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Technical Aspects and Clinical Limitations of Sperm Dna Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations Publisher



Agarwal A1, 2 ; Farkouh A1 ; Saleh R1, 3 ; Hamoda TAAAM1, 4, 5 ; Salvio G1, 6 ; Boitrelle F1, 7, 8 ; Harraz AM1, 9, 10, 11 ; Ghayda RA1, 12 ; Kavoussi P1, 13 ; Gul M1, 14 ; Toprak T1, 15 ; Russo GI1, 16 ; Durairajanayagam D1, 17 ; Rambhatla A1, 18 Show All Authors
Authors
  1. Agarwal A1, 2
  2. Farkouh A1
  3. Saleh R1, 3
  4. Hamoda TAAAM1, 4, 5
  5. Salvio G1, 6
  6. Boitrelle F1, 7, 8
  7. Harraz AM1, 9, 10, 11
  8. Ghayda RA1, 12
  9. Kavoussi P1, 13
  10. Gul M1, 14
  11. Toprak T1, 15
  12. Russo GI1, 16
  13. Durairajanayagam D1, 17
  14. Rambhatla A1, 18
  15. Birowo P1, 19
  16. Cannarella R1, 20, 21
  17. Phuoc NHV1, 22, 23
  18. Zini A1, 24
  19. Arafa M1, 25, 26, 27
  20. Wyns C1, 28
  21. Tremellen K1, 29
  22. Sarikaya S1, 30
  23. Lewis S1, 31
  24. Evenson DP1, 32
  25. Ko E1, 33
  26. Calogero AE1, 10
  27. Bahar F1, 34
  28. Martinez M1, 35
  29. Ambar RF1, 36, 37
  30. Colpi GM1, 38
  31. Bakircioglu ME1, 39
  32. Henkel R1, 40, 41
  33. Kandil H1, 42
  34. Serefoglu EC1, 43
  35. Alfakhri A1, 44
  36. Tsujimura A1, 45
  37. Kheradmand A1, 46
  38. Marino A1, 47
  39. Adamyan A1, 48
  40. Zilaitiene B1, 49
  41. Ozer C1, 50
  42. Pescatori E1, 51
  43. Vogiatzi P1, 52
  44. Busetto GM1, 53
  45. Balercia G1, 6
  46. Elbardisi H1, 25, 26, 54
  47. Akhavizadegan H1, 55
  48. Sajadi H1, 56
  49. Taniguchi H1, 57
  50. Park HJ1, 58, 59
  51. Rosas IM1, 60
  52. Almarhoon M1, 61
  53. Gilani MAS1, 56
  54. Alhathal N1, 62
  55. Quang N1, 63, 64
  56. Pinggera GM1, 65
  57. Kothari P1, 66
  58. Micic S1, 67
  59. Homa S1, 68
  60. Long TQT1, 69
  61. Zohdy W1, 27
  62. Atmoko W1, 19
  63. Ibrahim W1, 70
  64. Sabbaghian M1, 56
  65. Abumelha SM1, 71
  66. Chung E1, 72
  67. Ugur MR1, 73
  68. Ozkent MS1, 74
  69. Selim O1, 27
  70. Darbandi M1, 75, 76
  71. Fukuhara S1, 77
  72. Jamali M1, 78
  73. De La Rosette J1, 79
  74. Kuroda S21
  75. Smith RP1, 80
  76. Baser A1, 81
  77. Kalkanli A1, 82
  78. Tadros NN1, 83
  79. Aydos K1, 84
  80. Mierzwa TC1, 85
  81. Khalafalla K1, 25, 86, 87
  82. Malhotra V1, 88
  83. Moussa M1, 89, 90
  84. Finocchi F1, 6
  85. Rachman RI1, 19
  86. Giulioni C1, 6
  87. Avidorreiss T1, 91, 92
  88. Kahraman O1, 51
  89. Ceker G93
  90. Zenoagabarbarosie C1, 94
  91. Barrett TL1, 95
  92. Yilmaz M1, 96
  93. Kadioglu A1, 97
  94. Jindal S1, 98
  95. Omran H1, 99
  96. Bocu K1, 100
  97. Karthikeyan VS1, 101
  98. Franco G1, 102
  99. Solorzano JF1, 60
  100. Vishwakarma RB1, 103
  101. Arianto E1, 104
  102. Garrido N1, 105
  103. Jain D1, 106
  104. Gherabi N1, 107
  105. Sokolakis I1, 108
  106. Palani A1, 109
  107. Calik G1, 79
  108. Kulaksiz D1, 110
  109. Simanaviciene V1, 111
  110. Simopoulou M1, 112
  111. Gungor ND1, 113
  112. Blecher G1, 114
  113. Falcone M1, 115
  114. Jezek D1, 116
  115. Preto M1, 115
  116. Amar E1, 117
  117. Le TV1, 22, 23
