Controversy and Consensus on Indications for Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations.

Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus.

The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing.

This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians.

The world journal of men's health. 2023 Apr 10 [Epub ahead of print]

Ashok Agarwal, Ala'a Farkouh, Ramadan Saleh, Taha Abo-Almagd Abdel-Meguid Hamoda, Ahmed M Harraz, Parviz Kavoussi, Mohamed Arafa, Gianmaria Salvio, Amarnath Rambhatla, Tuncay Toprak, Murat Gül, Nguyen Ho Vinh Phuoc, Florence Boitrelle, Ponco Birowo, Ramy Abou Ghayda, Rossella Cannarella, Shinnosuke Kuroda, Damayanthi Durairajanayagam, Armand Zini, Christine Wyns, Selcuk Sarikaya, Kelton Tremellen, Taymour Mostafa, Ioannis Sokolakis, Donald P Evenson, Ralf Henkel, Wael Zohdy, Eric Chung, Imad Ziouziou, Marco Falcone, Giorgio I Russo, Manaf Al-Hashimi, Aldo E Calogero, Edmund Ko, Giovanni Colpi, Sheena Lewis, Ege Can Serefoglu, Fahmi Bahar, Marlon Martinez, Quang Nguyen, Rafael F Ambar, Mustafa Emre Bakircioglu, Hussein Kandil, Nasser Mogharabian, Marjan Sabbaghian, Hisanori Taniguchi, Akira Tsujimura, Hesamoddin Sajadi, Wael Ibrahim, Widi Atmoko, Paraskevi Vogiatzi, Sezgin Gunes, Mohammad Ali Sadighi Gilani, Shubhadeep Roychoudhury, Nur Dokuzeylül Güngör, Lukman Hakim, Ricky Adriansjah, Priyank Kothari, Sunil Jindal, Edouard Amar, Hyun Jun Park, Tran Quang Tien Long, Sheryl Homa, Vilvapathy Senguttuvan Karthikeyan, Birute Zilaitiene, Israel Maldonado Rosas, Angelo Marino, Edoardo Pescatori, Cevahir Ozer, Hamed Akhavizadegan, Nicolas Garrido, Gian Maria Busetto, Aram Adamyan, Mohamed Al-Marhoon, Haitham Elbardisi, Parisa Dolati, Mahsa Darbandi, Sara Darbandi, Giancarlo Balercia, Germar-Michael Pinggera, Sava Micic, Christopher Chee Kong Ho, Mohamad Moussa, Mirko Preto, Cătălina Zenoaga-Barbăroșie, Ryan P Smith, Raghavender Kosgi, Jean de la Rosette, Ahmed I El-Sakka, Saad Mohammed Abumelha, Tiago Cesar Mierzwa, Teng Aik Ong, Saleem A Banihani, Kasonde Bowa, Shinichiro Fukuhara, Luca Boeri, Yavuz Onur Danacıoğlu, Fatih Gokalp, Osama Mohamed Selim, Chak-Lam Cho, Nicholas N Tadros, Muhammet Rasit Ugur, Mehmet Serkan Ozkent, Peter Chiu, Arif Kalkanli, Kareim Khalafalla, Ranjit B Vishwakarma, Federica Finocchi, Sotiris Andreadakis, Carlo Giulioni, Gökhan Çeker, Erman Ceyhan, Vineet Malhotra, Mehmet Yilmaz, Massimiliano Timpano, Trenton L Barrett, Shannon Hee Kyung Kim, Sun-Tae Ahn, Filippo Giacone, Ayad Palani, Gede Wirya Kusuma Duarsa, Ates Kadioglu, Franco Gadda, Daniel Suslik Zylbersztejn, Kaan Aydos, Deniz Kulaksız, Deepak Gupte, Gokhan Calik, Keshab Kumar Karna, Panagiotis Drakopoulos, Aykut Baser, Vijay Kumar, Juan Manuel Corral Molina, Osvaldo Rajmil, Raphael H Ferreira, Sofia Leonardi, Armen Avoyan, Emrullah Sogutdelen, Giorgio Franco, Jonathan Ramsay, Liliana Ramirez, Rupin Shah, Global Andrology Forum

