Does Varicocele Repair Improve Conventional Semen Parameters? A Meta-Analytic Study of Before-After Data
Rossella Cannarella 1 2, Rupin Shah 3, Taha Abo-Almagd Abdel-Meguid Hamoda 4 5, Florence Boitrelle 6 7, Ramadan Saleh 8, Murat Gul 9, Amarnath Rambhatla 10, Parviz Kavoussi 11, Tuncay Toprak 12, Ahmed M Harraz 13 14 15, Edmund Ko 16, Gökhan Çeker 17, Damayanthi Durairajanayagam 18, Noora Alkahidi 19, Shinnosuke Kuroda 2 20, Andrea Crafa 1, Ralf Henkel 21 22, Gianmaria Salvio 23, Berk Hazir 24, Mahsa Darbandi 25 26, Marion Bendayan 6 7, Sara Darbandi 25 26, Marco Falcone 27, Nicolas Garrido 28, Raghavender Kosgi 29, Raneen Sawaid Kaiyal 2, Keshab Karna 30, Nguyen Ho Vinh Phuoc 31 32, Ponco Birowo 33, Giovanni M Colpi 34, Jean de la Rosette 35, Germar-Michael Pinggera 36, Quang Nguyen 37 38, Armand Zini 39, Wael Zohdy 40, Rajender Singh 41, Pallavi Saini 42, Sidney Glina 43, Haocheng Lin 44, Taymour Mostafa 40, Cesar Rojas-Cruz 45, Mohamed Arafa 40 46 47 48, Aldo E Calogero 1, Fotios Dimitriadis 49, Priyank Kothari 50, Vilvapathy Senguttuvan Karthikeyan 51, Keisuke Okada 52, Koji Chiba 52, Ates Kadıoglu 53, Baris Altay 54, Tahsin Turunc 55, Birute Zilaitiene 56, Fatih Gokalp 57, Aram Adamyan 58, Darren Katz 59 60 61, Eric Chung 62, Tiago Cesar Mierzwa 43, Daniel Suslik Zylbersztejn 63, Gustavo Marquesine Paul 64, Nikolaos Sofikitis 65, Ioannis Sokolakis 66, Vineet Malhotra 67, Sakti Ronggowardhana Brodjonegoro 68, Ricky Adriansjah 69, Akira Tsujimura 70, Toshiyasu Amano 71, Giancarlo Balercia 23, Imad Ziouziou 72, Isaac Ardianson Deswanto 73, Marlon Martinez 74, Hyun Jun Park 75 76, Mustafa Emre Bakırcıoglu 77, Erman Ceyhan 78, Kaan Aydos 79, Jonathan Ramsay 80, Suks Minhas 81, Manaf Al Hashimi 82 83, Ramy Abou Ghayda 84, Nicholas Tadros 85, Puneet Sindhwani 86, Christopher C K Ho 87, Rinaldo Indra Rachman 33, Marcelo Rodriguez Pena 88, Ahmad Motawi 40, Arun Karthik Ponnusamy 89, Satish Dipankar 90, Azwar Amir 91, Saleh Binsaleh 92, Ege Can Serefoglu 93, Ravi Banthia 94, Kareim Khalafalla 47 95 96, Ari Basukarno 97, Nguyen Hoai Bac 98, Karun Singla 99, Rafael F Ambar 43 100, Konstantinos Makarounis 101, Shivam Priyadarshi 102, Gede Wirya Kusuma Duarsa 103, Widi Atmoko 33, Sunil Jindal 104, Eko Arianto 105, Hamed Akhavizadegan 106, Haitham El Bardisi 47 48, Ohad Shoshany 107, Gian Maria Busetto 108, Mohamad Moussa 109, Mounir Jamali 110, Mohamed S Al-Marhoon 111, Mikhail Ruzaev 112, Hasan M A Farsi 4, Shingai Mutambirwa 113, Dong Sup Lee 114, Deniz Kulaksiz 115, Yu-Sheng Cheng 116, Abderrazak Bouzouita 117, Selcuk Sarikaya 118, Hussein Kandil 119, Georgios Tsampoukas 120, Ala'a Farkouh 121, Kasonde Bowa 122, Missy Savira 33, Nasser Mogharabian 123, Tan V Le 31 32, Maruto Harjanggi 124, Dang Tuan Anh 125, Tran Quang Tien Long 126, Mohammad Ayodhia Soebadi 127, Lukman Hakim 128, Marko Tanic 129, Umut Cagin Ari 130, Firuza R Parikh 131, Gokhan Calik 35, Vinod Kv 132, Gyem Dorji 133, Andri Rezano 134 135, Osvaldo Rajmil 136, Dung Mai Ba Tien 31, Yiming Yuan 44, Juan Francisco Lizarraga-Salas 137, Balantine Eze 138, Kay Seong Ngoo 139, Joe Lee 140, Umut Arslan 12, Ashok Agarwal 122 141; Global Andrology Forum
Affiliations
Affiliations
Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.- 2Glickman Urological & Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
- 3Department of Urology, Lilavati Hospital and Research Centre, Mumbai, India.
