1.Protective effects of saffron against zearalenone-induced alterations in reproductive hormones in female mice (Mus musculus).
Bashir AHMAD ; Vinoy K SHRIVASTAVA ; Ramadan SALEH ; Ralf HENKEL ; Ashok AGARWAL
Clinical and Experimental Reproductive Medicine 2018;45(4):163-169
OBJECTIVE: Zearalenone (ZEA) is a mycotoxin with potent estrogenic effects. Saffron is an herbal product that has antioxidant activities. The objective of this study was to investigate the protective role of saffron against reproductive toxicity induced by ZEA in female mice. METHODS: Ninety 8-week-old female mice were randomly allocated into three treatment groups. The first group received an intraperitoneal injection of ZEA (2.5 mg/kg) on alternate days. The second group received ZEA (2.5 mg/kg) on alternate days plus oral saffron daily (50 mg/kg). The third group was treated with a vehicle of 1% dimethyl sulfoxide (DMSO) on alternate days, as a control. Ten mice were euthanized from each group at 30, 60, and 90 days of treatment. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P) were assessed. The uterus and ovaries were examined for changes in size or morphology. RESULTS: Serum levels of LH, FSH, E2, and P in the female mice treated with ZEA plus saffron were significantly higher than in those treated with ZEA alone, and were not significantly different from those treated with 1% DMSO. The female mice treated with ZEA alone showed a reduction in size of the uterus and abnormal architecture of the ovaries. CONCLUSION: The administration of saffron to female mice resulted in a significant reduction in ZEA-induced alterations in reproductive hormone levels, the size of the uterus, and the morphology of the ovaries.
Animals
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Antioxidants
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Crocus*
;
Dimethyl Sulfoxide
;
Estradiol
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Estrogens
;
Female*
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Follicle Stimulating Hormone
;
Humans
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Injections, Intraperitoneal
;
Luteinizing Hormone
;
Mice*
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Ovary
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Progesterone
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Uterus
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Zea mays
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Zearalenone
2.Estimate of oxygen consumption and intracellular zinc concentration of human spermatozoa in relation to motility.
Ralf R HENKEL ; Kerstin DEFOSSE ; Hans-Wilhelm KOYRO ; Norbert WEISSMANN ; Wolf-Bernhard SCHILL
Asian Journal of Andrology 2003;5(1):3-8
AIMTo investigate the human sperm oxygen/energy consumption and zinc content in relation to motility.
METHODSIn washed spermatozoa from 67 ejaculates, the oxygen consumption was determined. Following calculation of the total oxygen consumed by the Ideal Gas Law, the energy consumption of spermatozoa was calculated. In addition, the zinc content of the sperm was determined using an atomic absorption spectrometer. The resulting data were correlated to the vitality and motility.
RESULTSThe oxygen consumption averaged 0.24 micromol/10(6) sperm x 24h, 0.28 micromol/10(6) live sperm x 24h and 0.85 micromol/10(6) live motile sperm x 24h. Further calculations revealed that sperm motility was the most energy consuming process (164.31 mJ/10(6) motile spermatozoa x 24h), while the oxygen consumption of the total spermatozoa was 46.06 mJ/10(6) spermatozoa x 24h. The correlation of the oxygen/energy consumption and zinc content with motility showed significant negative correlations (r= -0.759; P<0.0001 and r=-0.441; P<0.0001, respectively). However, when correlating sperm energy consumption with the zinc content, a significant positive relation (r=0.323; P=0.01) was observed.
CONCLUSIONPoorly motile sperm are actually wasting the available energy. Moreover, our data clearly support the "Geometric Clutch Model" of the axoneme function and demonstrate the importance of the outer dense fibers for the generation of sperm motility, especially progressive motility.
Adult ; Energy Metabolism ; physiology ; Flagella ; physiology ; Humans ; Male ; Middle Aged ; Oxygen Consumption ; Sperm Motility ; physiology ; Spermatozoa ; metabolism ; Zinc ; metabolism
3.Age-related changes in seminal polymorphonuclear elastase in men with asymptomatic inflammation of the genital tract.
