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  1. Sharma R, Gupta S, Agarwal A, Henkel R, Finelli R, Parekh N, et al.
    World J Mens Health, 2022 Apr;40(2):191-207.
    PMID: 34169683 DOI: 10.5534/wjmh.210063
    The current WHO 2010 manual for human semen analysis defines leukocytospermia as the presence of peroxidase-positive leukocytes at a concentration >1×106/mL of semen. Granular leukocytes when activated are capable of generating high levels of reactive oxygen species in semen resulting in oxidative stress. Oxidative stress has been correlated with poor sperm quality, increased level of sperm DNA fragmentation and low fertility potential. The presence of leukocytes and pathogens in the semen may be a sign of infection and/or localized inflammatory response in the male genital tract and the accessory glands. Common uro-pathogens including Chlamydia trachomatis, Ureaplasma urealyticum, Neisseria gonorrhoeae, Mycoplasma hominis, and Escherichia coli can cause epididymitis, epididymo-orchitis, or prostatitis. The relationship between leukocytospermia and infection is unclear. Therefore, we describe the pathogens responsible for male genital tract infections and their association with leukocytospermia. The review also examines the diagnostic tests available to identify seminal leukocytes. The role of leukocytospermia in male infertility and its management is also discussed.
  2. 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.

  3. Shah R, Rambhatla A, Atmoko W, Martinez M, Ziouziou I, Kothari P, et al.
    World J Mens Health, 2024 Apr 03.
    PMID: 38606865 DOI: 10.5534/wjmh.230333
    PURPOSE: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations.

    MATERIALS AND METHODS: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations.

    RESULTS: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate.

    CONCLUSIONS: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

  4. Rambhatla A, Shah R, Ziouziou I, Kothari P, Salvio G, Gul M, et al.
    World J Mens Health, 2024 Apr 04.
    PMID: 38606867 DOI: 10.5534/wjmh.230339
    PURPOSE: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA.

    MATERIALS AND METHODS: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process.

    RESULTS: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit.

    CONCLUSIONS: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.

  5. Lay US, Pradhan B, Yusoff ZBM, Abdallah AFB, Aryal J, Park HJ
    Sensors (Basel), 2019 Aug 07;19(16).
    PMID: 31394777 DOI: 10.3390/s19163451
    Cameron Highland is a popular tourist hub in the mountainous area of Peninsular Malaysia. Most communities in this area suffer frequent incidence of debris flow, especially during monsoon seasons. Despite the loss of lives and properties recorded annually from debris flow, most studies in the region concentrate on landslides and flood susceptibilities. In this study, debris-flow susceptibility prediction was carried out using two data mining techniques; Multivariate Adaptive Regression Splines (MARS) and Support Vector Regression (SVR) models. The existing inventory of debris-flow events (640 points) were selected for training 70% (448) and validation 30% (192). Twelve conditioning factors namely; elevation, plan-curvature, slope angle, total curvature, slope aspect, Stream Transport Index (STI), profile curvature, roughness index, Stream Catchment Area (SCA), Stream Power Index (SPI), Topographic Wetness Index (TWI) and Topographic Position Index (TPI) were selected from Light Detection and Ranging (LiDAR)-derived Digital Elevation Model (DEM) data. Multi-collinearity was checked using Information Factor, Cramer's V, and Gini Index to identify the relative importance of conditioning factors. The susceptibility models were produced and categorized into five classes; not-susceptible, low, moderate, high and very-high classes. Models performances were evaluated using success and prediction rates where the area under the curve (AUC) showed a higher performance of MARS (93% and 83%) over SVR (76% and 72%). The result of this study will be important in contingency hazards and risks management plans to reduce the loss of lives and properties in the area.
  6. Kwan AC, Bao T, Chakkaphak S, Chang FY, Ke M, Law NM, et al.
    J Gastroenterol Hepatol, 2003 Jul;18(7):796-802.
    PMID: 12795751 DOI: 10.1046/j.1440-1746.2003.03081.x
    BACKGROUND: It has been unclear as to whether the Rome II criteria could be applied to patients in the Asia region with functional gastrointestinal (GI) diseases. The aim of the present study was to determine if symptoms of Asian patients with functional gastrointestinal disorders formed groups which corresponded to the Rome II diagnostic criteria.

