Controversy and Consensus on the Management of Elevated Sperm DNA Fragmentation in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Access content directly
Journal Articles The World Journal of Men's Health Year : 2023

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 , Ashok Agarwal (1) , Taha Abo-Almagd Abdel-Meguid Hamoda (2, 3) , Parviz Kavoussi , Ramadan Saleh (4) , Armand Zini (5) , Mohamed Arafa (6, 7, 8) , Ahmed M Harraz (9) , Murat Gul (10) , Vilvapathy Senguttuvan Karthikeyan (11) , Damayanthi Durairajanayagam (12) , Amarnath Rambhatla (13) , Florence Boitrelle (14, 15) , Eric Chung (16) , Ponco Birowo (17) , Tuncay Toprak , Ramy Abou Ghayda (18) , Rossella Cannarella (19, 1) , Nguyen Ho Vinh Phuoc , Fotios Dimitriadis (20) , Giorgio I Russo (19) , Ioannis Sokolakis (20) , Taymour Mostafa (7) , Konstantinos Makarounis , Imad Ziouziou (21) , Shinnosuke Kuroda (1) , Marion Bendayan (14, 15, 22) , Raneen Sawaid Kaiyal (1) , Andrian Japari , Mara Simopoulou (23) , Lucia Rocco (24) , Nicolas Garrido , Nazim Gherabi (25) , Kadir Bocu , Oguzhan Kahraman (26) , Tan V Le , Christine Wyns (27) , Kelton Tremellen (28) , Selcuk Sarikaya (29) , Sheena Lewis , Donald P Evenson , Edmund Ko (30) , Aldo E Calogero (31) , Fahmi Bahar , Marlon Martinez (32) , Andrea Crafa (31) , Quang Nguyen (33) , Rafael F Ambar , Giovanni Colpi , Mustafa Emre Bakircioglu , Ralf Henkel (34, 35) , Hussein Kandil , Ege Can Serefoglu (36) , Abdullah Alarbid , Akira Tsujimura , Alireza Kheradmand (37) , Christina Anagnostopoulou , Angelo Marino , Aram Adamyan , Birute Zilaitiene (38) , Cevahir Ozer (39) , Edoardo Pescatori , Paraskevi Vogiatzi , Gian Maria Busetto (40) , Giancarlo Balercia (41) , Haitham Elbardisi (42, 7) , Hamed Akhavizadegan (43) , Hesamoddin Sajadi (44) , Hisanori Taniguchi (45) , Hyun Jun Park (46) , Israel Maldonado Rosas , Mohamed Al-Marhoon (47) , Mohammad Ali Sadighi Gilani (44) , Naif Alhathal (48) , Germar-Michael Pinggera (49) , Priyank Kothari (50) , Nasser Mogharabian (51) , Sava Micic , Sheryl Homa (52) , Sara Darbandi (53) , Tran Quang Tien Long , Wael Zohdy (7) , Widi Atmoko (17) , Marjan Sabbaghian (44) , Wael Ibrahim , Ryan P Smith , Christopher Chee Kong Ho (54) , Jean de La Rosette (55) , Ahmed I El-Sakka (56) , Mirko Preto (57) , Cătălina Zenoaga-Barbăroșie (58) , Saad Mohammed Abumelha (59) , Aykut Baser , Kaan Aydos (60) , Liliana Ramirez-Dominguez , Vijay Kumar (61) , Teng Aik Ong (62) , Tiago Cesar Mierzwa , Ricky Adriansjah (63) , Saleem A Banihani (64) , Kasonde Bowa (65) , Shinichiro Fukuhara (66) , Marcelo Rodriguez Peña , Mohamad Moussa (67, 68) , Umut Çağın Ari (69) , Chak-Lam Cho (70) , Nicholas N Tadros (71) , Muhammet Rasit Ugur , Edouard Amar (72) , Marco Falcone (57) , Frederic Romain Santer (49) , Arif Kalkanli , Keshab Kumar Karna (73) , Kareim Khalafalla (42, 74, 75) , Ranjit B Vishwakarma (76) , Federica Finocchi (41) , Carlo Giulioni (41) , Erman Ceyhan (39) , Gökhan Çeker , Chadi Yazbeck (77) , Osvaldo Rajmil (78) , Mehmet Yilmaz , Baris Altay (79) , Trenton L Barrett , Kay Seong Ngoo , Shubhadeep Roychoudhury (80) , Gianmaria Salvio (41) , Haocheng Lin (81) , Ates Kadioglu (82) , Massimiliano Timpano (57) , Tomer Avidor-Reiss (83) , Lukman Hakim (84) , Puneet Sindhwani (84) , Giorgio Franco (85) , Rajender Singh (86) , Filippo Giacone , Mikhail Ruzaev , Raghavender Kosgi , Nikolaos Sofikitis (87) , Ayad Palani (88) , Gokhan Calik (55) , Deniz Kulaksız , Davor Jezek (89) , Manaf Al Hashmi (90, 91) , Panagiotis Drakopoulos (92) , Huda Omran , Sofia Leonardi , Ciler Celik-Ozenci (93) , Nur Dokuzeylül Güngör (94) , Jonathan Ramsay (95) , Toshiyasu Amano , Emrullah Sogutdelen (96) , Gede Wirya Kusuma Duarsa (97) , Koji Chiba (98) , Sunil Jindal , Missy Savira (17) , Luca Boeri (99) , Edson Borges , Deepak Gupte , Fatih Gokalp (100) , Guadalupe Hernández Hebrard , Suks Minhas (34) , Rupin Shah (76)
