    PMID: 33236365 DOI: 10.1111/and.13842
    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.
  4. Swain N, Samanta L, Agarwal A, Kumar S, Dixit A, Gopalan B, et al.
    Antioxid Redox Signal, 2020 03 10;32(8):504-521.
    PMID: 31691576 DOI: 10.1089/ars.2019.7828
    Aims:
    To understand the molecular pathways involved in oxidative stress (OS)-mediated sperm dysfunction against a hypoxic and hyperthermic microenvironment backdrop of varicocele through a proteomic approach.
    Results:
    Protein selection (261) based on their role in redox homeostasis and/or oxidative/hyperthermic/hypoxic stress response from the sperm proteome data set of unilateral varicocele (UV) in comparison with fertile control displayed 85 to be differentially expressed. Upregulation of cellular oxidant detoxification and glutathione and reduced nicotinamide adenine dinucleotide (NADH) metabolism accompanied with downregulation of protein folding, energy metabolism, and heat stress responses were observed in the UV group. Ingenuity pathway analysis (IPA) predicted suppression of oxidative phosphorylation (OXPHOS) (validated by Western blotting [WB]) along with augmentation in OS and mitochondrial dysfunction in UV. The top affected networks indicated by IPA involved heat shock proteins (HSPs: HSPA2 and HSP90B1). Their expression profile was corroborated by immunocytochemistry and WB. Hypoxia-inducible factor 1A as an upstream regulator of HSPs was predicted by MetaCore. Occurrence of reductive stress in UV spermatozoa was corroborated by thiol redox status.
    Innovation:
    This is the first evidence of a novel pathway showing aberrant redox homeostasis against chronic hypoxic insult in varicocele leading to sperm dysfunction.
    Conclusions:
    Upregulation of antioxidant system and dysfunctional OXPHOS would have shifted the redox balance of biological redox couples (GSH/GSSG, NAD+/NADH, and NADP+/NADPH) to a more reducing state leading to reductive stress. Chronic reductive stress-induced OS may be involved in sperm dysfunction in infertile men with UV, where the role of HSPs cannot be ignored. Intervention with antioxidant therapy warrants proper prior investigation.
  5. Durairajanayagam D, Agarwal A, Baskaran S, Ko E, Ramasamy R
    Andrologia, 2021 Feb;53(1):e13752.
    PMID: 33484502 DOI: 10.1111/and.13752
  6. Agarwal A, Leisegang K, Panner Selvam MK, Durairajanayagam D, Barbarosie C, Finelli R, et al.
    Andrologia, 2021 Apr;53(3):e13961.
    PMID: 33491204 DOI: 10.1111/and.13961
    In 2020, the COVID-19 pandemic led to the suspension of the annual Summer Internship at the American Center for Reproductive Medicine (ACRM). To transit it into an online format, an inaugural 6-week 2020 ACRM Online Mentorship Program was developed focusing on five core pillars of andrology research: scientific writing, scientific methodology, plagiarism understanding, soft skills development and mentee basic andrology knowledge. This study aims to determine mentee developmental outcomes based on student surveys and discuss these within the context of the relevant teaching and learning methodology. The mentorship was structured around scientific writing projects established by the team using a student-centred approach, with one-on-one expert mentorship through weekly formative assessments. Furthermore, weekly online meetings were conducted, including expert lectures, formative assessments and social engagement. Data were collected through final assessments and mentee surveys on mentorship outcomes. Results show that mentees (n = 28) reported a significant (p 
  7. Ko E, Ramasamy R, Durairajanayagam D, Baskaran S, Agarwal A
    Andrologia, 2021 02;53(1):e13741.
    PMID: 33135797 DOI: 10.1111/and.13741
  8. Gupta S, Sharma R, Agarwal A, Boitrelle F, Finelli R, Farkouh A, et al.
    World J Mens Health, 2022 Jul;40(3):380-398.
    PMID: 35021297 DOI: 10.5534/wjmh.210164
    Antisperm antibodies (ASA), as a cause of male infertility, have been detected in infertile males as early as 1954. Multiple causes of ASA production have been identified, and they are due to an abnormal exposure of mature germ cells to the immune system. ASA testing (with mixed anti-globulin reaction, and immunobead binding test) was described in the WHO manual 5th edition and is most recently listed among the extended semen tests in the WHO manual 6th edition. The relationship between ASA and infertility is somewhat complex. The presence of sperm agglutination, while insufficient to diagnose immunological infertility, may indicate the presence of ASA. However, ASA can also be present in the absence of any sperm agglutination. The andrological management of ASA depends on the etiology and individual practices of clinicians. In this article, we provide a comprehensive review of the causes of ASA production, its role in immunological male infertility, clinical indications of ASA testing, and the available therapeutic options. We also provide the details of laboratory procedures for assessment of ASA together with important measures for quality control. Additionally, laboratory and clinical scenarios are presented to guide the reader in the management of ASA and immunological male infertility. Furthermore, we report the results of a recent worldwide survey, conducted to gather information about clinical practices in the management of immunological male infertility.
  9. Ghayda RA, Cannarella R, Calogero AE, Shah R, Rambhatla A, Zohdy W, et al.
    World J Mens Health, 2024 Jan;42(1):39-61.
    PMID: 37382282 DOI: 10.5534/wjmh.230050
    Artificial intelligence (AI) in medicine has gained a lot of momentum in the last decades and has been applied to various fields of medicine. Advances in computer science, medical informatics, robotics, and the need for personalized medicine have facilitated the role of AI in modern healthcare. Similarly, as in other fields, AI applications, such as machine learning, artificial neural networks, and deep learning, have shown great potential in andrology and reproductive medicine. AI-based tools are poised to become valuable assets with abilities to support and aid in diagnosing and treating male infertility, and in improving the accuracy of patient care. These automated, AI-based predictions may offer consistency and efficiency in terms of time and cost in infertility research and clinical management. In andrology and reproductive medicine, AI has been used for objective sperm, oocyte, and embryo selection, prediction of surgical outcomes, cost-effective assessment, development of robotic surgery, and clinical decision-making systems. In the future, better integration and implementation of AI into medicine will undoubtedly lead to pioneering evidence-based breakthroughs and the reshaping of andrology and reproductive medicine.
  10. Durairajanayagam D, Singh D, Agarwal A, Henkel R
    Andrologia, 2021 Feb;53(1):e13666.
    PMID: 32510691 DOI: 10.1111/and.13666
    Mitochondria have multiple functions, including synthesis of adenine triphosphate, production of reactive oxygen species, calcium signalling, thermogenesis and apoptosis. Mitochondria have a significant contribution in regulating the various physiological aspects of reproductive function, from spermatogenesis up to fertilisation. Mitochondrial functionality and intact mitochondrial membrane potential are a pre-requisite for sperm motility, hyperactivation, capacitation, acrosin activity, acrosome reaction and DNA integrity. Optimal mitochondrial activity is therefore crucial for human sperm function and semen quality. However, the precise role of mitochondria in spermatozoa remains to be fully explored. Defects in sperm mitochondrial function severely impair the maintenance of energy production required for sperm motility and may be an underlying cause of asthenozoospermia. Sperm mtDNA is susceptible to oxidative damage and mutations that could compromise sperm function leading to infertility. Males with abnormal semen parameters have increased mtDNA copy number and reduced mtDNA integrity. This review discusses the role of mitochondria in sperm function, along with the causes and impact of its dysfunction on male fertility. Greater understanding of sperm mitochondrial function and its correlation with sperm quality could provide further insights into their contribution in the assessment of the infertile male.
  11. Agarwal A, Finelli R, Durairajanayagam D, Leisegang K, Henkel R, Salvio G, et al.
    World J Mens Health, 2022 01 25.
    PMID: 35118839 DOI: 10.5534/wjmh.210202
    PURPOSE: This study provides a comprehensive analysis of research trends on the etiology, mechanisms, potential risk factors, diagnosis, prognosis, surgical and non-surgical treatment of varicocele, and clinical outcomes before and after varicocele repair.