    METHODS: A modified English version of Talley's bowel disease questionnaire was developed in collaboration with various research teams in accordance with the Rome II criteria. This instrument was translated into the local languages of the following nine Asian regions: China, Hong Kong, Indonesia, Korea, Malaysia, Singapore, Taiwan, Thailand and Vietnam. From September to December 2001, newly enrolled outpatients attending 14 GI or medical clinics in these regions were invited to complete the questionnaire. From these respondents, patients with functional gastrointestinal disorders fulfilling the '12 weeks out of 12 months' criteria were separated for further analysis. Principal component factor analysis with varimax rotation was used to identify symptom clusters or factors. These factors were compared with the existing classification of functional GI diseases derived from the Rome II criteria.

    RESULTS: Factor analysis of symptoms from 1012 functional GI patients supported the Rome II classification of the following groups of functional GI disorders: diarrhea-predominant irritable bowel syndrome, functional constipation, functional dyspepsia, functional abdominal pain syndrome, functional heartburn, and functional vomiting. Functional diarrhea was combined with functional anorectal disorders, and globus merged with functional dysphagia into one factor. Some of the functional dyspepsia, abdominal bloating and belching symptoms were loaded into one factor.

    CONCLUSIONS: Factor analysis of symptoms from a sample of Asian patients with functional GI disorders partially supported the use of the Rome II classification.
  7. Kim H, Kang DY, Ahn JM, Lee J, Choi Y, Hur SH, et al.
    JACC Cardiovasc Interv, 2023 Oct 09;16(19):2412-2422.
    PMID: 37821187 DOI: 10.1016/j.jcin.2023.07.028
    BACKGROUND: Diabetes mellitus is associated with more complex coronary artery diseases. Coronary artery bypass grafting (CABG) is a preferred revascularization strategy over percutaneous coronary intervention (PCI) in diabetics with multivessel coronary artery disease (MVD).

    OBJECTIVES: This study sought to examine the different prognostic effects of revascularization strategies according to the diabetes status from the randomized BEST (Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease) trial.

    METHODS: Patients (n = 880) with MVD were randomly assigned to undergo PCI with an everolimus-eluting stent vs CABG stratified by diabetics (n = 363) and nondiabetics (n = 517). The primary endpoint was the composite of death, myocardial infarction, or target vessel revascularization during a median follow-up of 11.8 years (IQR: 10.6-12.5 years).

    RESULTS: In diabetics, the primary endpoint rate was significantly higher in the PCI group than in the CABG group (43% and 32%; HR: 1.53; 95% CI: 1.12-2.08; P = 0.008). However, in nondiabetics, no significant difference was found between the groups (PCI group, 29%; CABG group, 29%; HR: 0.97; 95% CI: 0.67-1.39; P = 0.86; Pinteraction= 0.009). Irrespective of the presence of diabetes, no significant between-group differences were found in the rate of a safety composite of death, myocardial infarction, or stroke and mortality rate. However, the rate of any repeat revascularization was significantly higher in the PCI group than in the CABG group.

    CONCLUSIONS: In diabetics with MVD, CABG was associated with better clinical outcomes than PCI. However, the mortality rate was similar between PCI and CABG irrespective of diabetes status during an extended follow-up. (Ten-Year Outcomes of Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease [BEST Extended], NCT05125367; Randomized Comparison of Coronary Artery Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease [BEST], NCT00997828).

