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



Farkouh A1 ; Agarwal A1, 2 ; Abdelmeguid Hamoda TAA3, 4 ; Kavoussi P5 ; Saleh R6, 7 ; Zini A8 ; Arafa M9, 10, 11 ; Harraz AM12, 13, 14 ; Gul M15 ; Karthikeyan VS16 ; Durairajanayagam D17 ; Rambhatla A18 ; Boitrelle F19, 20 ; Chung E21 Show All Authors
Authors
  1. Farkouh A1
  2. Agarwal A1, 2
  3. Abdelmeguid Hamoda TAA3, 4
  4. Kavoussi P5
  5. Saleh R6, 7
  6. Zini A8
  7. Arafa M9, 10, 11
  8. Harraz AM12, 13, 14
  9. Gul M15
  10. Karthikeyan VS16
  11. Durairajanayagam D17
  12. Rambhatla A18
  13. Boitrelle F19, 20
  14. Chung E21
  15. Birowo P22
  16. Toprak T23
  17. Ghayda RA24
  18. Cannarella R25, 26
  19. Phuoc NHV27, 28
  20. Dimitriadis F29
  21. Russo GI30
  22. Sokolakis I29
  23. Mostafa T10
  24. Makarounis K31
  25. Ziouziou I32
  26. Kuroda S26
  27. Bendayan M19
  28. Kaiyal RS26
  29. Japari A33
  30. Simopoulou M34
  31. Rocco L35
  32. Garrido N36
  33. Gherabi N37
  34. Bocu K38
  35. Kahraman O39
  36. Le TV27, 28
  37. Wyns C40
  38. Tremellen K41
  39. Sarikaya S42
  40. Lewis S43
  41. Evenson DP44
  42. Ko E45
  43. Calogero AE25
  44. Bahar F46
  45. Martinez M47
  46. Crafa A25
  47. Nguyen Q48, 49
  48. Ambar RF50, 51
  49. Colpi G52
  50. Bakircioglu ME53
  51. Henkel R54, 55
  52. Kandil H56
  53. Serefoglu EC57
  54. Alarbid A13
  55. Tsujimura A58
  56. Kheradmand A59
  57. Anagnostopoulou C60
  58. Marino A61
  59. Adamyan A62
  60. Zilaitiene B63
  61. Ozer C39
  62. Pescatori E64
  63. Vogiatzi P65
  64. Busetto GM66
  65. Balercia G67
  66. Elbardisi H9, 10
  67. Akhavizadegan H68
  68. Sajadi H69
  69. Taniguchi H70
  70. Park HJ71, 72
  71. Rosas IM73
  72. Almarhoon M74
  73. Gilani MAS69
  74. Alhathal N75
  75. Pinggera GM76
  76. Kothari P77
  77. Mogharabian N78
  78. Micic S79
  79. Homa S80
  80. Darbandi S81, 82
  81. Long TQT83
  82. Zohdy W10
  83. Atmoko W22
  84. Sabbaghian M69
  85. Ibrahim W84
  86. Smith RP85
  87. Ho CCK86
  88. De La Rosette J87
  89. Elsakka AI88
  90. Preto M89
  91. Zenoagabarbarosie C90
  92. Abumelha SM91
  93. Baser A92
  94. Aydos K93
  95. Ramirezdominguez L73
  96. Kumar V94
  97. Ong TA95
  98. Mierzwa TC96
  99. Adriansjah R97
  100. Banihani SA98
  101. Bowa K99
  102. Fukuhara S100
  103. Pena MRR101
  104. Moussa M102, 103
  105. Cagin Ari U104
  106. Cho CL105
  107. Tadros NN106
  108. Ugur MR107
  109. Amar E108
  110. Falcone M109
  111. Santer FR76
  112. Kalkanli A110
  113. Karna KK111
  114. Khalafalla K9, 112, 113
  115. Vishwakarma RB114
  116. Finocchi F67
  117. Giulioni C115
  118. Ceyhan E39
  119. Ceker G116
  120. Yazbeck C117
  121. Rajmil O118
  122. Yilmaz M119
  123. Altay B120
  124. Barrett TL121
  125. Ngoo KS122
  126. Roychoudhury S123
  127. Salvio G67
  128. Lin H124
  129. Kadioglu A125
  130. Timpano M109
  131. Avidorreiss T126, 127
  132. Hakim L128
  133. Sindhwani P128
  134. Franco G129
  135. Singh R130
  136. Giacone F131
  137. Ruzaev M132
  138. Kosgi R133
  139. Sofikitis N134
  140. Palani A135
  141. Calik G87
  142. Kulaksiz D136
  143. Jezek D137
  144. Hashmi MA138, 139
  145. Drakopoulos P140, 141
  146. Omran H142
  147. Leonardi S143
  148. Celikozenci C144
  149. Gungor ND145
  150. Ramsay J146
  151. Amano T147
  152. Sogutdelen E148
  153. Duarsa GWK149
  154. Chiba K150
  155. Jindal S151
  156. Savira M22
  157. Boeri L152
  158. Borges E153
  159. Gupte D154
  160. Gokalp F155
  161. Hebrard GH73
  162. Minhas S156
  163. Shah R114
Show Affiliations
