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Gastro-oesophageal reflux disease in Asia

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.
Fulltext Data Mining and Statistical Approaches in Debris-Flow Susceptibility Modelling Using Airborne LiDAR Data

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.
Spatial identification and temporal prediction of air pollution sources using conditional bivariate probability function and time series signature

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.
Demystifying uncertainty in PM10 susceptibility mapping using variable drop-off in extreme-gradient boosting (XGB) and random forest (RF) algorithms

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).
Validation of Rome II criteria for functional gastrointestinal disorders by factor analysis of symptoms in Asian patient sample

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.
Clinical recommendations on penile reconstructive and prosthetic surgery: a consensus statement from the Asia-Pacific Society of Sexual Medicine

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.
Fulltext Impact of Antioxidant Therapy on Natural Pregnancy Outcomes and Semen Parameters in Infertile Men: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Agarwal A, Cannarella R, Saleh R, Harraz AM, Kandil H, Salvio G, et al.

World J Mens Health, 2023 Jan;41(1):14-48.
PMID: 36102104 DOI: 10.5534/wjmh.220067

PURPOSE: Seminal oxidative stress (OS) is a recognized factor potentially associated with male infertility, but the efficacy of antioxidant (AOX) therapy is controversial and there is no consensus on its utility. Primary outcomes of this study were to investigate the effect of AOX on spontaneous clinical pregnancy, live birth and miscarriage rates in male infertile patients. Secondary outcomes were conventional semen parameters, sperm DNA fragmentation (SDF) and seminal OS.
MATERIALS AND METHODS: Literature search was performed using Scopus, PubMed, Ovid, Embase, and Cochrane databases. Only randomized controlled trials (RCTs) were included and the meta-analysis was conducted according to PRISMA guidelines.
RESULTS: We assessed for eligibility 1,307 abstracts, and 45 RCTs were finally included, for a total of 4,332 infertile patients. We found a significantly higher pregnancy rate in patients treated with AOX compared to placebo-treated or untreated controls, without significant inter-study heterogeneity. No effects on live-birth or miscarriage rates were observed in four studies. A significantly higher sperm concentration, sperm progressive motility, sperm total motility, and normal sperm morphology was found in patients compared to controls. We found no effect on SDF in analysis of three eligible studies. Seminal levels of total antioxidant capacity were significantly higher, while seminal malondialdehyde acid was significantly lower in patients than controls. These results did not change after exclusion of studies performed following varicocele repair.
CONCLUSIONS: The present analysis upgrades the level of evidence favoring a recommendation for using AOX in male infertility to improve the spontaneous pregnancy rate and the conventional sperm parameters. The failure to demonstrate an increase in live-birth rate, despite an increase in pregnancy rates, is due to the very few RCTs specifically assessing the impact of AOX on live-birth rate. Therefore, further RCTs assessing the impact of AOX on live-birth rate and miscarriage rate, and SDF will be helpful.
Everolimus-Eluting Stents or Bypass Surgery for Multivessel Coronary Artery Disease: Extended Follow-Up Outcomes of Multicenter Randomized Controlled BEST Trial

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.
Everolimus-Eluting Stents or Bypass Surgery for Multivessel Disease in Diabetics: The BEST Extended Follow-Up Study

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).
Management of Male Infertility with Coexisting Sexual Dysfunction: A Consensus Statement and Clinical Recommendations from the Asia-Pacific Society of Sexual Medicine (APSSM) and the Asian Society of Men's Health and Aging (ASMHA)

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.
Fulltext The Renaissance of Male Infertility Management in the Golden Age of Andrology

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.
Fulltext Relevance of Leukocytospermia and Semen Culture and Its True Place in Diagnosing and Treating Male Infertility

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.
Fulltext Impact of Varicocele Repair on Semen Parameters in Infertile Men: A Systematic Review and Meta-Analysis

Agarwal A, Cannarella R, Saleh R, Boitrelle F, Gül M, Toprak T, et al.

World J Mens Health, 2023 Apr;41(2):289-310.
PMID: 36326166 DOI: 10.5534/wjmh.220142