  8. Gupta S, Sharma R, Agarwal A, Parekh N, Finelli R, Shah R, et al.
    World J Mens Health, 2022 Apr;40(2):208-216.
    PMID: 34169680 DOI: 10.5534/wjmh.210069
    Retrograde ejaculation (RE) is a condition defined as the backward flow of the semen during ejaculation, and when present can result in male infertility. RE may be partial or complete, resulting in either low seminal volume or complete absence of the ejaculate (dry ejaculate). RE can result from anatomic, neurological or pharmacological conditions. The treatment approaches outlined are determined by the cause. Alkalinizing urinary pH with oral medications or by adding sperm wash media into the bladder prior to ejaculation may preserve the viability of the sperm. This article provides a step-by-step guide to diagnose RE and the optimal techniques to retrieve sperm.
  9. 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.
  10. Goh KL, Chang CS, Fock KM, Ke M, Park HJ, Lam SK
    J Gastroenterol Hepatol, 2000 Mar;15(3):230-8.
    PMID: 10764021
    Gastro-oesophageal reflux disease (GORD) occurs more frequently in Europe and North America than in Asia but its prevalence is now increasing in many Asian countries. Many reasons have been given for the lower prevalence of GORD in Asia. Low dietary fat and genetically determined factors, such as body mass index and maximal acid output, may be important. Other dietary factors appear to be less relevant. Increased intake of carbonated drinks or aggravating medicines may influence the increasing rates of GORD in some Asian countries but no strong evidence links other factors, such as the age of the population, smoking or alcohol consumption, to GORD. The management of GORD in Asia is similar to that in Europe and North America but the lower incidence of severe oesophagitis in Asia may alter the approach slightly. Also, because Asians tend to develop stomach cancer at an earlier age, endoscopy is used routinely at an earlier stage of investigation. Gastro-oesophageal reflux disease is essentially a motility disorder, so short-term management of the disease can usually be achieved using prokinetic agents (or histamine (H2)-receptor antagonists). More severe and recurrent GORD may require proton pump inhibitors (PPI) or a combination of prokinetic agents and PPI. The choice of long-term treatment may be influenced by the relative costs of prokinetic agents and PPI.
  11. 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.
  12. 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.

  13. Chung E, Moon DG, Hui J, Chang HC, Hakim L, Nagao K, et al.
    Sex Med, 2023 Apr;11(2):qfad003.
    PMID: 37056790 DOI: 10.1093/sexmed/qfad003
    INTRODUCTION: Penile reconstructive and prosthetic surgery remains a highly specialized field where potential complications can be devastating, and unrealistic patient expectations can often be difficult to manage. Furthermore, surgical practice can vary depending on locoregional expertise and sociocultural factors.

    METHODS: The Asia Pacific Society of Sexual Medicine (APSSM) panel of experts reviewed contemporary evidence regarding penile reconstructive and prosthetic surgery with an emphasis on key issues relevant to the Asia-Pacific (AP) region and developed a consensus statement and set of clinical practice recommendations on behalf of the APSSM. The Medline and EMBASE databases were searched using the following terms: "penile prosthesis implant," "Peyronie's disease," "penile lengthening," "penile augmentation," "penile enlargement," "buried penis," "penile disorders," "penile trauma," "transgender," and "penile reconstruction" between January 2001 and June 2022. A modified Delphi method was undertaken, and the panel evaluated, agreed, and provided consensus statements on clinically relevant penile reconstructive and prosthetic surgery, namely (1) penile prosthesis implantation, (2) Peyronie's disease, (3) penile trauma, (4) gender-affirming (phalloplasty) surgery, and (5) penile esthetic (length and/or girth enlargement) surgery.

    MAIN OUTCOME MEASURES: Outcomes were specific statements and clinical recommendations according to the Oxford Centre for Evidence-Based Medicine, and if clinical evidence is lacking, a consensus agreement is adopted. The panel provided statements on clinical aspects of surgical management in penile reconstructive and prosthetic surgery.