Authors Affiliations
  1. 1. Global Andrology Forum, American Center for Reproductive Medicine, Moreland Hills, OH, United States
  2. 2. Cleveland Clinic Foundation, Cleveland, OH, United States
  3. 3. Department of Urology, King Abdulaziz University, Jeddah, Saudi Arabia
  4. 4. Department of Urology, Faculty of Medicine, Minia University, Minia, Egypt
  5. 5. Department of Reproductive Urology, Austin Fertility & Reproductive Medicine/Westlake IVF, Austin, TX, United States
  6. 6. Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt
  7. 7. Ajyal IVF Center, Ajyal Hospital, Sohag, Egypt
  8. 8. Department of Surgery, McGill University, Montreal, QC, Canada
  9. 9. Department of Urology, Hamad Medical Corporation, Doha, Qatar
  10. 10. Department of Andrology, Sexology & STIs, Cairo University, Cairo, Egypt
  11. 11. Department of Urology, Weill Cornell Medical-Qatar, Doha, Qatar
  12. 12. Urology Department, Urology and Nephrology Center, Mansoura University, Mansura, Egypt
  13. 13. Department of Surgery, Urology Unit, Farwaniya Hospital, Farwaniya, Kuwait
  14. 14. Department of Urology, Sabah Al Ahmad Urology Center, Kuwait City, Kuwait
  15. 15. Department of Urology, Selcuk University, School of Medicine, Konya, Turkey
  16. 16. Andrology Unit, Department of Urology, Apollo Hospitals, Chennai, India
  17. 17. Department of Physiology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia
  18. 18. Department of Urology, Henry Ford Health System, Vattikuti Urology Institute, Detroit, MI, United States
  19. 19. Reproductive Biology, Fertility Preservation, Andrology, CECOS, Poissy Hospital, Poissy, France
  20. 20. Department of Biology, Reproduction, Epigenetics, Environment and Development, Paris Saclay University, UVSQ, INRAE, BREED, Jouy-en-Josas, France
  21. 21. Department of Urology, Princess Alexandra Hospital, University of Queensland, Brisbane, QLD, Australia
  22. 22. Department of Urology, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  23. 23. Department of Urology, Fatih Sultan Mehmet Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
  24. 24. Urology Institute, University Hospitals, Case Western Reserve University, Cleveland, OH, United States
  25. 25. Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
  26. 26. Department of Urology, Glickman Urological & Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH, United States
  27. 27. Department of Andrology, Binh Dan Hospital, Ho Chi Minh City, Viet Nam
  28. 28. Department of Urology and Andrology, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Viet Nam
  29. 29. Department of Urology, Aristotle University, School of Medicine, Thessaloniki, Greece
  30. 30. Urology Section, University of Catania, Catania, Italy
  31. 31. Department of Urology and Andrology, Locus Medicus, Athens, Greece
  32. 32. Department of Urology, College of Medicine and Pharmacy, Ibn Zohr University, Agadir, Morocco
  33. 33. Fertility Clinic, Telogorejo Hospital, Semarang, Indonesia
  34. 34. Department of Physiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
  35. 35. Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, Caserta, Italy
  36. 36. IVI Foundation, Instituto de Investigacion Sanitaria La Fe (IIS La Fe), Valencia, Spain
  37. 37. Department of Urology, University of Algiers, Algiers, Algeria
  38. 38. Department of Urology, Silopi State Hospital, Sirnak, Turkey
  39. 39. Department of Urology, Faculty of Medicine, Baskent University, Ankara, Turkey