- 4Department of Urology, King Abdulaziz University, Jeddah, Saudi Arabia.
- 5Department of Urology, Faculty of Medicine, Minia University, Minia, Egypt.
- 6Department of Reproductive Biology, Fertility Preservation, Andrology, CECOS, Poissy Hospital, Poissy, France.
- 7Department of Biology, Reproduction, Epigenetics, Environment and Development, Paris Saclay University, UVSQ, INRAE, BREED, Jouy-en-Josas, France.
- 8Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt.
- 9Department of Urology, Selcuk University School of Medicine, Konya, Turkey.
- 10Department of Urology, Henry Ford Health System, Vattikuti Urology Institute, Detroit, MI, USA.
- 11Department of Reproductive Urology, Austin Fertility & Reproductive Medicine/Westlake IVF, Austin, TX, USA.
- 12Department of Urology, Fatih Sultan Mehmet Training and Research Hospital, University of Health Sciences, Istanbul, Turkey.
- 13Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
- 14Department of Surgery, Urology Unit, Farwaniya Hospital, Farwaniya, Kuwait.
- 15Department of Urology, Sabah Al Ahmad Urology Center, Kuwait City, Kuwait.
- 16Department of Urology, Loma Linda University Health, Loma Linda, CA, USA.
- 17Department of Urology, Ba\xc5\x9fak\xc5\x9fehir Cam and Sakura City Hospital, Istanbul, Turkey.
- 18Department of Physiology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia.
- 19Department of Internal Medicine, Trinity Health/Mercy Health, Muskegon, MI, USA.
- 20Department of Urology, Reproduction Center, Yokohama City University Medical Center, Yokohama, Japan.
- 21Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
- 22Department of Medical Bioscience, University of the Western Cape, Bellville, South Africa.
- 23Department of Endocrinology, Polytechnic University of Marche, Ancona, Italy.
- 24Reproductive Medicine, Clinical Research Centre, Lund University, Malmö, Sweden.
- 25Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran.
- 26Gene Therapy and Regenerative Medicine Research Center, Hope Generation Foundation, Tehran, Iran.
- 27Department of Urology, Molinette Hospital, A.O.U. Città della Salute e della Scienza, University of Turin, Torino, Italy.
- 28IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain.
- 29Department of Urology, Andrology and Renal Transplant, AIG Hospitals, Hyderabad, India.
- 30Department of Molecular Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
- 31Department of Andrology, Binh Dan Hospital, Ho Chi Minh, Vietnam.
- 32Department of Urology and Andrology, Pham Ngoc Thach University of Medicine, Ho Chi Minh, Vietnam.
- 33Department of Urology, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
- 34Andrology and IVF Center, Next Fertility Procrea, Lugano, Switzerland.
- 35Department of Urology, Istanbul Medipol Mega University Hospital, Istanbul, Turkey.
- 36Department of Urology, Innsbruck Medical University, Innsbruck, Austria.
- 37Center for Andrology and Sexual Medicine, Viet Duc University Hospital, Hanoi, Vietnam.
- 38Department of Urology, Andrology and Sexual Medicine, University of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam.
- 39Division of Urology, Department of Surgery, McGill University, Montreal, QC, Canada.
- 40Department of Andrology, Sexology & STIs, Faculty of Medicine, Cairo University, Cairo, Egypt.
- 41Central Drug Research Institute, Male Reproductive Health Research Laboratory, Lucknow, Uttar Pradesh, India.
- 42Division of Endocrinology, Central Drug Research Institute, Lucknow, India.
- 43Division of Urology, Centro Universitario FMABC, Santo André, Brazil.
- 44Department of Urology, Peking University Third Hospital, Peking University, Beijing, China.
- 45Department of Urology, University Hospital of Rostock, Rostock, Germany.
- 46American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA.
- 47Department of Urology, Hamad Medical Corporation, Doha, Qatar.
- 48Department of Urology, Weill Cornell Medical-Qatar, Doha, Qatar.
