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

Agarwal A 1 , Cannarella R 2 , Saleh R 3 , Boitrelle F 4 , Gül M 5 , Toprak T 6 Show all authors , Salvio G 7 , Arafa M 8 , Russo GI 9 , Harraz AM 10 , Singh R 11 , Garrido N 12 , Hamoda TAA 13 , Rambhatla A 14 , Kavoussi P 15 , Kuroda S 16 , Çalik G 17 , Saini P 11 , Ceyhan E 18 , Dimitriadis F 19 , Henkel R 20 , Crafa A 2 , Palani A 21 , Duran MB 22 , Maziotis E 23 , Saïs É 4 , Bendayan M 4 , Darbandi M 24 , Le TV 25 , Gunes S 26 , Tsioulou P 23 , Sengupta P 27 , Hazir B 28 , Çeker G 29 , Darbandi S 24 , Durairajanayagam D 30 , Aghamajidi A 31 , Alkhalidi N 32 , Sogutdelen E 33 , Leisegang K 34 , Alarbid A 35 , Ho CCK 36 , Malhotra V 37 , Finocchi F 7 , Crisóstomo L 38 , Kosgi R 39 , ElBardisi H 8 , Zini A 40 , Birowo P 41 , Colpi G 42 , Park HJ 43 , Serefoglu EC 44 , Nguyen Q 45 , Ko E 46 , de la Rosette J 47 , Pinggera GM 48 , Nguyen HVP 25 , Kandil H 49 , Shah R 50

Affiliations 

  • 1 Global Andrology Forum, American Center for Reproductive Medicine, Moreland Hills, OH, USA. agarwaa32099@outlook.com
  • 2 Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
  • 3 Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt
  • 4 Department of Reproductive Biology, Fertility Preservation, Andrology, CECOS, Poissy Hospital, Poissy, France
  • 5 Department of Urology, Selcuk University School of Medicine, Konya, Türkiye
  • 6 Department of Urology, Fatih Sultan Mehmet Training and Research Hospital, University of Health Sciences, Istanbul, Türkiye
  • 7 Department of Endocrinology, Polytechnic University of Marche, Ancona, Italy
  • 8 Department of Urology, Hamad Medical Corporation, Doha, Qatar
  • 9 Urology Section, University of Catania, Catania, Italy
  • 10 Mansoura University Urology and Nephrology Center, Mansoura, Egypt
  • 11 Division of Endocrinology, Central Drug Research Institute, Lucknow, India
  • 12 IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain
  • 13 Department of Urology, King Abdulaziz University, Jeddah, Saudi Arabia
  • 14 Department of Urology, Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI, USA
  • 15 Austin Fertility & Reproductive Medicine/Westlake IVF, Austin, TX, USA
  • 16 Glickman Urological & Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
  • 17 Department of Urology, Faculty of Medicine, Istanbul Medipol University, Istanbul, Türkiye
  • 18 Department of Urology, Baskent University Faculty of Medicine, Ankara, Türkiye
  • 19 Department of Urology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
  • 20 Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
  • 21 Research Centre, University of Garmian, Kalar, Iraq
  • 22 Department of Urology, School of Medicine, Pamukkale University, Denizli, Türkiye
  • 23 Laboratory of Physiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
  • 24 Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran
  • 25 Department of Andrology, Binh Dan Hospital, Ho Chi Minh City, Vietnam
  • 26 Department of Medical Biology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Türkiye
  • 27 Department of Biomedical Sciences, College of Medicine, Gulf Medical University, Ajman, UAE
  • 28 Reproductive Medicine, Department of Translational Medicine, Lund University, Malmö, Sweden
  • 29 Department of Urology, Başakşehir Çam and Sakura City Hospital, Istanbul, Türkiye
  • 30 Department of Physiology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia
  • 31 Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  • 32 Department of Internal Medicine, Trinity Health/Mercy Health, Muskegon, MI, USA
  • 33 Department of Urology, Bolu Abant Izzet Baysal University, Bolu, Türkiye
  • 34 School of Natural Medicine, Faculty of Community and Health Sciences, University of the Western Cape, Bellville, South Africa
  • 35 Department of Surgery, Urology Unit, Farwaniya Hospital, Farwaniya, Kuwait
  • 36 Department of Surgery, School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia
  • 37 Department of Urology and Andrology, VNA Hospital, New Delhi, India
  • 38 Unidade Multidisciplinar de Investigação Biomédica (UMIB), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, Portugal
  • 39 Department of Urology and Andrology, AIG Hospitals, Gachibowli, Hyderabad, India
  • 40 Department of Surgery, McGill University, Montreal, QC, Canada
  • 41 Department of Urology, Cipto Mangunkusumo General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • 42 Andrology and IVF Center, Next Fertility Procrea, Lugano, Switzerland
  • 43 Department of Urology, Pusan National University School of Medicine, Busan, Korea
  • 44 Department of Urology, Biruni University School of Medicine, Istanbul, Türkiye
  • 45 Center for Andrology and Sexual Medicine, Viet Duc University Hospital, Hanoi, Vietnam
  • 46 Department of Urology, Loma Linda University Health, Loma Linda, CA, USA
  • 47 Department of Urology, Faculty of Medicine, Istanbul Medipol Mega University Hospital, Istanbul, Türkiye
  • 48 Department of Urology, Innsbruck Medical University, Innsbruck, Austria
  • 49 Fakih IVF Fertility Center, Abu Dhabi, UAE
  • 50 Division of Andrology, Department of Urology, Lilavati Hospital and Research Centre, Mumbai, India
World J Mens Health, 2023 Apr;41(2):289-310.
PMID: 36326166 DOI: 10.5534/wjmh.220142

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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