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

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

Affiliations
  • 1Global Andrology Forum, American Center for Reproductive Medicine, Moreland Hills, OH, USA
  • 2Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
  • 3Glickman Urological & Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
  • 4Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt
  • 5Department of Reproductive Biology, Fertility Preservation, Andrology, CECOS, Poissy Hospital, Poissy, France
  • 6Department of Biology, Reproduction, Epigenetics, Environment and Development, Paris Saclay University, UVSQ, INRAE, BREED, Jouy-en-Josas, France
  • 7Department of Urology, Selcuk University School of Medicine, Konya, Türkiye
  • 8Department of Urology, Fatih Sultan Mehmet Training and Research Hospital, University of Health Sciences, Istanbul, Türkiye
  • 9Department of Endocrinology, Polytechnic University of Marche, Ancona, Italy
  • 10Department of Urology, Hamad Medical Corporation, Doha, Qatar
  • 11Department of Urology, Weill Cornell Medical-Qatar, Doha, Qatar
  • 12Urology Section, University of Catania, Catania, Italy
  • 13Mansoura University Urology and Nephrology Center, Mansoura, Egypt
  • 14Department of Surgery, Urology Unit, Farwaniya Hospital, Farwaniya, Kuwait
  • 15Department of Urology, Sabah Al Ahmad Urology Center, Kuwait City, Kuwait
  • 16Division of Endocrinology, Central Drug Research Institute, Lucknow, India
  • 17IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain
  • 18Department of Urology, King Abdulaziz University, Jeddah, Saudi Arabia
  • 19Department of Urology, Faculty of Medicine, Minia University, Minia, Egypt
  • 20Department of Urology, Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI, USA
  • 21Austin Fertility & Reproductive Medicine/Westlake IVF, Austin, TX, USA
  • 22Department of Urology, Faculty of Medicine, Istanbul Medipol University, Istanbul, Türkiye
  • 23Department of Urology, Baskent University Faculty of Medicine, Ankara, Türkiye
  • 24Department of Urology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
  • 25Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
  • 26Department of Medical Bioscience, University of the Western Cape, Bellville, South Africa
  • 27LogixX Pharma, Theale, Berkshire, UK
  • 28Research Centre, University of Garmian, Kalar, Iraq
  • 29Department of Urology, School of Medicine, Pamukkale University, Denizli, Türkiye
  • 30Laboratory of Physiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
  • 31Assisted Reproduction Unit, Second Department of Obstetrics and Gynecology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
  • 32Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran
  • 33Gene Therapy and Regenerative Medicine Research Center, Hope Generation Foundation, Tehran, Iran
  • 34Department of Andrology, Binh Dan Hospital, Ho Chi Minh City, Vietnam
  • 35Department of Urology and Andrology, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam
  • 36Department of Medical Biology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Türkiye
  • 37Department of Biomedical Sciences, College of Medicine, Gulf Medical University, Ajman, UAE
  • 38Reproductive Medicine, Department of Translational Medicine, Lund University, Malmö, Sweden
  • 39Department of Urology, Başakşehir Çam and Sakura City Hospital, Istanbul, Türkiye
  • 40Department of Embryology and Histology, Zonguldak Bülent Ecevit University Institute of Health Sciences, Zonguldak, Türkiye
  • 41Department of Physiology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia
  • 42Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  • 43Department of Internal Medicine, Trinity Health/Mercy Health, Muskegon, MI, USA
  • 44Department of Urology, Bolu Abant Izzet Baysal University, Bolu, Türkiye
  • 45School of Natural Medicine, Faculty of Community and Health Sciences, University of the Western Cape, Bellville, South Africa
  • 46Department of Surgery, School of Medicine, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya, Malaysia
  • 47Department of Urology and Andrology, VNA Hospital, New Delhi, India
  • 48Unit of Andrology and Reproductive Medicine, Department of Medicine, University of Padua, Padua, Italy
  • 49Unidade Multidisciplinar de Investigação Biomédica (UMIB), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, Portugal
  • 50Laboratory for Integrative and Translational Research in Population Health (ITR), Universidade do Porto, Porto, Portugal
  • 51Institute of Biomedicine, University of Turku, Turku, Finland
  • 52Department of Urology and Andrology, AIG Hospitals, Gachibowli, Hyderabad, India
  • 53Department of Surgery, McGill University, Montreal, QC, Canada
  • 54Department of Urology, Cipto Mangunkusumo General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • 55Andrology and IVF Center, Next Fertility Procrea, Lugano, Switzerland
  • 56Department of Urology, Pusan National University School of Medicine, Busan, Korea
  • 57Medical Research Institute of Pusan National University Hospital, Busan, Korea
  • 58Department of Urology, Biruni University School of Medicine, Istanbul, Türkiye
  • 59Center for Andrology and Sexual Medicine, Viet Duc University Hospital, Hanoi, Vietnam
  • 60Department of Urology, Andrology and Sexual Medicine, University of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam
  • 61Department of Urology, Loma Linda University Health, Loma Linda, CA, USA
  • 62Department of Urology, Faculty of Medicine, Istanbul Medipol Mega University Hospital, Istanbul, Türkiye
  • 63Department of Urology, Innsbruck Medical University, Innsbruck, Austria
  • 64Fakih IVF Fertility Center, Abu Dhabi, UAE
  • 65Division of Andrology, Department of Urology, Lilavati Hospital and Research Centre, Mumbai, India

Abstract

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.

Keyword

Male infertility; Semen; Varicocele
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