  40. 40. Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Brussels, Belgium
  41. 41. Department of Obstetrics Gynaecology and Reproductive Medicine, Flinders University, SA, Australia
  42. 42. Department of Urology, Gulhane Research and Training Hospital, University of Health Sciences, Ankara, Turkey
  43. 43. Examen Lab Ltd., Northern Ireland, United Kingdom
  44. 44. SCSA Diagnostics, Brookings, SD, United States
  45. 45. Department of Urology, Loma Linda University Health, Loma Linda, CA, United States
  46. 46. Andrology Section, Siloam Sriwijaya Hospital, Palembang, Indonesia
  47. 47. Section of Urology, Department of Surgery, University of Santo Tomas Hospital, Manila, Philippines
  48. 48. Center for Andrology and Sexual Medicine, Viet Duc University Hospital, Hanoi, Viet Nam
  49. 49. Department of Urology, Andrology and Sexual Medicine, University of Medicine and Pharmacy, Vietnam National University, Hanoi, Viet Nam
  50. 50. Department of Urology, Centro Universitario em Saude do ABC, Santo Andre, Brazil
  51. 51. Andrology Group, Ideia Fertil Institute of Human Reproduction, Santo Andre, Brazil
  52. 52. Andrology and IVF Center, Next Fertility Procrea, Lugano, Switzerland
  53. 53. SENSART Clinic, Urology, Fulya, Istanbul, Turkey
  54. 54. Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
  55. 55. Department of Medical Bioscience, University of the Western Cape, Bellville, South Africa
  56. 56. Fakih IVF Fertility Center, Abu Dhabi, United Arab Emirates
  57. 57. Department of Urology, Biruni University, School of Medicine, Istanbul, Turkey
  58. 58. Department of Urology, Juntendo University Urayasu Hospital, Chiba, Japan
  59. 59. Urology Department, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  60. 60. Unit of Reproductive Medicine-EmbryoART, Leto Maternity Hospital, Athens, Greece
  61. 61. ANDROS Day Surgery Clinic, Reproductive Medicine Unit, Palermo, Italy
  62. 62. IVF Department, Astghik Medical Center, Yerevan, Armenia
  63. 63. Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
  64. 64. Andrology and Reproductive Medicine Unit, Gynepro Medical, Bologna, Italy
  65. 65. Andromed Health & Reproduction, Fertility & Reproductive Health Diagnostic Center, Athens, Greece
  66. 66. Department of Urology and Renal Transplantation, University of Foggia, Policlinico Riuniti, Foggia, Italy
  67. 67. Department of Endocrinology, Polytechnic University of Marche, Ancona, Italy
  68. 68. Department of Urology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
  69. 69. Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Teheran, Iran
  70. 70. Department of Urology and Andrology, Kansai Medical University, Hirakata, Osaka, Japan
  71. 71. Department of Urology, Pusan National University, School of Medicine, Busan, South Korea
  72. 72. Medical Research Institute, Pusan National University Hospital, Busan, South Korea
  73. 73. IVF Laboratory, CITMER Reproductive Medicine, Mexico City, Mexico
  74. 74. Division of Urology, Department of Surgery, Sultan Qaboos University, Muscat, Oman
  75. 75. King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  76. 76. Department of Urology, Innsbruck Medical University, Innsbruck, Austria
  77. 77. Department of Urology, Topiwala National Medical College, B.Y.L Nair Ch Hospital, Mumbai, India
  78. 78. Sexual Health and Fertility Research Center, Shahroud University of Medical Sciences, Shahroud, Iran
  79. 79. Department of Andrology, Uromedica Polyclinic, Belgrade, Serbia
  80. 80. Department of Biosciences, University of Kent, Canterbury, United Kingdom