    MATERIALS AND METHODS: Varicocele studies published between 1988 and 2020 were retrieved from the Scopus database on April 5, 2021. Original studies on human varicocele were included, irrespective of language. Retrieved articles were manually screened for inclusion in various sub-categories. Bibliometric data was subjected to scientometric analysis using descriptive statistics. Network, heat and geographic mapping were generated using relevant software.

    RESULTS: In total, 1,943 original human studies on varicocele were published. These were predominantly from the northern hemisphere and developed countries, and published in journals from the United States and Germany. Network map analysis for countries showed several interconnected nodal points, with the USA being the largest, and Agarwal A. from Cleveland Clinic, USA, being a center point of worldwide varicocele research collaborations. Studies of adolescents were underrepresented compared with studies of adults. Studies on diagnostic and prognostic aspects of varicocele were more numerous than studies on varicocele prevalence, mechanistic studies and studies focusing on etiological and risk factors. Varicocele surgery was more investigated than non-surgical approaches. To evaluate the impact of varicocele and its treatment, researchers mainly analyzed basic semen parameters, although markers of seminal oxidative stress are being increasingly investigated in the last decade, while reproductive outcomes such as live birth rate were under-reported in the literature.

    CONCLUSIONS: This study analyzes the publication trends in original research on human varicocele spanning over the last three decades. Our analysis emphasizes areas for further exploration to better understand varicocele's impact on men's health and male fertility.

