1.Effects of Varicocele Repair on Sperm DNA Fragmentation and Seminal Malondialdehyde Levels in Infertile Men with Clinical Varicocele:A Systematic Review and Meta-Analysis
Rossella CANNARELLA ; Rupin SHAH ; Ramadan SALEH ; Florence BOITRELLE ; Taha Abo-Almagd Abdel-Meguid HAMODA ; Rajender SINGH ; Gianmaria SALVIO ; Tuncay TOPRAK ; Marco FALCONE ; Murat GUL ; Fotios DIMITRIADIS ; Amarnath RAMBHATLA ; Giorgio I. RUSSO ; Edmund KO ; Armand ZINI ; Parviz KAVOUSSI ; Nguyen Ho Vinh PHUOC ; Hussein KANDIL ; Ramy Abou GHAYDA ; Ponco BIROWO ; Nazim GHERABI ; Erman CEYHAN ; Jie DONG ; Vineet MALHOTRA ; Damayanthi DURAIRAJANAYAGAM ; Bircan KOLBASI ; Fahmi BAHAR ; Gokhan CALIK ; Selahittin ÇAYAN ; Germar-Michael PINGGERA ; Aldo E. CALOGERO ; Osvaldo RAJMIL ; Taymour MOSTAFA ; Widi ATMOKO ; Ahmed M. HARRAZ ; Tan V. LE ; Jean de la ROSETTE ; Lukman HAKIM ; Edoardo PESCATORI ; Oleg SERGEYEV ; Ayman RASHED ; Pallavi SAINI ; Ashok AGARWAL
The World Journal of Men's Health 2024;42(2):321-337
Purpose:
Varicoceles can be a source of elevated seminal oxidative stress (OS) and sperm DNA fragmentation (SDF). However, it remains unclear whether varicocele repair (VR) could reduce these parameters. This systematic review and meta-analysis (SRMA) aims to investigate the impact of VR on SDF and seminal malondialdehyde (MDA).
Materials and Methods:
A literature search was performed in Scopus, PubMed, Ovid, Embase, and Cochrane databases. This SRMA included randomized controlled trials and observational studies reporting the pre- and postoperative levels of SDF and seminal OS in infertile men with clinical varicocele that underwent VR. Subgroup analyses included techniques of VR and SDF testing. The effect size was expressed as standardized mean difference (SMD).
Results:
Out of 1,632 abstracts assessed for eligibility, 29 studies with 1,491 infertile men were included. The analysis showed a significant reduction in SDF after VR, compared to preoperative values (SMD −1.125, 95% confidence interval [CI] −1.410, −0.840; p<0.0001) with high inter-study heterogeneity (I2=90.965%). Reduction in SDF was evident with microsurgical technique and non-microsurgical inguinal approaches (SMD −1.014, 95% CI −1.263, −0.765; p<0.0001, and SMD −1.495, 95% CI −2.116, −0.873; p<0.0001), respectively. Reduction in SDF was significant irrespective of testing was done by sperm chromatin dispersion (SMD −2.197, 95% CI −3.187, −1.207; p<0.0001), sperm chromatin structure assay (SMD −0.857, 95% CI −1.156, −0.559; p<0.0001) or TUNEL (SMD −1.599, 95% CI −2.478, −0.719; p<0.0001). A significant decrease in seminal MDA levels was observed following VR (SMD −2.450, 95% CI −3.903 to −0.997, p=0.001) with high inter-study heterogeneity (I2=93.7%).
Conclusions
Using pre- and post-intervention data, this SRMA indicates a significant reduction in SDF and seminal MDA levels in infertile men with clinical varicocele treated with VR. These findings may have important implications for the future management of this selected group of infertile patients.
2.Impact of Varicocele Repair on Semen Parameters in Infertile Men: A Systematic Review and Meta-Analysis
Ashok AGARWAL ; Rossella CANNARELLA ; Ramadan SALEH ; Florence BOITRELLE ; Murat GÜL ; Tuncay TOPRAK ; Gianmaria SALVIO ; Mohamed ARAFA ; Giorgio I. RUSSO ; Ahmed M. HARRAZ ; Rajender SINGH ; Nicolas GARRIDO ; Taha Abo-Almagd ABDEL-MEGUID HAMODA ; Amarnath RAMBHATLA ; Parviz KAVOUSSI ; Shinnosuke KURODA ; Gökhan ÇALIK ; Pallavi SAINI ; Erman CEYHAN ; Fotios DIMITRIADIS ; Ralf HENKEL ; Andrea CRAFA ; Ayad PALANI ; Mesut Berkan DURAN ; Evangelos MAZIOTIS ; Émine SAÏS ; Marion BENDAYAN ; Mahsa DARBANDI ; Tan V. LE ; Sezgin GUNES ; Petroula TSIOULOU ; Pallav SENGUPTA ; Berk HAZIR ; Gökhan ÇEKER ; Sara DARBANDI ; Damayanthi DURAIRAJANAYAGAM ; Azin AGHAMAJIDI ; Noora ALKHALIDI ; Emrullah SOGUTDELEN ; Kristian LEISEGANG ; Abdullah ALARBID ; Christopher C. K. HO ; Vineet MALHOTRA ; Federica FINOCCHI ; Luís CRISÓSTOMO ; Raghavender KOSGI ; Haitham ELBARDISI ; Armand ZINI ; Ponco BIROWO ; Giovanni COLPI ; Hyun Jun PARK ; Ege Can SEREFOGLU ; Quang NGUYEN ; Edmund KO ; Jean de la ROSETTE ; Germar M. PINGGERA ; Ho Vinh Phuoc NGUYEN ; Hussein KANDIL ; Rupin SHAH
The World Journal of Men's Health 2023;41(2):289-310
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.
3.Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility
Ashok AGARWAL ; Neel PAREKH ; Manesh Kumar PANNER SELVAM ; Ralf HENKEL ; Rupin SHAH ; Sheryl T HOMA ; Ranjith RAMASAMY ; Edmund KO ; Kelton TREMELLEN ; Sandro ESTEVES ; Ahmad MAJZOUB ; Juan G ALVAREZ ; David K GARDNER ; Channa N JAYASENA ; Jonathan W RAMSAY ; Chak Lam CHO ; Ramadan SALEH ; Denny SAKKAS ; James M HOTALING ; Scott D LUNDY ; Sarah VIJ ; Joel MARMAR ; Jaime GOSALVEZ ; Edmund SABANEGH ; Hyun Jun PARK ; Armand ZINI ; Parviz KAVOUSSI ; Sava MICIC ; Ryan SMITH ; Gian Maria BUSETTO ; Mustafa Emre BAKIRCIOĞLU ; Gerhard HAIDL ; Giancarlo BALERCIA ; Nicolás Garrido PUCHALT ; Moncef BEN-KHALIFA ; Nicholas TADROS ; Jackson KIRKMAN-BROWNE ; Sergey MOSKOVTSEV ; Xuefeng HUANG ; Edson BORGES ; Daniel FRANKEN ; Natan BAR-CHAMA ; Yoshiharu MORIMOTO ; Kazuhisa TOMITA ; Vasan Satya SRINI ; Willem OMBELET ; Elisabetta BALDI ; Monica MURATORI ; Yasushi YUMURA ; Sandro LA VIGNERA ; Raghavender KOSGI ; Marlon P MARTINEZ ; Donald P EVENSON ; Daniel Suslik ZYLBERSZTEJN ; Matheus ROQUE ; Marcello COCUZZA ; Marcelo VIEIRA ; Assaf BEN-MEIR ; Raoul ORVIETO ; Eliahu LEVITAS ; Amir WISER ; Mohamed ARAFA ; Vineet MALHOTRA ; Sijo Joseph PAREKATTIL ; Haitham ELBARDISI ; Luiz CARVALHO ; Rima DADA ; Christophe SIFER ; Pankaj TALWAR ; Ahmet GUDELOGLU ; Ahmed M A MAHMOUD ; Khaled TERRAS ; Chadi YAZBECK ; Bojanic NEBOJSA ; Damayanthi DURAIRAJANAYAGAM ; Ajina MOUNIR ; Linda G KAHN ; Saradha BASKARAN ; Rishma Dhillon PAI ; Donatella PAOLI ; Kristian LEISEGANG ; Mohamed Reza MOEIN ; Sonia MALIK ; Onder YAMAN ; Luna SAMANTA ; Fouad BAYANE ; Sunil K JINDAL ; Muammer KENDIRCI ; Baris ALTAY ; Dragoljub PEROVIC ; Avi HARLEV
The World Journal of Men's Health 2019;37(3):296-312
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.