  81. 81. Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran
  82. 82. Gene Therapy and Regenerative Medicine Research Center, Hope Generation Foundation, Tehran, Iran
  83. 83. Department of Obstetrics and Gynecology, Hanoi Obstetrics and Gynecology Hospital, Hanoi, Viet Nam
  84. 84. Department of Obstetrics Gynaecology and Reproductive Medicine, Fertility Care Center in Cairo, Cairo, Egypt
  85. 85. Department of Urology, University of Virginia, School of Medicine, VA, United States
  86. 86. Department of Surgery, School of Medicine, Taylor's University, Selangor, Subang Jaya, Malaysia
  87. 87. Department of Urology, Istanbul Medipol University, Istanbul, Turkey
  88. 88. Department of Urology, Suez Canal University, Ismailia, Egypt
  89. 89. Department of Urology, University of Turin, Turin, Italy
  90. 90. Department of Genetics, Faculty of Biology, University of Bucharest, Bucharest, Romania
  91. 91. Division of Urology, Department of Surgery, King Abdulaziz Medical City, Riyadh, Saudi Arabia
  92. 92. Department of Urology, Bandirma Onyedi Eylul University, Balikesir, Turkey
  93. 93. Department of Urology, Ankara University, Ankara, Turkey
  94. 94. Department of Microbiology, Kurukshetra University, Kurukshetra, India
  95. 95. Department of Surgery, University of Malaya, Kuala Lumpur, Malaysia
  96. 96. Androlab, Fertility Clinic, PR, Curitiba, Brazil
  97. 97. Department of Urology, Faculty of Medicine of Padjadjaran University, Hasan Sadikin General Hospital, Bandung, Indonesia
  98. 98. Department of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid, Jordan
  99. 99. Department of Urology, University of Lusaka, Lusaka, Zambia
  100. 100. Department of Urology, Graduate School of Medicine, Osaka University, Osaka, Japan
  101. 101. Instituto de Ginecologia y Fertilidad (IFER), Buenos Aires, Argentina
  102. 102. Department of Urology, Lebanese University, Beirut, Lebanon
  103. 103. Department of Urology, Al Zahraa Hospital, UMC, Lebanon
  104. 104. Department of Reproduction, Kafkas University, Kars, Turkey
  105. 105. S. H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong, Hong Kong
  106. 106. Division of Urology, Southern Illinois University, Springfield, IL, United States
  107. 107. IVF Michigan, Bloomfield Hills, MI, United States
  108. 108. American Hospital of Paris, Paris, France
  109. 109. Department of Urology, Molinette Hospital, A.O.U. Citta della Salute e della Scienza, University of Turin, Torino, Italy
  110. 110. Department of Urology, Taksim Education and Research Hospital, Istanbul, Turkey
  111. 111. Department of Molecular Cell and Cancer Biology, University of Massachusetts, Medical School, Worcester, MA, United States
  112. 112. Urology Department, University of Texas, McGovern Medical School, Houston, TX, United States
  113. 113. Urology Department, MD Anderson Cancer Center, Houston, TX, United States
  114. 114. Division of Andrology, Department of Urology, Lilavati Hospital and Research Centre, Mumbai, India
  115. 115. Department of Urology, Polytechnic University of Marche Region, Ancona, Italy
  116. 116. Department of Urology, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
  117. 117. Obstetrics Gynecology and Reproductive Medicine, Reprogynes Medical Institute, Paris, France
  118. 118. Department of Andrology, Fundacio Puigvert, Barcelona, Spain
  119. 119. Asklepios Clinic Triberg, Urology, Freiburg, Germany
  120. 120. Department of Urology, Ege University, Izmir, Turkey