    RESULTS: There is a variation in surgical algorithms in patients based on sociocultural characteristics and the availability of local resources. Performing preoperative counseling and obtaining adequate informed consent are paramount and should be conducted to discuss various treatment options, including the pros and cons of each surgical intervention. Patients should be provided with information regarding potential complications related to surgery, and strict adherence to safe surgical principles, preoperative optimization of medical comorbidities and stringent postoperative care are important to improve patient satisfaction rates. For complex patients, surgical intervention should ideally be referred and performed by expert high-volume surgeons to maximize clinical outcomes.

    CLINICAL IMPLICATIONS: Due to the uneven distribution of surgical access and expertise across the AP region, development of relevant comprehensive surgical protocols and regular training programs is desirable.

    STRENGTHS AND LIMITATIONS: This consensus statement covers comprehensive penile reconstructive and prosthetic surgery topics and is endorsed by the APSSM. The variations in surgical algorithms and lack of sufficient high-level evidence in these areas could be stated as a limitation.

    CONCLUSION: This APSSM consensus statement provides clinical recommendations on the surgical management of various penile reconstructive and prosthetic surgeries. The APSSM advocates for surgeons in AP to individualize surgical options based on patient condition(s) and needs, surgeon expertise, and local resources.

  14. Chung E, Hui J, Xin ZC, Kim SW, Moon DG, Yuan Y, et al.
    World J Mens Health, 2023 Oct 16.
    PMID: 37853539 DOI: 10.5534/wjmh.230180
    Male infertility (MI) and male sexual dysfunction (MSD) can often coexist together due to various interplay factors such as psychosexual, sociocultural and relationship dynamics. The presence of each form of MSD can adversely impact male reproduction and treatment strategies will need to be individualized based on patients' factors, local expertise, and geographical socioeconomic status. The Asia Pacific Society of Sexual Medicine (APSSM) and the Asian Society of Men's Health and Aging (ASMHA) aim to provide a consensus statement and practical set of clinical recommendations based on current evidence to guide clinicians in the management of MI and MSD within the Asia-Pacific (AP) region. A comprehensive, narrative review of the literature was performed to identify the various forms of MSD and their association with MI. MEDLINE and EMBASE databases were searched for the following English language articles under the following terms: "low libido", "erectile dysfunction", "ejaculatory dysfunction", "premature ejaculation", "retrograde ejaculation", "delayed ejaculation", "anejaculation", and "orgasmic dysfunction" between January 2001 to June 2022 with emphasis on published guidelines endorsed by various organizations. This APSSM consensus committee panel evaluated and provided evidence-based recommendations on MI and clinically relevant MSD areas using a modified Delphi method by the panel and specific emphasis on locoregional socio-economic-cultural issues relevant to the AP region. While variations exist in treatment strategies for managing MI and MSD due to geographical expertise, locoregional resources, and sociocultural factors, the panel agreed that comprehensive fertility evaluation with a multidisciplinary management approach to each MSD domain is recommended. It is important to address individual MI issues with an emphasis on improving spermatogenesis and facilitating reproductive avenues while at the same time, managing various MSD conditions with evidence-based treatments. All therapeutic options should be discussed and implemented based on the patient's individual needs, beliefs and preferences while incorporating locoregional expertise and available resources.
  15. Cannarella R, Shah R, Hamoda TAA, Boitrelle F, Saleh R, Gul M, et al.
    World J Mens Health, 2024 Jan;42(1):92-132.
    PMID: 37382284 DOI: 10.5534/wjmh.230034
    PURPOSE: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles.

    MATERIALS AND METHODS: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies).

    RESULTS: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129-0.278; p<0.001; I²=83.62%, Egger's p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474-1.706; p<0.001; I²=97.86%, Egger's p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526-2.121; p<0.001; I²=97.88%, Egger's p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318-1.968; p<0.001; I²=98.65%, Egger's p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%-2.153%; p<0.001; I²=98.97%, Egger's p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%-1.759%; p<0.001; l2=97.98%, Egger's p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%-1.211%; p<0.001; I²=97.87%, Egger's p=0.1864.

    CONCLUSIONS: The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele.

  16. Calogero AE, Cannarella R, Agarwal A, Hamoda TAA, Rambhatla A, Saleh R, et al.
    World J Mens Health, 2023 Apr;41(2):237-254.
    PMID: 36649928 DOI: 10.5534/wjmh.220213
    Infertility affects nearly 186 million people worldwide and the male partner is the cause in about half of the cases. Meta-regression data indicate an unexplained decline in sperm concentration and total sperm count over the last four decades, with an increasing prevalence of male infertility. This suggests an urgent need to implement further basic and clinical research in Andrology. Andrology developed as a branch of urology, gynecology, endocrinology, and, dermatology. The first scientific journal devoted to andrological sciences was founded in 1969. Since then, despite great advancements, andrology has encountered several obstacles in its growth. In fact, for cultural reasons, the male partner has often been neglected in the diagnostic and therapeutic workup of the infertile couple. Furthermore, the development of assisted reproductive techniques (ART) has driven a strong impression that this biotechnology can overcome all forms of infertility, with a common belief that having a spermatozoon from a male partner (a sort of sperm donor) is all that is needed to achieve pregnancy. However, clinical practice has shown that the quality of the male gamete is important for a successful ART outcome. Furthermore, the safety of ART has been questioned because of the high prevalence of comorbidities in the offspring of ART conceptions compared to spontaneous conceptions. These issues have paved the way for more research and a greater understanding of the mechanisms of spermatogenesis and male infertility. Consequently, numerous discoveries have been made in the field of andrology, ranging from genetics to several "omics" technologies, oxidative stress and sperm DNA fragmentation, the sixth edition of the WHO manual, artificial intelligence, management of azoospermia, fertility in cancers survivors, artificial testis, 3D printing, gene engineering, stem cells therapy for spermatogenesis, and reconstructive microsurgery and seminal microbiome. Nevertheless, as many cases of male infertility remain idiopathic, further studies are required to improve the clinical management of infertile males. A multidisciplinary strategy involving both clinicians and scientists in basic, translational, and clinical research is the core principle that will allow andrology to overcome its limits and reach further goals. This state-of-the-art article aims to present a historical review of andrology, and, particularly, male infertility, from its "Middle Ages" to its "Renaissance", a golden age of andrology.
  17. Althuwaynee OF, Pokharel B, Aydda A, Balogun AL, Kim SW, Park HJ
    J Expo Sci Environ Epidemiol, 2021 07;31(4):709-726.
    PMID: 33159165 DOI: 10.1038/s41370-020-00271-8
    Accurate identification of distant, large, and frequent sources of emission in cities is a complex procedure due to the presence of large-sized pollutants and the existence of many land use types. This study aims to simplify and optimize the visualization mechanism of long time-series of air pollution data, particularly for urban areas, which is naturally correlated in time and spatially complicated to analyze. Also, we elaborate different sources of pollution that were hitherto undetectable using ordinary plot models by leveraging recent advances in ensemble statistical approaches. The high performing conditional bivariate probability function (CBPF) and time-series signature were integrated within the R programming environment to facilitate the study's analysis. Hourly air pollution data for the period between 2007 to 2016 is collected using four air quality stations, (ca0016, ca0058, ca0054, and ca0025), situated in highly urbanized locations that are characterized by complex land use and high pollution emitting activities. A conditional bivariate probability function (CBPF) was used to analyze the data, utilizing pollutant concentration values such as Sulfur dioxide (SO2), Nitrogen oxides (NO2), Carbon monoxide (CO) and Particulate Matter (PM10) as a third variable plotted on the radial axis, with wind direction and wind speed variables. Generalized linear model (GLM) and sensitivity analysis are applied to verify and visualize the relationship between Air Pollution Index (API) of PM10 and other significant pollutants of GML outputs based on quantile values. To address potential future challenges, we forecast 3 months PM10 values using a Time Series Signature statistical algorithm with time functions and validated the outcome in the 4 stations. Analysis of results reveals that sources emitting PM10 have similar activities producing other pollutants (SO2, CO, and NO2). Therefore, these pollutants can be detected by cross selection between the pollution sources in the affected city. The directional results of CBPF plot indicate that ca0058 and ca0054 enable easier detection of pollutants' sources in comparison to ca0016 and ca0025 due to being located on the edge of industrial areas. This study's CBPF technique and time series signature analysis' outcomes are promising, successfully elaborating different sources of pollution that were hitherto undetectable using ordinary plot models and thus contribute to existing air quality assessment and enhancement mechanisms.
  18. AlThuwaynee OF, Kim SW, Najemaden MA, Aydda A, Balogun AL, Fayyadh MM, et al.
    Environ Sci Pollut Res Int, 2021 Aug;28(32):43544-43566.
    PMID: 33834339 DOI: 10.1007/s11356-021-13255-4
    This study investigates uncertainty in machine learning that can occur when there is significant variance in the prediction importance level of the independent variables, especially when the ROC fails to reflect the unbalanced effect of prediction variables. A variable drop-off loop function, based on the concept of early termination for reduction of model capacity, regularization, and generalization control, was tested. A susceptibility index for airborne particulate matter of less than 10 μm diameter (PM10) was modeled using monthly maximum values and spectral bands and indices from Landsat 8 imagery, and Open Street Maps were used to prepare a range of independent variables. Probability and classification index maps were prepared using extreme-gradient boosting (XGBOOST) and random forest (RF) algorithms. These were assessed against utility criteria such as a confusion matrix of overall accuracy, quantity of variables, processing delay, degree of overfitting, importance distribution, and area under the receiver operating characteristic curve (ROC).
  19. Ahn JM, Kang DY, Yun SC, Ho Hur S, Park HJ, Tresukosol D, et al.
    Circulation, 2022 Nov 22;146(21):1581-1590.
    PMID: 36121700 DOI: 10.1161/CIRCULATIONAHA.122.062188
    BACKGROUND: Long-term comparative outcomes after percutaneous coronary intervention (PCI) with everolimus-eluting stents and coronary artery bypass grafting (CABG) are limited in patients with multivessel coronary artery disease.