1 Cleveland Clinic
2 King Abdulaziz University
3 Minia University
4 Sohag University
5 McGill University = Université McGill [Montréal, Canada]
6 Hamad Medical Corporation [Doha, Qatar]
7 Cairo University
8 Weill Cornell Medicine [Qatar]
9 Mansoura University [Egypt]
10 Faculty of Medicine - Selcuk University [Konya, Turkey]
11 Apollo Hospital, Bilaspur(C. G.), India
12 UiTM - Universiti Teknologi MARA [Shah Alam]
13 Vattikuti Urology Institute
14 CHI Poissy-Saint-Germain
15 BREED - Biologie de la Reproduction, Environnement, Epigénétique & Développement
16 Princess Alexandra Hospital, Brisbane
17 Cipto Mangunkusumo Hospital [Jakarta]
18 Case Western Reserve University [Cleveland]
19 University of Catania [Italy]
20 Aristotle University of Thessaloniki
21 Université Ibn Zohr [Agadir]
22 CECOS - Centre d’Études et de Conservation des Œufs et du Sperme [CHU Jean Verdier]
23 NKUA - National and Kapodistrian University of Athens
24 Università degli studi della Campania "Luigi Vanvitelli" = University of the Study of Campania Luigi Vanvitelli
25 University of Algiers 3 : Université d' Alger 3
26 Başkent University Hospital [Adana, Turkey]
27 UCL - Université Catholique de Louvain = Catholic University of Louvain
28 Flinders University of South Australia
29 Gulhane Training and Research Hospital
30 Loma Linda University
31 Unict - Università degli studi di Catania = University of Catania
32 University of Santo Tomas [Manila, Philippines]
33 VNU - Vietnam National University [Hanoï]
34 Imperial College London
35 UWC - University of the Western Cape
36 BU - Biruni University [Istanbul]
37 AJUMS - Ahvaz Jundishapur University of Medical Sciences
38 Lithuanian University of Health Sciences [Kaunas, Lithuania]
39 Baskent University
40 Unifg - Università degli Studi di Foggia = University of Foggia
41 UNIVPM - Università Politecnica delle Marche [Ancona]
42 Hamad medical corporation
43 TUMS - Tehran University of Medical Sciences
44 Royan Institute for Reproductive Biomedicine [Tehran, Iran]
45 Kansai Medical University
46 Pusan National University
47 SQU - Sultan Qaboos University
48 KFSH & RC - King Faisal Specialist Hospital and Research Centre
49 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
50 Dept. of Microbiology, Topiwala National Medical College and B. Y. L. Nair Charitable Hospital, Mumbai: 400008, India
51 Shahroud University of Medical Sciences
52 University of Kent [Canterbury]
53 Hope Generation Foundation
54 Taylor’s University
55 Istanbul Medipol University
56 Suez Canal University, Ismailia, Egypt
57 UNITO - Università degli studi di Torino = University of Turin
58 UniBuc - University of Bucharest
59 King Abdulaziz Medical City
60 Ankara University School of Medicine [Turkey]
61 Kurukshetra University
62 UM - University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie]
63 UnPad - Universitas Padjadjaran
64 JUST - Jordan University of Science and Technology [Irbid, Jordan]
65 UNZA - University of Zambia [Lusaka]