Ralf HENKEL ; Gesa MAASS ; Andreas JUNG ; Gerhard HAIDL ; Wolf-Bernhard SCHILL ; Hans-Christian SCHUPPE
Asian Journal of Andrology 2007;9(3):299-304
AIMTo investigate age-related inflammatory events in the male genital tract.
METHODSIn a total of 4265 randomly collected patients attending the andrological outpatient clinic of the Center for Dermatology and Andrology, University of Giessen, Germany, ejaculate volume, pH-value, sperm concentration, total and progressive sperm motility, concentration of polymorphonuclear (PMN) elastase, number of peroxidase-positive cells and fructose were measured and correlated with patient's age.
RESULTSWhile ejaculate volume, motility and fructose all correlated negatively with age, sperm concentration, PMN elastase and the pH-value showed a positive correlation. The prevalence of male genital tract inflammation (as defined by PMN elastase > 250 ng/mL) and its severity increased significantly. PMN elastase did not correlate with sperm motility. Fructose as a marker of seminal vesicle function showed a significant negative relationship with the PMN elastase levels, the number of peroxidase-positive cells and sperm motility.
CONCLUSIONThe significant increases of PMN-elastase levels as marker of male genital tract inflammation in older men appear to be indicative of age-related changes in local immunoregulatory mechanisms. Because there is no association of PMN elastase with sperm motility, a direct inhibitory effect of this enzyme can be excluded.
Adolescent ; Adult ; Aged ; Aging ; physiology ; Biomarkers ; metabolism ; Ejaculation ; Genital Diseases, Male ; enzymology ; pathology ; Humans ; Infertility, Male ; enzymology ; pathology ; Inflammation ; enzymology ; pathology ; Leukocyte Elastase ; metabolism ; Male ; Middle Aged ; Retrospective Studies ; Semen ; cytology ; enzymology ; physiology ; Sperm Count
6.Critical evaluation of two models of flow cytometers for the assessment of sperm DNA fragmentation: an appeal for performance verification.
Rakesh SHARMA ; Sajal GUPTA ; Ralf HENKEL ; Ashok AGARWAL
Asian Journal of Andrology 2019;21(5):438-444
Lack of standardized, reproducible protocols and reference values is among the challenges faced when using new or upgraded versions of instruments in reproductive laboratories and flow cytometry. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay combined with flow cytometry routinely used for diagnostic measurement of sperm DNA fragmentation (SDF) is a unique example. Any change in the setting of the standard instrument, including upgrades of hardware or software, can lead to different results and may affect clinicians' decision for treatment. Therefore, we compared TUNEL results of SDF obtained from a standard (C6) flow cytometer with a newer version of the same instrument (C6 Plus) and examined the cutoff, sensitivity, and specificity without calibration (adjustment) and after adjustment. Identical sperm preparation and matched acquisition settings were used to examine the performance of two flow cytometers. The strength of agreement of the results between the two observers was also assessed. After adjustment of the settings, overall concordance became high and the two cytometers showed 100% positive and negative predictive value with 100% area under the curve. The overall correlation coefficient observed between C6 and C6 Plus was highly significant (P < 0.0001; r = 0.992; 95% confidence interval [CI]: 0.982-0.997). After adjustment, the two cytometers showed very high precision of 98% and accuracy of >99%. The interobserver agreement on C6 flow cytometer for the two observers was 0.801 ± 0.062 and 0.746 ± 0.044 for C6 Plus. We demonstrated a strong agreement between the samples tested on the two flow cytometers after calibration and established the robustness of both instruments.
Adult
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Calibration
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DNA Fragmentation
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Flow Cytometry/instrumentation*
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Humans
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In Situ Nick-End Labeling
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Male
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Observer Variation
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Reference Values
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Reproducibility of Results
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Semen Analysis/methods*
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Sensitivity and Specificity
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Spermatozoa/chemistry*
7.The new 6th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen: is it a step toward better standard operating procedure?
Eric CHUNG ; Mohamed ARAFA ; Florence BOITRELLE ; Hussein KANDIL ; Ralf HENKEL ; Ramadan SALEH ; Rupin SHAH ; Paraskevi VOGIATZI ; Armand ZINI ; Ashok AGARWAL
Asian Journal of Andrology 2022;24(2):123-124
8.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.
9.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
;
Subject Headings
10.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.