Controversy and Consensus on the Management of Elevated Sperm DNA Fragmentation in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations

Ala'a Farkouh 1Ashok Agarwal 1 2Taha Abo-Almagd Abdel-Meguid Hamoda 3 4Parviz Kavoussi 5Ramadan Saleh 6 7Armand Zini 8Mohamed Arafa 9 10 11Ahmed M Harraz 12 13 14Murat Gul 15Vilvapathy Senguttuvan Karthikeyan 16Damayanthi Durairajanayagam 17Amarnath Rambhatla 18Florence Boitrelle 19 20Eric Chung 21Ponco Birowo 22Tuncay Toprak 23Ramy Abou Ghayda 24Rossella Cannarella 25 26Nguyen Ho Vinh Phuoc 27 28Fotios Dimitriadis 29Giorgio I Russo 30Ioannis Sokolakis 29Taymour Mostafa 10Konstantinos Makarounis 31Imad Ziouziou 32Shinnosuke Kuroda 26Marion Bendayan 19Raneen Sawaid Kaiyal 26Andrian Japari 33Mara Simopoulou 34Lucia Rocco 35Nicolas Garrido 36Nazim Gherabi 37Kadir Bocu 38Oguzhan Kahraman 39Tan V Le 27 28Christine Wyns 40Kelton Tremellen 41Selcuk Sarikaya 42Sheena Lewis 43Donald P Evenson 44Edmund Ko 45Aldo E Calogero 25Fahmi Bahar 46Marlon Martinez 47Andrea Crafa 25Quang Nguyen 48 49Rafael F Ambar 50 51Giovanni Colpi 52Mustafa Emre Bakircioglu 53Ralf Henkel 54 55Hussein Kandil 56Ege Can Serefoglu 57Abdullah Alarbid 13Akira Tsujimura 58Alireza Kheradmand 59Christina Anagnostopoulou 60Angelo Marino 61Aram Adamyan 62Birute Zilaitiene 63Cevahir Ozer 39Edoardo Pescatori 64Paraskevi Vogiatzi 65Gian Maria Busetto 66Giancarlo Balercia 67Haitham Elbardisi 9 10Hamed Akhavizadegan 68Hesamoddin Sajadi 69Hisanori Taniguchi 70Hyun Jun Park 71 72Israel Maldonado Rosas 73Mohamed Al-Marhoon 74Mohammad Ali Sadighi Gilani 69Naif Alhathal 75Germar-Michael Pinggera 76Priyank Kothari 77Nasser Mogharabian 78Sava Micic 79Sheryl Homa 80Sara Darbandi 81 82Tran Quang Tien Long 83Wael Zohdy 10Widi Atmoko 22Marjan Sabbaghian 69Wael Ibrahim 84Ryan P Smith 85Christopher Chee Kong Ho 86Jean de la Rosette 87Ahmed I El-Sakka 88Mirko Preto 89Cătălina Zenoaga-Barbăroșie 90Saad Mohammed Abumelha 91Aykut Baser 92Kaan Aydos 93Liliana Ramirez-Dominguez 73Vijay Kumar 94Teng Aik Ong 95Tiago Cesar Mierzwa 96Ricky Adriansjah 97Saleem A Banihani 98Kasonde Bowa 99Shinichiro Fukuhara 100Marcelo Rodriguez Peña 101Mohamad Moussa 102 103Umut Çağın Ari 104Chak-Lam Cho 105Nicholas N Tadros 106Muhammet Rasit Ugur 107Edouard Amar 108Marco Falcone 109Frederic Romain Santer 76Arif Kalkanli 110Keshab Kumar Karna 111Kareim Khalafalla 9 112 113Ranjit B Vishwakarma 114Federica Finocchi 67Carlo Giulioni 115Erman Ceyhan 39Gökhan Çeker 116Chadi Yazbeck 117Osvaldo Rajmil 118Mehmet Yilmaz 119Baris Altay 120Trenton L Barrett 121Kay Seong Ngoo 122Shubhadeep Roychoudhury 123Gianmaria Salvio 67Haocheng Lin 124Ates Kadioglu 125Massimiliano Timpano 109Tomer Avidor-Reiss 126 127Lukman Hakim 128Puneet Sindhwani 128Giorgio Franco 129Rajender Singh 130Filippo Giacone 131Mikhail Ruzaev 132Raghavender Kosgi 133Nikolaos Sofikitis 134Ayad Palani 135Gokhan Calik 87Deniz Kulaksız 136Davor Jezek 137Manaf Al Hashmi 138 139Panagiotis Drakopoulos 140 141Huda Omran 142Sofia Leonardi 143Ciler Celik-Ozenci 144Nur Dokuzeylül Güngör 145Jonathan Ramsay 146Toshiyasu Amano 147Emrullah Sogutdelen 148Gede Wirya Kusuma Duarsa 149Koji Chiba 150Sunil Jindal 151Missy Savira 22Luca Boeri 152Edson Borges 153Deepak Gupte 154Fatih Gokalp 155Guadalupe Hernández Hebrard 73Suks Minhas 156Rupin Shah 114Global Andrology Forum

Affiliations


Abstract

Purpose: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition.

Materials and methods: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method.

Results: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4-6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated.

Conclusions: This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians.

Keywords: DNA fragmentation; Delphi method; Disease management; Male infertility; Practice guideline; Survey.

Conflict of interest statement

The authors have nothing to disclose.


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