66 Osaka University [Osaka]
67 LU - Lebanese University [Beirut]
68 ZHUMC - Al-Zahraa Hospital University Medical Center
69 Kafkas University
70 The Chinese University of Hong Kong [Hong Kong]
71 University of Illinois [Springfield]
72 Hôpital Américain de Paris
73 UMASS - University of Massachusetts Medical School [Worcester]
74 McGovern Medical School [Houston, Texas]
75 MD Anderson Cancer Center [Houston]
76 Lilavati Hospital and Research Centre
77 Institut médical Reprogynes
78 Fundació Puigvert [Barcelona, Spain]
79 Ege University [Izmir]
80 Assam University
81 Peking University [Beijing]
82 Istanbul University
83 University of Toledo
84 UNAIR - Universitas Airlangga
85 UNIROMA - Università degli Studi di Roma "La Sapienza" = Sapienza University [Rome]
86 CSIR-CDRI - CSIR-Central Drug Research Institute
87 University of Ioannina
88 University of Garmian
89 University Hospital Centre Zagreb
90 Burjeel Hospital
91 Khalifa University
92 UZ Brussel - Universitair Ziekenhuis Brussel = University Hospital of Brussels
93 Koç University
94 Bahcesehir University [Istanbul]
95 Hammersmith Hospital NHS Imperial College Healthcare
96 Abant Izzet Baysal University - Bolu Abant İzzet Baysal Üniversitesi
97 Udayana University [Bali]
98 Graduate School of Science [Kobe]
99 Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
100 Hatay Mustafa Kemal University
Ala’a Farkouh
Ashok Agarwal
Cleveland Clinic
Taha Abo-Almagd Abdel-Meguid Hamoda
King Abdulaziz University
Minia University
Parviz Kavoussi
Ramadan Saleh
Sohag University
Armand Zini
McGill University = Université McGill [Montréal, Canada]
Mohamed Arafa
Hamad Medical Corporation [Doha, Qatar]
Cairo University
Weill Cornell Medicine [Qatar]
Ahmed M Harraz
Mansoura University [Egypt]
Murat Gul
Selcuk University [Konya, Turkey]
Vilvapathy Senguttuvan Karthikeyan
Apollo Hospital, Bilaspur(C. G.), India
Damayanthi Durairajanayagam
Universiti Teknologi MARA [Shah Alam]
Amarnath Rambhatla
Vattikuti Urology Institute
Florence Boitrelle
CHI Poissy-Saint-Germain
Biologie de la Reproduction, Environnement, Epigénétique & Développement
Eric Chung
Princess Alexandra Hospital, Brisbane
Ponco Birowo
Cipto Mangunkusumo Hospital [Jakarta]
Tuncay Toprak
Ramy Abou Ghayda
Case Western Reserve University [Cleveland]
Rossella Cannarella
University of Catania [Italy]
Cleveland Clinic
Nguyen Ho Vinh Phuoc
Fotios Dimitriadis
Aristotle University of Thessaloniki
Giorgio I Russo
University of Catania [Italy]
Ioannis Sokolakis
Aristotle University of Thessaloniki
Taymour Mostafa
Cairo University
Konstantinos Makarounis
Imad Ziouziou
Université Ibn Zohr [Agadir]
Shinnosuke Kuroda
Cleveland Clinic
Marion Bendayan
CHI Poissy-Saint-Germain
Biologie de la Reproduction, Environnement, Epigénétique & Développement
Centre d’Études et de Conservation des Œufs et du Sperme [CHU Jean Verdier]
Raneen Sawaid Kaiyal
Cleveland Clinic
Andrian Japari
Mara Simopoulou
National and Kapodistrian University of Athens
Lucia Rocco
Università degli studi della Campania "Luigi Vanvitelli" = University of the Study of Campania Luigi Vanvitelli
Nicolas Garrido
Nazim Gherabi
University of Algiers 3 : Université d' Alger 3
Kadir Bocu
Oguzhan Kahraman
Başkent University Hospital [Adana, Turkey]
Tan V Le
Christine Wyns
Université Catholique de Louvain = Catholic University of Louvain
Kelton Tremellen
Flinders University of South Australia
Selcuk Sarikaya
Gulhane Training and Research Hospital