PURPOSE: Despite the significant role of varicocele in the pathogenesis of male infertility, the impact of varicocele repair (VR) on conventional semen parameters remains controversial. Only a few systematic reviews and meta-analyses (SRMAs) have evaluated the impact of VR on sperm concentration, total motility, and progressive motility, mostly using a before-after analytic approach. No SRMA to date has evaluated the change in conventional semen parameters after VR compared to untreated controls. This study aimed to evaluate the effect of VR on conventional semen parameters in infertile patients with clinical varicocele compared to untreated controls.
MATERIALS AND METHODS: A literature search was performed using Scopus, PubMed, Embase, and Cochrane databases following the Population Intervention Comparison Outcome (PICOS) model (Population: infertile patients with clinical varicocele; Intervention: VR [any technique]; Comparison: infertile patients with clinical varicocele that were untreated; Outcome: sperm concentration, sperm total count, progressive sperm motility, total sperm motility, sperm morphology, and semen volume; Study type: randomized controlled trials and observational studies).
RESULTS: A total of 1,632 abstracts were initially assessed for eligibility. Sixteen studies were finally included with a total of 2,420 infertile men with clinical varicocele (1,424 patients treated with VR vs. 996 untreated controls). The analysis showed significantly improved post-operative semen parameters in patients compared to controls with regards to sperm concentration (standardized mean difference [SMD] 1.739; 95% CI 1.129 to 2.349; p<0.001; I²=97.6%), total sperm count (SMD 1.894; 95% CI 0.566 to 3.222; p<0.05; I²=97.8%), progressive sperm motility (SMD 3.301; 95% CI 2.164 to 4.437; p<0.01; I²=98.5%), total sperm motility (SMD 0.887; 95% CI 0.036 to 1.738; p=0.04; I²=97.3%) and normal sperm morphology (SMD 1.673; 95% CI 0.876 to 2.470; p<0.05; I²=98.5%). All the outcomes showed a high inter-study heterogeneity, but the sensitivity analysis showed that no study was sensitive enough to change these results. Publication bias was present only in the analysis of the sperm concentration and progressive motility. No significant difference was found for the semen volume (SMD 0.313; 95% CI -0.242 to 0.868; I²=89.7%).
CONCLUSIONS: This study provides a high level of evidence in favor of a positive effect of VR to improve conventional semen parameters in infertile men with clinical varicocele. To the best of our knowledge, this is the first SRMA to compare changes in conventional semen parameters after VR with changes in parameters of a control group over the same period. This is in contrast to other SRMAs which have compared semen parameters before and after VR, without reference to a control group. Our findings strengthen the available evidence and have a potential to upgrade professional societies' practice recommendations favoring VR to improve conventional semen parameters in infertile men.
Fulltext A Comprehensive Guide to Sperm Recovery in Infertile Men with Retrograde Ejaculation

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.
Fulltext Artificial Intelligence in Andrology: From Semen Analysis to Image Diagnostics

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.
Fulltext A Global Survey of Reproductive Specialists to Determine the Clinical Utility of Oxidative Stress Testing and Antioxidant Use in Male Infertility

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

Agarwal A, Parekh N, Panner Selvam MK, Henkel R, Shah R, Homa ST, et al.

World J Mens Health, 2019 Sep;37(3):296-312.
PMID: 31081299 DOI: 10.5534/wjmh.190055

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.
Fulltext Antisperm Antibody Testing: A Comprehensive Review of Its Role in the Management of Immunological Male Infertility and Results of a Global Survey of Clinical Practices

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.
Fulltext Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations

Agarwal A, Farkouh A, Saleh R, Hamoda TAA, Salvio G, Boitrelle F, et al.

World J Mens Health, 2024 Jan;42(1):202-215.
PMID: 37635341 DOI: 10.5534/wjmh.230076

PURPOSE: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice.
MATERIALS AND METHODS: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured.
RESULTS: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%).
CONCLUSIONS: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial.
Fulltext Post-Vasectomy Semen Analysis: Optimizing Laboratory Procedures and Test Interpretation through a Clinical Audit and Global Survey of Practices

Agarwal A, Gupta S, Sharma RK, Finelli R, Kuroda S, Vij SC, et al.

World J Mens Health, 2022 Jul;40(3):425-441.
PMID: 35021311 DOI: 10.5534/wjmh.210191

PURPOSE: The success of vasectomy is determined by the outcome of a post-vasectomy semen analysis (PVSA). This article describes a step-by-step procedure to perform PVSA accurately, report data from patients who underwent post vasectomy semen analysis between 2015 and 2021 experience, along with results from an international online survey on clinical practice.
MATERIALS AND METHODS: We present a detailed step-by-step protocol for performing and interpretating PVSA testing, along with recommendations for proficiency testing, competency assessment for performing PVSA, and clinical and laboratory scenarios. Moreover, we conducted an analysis of 1,114 PVSA performed at the Cleveland Clinic's Andrology Laboratory and an online survey to understand clinician responses to the PVSA results in various countries.
RESULTS: Results from our clinical experience showed that 92.1% of patients passed PVSA, with 7.9% being further tested. A total of 78 experts from 19 countries participated in the survey, and the majority reported to use time from vasectomy rather than the number of ejaculations as criterion to request PVSA. A high percentage of responders reported permitting unprotected intercourse only if PVSA samples show azoospermia while, in the presence of few non-motile sperm, the majority of responders suggested using alternative contraception, followed by another PVSA. In the presence of motile sperm, the majority of participants asked for further PVSA testing. Repeat vasectomy was mainly recommended if motile sperm were observed after multiple PVSA's. A large percentage reported to recommend a second PVSA due to the possibility of legal actions.
CONCLUSIONS: Our results highlighted varying clinical practices around the globe, with controversy over the significance of non-motile sperm in the PVSA sample. Our data suggest that less stringent AUA guidelines would help improve test compliance. A large longitudinal multi-center study would clarify various doubts related to timing and interpretation of PVSA and would also help us to understand, and perhaps predict, recanalization and the potential for future failure of a vasectomy.

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