- 49Department of Urology, Aristotle University School of Medicine, Thessaloniki, Greece.
- 50Department of Urology, Topiwala National Medical College, B.Y.L Nair Ch Hospital, Mumbai, India.
- 51Andrology Unit, Department of Urology, Apollo Hospitals, Greams Road, Chennai, India.
- 52Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
- 53Department of Urology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
- 54Department of Urology, Ege University, Izmir, Turkey.
- 55Urocentre Urology Clinic, Adana, Turkey.
- 56Institute of Endocrinology, Lithuanian University of Health Sciences, Kaunas, Lithuania, Turkey.
- 57Department of Urology, Faculty of Medicine, Hatay Mustafa Kemal University, Antakya, Hatay, Turkey.
- 58Department of Urology, Astghik Medical Center, Yerevan, Armenia.
- 59Men's Health Melbourne, Victoria, Australia.
- 60Department of Surgery, Western Precinct, University of Melbourne, Victoria, Australia.
- 61Department of Urology, Western Health, Victoria, Australia.
- 62Department of Urology, Princess Alexandra Hospital, University of Queensland, Brisbane, Australia.
- 63Fleury Group and Hospital Israelita Albert Einstein, São Paulo, Brazil.
- 64Department of Clinical Surgery, Health Sciences Sector of the Federal University of Parana (UFPR), Curitiba, Paraná, Brazil.
- 65Department of Urology, Ioannina University School of Medicine, Ioannina, Greece.
- 662nd Department of Urology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
- 67SCM Clinic and Hospital, New Delhi, India.
- 68Division of Urology, Department of Surgery, Prof. Dr. Sardjito Hospital, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.
- 69Department of Urology, Hasan Sadikin Hospital, Medical Faculty of Padjadjaran University, Bandung, Indonesia.
- 70Department of Urology, Juntendo University Urayasu Hospital, Chiba, Japan.
- 71Department of Urology, Nagano Red Cross Hospital, Nagano, Japan.
- 72Department of Urology, College of Medicine and Pharmacy, Ibn Zohr University, Agadir, Morocco.
- 73Elang Medika Corpora Hospital, Tangerang, Indonesia.
- 74Section of Urology, Department of Surgery, University of Santo Tomas Hospital, Manila, Philippines.
- 75Department of Urology, Pusan National University School of Medicine, Busan, Korea.
- 76Medical Research Institute of Pusan National University Hospital, Busan, Korea.
- 77SENSART Clinic, Istanbul, Turkey.
- 78Department of Urology, Baskent University Faculty of Medicine, Ankara, Turkey.
- 79Department of Urology, Ankara University School of Medicine, Ankara, Turkey.
- 80Department of Andrology, Hammersmith Hospital, Imperial, London, UK.
- 81Department of Urology, Imperial Healthcare NHS Trust, Charing Cross Hospital, London, UK.
- 82Department of Urology, Burjeel Hospital, Abu Dhabi, UAE.
- 83Clinical Urology, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, UAE.
- 84Institute of Urology, University Hospitals, Case Western Reserve University, Cleveland, OH, USA.
- 85Division of Urology, Southern Illinois University School of Medicine, Springfield, IL, USA.
- 86Department of Urology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH, USA.
- 87Department of Surgery, School of Medicine, Taylor's University, Subang Jaya, Selangor, Malaysia.
- 88Instituto de Ginecología y Fertilidad (IFER) y Universidad Barcelo, Buenos Aires, Argentina.
- 89AndroOne Men's Health Clinic, Salem, India.
- 90Department of Physiology, All India Institute of Medical Sciences Mangalagiri, Mangalagiri, India.
- 91Department of Urology, Dr Wahidin Sudirohusodo Hospital, Makassar, Indonesia.
- 92Division of Urology, Department of Surgery, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia.
- 93Department of Urology, Biruni University School of Medicine, Istanbul, Turkey.
- 94Department of Urology, Western General Hospital, Edinburgh, UK.
- 95Urology Department, University of Texas McGovern Medical School, Houston, TX, USA.
- 96Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.
- 97Department of Urology, Dr. Dradjat Hospital, Serang, Indonesia.
- 98Department of Andrology and Sexual Medicine, Hanoi Medical University's Hospital, Hanoi, Vietnam.
- 99Clarity Health, Chandigarh, India.
- 100Andrology Department at Ideia Fertil Institute, Santo Andre, São Paulo, Brazil.
- 101Department of Urology and Andrology, Locus Medicus, Athens, Greece.