Sheena Lewis
Donald P Evenson
Edmund Ko
Loma Linda University
Aldo E Calogero
Università degli studi di Catania = University of Catania
Fahmi Bahar
Marlon Martinez
University of Santo Tomas [Manila, Philippines]
Andrea Crafa
Università degli studi di Catania = University of Catania
Quang Nguyen
Vietnam National University [Hanoï]
Rafael F Ambar
Giovanni Colpi
Mustafa Emre Bakircioglu
Ralf Henkel
Imperial College London
University of the Western Cape
Hussein Kandil
Ege Can Serefoglu
Biruni University [Istanbul]
Abdullah Alarbid
Akira Tsujimura
Alireza Kheradmand
Ahvaz Jundishapur University of Medical Sciences
Christina Anagnostopoulou
Angelo Marino
Aram Adamyan
Birute Zilaitiene
Lithuanian University of Health Sciences [Kaunas, Lithuania]
Cevahir Ozer
Baskent University
Edoardo Pescatori
Paraskevi Vogiatzi
Gian Maria Busetto
Università degli Studi di Foggia = University of Foggia
Giancarlo Balercia
Università Politecnica delle Marche [Ancona]
Haitham Elbardisi
Hamad medical corporation
Cairo University
Hamed Akhavizadegan
Tehran University of Medical Sciences
Hesamoddin Sajadi
Royan Institute for Reproductive Biomedicine [Tehran, Iran]
Hisanori Taniguchi
Kansai Medical University
Hyun Jun Park
Pusan National University
Israel Maldonado Rosas
Mohamed Al-Marhoon
Sultan Qaboos University
Mohammad Ali Sadighi Gilani
Royan Institute for Reproductive Biomedicine [Tehran, Iran]
Naif Alhathal
King Faisal Specialist Hospital and Research Centre
Germar-Michael Pinggera
Innsbruck Medical University = Medizinische Universität Innsbruck
Priyank Kothari
Dept. of Microbiology, Topiwala National Medical College and B. Y. L. Nair Charitable Hospital, Mumbai: 400008, India
Nasser Mogharabian
Shahroud University of Medical Sciences
Sava Micic
Sheryl Homa
University of Kent [Canterbury]
Sara Darbandi
Hope Generation Foundation
Tran Quang Tien Long
Wael Zohdy
Cairo University
Widi Atmoko
Cipto Mangunkusumo Hospital [Jakarta]
Marjan Sabbaghian
Royan Institute for Reproductive Biomedicine [Tehran, Iran]
Wael Ibrahim
Ryan P Smith
Christopher Chee Kong Ho
Taylor’s University
Jean de La Rosette
Istanbul Medipol University
Ahmed I El-Sakka
Suez Canal University, Ismailia, Egypt
Mirko Preto
Università degli studi di Torino = University of Turin
Cătălina Zenoaga-Barbăroșie
University of Bucharest
Saad Mohammed Abumelha
King Abdulaziz Medical City
Aykut Baser
Kaan Aydos
Ankara University School of Medicine [Turkey]
Liliana Ramirez-Dominguez
Vijay Kumar
Kurukshetra University
Teng Aik Ong
University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie]
Tiago Cesar Mierzwa
Ricky Adriansjah
Universitas Padjadjaran
Saleem A Banihani
Jordan University of Science and Technology [Irbid, Jordan]
Kasonde Bowa
University of Zambia [Lusaka]
Shinichiro Fukuhara
Osaka University [Osaka]
Marcelo Rodriguez Peña
Mohamad Moussa
Lebanese University [Beirut]
Al-Zahraa Hospital University Medical Center
Umut Çağın Ari
Kafkas University
Chak-Lam Cho
The Chinese University of Hong Kong [Hong Kong]
Nicholas N Tadros
University of Illinois [Springfield]
Muhammet Rasit Ugur
Edouard Amar
Hôpital Américain de Paris
Marco Falcone
Università degli studi di Torino = University of Turin
Frederic Romain Santer
Innsbruck Medical University = Medizinische Universität Innsbruck
Arif Kalkanli
Keshab Kumar Karna
University of Massachusetts Medical School [Worcester]
Kareim Khalafalla
Hamad medical corporation
McGovern Medical School [Houston, Texas]