  12. Shah R, Agarwal A, Kavoussi P, Rambhatla A, Saleh R, Cannarella R, et al.
    World J Mens Health, 2023 Jan;41(1):164-197.
    PMID: 35791302 DOI: 10.5534/wjmh.220048
    PURPOSE: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility.

    MATERIALS AND METHODS: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological Association [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field.

    RESULTS: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the responses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identified where no guidelines are available.

    CONCLUSIONS: This study is the largest global survey performed to date on the clinical management of varicocele for male infertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical practice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men.

  13. Agarwal A, Farkouh A, Saleh R, Abdel-Meguid Hamoda TA, Harraz AM, Kavoussi P, et al.
    World J Mens Health, 2023 Jul;41(3):575-602.
    PMID: 37118960 DOI: 10.5534/wjmh.220282
    PURPOSE: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations.

    MATERIALS AND METHODS: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus.

    RESULTS: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing.

    CONCLUSIONS: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians.

  14. Farkouh A, Agarwal A, Hamoda TAA, Kavoussi P, Saleh R, Zini A, et al.
    World J Mens Health, 2023 Oct;41(4):809-847.
    PMID: 37118965 DOI: 10.5534/wjmh.230008
    PURPOSE: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition.

    MATERIALS AND METHODS: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method.

    RESULTS: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4-6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated.

    CONCLUSIONS: This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians.

  15. Abd-Aziz, N.A.A., Chatterjee, A., Chatterjee, R., Durairajanayagam, D.
    ASM Science Journal, 2014;8(2):117-124.
    MyJurnal
    Elevated glucocorticoid levels during stressed conditions have been demonstrated to impair reproductive function in rats. In our previous study investigating the dose-related effects of corticosterone (CORT) on the fertilising capacity of epididymal sperm in surgically-manipulated rats, we found that 25 mg/kg/day of CORT given subcutaneously for seven consecutive days significantly decreased the number of implantation sites and increased intrauterine embryonic loss compared to controls. Based on these findings, the current study aims to elucidate the possible mechanisms of action of CORT-induced stress on impaired sperm fertility in rats. Results of the present study showed that compared to controls, 25 mg/kg/day of CORT given subcutaneously for 7 consecutive days significantly increased the level of plasma malondialdehyde (MDA) with corresponding attenuated levels of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. Plasma adrenocorticotropin (ACTH) and testosterone levels were also found to be decreased in CORTtreated rats. These findings suggest that CORT-induced oxidative stress and exert an inhibitory effect at the hypothalamic-pituitary-gonadal (HPG) axis, as evidenced by increased lipid peroxidation, reduced enzymatic antioxidant activities, and decreased testosterone production. These subsequently result in decreased fertilising capacity of epididymal sperm leading to poor pregnancy outcomes.
  16. Almabhouh F, Abdul Aziz NAA, Durairajanayagam D, Singh HJ
    Reprod Biol, 2020 Mar;20(1):106-110.
    PMID: 31987773 DOI: 10.1016/j.repbio.2020.01.003
    Low sperm concentration, increased fraction of morphologically abnormal sperm, and raised levels of markers of oxidative stress are often reported in the seminal plasma of infertile obese males. The precise reason for changes remains unknown. This short review summarises evidence from human and animal studies linking leptin to the reproductive dysfunction reported in obese males and presents a possible mechanism for this based on the available data in the literature. Serum leptin concentrations correlate positively with body fat mass but its precise link to semen abnormalities reported in obese males has yet to be conclusively established. Decreased sperm concentration, increased fraction of morphologically abnormal sperm and increased markers of oxidative stress have been reported following six weeks of daily leptin treatment to normal weight rats. In addition, decreased expression of endogenous antioxidant enzymes and increased expression of respiratory chain enzymes noted in the testes of leptin treated rats increases the propensity to oxidative stress. Besides that, leptin's interference with histone to protamine transition in the DNA of sperm increases the susceptibility of sperm to free radical attack and may explain the often reported higher DNA fragmentation index in sperm of obese males. Concurrent supplementation of melatonin, a natural anti-oxidant, to these rats prevents the effects of leptin. The role of leptin in obesity-related reproductive dysfunction has to be considered seriously and these effects of leptin might involve increased oxidative stress.
  17. Agarwal A, Sharma R, Durairajanayagam D, Cui Z, Ayaz A, Gupta S, et al.
    Urology, 2015 Mar;85(3):580-8.
    PMID: 25733269 DOI: 10.1016/j.urology.2014.11.030
    To compare the sperm protein profile between infertile men with unilateral varicocele and infertile men with bilateral varicocele.
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