Global Andrology Forum, American Center for Reproductive Medicine, Moreland Hills, OH, USA., Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt., Department of Urology, King Abdulaziz University, Jeddah, Saudi Arabia., Urology and Nephrology Center, Mansoura University, Mansoura, Egypt., Department of Reproductive Urology, Austin Fertility & Reproductive Medicine/Westlake IVF, Austin, TX, USA., Department of Urology, Hamad Medical Corporation, Doha, Qatar., Department of Endocrinology, Polytechnic University of Marche, Ancona, Italy., Department of Urology, Henry Ford Health System, Vattikuti Urology Institute, Detroit, MI, USA., Department of Urology, Fatih Sultan Mehmet Training and Research Hospital, University of Health Sciences, Istanbul, Turkey., Department of Urology, Selçuk University School of Medicine, Konya, Turkey., Department of Andrology, Binh Dan Hospital, Ho Chi Minh City, Vietnam., Reproductive Biology, Fertility Preservation, Andrology, CECOS, Poissy Hospital, Poissy, France., Department of Urology, Cipto Mangunkusumo General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia., Urology Institute, University Hospitals, Case Western Reserve University, Cleveland, OH, USA., Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy., Department of Urology, Cleveland Clinic, Cleveland, OH, USA., Department of Physiology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia., Department of Surgery, McGill University, Montreal, QC, Canada., Department of Gynaecology-Andrology, Cliniques universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium., Department of Urology, Gülhane Research and Training Hospital, University of Health Sciences, Ankara, Turkey., Department of Obstetrics Gynaecology and Reproductive Medicine, Flinders University, Bedford Park, Australia., Department of Andrology, Sexology and STIs, Faculty of Medicine, Cairo University, Cairo, Egypt., Department of Urology, Martha-Maria Hospital Nuremberg, Nuremberg, Germany., SCSA Diagnostics, Brookings, SD, USA., Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK., Department of Urology, Princess Alexandra Hospital, University of Queensland, Brisbane, QLD, Australia., Department of Urology, College of Medicine and Pharmacy, Ibn Zohr University, Agadir, Morocco., Department of Urology, Molinette Hospital, A.O.U. Città della Salute e della Scienza, University of Turin, Torino, Italy., Urology Section, University of Catania, Catania, Italy., Department of Urology, Burjeel Hospital, Abu Dhabi, UAE., Department of Urology, Loma Linda University Health, Loma Linda, CA, USA., Andrology and IVF Center, Next Fertility Procrea, Lugano, Switzerland., Examen Lab Ltd., Northern Ireland, UK., Department of Urology, Biruni University School of Medicine, Istanbul, Turkey., Andrology Section, Siloam Sriwijaya Hospital, Palembang, Indonesia., Section of Urology, Department of Surgery, University of Santo Tomas Hospital, Manila, Philippines., Center for Andrology and Sexual Medicine, Viet Duc University Hospital, Hanoi, Vietnam., Department of Urology, Centro Universitario em Saude do ABC, Santo André, Brazil., SENSART Clinic, Urology, Fulya, Istanbul, Turkiye., Fakih IVF Fertility Center, Abu Dhabi, UAE., Sexual Health and Fertility Research Center, Shahroud University of Medical Sciences, Shahroud, Iran., Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran., Department of Urology and Andrology, Kansai Medical University, Hirakata, Osaka, Japan., Department of Urology, Juntendo University Urayasu Hospital, Chiba, Japan., Department of Obstetrics Gynaecology and Reproductive Medicine, Fertility Care Center in Cairo, Cairo, Egypt., Andromed Health & Reproduction, Fertility & Reproductive Health Diagnostic Center, Athens, Greece., Department of Medical Biology, Medical Faculty, Ondokuz Mayis University, Samsun, Turkey., Department of Life Science and Bioinformatics, Assam University, Silchar, India., Department of Obstetrics and Gynecology, Reproductive Endocrinology and IVF Unit, School of Medicine, Bahcesehir University, Istanbul, Turkey., Department of Urology, Faculty of Medicine Universitas Airlangga, Universitas Airlangga Teaching Hospital, Surabaya, Indonesia., Department of Urology, Faculty of Medicine Universitas Padjajaran, Hasan Sadikin General Hospital, Bandung, Indonesia., Department of Urology, Topiwala National Medical College, B.Y.L Nair Ch Hospital, Mumbai, India., Department of Andrology and Reproductive Medicine, Jindal Hospital, Meerut, India., Department of Urology, American Hospital of Paris, Paris, France., Department of Urology, Pusan National University School of Medicine, Busan, Korea., Department of Obstetrics and Gynecology, Hanoi Obstetric and Gynecology Hospital, Hanoi, Vietnam., Department of Biosciences, University of Kent, Canterbury, UK., Andrology Unit, Department of Urology, Apollo