MD Anderson Cancer Center [Houston]
Ranjit B Vishwakarma
Lilavati Hospital and Research Centre
Federica Finocchi
Università Politecnica delle Marche [Ancona]
Carlo Giulioni
Università Politecnica delle Marche [Ancona]
Erman Ceyhan
Baskent University
Gökhan Çeker
Chadi Yazbeck
Institut médical Reprogynes
Osvaldo Rajmil
Fundació Puigvert [Barcelona, Spain]
Mehmet Yilmaz
Baris Altay
Ege University [Izmir]
Trenton L Barrett
Kay Seong Ngoo
Shubhadeep Roychoudhury
Assam University
Gianmaria Salvio
Università Politecnica delle Marche [Ancona]
Haocheng Lin
Peking University [Beijing]
Ates Kadioglu
Istanbul University
Massimiliano Timpano
Università degli studi di Torino = University of Turin
Tomer Avidor-Reiss
University of Toledo
Lukman Hakim
Universitas Airlangga
Puneet Sindhwani
Universitas Airlangga
Giorgio Franco
Università degli Studi di Roma "La Sapienza" = Sapienza University [Rome]
Rajender Singh
CSIR-Central Drug Research Institute
Filippo Giacone
Mikhail Ruzaev
Raghavender Kosgi
Nikolaos Sofikitis
University of Ioannina
Ayad Palani
University of Garmian
Gokhan Calik
Istanbul Medipol University
Deniz Kulaksız
Davor Jezek
University Hospital Centre Zagreb
Manaf Al Hashmi
Burjeel Hospital
Khalifa University
Panagiotis Drakopoulos
Universitair Ziekenhuis Brussel = University Hospital of Brussels
Huda Omran
Sofia Leonardi
Ciler Celik-Ozenci
Koç University
Nur Dokuzeylül Güngör
Bahcesehir University [Istanbul]
Jonathan Ramsay
Hammersmith Hospital NHS Imperial College Healthcare
Toshiyasu Amano
Emrullah Sogutdelen
Abant Izzet Baysal University - Bolu Abant İzzet Baysal Üniversitesi
Gede Wirya Kusuma Duarsa
Udayana University [Bali]
Koji Chiba
Graduate School of Science [Kobe]
Sunil Jindal
Missy Savira
Cipto Mangunkusumo Hospital [Jakarta]
Luca Boeri
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
Edson Borges
Deepak Gupte
Fatih Gokalp
Hatay Mustafa Kemal University
Guadalupe Hernández Hebrard
Suks Minhas
Imperial College London
Rupin Shah
Lilavati Hospital and Research Centre

Abstract

Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproduc-tive 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. An online global survey on clinical practices related to SDF was disseminated to reproductive clini-cians, 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 formu-lated and adapted using the Delphi method. 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 unex-plained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respon-dents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical vari-cocele, 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. 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.

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Reproductive Biology
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Submitted on : Thursday, July 13, 2023-9:05:11 AM

Last modification on : Wednesday, July 19, 2023-3:39:17 AM

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hal-04161008 , version 1 (13-07-2023)

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Ala’a Farkouh, Ashok Agarwal, Taha Abo-Almagd Abdel-Meguid Hamoda, Parviz Kavoussi, Ramadan Saleh, et al.. Controversy and Consensus on the Management of Elevated Sperm DNA Fragmentation in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations. The World Journal of Men's Health, 2023, 41, ⟨10.5534/wjmh.230008⟩. ⟨hal-04161008⟩

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