- 102Department of Urology, Sawai Man Singh Medical College and Hospital, Jaipur, Rajasthan, India.
- 103Department of Urology, Prof. Dr. I.G.N.G Ngoerah General Hospital, Faculty of Medicine, Universitas Udayana, Bali, Indonesia.
- 104Department of Andrology & Reproductive Medicine, Jindal Hospital & Fertility Center, Meerut, India.
- 105Department of Urology, Prof R.D. Kandou Hospital, Manado, Indonesia.
- 106Urology Department, Tehran University of Medical Scienes, Tehran, Iran.
- 107Department of Urology, University of Illinois at Chicago, Chicago, IL, USA.
- 108Department of Urology and Renal Transplantation, Univeristy of Foggia, Foggia, Italy.
- 109Department of Urology, Lebanese University, Beirut, Lebanon.
- 110Department of Urology, Military Teaching Hospital, Rabat, Morocco.
- 111Department of Surgery, Urology Division, Sultan Qaboos University, Muscat, Oman.
- 112Urology Clinic, Moscow, Russia.
- 113Department of Urology, Dr. George Mukhari Academic Hospital, Sefako Makgatho Health Science University, Medunsa, Ga-Rankuwa, South Africa.
- 114Department of Urology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
- 115Department of Obstetrics and Gynecology, University of Health Sciences, Kanuni Training and Research Hospital, Trabzon, Turkey.
- 116Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
- 117Department of Anatomy, Faculty of Medicine, Faculty Tunis Manar, Tunis, Tunisia.
- 118Department of Urology, Gulhane Research and Training Hospital, University of Health Sciences, Ankara, Turkey.
- 119Fakih IVF Fertility Center, Abu Dhabi, UAE.
- 120Department of Urology, Oxford University Hospital, Oxford, UK.
- 121Global Andrology Forum, Moreland Hills, OH, USA.
- 122Department of Urology, School of Medicine and Health Sciences, University of Lusaka, Lusaka, Zambia.
- 123Sexual Health and Fertility Research Center, Shahroud University of Medical Sciences, Shahroud, Iran.
- 124IVF Jakarta - YPK Mandiri, Jakarta, Indonesia.
- 125Tam Anh IVF Center, Tam Anh General Hospital, Hanoi, Vietnam.
- 126Department of Obstetrics and Gynecology, Hanoi Obstetric and Gynecology Hospital, Hanoi, Vietnam.
- 127Department of Urology, Soetomo Hospital, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.
- 128Department of Urology, Universitas Airlangga Teaching Hospital, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.
- 129Department of Urology, General Hospital, Cuprija, Serbia.
- 130Department of Reproduction and Artificial Insemination, Faculty of Veterinary Medicine, Kafkas University, Kars, Turkey.
- 131FertilTree-Jaslok International Fertility Centre, Jaslok Hospital, Mumbai, Maharashtra, India.
- 132Cure & SK Hospital, Trivandrum, India.
- 133Department of Anatomy, Khesar Gyalpo University of Medical Sciences of Bhutan, Thimphu, Bhutan.
- 134Andrology Study Program, Department of Biomedical Sciences, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, Indonesia.
- 135Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Sumedang, West Java, Indonesia.
- 136Department of Andrology, Fundacio Puigvert, Barcelona, Spain.
- 137Instituto de Ciencias en Reproducción Humana Vida, León, Mexico.
- 138Department of Surgery, College of Medicine, Enugu State University of Science and Technology, Enugu, Nigeria.
- 139Urology Unit, Department of Surgery, Hospital Angkatan Tentera Tuanku Mizan, Kuala Lumpur, Malaysia.
- 140Department of Urology, National University Hospital, Singapore.
- 141Cleveland Clinic, Cleveland, OH, USA. Agarwal@globalandrology.org.
Purpose: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles.
Materials and methods: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies).
Results: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129-0.278; p<0.001; I²=83.62%, Egger's p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474-1.706; p<0.001; I²=97.86%, Egger's p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526-2.121; p<0.001; I²=97.88%, Egger's p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318-1.968; p<0.001; I²=98.65%, Egger's p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%-2.153%; p<0.001; I²=98.97%, Egger's p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%-1.759%; p<0.001; l2=97.98%, Egger's p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%-1.211%; p<0.001; I²=97.87%, Egger's p=0.1864.
Conclusions: The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele.
Keywords: Controlled before-after studies; Infertility, male; Meta-analysis; Varicocele.
Conflict of interest statement
The authors have nothing to disclose.