Hospitals, Greams Road, Chennai, India., Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania., IVF Laboratory, CITMER Reproductive Medicine, Mexico City, Mexico., Reproductive Medicine Unit, ANDROS Day Surgery Clinic, Palermo, Italy., Andrology and Reproductive Medicine Unit, Gynepro Medical, Bologna, Italy., Department of Urology, Faculty of Medicine, Baskent University, Ankara, Turkey., Department of Urology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran., IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain., Department of Urology and Renal Transplantation, University of Foggia, Policlinico Riuniti, Foggia, Italy., IVF Department, Astghik Medical Center, Yerevan, Armenia., Division of Urology, Department of Surgery, Sultan Qaboos University, Muscat, Sultanate of Oman., Department of Animal Science, Faculty of Agriculture, University of Shiraz, Iran., Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran., Department of Urology, Innsbruck Medical University, Innsbruck, Austria., Department of Andrology, Uromedica Polyclinic, Belgrade, Serbia., Department of Surgery, School of Medicine, Taylor's University, Subang Jaya, Selangor, Malaysia., Department of Urology, Lebanese University, Beirut, Lebanon., Department of Genetics, Faculty of Biology, University of Bucharest, Bucharest, Romania., Department of Urology, University of Virginia School of Medicine, Virginia, USA., Department of Urology, Andrology and Renal Transplant, AIG Hospitals, Hyderabad, India., Department of Urology, Istanbul Medipol Mega University Hospital, Istanbul, Turkey., Department of Urology, Suez Canal University, Ismailia, Egypt., Division of Urology, Department of Surgery, King Abdulaziz Medical City, Riyadh, Saudi Arabia., Androlab, Fertility Clinic, Curitiba, PR, Brazil., Department of Surgery, University of Malaya, Kuala Lumpur, Malaysia., Department of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid, Jordan., Department of Urology, University of Lusaka, Lusaka, Zambia., Department of Urology, Graduate School of Medicine, Osaka University, Osaka, Japan., Department of Urology, IRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy., Department of Urology, University of Health Science Istanbul Bakırköy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey., Department of Urology, Hatay Mustafa Kemal University, Antakya, Turkey., S. H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong, Hong Kong., Division of Urology, Southern Illinois University, Springfield, IL, USA., IVF Michigan, Bloomfield Hills, MI, USA., Department of Urology, Konya City Hospital, Konya, Turkey., Department of Urology, Taksim Education and Research Hospital, Istanbul, Turkey., Department of Urology, Lilavati Hospital and Research Centre, Mumbai, India., Private Practice, Thessaloniki, Greece., Department of Urology, Polytechnic University of Marche Region, Ancona, Italy., Department of Urology, Başakşehir Çam and Sakura City Hospital, Istanbul, Turkey., Department of Urology, SCM Clinic and Hospital, New Delhi, India., Department of Urology, Faculty of Medicine, University of Freiburg-Medical Centre, Freiburg, Germany., Perth Urology Clinic, Perth, WA, Australia., IVF Australia, Sydney, Australia., Department of Urology, Korea University College of Medicine, Seoul, Korea., Centro HERA, Unità di Medicina della Riproduzione, Sant'Agata Li Battiati, Catania, Italy., Research Centre, University of Garmian, Kalar, Iraq., Department of Urology, Udayana University, Denpasar, Indonesia., Section of Andrology, Department of Urology, Istanbul University, Istanbul, Turkey., Fleury Group and Hospital Israelita Albert Einstein, São Paulo, Brazil., Department of Urology, Ankara University, Ankara, Turkey., Department of Obstetrics and Gynecology, University of Health Sciences Kanuni Training and Research Hospital, Trabzon, Turkey., Department of Urology, Bombay Hospital and Medical Research Center, Mumbai, India., Department of Urology, Istanbul Medipol University, Istanbul, Turkey., Department of Molecular Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA., Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium., Department of Urology, Bandirma Onyedi Eylül University, Balikesir, Turkey., Department of Microbiology, Kurukshetra University, Kurukshetra, India., Urology Department, Hospital Clinic of Barcelona, Barcelona, Spain., Department of Andrology, Fundacio Puigvert, Barcelona, Spain., Department of Urology, Santa Casa de Ribeirão Preto, São Paulo, Brazil., Central Laboratory, Hospital Publico Materno Infantil de Salta, Salta, Argentina., Urology Department, Astghik Medical Center, Yerevan, Armenia., Department of Urology, Bolu Abant Izzet Baysal University, Bolu, Turkey., Department of Urology, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy., Department of Andrology, Hammersmith Hospital, London, UK.