Antioxidants
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Classification
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Clinical Protocols
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Diagnosis
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DNA
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Embryonic Structures
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Female
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Fertility
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Health Expenditures
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Humans
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Infertility
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Infertility, Male
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Male
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Membranes
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Ovum
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Oxidants
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Oxidation-Reduction
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Oxidative Stress
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Reactive Oxygen Species
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Reducing Agents
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Reproductive Health
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Semen
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Spermatozoa
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Subject Headings
4.Consensus and Diversity in the Management of Varicocele for Male Infertility: Results of a Global Practice Survey and Comparison with Guidelines and Recommendations
Rupin SHAH ; Ashok AGARWAL ; Parviz KAVOUSSI ; Amarnath RAMBHATLA ; Ramadan SALEH ; Rossella CANNARELLA ; Ahmed M. HARRAZ ; Florence BOITRELLE ; Shinnosuke KURODA ; Taha Abo-Almagd Abdel-Meguid HAMODA ; Armand ZINI ; Edmund KO ; Gokhan CALIK ; Tuncay TOPRAK ; Hussein KANDIL ; Murat GÜL ; Mustafa Emre BAKIRCIOĞLU ; Neel PAREKH ; Giorgio Ivan RUSSO ; Nicholas TADROS ; Ates KADIOGLU ; Mohamed ARAFA ; Eric CHUNG ; Osvaldo RAJMIL ; Fotios DIMITRIADIS ; Vineet MALHOTRA ; Gianmaria SALVIO ; Ralf HENKEL ; Tan V. LE ; Emrullah SOGUTDELEN ; Sarah VIJ ; Abdullah ALARBID ; Ahmet GUDELOGLU ; Akira TSUJIMURA ; Aldo E. CALOGERO ; Amr El MELIEGY ; Andrea CRAFA ; Arif KALKANLI ; Aykut BASER ; Berk HAZIR ; Carlo GIULIONI ; Chak-Lam CHO ; Christopher C.K. HO ; Ciro SALZANO ; Daniel Suslik ZYLBERSZTEJN ; Dung Mai Ba TIEN ; Edoardo PESCATORI ; Edson BORGES ; Ege Can SEREFOGLU ; Emine SAÏS-HAMZA ; Eric HUYGHE ; Erman CEYHAN ; Ettore CAROPPO ; Fabrizio CASTIGLIONI ; Fahmi BAHAR ; Fatih GOKALP ; Francesco LOMBARDO ; Franco GADDA ; Gede Wirya Kusuma DUARSA ; Germar-Michael PINGGERA ; Gian Maria BUSETTO ; Giancarlo BALERCIA ; Gianmartin CITO ; Gideon BLECHER ; Giorgio FRANCO ; Giovanni LIGUORI ; Haitham ELBARDISI ; Hakan KESKIN ; Haocheng LIN ; Hisanori TANIGUCHI ; Hyun Jun PARK ; Imad ZIOUZIOU ; Jean de la ROSETTE ; Jim HOTALING ; Jonathan RAMSAY ; Juan Manuel Corral MOLINA ; Ka Lun LO ; Kadir BOCU ; Kareim KHALAFALLA ; Kasonde BOWA ; Keisuke OKADA ; Koichi NAGAO ; Koji CHIBA ; Lukman HAKIM ; Konstantinos MAKAROUNIS ; Marah HEHEMANN ; Marcelo Rodriguez PEÑA ; Marco FALCONE ; Marion BENDAYAN ; Marlon MARTINEZ ; Massimiliano TIMPANO
The World Journal of Men's Health 2023;41(1):164-197
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.