Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations
Ashok Agarwal, Ala’a Farkouh, Ramadan Saleh, Taha Abo-Almagd Abdel-Meguid Hamoda, Gianmaria Salvio, Florence Boitrelle, Ahmed M. Harraz, Ramy Abou Ghayda, Parviz K. Kavoussi, Murat Gül, Tuncay Toprak, Giorgio Ivan Russo, Damayanthi Durairajanayagam, Amarnath Rambhatla, Ponco Birowo, Rossella Cannarella, Nguyen Ho Vinh Phuoc, Armand Zini, Mohamed Arafa, Christine Wyns, Kelton Tremellen, Selçuk Sarıkaya, Sheena Lewis, Donald P. Evenson, Edmund Ko, Aldo E. Calogero, Fahmi Bahar, Marlon Martínez, Rafael F. Ambar, Giovanni M. Colpi, Emre Bakırcıoğlu, Ralf Henkel, Hussein Kandil, Ege Can Şerefoğlu, Abdullah Alfakhri, Akira Tsujimura, Alireza Kheradmand, Angelo Marino, Aram Adamyan, Birutė Žilaitienė, Cevahir Özer, Edoardo Pescatori, Paraskevi Vogiatzi, Gian Maria Busetto, Giancarlo Balercia, Haitham Elbardisi, Hamed Akhavizadegan, Hesamoddin Sajadi, Hisanori Taniguchi, Hyun Jun Park, Israel Maldonado Rosas, Mohamed S. Al‐Marhoon, Mohammad Ali Sadighi Gilani, Naif Alhathal, Nguyen Hong Quang, Germar‐Michael Pinggera, Priyank Kothari, S. Mičić, Sheryl T. Homa, Tran Quang Tien Long, Wael Zohdy, Widi Atmoko, Wael Ibrahim, Marjan Sabbaghian, Saad Abumelha, Eric Chung, Muhammet Raşit Uğur, Mehmet Serkan Özkent, Osama Selim, Mahsa Darbandi, Shinichiro Fukuhara, Mounir Jamali, Jean de la Rosette, Shinnosuke Kuroda, Ryan P. Smith, Aykut Başer, Arif Kalkanlı, Nicholas N. Tadros, Kaan Aydos, Tiago César Mierzwa, Kareim Khalafalla, Vineet Malhotra, Mohamad Moussa, Federica Finocchi, Rinaldo Indra Rachman, Carlo Giulioni, Tomer Avidor‐Reiss, Oğuzhan Kahraman, Gökhan Çeker, Cătălina Zenoaga-Barbăroşie, Trenton Barrett, Mehmet Yılmaz, Ateş Kadıoğlu, Sunil Jindal, Huda Omran, Kadir Böcü, Vilvapathy Senguttuvan Karthikeyan, Giorgio Franco, Jesus Fernando Solorzano Vazquez, Ranjit B. Vishwakarma
Abstract
PURPOSE: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. MATERIALS AND METHODS: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. RESULTS: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). CONCLUSIONS: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial.