Fulltext

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

Farkouh A 1 , Agarwal A 1 , Hamoda TAA 2 , Kavoussi P 3 , Saleh R 4 , Zini A 5 Show all authors , Arafa M 6 , Harraz AM 7 , Gul M 8 , Karthikeyan VS 9 , Durairajanayagam D 10 , Rambhatla A 11 , Boitrelle F 12 , Chung E 13 , Birowo P 14 , Toprak T 15 , Ghayda RA 16 , Cannarella R 17 , Phuoc NHV 18 , Dimitriadis F 19 , Russo GI 20 , Sokolakis I 19 , Mostafa T 21 , Makarounis K 22 , Ziouziou I 23 , Kuroda S 24 , Bendayan M 12 , Kaiyal RS 24 , Japari A 25 , Simopoulou M 26 , Rocco L 27 , Garrido N 28 , Gherabi N 29 , Bocu K 30 , Kahraman O 31 , Le TV 18 , Wyns C 32 , Tremellen K 33 , Sarikaya S 34 , Lewis S 35 , Evenson DP 36 , Ko E 37 , Calogero AE 17 , Bahar F 38 , Martinez M 39 , Crafa A 17 , Nguyen Q 40 , Ambar RF 41 , Colpi G 42 , Bakircioglu ME 43 , Henkel R 44 , Kandil H 45 , Serefoglu EC 46 , Alarbid A 47 , Tsujimura A 48 , Kheradmand A 49 , Anagnostopoulou C 50 , Marino A 51 , Adamyan A 52 , Zilaitiene B 53 , Ozer C 31 , Pescatori E 54 , Vogiatzi P 55 , Busetto GM 56 , Balercia G 57 , Elbardisi H 6 , Akhavizadegan H 58 , Sajadi H 59 , Taniguchi H 60 , Park HJ 61 , Maldonado Rosas I 62 , Al-Marhoon M 63 , Sadighi Gilani MA 59 , Alhathal N 64 , Pinggera GM 65 , Kothari P 66 , Mogharabian N 67 , Micic S 68 , Homa S 69 , Darbandi S 70 , Long TQT 71 , Zohdy W 21 , Atmoko W 14 , Sabbaghian M 59 , Ibrahim W 72 , Smith RP 73 , Ho CCK 74 , de la Rosette J 75 , El-Sakka AI 76 , Preto M 77 , Zenoaga-Barbăroșie C 78 , Abumelha SM 79 , Baser A 80 , Aydos K 81 , Ramirez-Dominguez L 62 , Kumar V 82 , Ong TA 83 , Mierzwa TC 84 , Adriansjah R 85 , Banihani SA 86 , Bowa K 87 , Fukuhara S 88 , Rodriguez Peña M 89 , Moussa M 90 , Ari UÇ 91 , Cho CL 92 , Tadros NN 93 , Ugur MR 94 , Amar E 95 , Falcone M 96 , Santer FR 65 , Kalkanli A 97 , Karna KK 98 , Khalafalla K 6 , Vishwakarma RB 99 , Finocchi F 57 , Giulioni C 100 , Ceyhan E 31 , Çeker G 101 , Yazbeck C 102 , Rajmil O 103 , Yilmaz M 104 , Altay B 105 , Barrett TL 106 , Ngoo KS 107 , Roychoudhury S 108 , Salvio G 57 , Lin H 109 , Kadioglu A 110 , Timpano M 96 , Avidor-Reiss T 111 , Hakim L 112 , Sindhwani P 112 , Franco G 113 , Singh R 114 , Giacone F 115 , Ruzaev M 116 , Kosgi R 117 , Sofikitis N 118 , Palani A 119 , Calik G 75 , Kulaksız D 120 , Jezek D 121 , Al Hashmi M 122 , Drakopoulos P 123 , Omran H 124 , Leonardi S 125 , Celik-Ozenci C 126 , Güngör ND 127 , Ramsay J 128 , Amano T 129 , Sogutdelen E 130 , Duarsa GWK 131 , Chiba K 132 , Jindal S 133 , Savira M 14 , Boeri L 134 , Borges E 135 , Gupte D 136 , Gokalp F 137 , Hebrard GH 62 , Minhas S 138 , Shah R 99 , Global Andrology Forum

Affiliations 

  • 1 Global Andrology Forum, American Center for Reproductive Medicine, Moreland Hills, OH, USA
  • 2 Department of Urology, King Abdulaziz University, Jeddah, Saudi Arabia
  • 3 Department of Reproductive Urology, Austin Fertility & Reproductive Medicine/Westlake IVF, Austin, TX, USA
  • 4 Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt
  • 5 Department of Surgery, McGill University, Montreal, QC, Canada
  • 6 Department of Urology, Hamad Medical Corporation, Doha, Qatar
  • 7 Urology Department, Urology and Nephrology Center, Mansoura University, Mansura, Egypt
  • 8 Department of Urology, Selçuk University School of Medicine, Konya, Turkey
  • 9 Andrology Unit, Department of Urology, Apollo Hospitals, Chennai, India
  • 10 Department of Physiology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia
  • 11 Department of Urology, Henry Ford Health System, Vattikuti Urology Institute, Detroit, MI, USA
  • 12 Reproductive Biology, Fertility Preservation, Andrology, CECOS, Poissy Hospital, Poissy, France
  • 13 Department of Urology, Princess Alexandra Hospital, University of Queensland, Brisbane, QLD, Australia
  • 14 Department of Urology, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  • 15 Department of Urology, Fatih Sultan Mehmet Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
  • 16 Urology Institute, University Hospitals, Case Western Reserve University, Cleveland, OH, USA
  • 17 Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
  • 18 Department of Andrology, Binh Dan Hospital, Ho Chi Minh City, Vietnam
  • 19 Department of Urology, Aristotle University, School of Medicine, Thessaloniki,
  • 20 Urology Section, University of Catania, Catania, Italy
  • 21 Department of Andrology, Sexology & STIs, Cairo University, Cairo, Egypt
  • 22 Department of Urology and Andrology, Locus Medicus, Athens, Greece
  • 23 Department of Urology, College of Medicine and Pharmacy, Ibn Zohr University, Agadir, Morocco
  • 24 Department of Urology, Glickman Urological & Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
  • 25 Fertility Clinic, Telogorejo Hospital, Semarang, Indonesia
  • 26 Department of Physiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
  • 27 Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, Caserta, Italy
  • 28 IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain
  • 29 Department of Urology, University of Algiers, Algiers, Algeria
  • 30 Department of Urology, Silopi State Hospital, Sirnak, Turkey
  • 31 Department of Urology, Faculty of Medicine, Baskent University, Ankara, Turkey
  • 32 Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
  • 33 Department of Obstetrics Gynaecology and Reproductive Medicine, Flinders University, South Australia, Australia
  • 34 Department of Urology, Gülhane Research and Training Hospital, University of Health Sciences, Ankara, Turkey
  • 35 Examen Lab Ltd., Northern Ireland, UK
  • 36 SCSA Diagnostics, Brookings, SDUSA, USA
  • 37 Department of Urology, Loma Linda University Health, Loma Linda, CA, USA
  • 38 Andrology Section, Siloam Sriwijaya Hospital, Palembang, Indonesia
  • 39 Section of Urology, Department of Surgery, University of Santo Tomas Hospital, Manila, Philippines
  • 40 Center for Andrology and Sexual Medicine, Viet Duc University Hospital, Hanoi, Vietnam
  • 41 Department of Urology, Centro Universitario em Saude do ABC, Santo André, Brazil
  • 42 Andrology and IVF Center, Next Fertility Procrea, Lugano, Switzerland
  • 43 SENSART Clinic, Urology, Fulya, Istanbul, Turkey
  • 44 Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
  • 45 Fakih IVF Fertility Center, Abu Dhabi, UAE
  • 46 Department of Urology, Biruni University School of Medicine, Istanbul, Turkey
  • 47 Department of Surgery, Urology Unit, Farwaniya Hospital, Farwaniya, Kuwait
  • 48 Department of Urology, Juntendo University Urayasu Hospital, Chiba, Japan
  • 49 Urology Department, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  • 50 Unit of Reproductive Medicine-EmbryoART, Leto Maternity Hospital, Athens, Greece
  • 51 ANDROS Day Surgery Clinic, Reproductive Medicine Unit, Palermo, Italy
  • 52 IVF Department, Astghik Medical Center, Yerevan, Armenia
  • 53 Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
  • 54 Andrology and Reproductive Medicine Unit, Gynepro Medical, Bologna, Italy
  • 55 Andromed Health & Reproduction, Fertility & Reproductive Health Diagnostic Center, Athens, Greece
  • 56 Department of Urology and Renal Transplantation, University of Foggia, Policlinico Riuniti, Foggia, Italy
  • 57 Department of Endocrinology, Polytechnic University of Marche, Ancona, Italy
  • 58 Department of Urology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
  • 59 Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Teheran, Iran
  • 60 Department of Urology and Andrology, Kansai Medical University, Hirakata, Osaka, Japan
  • 61 Department of Urology, Pusan National University School of Medicine, Busan, Korea
  • 62 IVF Laboratory, CITMER Reproductive Medicine, Mexico City, Mexico
  • 63 Division of Urology, Department of Surgery, Sultan Qaboos University, Muscat, Sultanate of Oman
  • 64 King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  • 65 Department of Urology, Innsbruck Medical University, Innsbruck, Austria
  • 66 Department of Urology, Topiwala National Medical College, B.Y.L Nair Ch Hospital, Mumbai, India
  • 67 Sexual Health and Fertility Research Center, Shahroud University of Medical Sciences, Shahroud, Iran
  • 68 Department of Andrology, Uromedica Polyclinic, Belgrade, Serbia
  • 69 Department of Biosciences, University of Kent, Canterbury, UK
  • 70 Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran
  • 71 Department of Obstetrics and Gynecology, Hanoi Obstetrics and Gynecology Hospital, Hanoi, Vietnam
  • 72 Department of Obstetrics Gynaecology and Reproductive Medicine, Fertility Care Center in Cairo, Cairo, Egypt
  • 73 Department of Urology, University of Virginia School of Medicine, Virginia, USA
  • 74 Department of Surgery, School of Medicine, Taylor's University, Subang Jaya, Selangor, Malaysia
  • 75 Department of Urology, Istanbul Medipol University, Istanbul, Turkey
  • 76 Department of Urology, Suez Canal University, Ismailia, Egypt
  • 77 Department of Urology, University of Turin, Turin, Italy
  • 78 Department of Genetics, Faculty of Biology, University of Bucharest, Bucharest, Romania
  • 79 Division of Urology, Department of Surgery, King Abdulaziz Medical City, Riyadh, Saudi Arabia
  • 80 Department of Urology, Bandirma Onyedi Eylül University, Balikesir, Turkey
  • 81 Department of Urology, Ankara University, Ankara, Turkey
  • 82 Department of Microbiology, Kurukshetra University, Kurukshetra, India
  • 83 Department of Surgery, University of Malaya, Kuala Lumpur, Malaysia
  • 84 Androlab, Fertility Clinic, Curitiba, PR, Brazil
  • 85 Department of Urology, Faculty of Medicine of Padjadjaran University, Hasan Sadikin General Hospital, Bandung, Indonesia
  • 86 Department of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid, Jordan
  • 87 Department of Urology, University of Lusaka, Lusaka, Zambia
  • 88 Department of Urology, Graduate School of Medicine, Osaka University, Osaka, Japan
  • 89 Instituto de Ginecologia y Fertilidad (IFER), Buenos Aire, Argentina
  • 90 Department of Urology, Lebanese University, Beirut, Lebanon
  • 91 Department of Reproduction, Kafkas University, Kars, Turkey
  • 92 S. H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong, Hong Kong
  • 93 Division of Urology, Southern Illinois University, Springfield, IL, USA
  • 94 IVF Michigan, Bloomfield Hills, MI, USA
  • 95 American Hospital of Paris, Paris, France
  • 96 Department of Urology, Molinette Hospital, A.O.U. Città della Salute e della Scienza, University of Turin, Torino, Italy
  • 97 Department of Urology, Taksim Education and Research Hospital, Istanbul, Turkey
  • 98 Department of Molecular Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA
  • 99 Division of Andrology, Department of Urology, Lilavati Hospital and Research Centre, Mumbai, India
  • 100 Department of Urology, Polytechnic University of Marche Region, Ancona, Italy
  • 101 Department of Urology, Başakşehir Çam and Sakura City Hospital, Istanbul, Turkey
  • 102 Obstetrics Gynecology and Reproductive Medicine, Reprogynes Medical Institute, Paris, France
  • 103 Department of Andrology, Fundacio Puigvert, Barcelona, Spain
  • 104 Asklepios Clinic Triberg, Urology, Freiburg, Germany
  • 105 Department of Urology, Ege University, Izmir, Turkey
  • 106 Perth Urology Clinic, Perth, WA, Australia
  • 107 Hospital Angkatan Tentera Tuanku Mizan, Kuala Lumpur, Malaysia
  • 108 Department of Life Science and Bioinformatics, Assam University, Silchar, India
  • 109 Department of Urology, Peking University Third Hospital, Beijing, China
  • 110 Section of Andrology, Department of Urology, Istanbul University, Istanbul, Turkey
  • 111 Department of Biological Sciences, University of Toledo, Toledo, OH, USA
  • 112 Department of Urology, Universitas Airlangga, Rumah Sakit Universitas Airlangga Teaching Hospital, Surabaya, Indonesia
  • 113 Department of Urology, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
  • 114 Division of Endocrinology, Central Drug Research Institute, Lucknow, India
  • 115 Centro HERA, Unità di Medicina della Riproduzione, Sant'Agata Li Battiati, Catania, Italy
  • 116 Private Clinic, Moscow, Russia
  • 117 Department of Urology, Andrology and Renal Transplant, AIG Hospitals, Hyderabad, India
  • 118 Department of Urology, Ioannina University School of Medicine, Ioannina, Greece
  • 119 Research Centre, University of Garmian, Kalar, Iraq
  • 120 Department of Obstetrics and Gynecology, University of Health Sciences Kanuni Training and Research Hospital, Trabzon, Turkey
  • 121 Department for Transfusion Medicine and Transplantation Biology, Reproductive Tissue Bank, University Hospital Zagreb, Zagreb, Croatia
  • 122 Department of Urology, Burjeel Hospital, Abu Dhabi, UAE
  • 123 Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium
  • 124 Al Aljenan Medical Center, Pulse Health Training Center, Manama, Kingdom of Bahrain
  • 125 Central Laboratory, Hospital Público Materno Infantil de Salta, Salta, Argentina
  • 126 Department of Histology and Embryology, Faculty of Medicine, Koç University, Istanbul, Turkey
  • 127 Department of Obstetrics and Gynecology, Reproductive Endocrinology and IVF Unit, School of Medicine, Bahcesehir University, Istanbul, Turkey
  • 128 Department of Andrology, Hammersmith Hospital, London, UK
  • 129 Department of Urology, Nagano Red Cross Hospital, Nagano, Japan
  • 130 Department of Urology, Bolu Abant Izzet Baysal University, Bolu, Turkey
  • 131 Department of Urology, Udayana University, Denpasar, Indonesia
  • 132 Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
  • 133 Department of Andrology and Reproductive Medicine, Jindal Hospital, Meerut, India
  • 134 Department of Urology, IRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
  • 135 Fertility Assisted Fertilization Center, São Paulo, Brazil
  • 136 Department of Urology, Bombay Hospital and Medical Research Center, Mumbai, India
  • 137 Department of Urology, Hatay Mustafa Kemal University, Antakya, Turkey
  • 138 Division of Surgery, Department of Surgery and Cancer, Imperial College, London, UK
World J Mens Health, 2023 Oct;41(4):809-847.
PMID: 37118965 DOI: 10.5534/wjmh.230008

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Similar publications