  121. 121. Perth Urology Clinic, Perth, WA, Australia
  122. 122. Hospital Angkatan Tentera Tuanku Mizan, Kuala Lumpur, Malaysia
  123. 123. Department of Life Science and Bioinformatics, Assam University, Silchar, India
  124. 124. Department of Urology, Peking University Third Hospital, Beijing, China
  125. 125. Section of Andrology, Department of Urology, Istanbul University, Istanbul, Turkey
  126. 126. Department of Biological Sciences, University of Toledo, Toledo, OH, United States
  127. 127. Department of Urology and Transplantation, University of Toledo, Toledo, OH, United States
  128. 128. Department of Urology, Universitas Airlangga, Rumah Sakit Universitas Airlangga Teaching Hospital, Surabaya, Indonesia
  129. 129. Department of Urology, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
  130. 130. Division of Endocrinology, Central Drug Research Institute, Lucknow, India
  131. 131. Centro HERA, Unita di Medicina della Riproduzione, Sant'Agata Li Battiati, Catania, Italy
  132. 132. Private Clinic, Moscow, Russian Federation
  133. 133. Department of Urology, Andrology and Renal Transplant, AIG Hospitals, Hyderabad, India
  134. 134. Department of Urology, Ioannina University, School of Medicine, Ioannina, Greece
  135. 135. Research Centre, University of Garmian, Kalar, Iraq
  136. 136. Department of Obstetrics and Gynecology, University of Health Sciences, Kanuni Training and Research Hospital, Trabzon, Turkey
  137. 137. Department for Transfusion Medicine and Transplantation Biology, Reproductive Tissue Bank, University Hospital Zagreb, Zagreb, Croatia
  138. 138. Department of Urology, Burjeel Hospital, Abu Dhabi, United Arab Emirates
  139. 139. Department of Urology, College of Medicine and Health Science, Khalifa University, Abu Dhabi, United Arab Emirates
  140. 140. Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium
  141. 141. IVF Athens, Athens, Greece
  142. 142. Al Aljenan Medical Center, Pulse Health Training Center, Manama, Bahrain
  143. 143. Central Laboratory, Hospital Publico Materno Infantil de Salta, Salta, Argentina
  144. 144. Department of Histology and Embryology, Faculty of Medicine, Koc University, Istanbul, Turkey
  145. 145. Department of Obstetrics and Gynecology, Reproductive Endocrinology and IVF Unit, School of Medicine, Bahcesehir University, Istanbul, Turkey
  146. 146. Department of Andrology, Hammersmith Hospital, London, United Kingdom
  147. 147. Department of Urology, Nagano Red Cross Hospital, Nagano, Japan
  148. 148. Department of Urology, Bolu Abant Izzet Baysal University, Bolu, Turkey
  149. 149. Department of Urology, Udayana University, Denpasar, Indonesia
  150. 150. Department of Urology, Kobe University, Graduate School of Medicine, Kobe, Japan
  151. 151. Department of Andrology and Reproductive Medicine, Jindal Hospital, Meerut, India
  152. 152. Department of Urology, IRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
  153. 153. Fertility Assisted Fertilization Center, Sao Paulo, Brazil
  154. 154. Department of Urology, Bombay Hospital and Medical Research Center, Mumbai, India
  155. 155. Department of Urology, Hatay Mustafa Kemal University, Antakya, Turkey
  156. 156. Division of Surgery, Department of Surgery and Cancer, Imperial College, London, United Kingdom

Source: World Journal of Men's Health Published:2023


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. © The Author(s), 2023.
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