    METHODS: This prospective, multicenter, randomized controlled trial was conducted in 27 international heart centers and was designed to randomly assign 1776 patients with angiographic multivessel coronary artery disease to receive PCI with everolimus-eluting stents or CABG. After inclusion of 880 patients (438 in the PCI group and 442 in the CABG group) between July 2008 and September 2013, the study was terminated early because of slow enrollment. The primary end point was the composite of death from any cause, myocardial infarction, or target vessel revascularization.

    RESULTS: During a median follow-up of 11.8 years (interquartile range, 10.6-12.5 years; maximum, 13.7 years), the primary end point occurred in 151 patients (34.5%) in the PCI group and 134 patients (30.3%) in the CABG group (hazard ratio [HR], 1.18 [95% CI, 0.88-1.56]; P=0.26). No significant differences were seen in the occurrence of a safety composite of death, myocardial infarction, or stroke between groups (28.8% and 27.1%; HR, 1.07 [95% CI, 0.75-1.53]; P=0.70), as well as the occurrence of death from any cause (20.5% and 19.9%; HR, 1.04 [95% CI, 0.65-1.67]; P=0.86). However, spontaneous myocardial infarction (7.1% and 3.8%; HR, 1.86 [95% CI, 1.06-3.27]; P=0.031) and any repeat revascularization (22.6% and 12.7%; HR, 1.92 [95% CI, 1.58-2.32]; P<0.001) were more frequent after PCI than after CABG.

    CONCLUSIONS: In patients with multivessel coronary artery disease, there were no significant differences between PCI and CABG in the incidence of major adverse cardiac events, the safety composite end point, and all-cause mortality during the extended follow-up.

    REGISTRATION: URL: https://www.

    CLINICALTRIALS: gov; Unique identifiers: NCT05125367 and NCT00997828.

  20. 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.

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