  118. Ahn ST1, 118
  119. Rezano A1, 119
  120. Singh K1, 120
  121. Rocco L1, 121
  122. Savira M1, 19
  123. Rajmil O1, 122
  124. Darbandi S1, 75, 76
  125. Sogutdelen E1, 123
  126. Boeri L1, 124
  127. Hernandez G1, 125
  128. Hakim L1, 126
  129. Morimoto Y1, 127
  130. Japari A1, 128
  131. Sofikitis N1, 129
  132. Altay B1, 130
  133. Mahmutoglu AM1, 131
  134. Al Hashimi M1, 132
  135. Ziouziou I1, 133
  136. Anagnostopoulou C1, 134
  137. Lin H1, 135
  138. Shah R1, 103
Show Affiliations
Authors Affiliations
  1. 1. Global Andrology Forum, Moreland Hills, OH, United States
  2. 2. Cleveland Clinic, Cleveland, OH, United States
  3. 3. Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt
  4. 4. Department of Urology, King Abdulaziz University, Jeddah, Saudi Arabia
  5. 5. Department of Urology, Faculty of Medicine, Minia University, Minia, Egypt
  6. 6. Department of Endocrinology, Polytechnic University of Marche, Ancona, Italy
  7. 7. Reproductive Biology, Fertility Preservation, Andrology, CECOS, Poissy Hospital, Poissy, France
  8. 8. Department of Biology, Reproduction, Epigenetics, Environment, and Development, Paris Saclay University, UVSQ, INRAE, BREED, Jouy-en-Josas, France
  9. 9. Urology and Nephrology Center, Mansoura, Egypt
  10. 10. Department of Surgery, Urology Unit, Farwaniya Hospital, Farwaniya, Kuwait
  11. 11. Department of Urology, Sabah Al Ahmad Urology Center, Kuwait City, Kuwait
  12. 12. Urology Institute, University Hospitals, Case Western Reserve University, Cleveland, OH, United States
  13. 13. Department of Reproductive Urology, Austin Fertility & Reproductive Medicine, Westlake IVF, Austin, TX, United States
  14. 14. Department of Urology, SelA§uk University School of Medicine, Konya, Turkey
  15. 15. Department of Urology, Fatih Sultan Mehmet Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
  16. 16. Urology Section, University of Catania, Catania, Italy
  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. Department of Urology, Dr. Cipto Mangunkusumo General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
  20. 20. Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
  21. 21. Department of Urology, Glickman Urological & Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH, United States
  22. 22. Department of Andrology, Binh Dan Hospital, Ho Chi Minh City, Viet Nam
  23. 23. Department of Urology and Andrology, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Viet Nam
  24. 24. Department of Surgery, McGill University, Montreal, QC, Canada
  25. 25. Department of Urology, Hamad Medical Corporation, Doha, Qatar
  26. 26. Department of Urology, Weill Cornell Medical-Qatar, Doha, Qatar
  27. 27. Department of Andrology and STDs, Cairo University, Cairo, Egypt
  28. 28. Department of Gynaecology-Andrology, Cliniques Universitaires Saint-Luc, Universitat Catholique de Louvain, Brussels, Belgium
  29. 29. Department of Obstetrics Gynaecology and Reproductive Medicine, Flinders University, Bedford Park, Australia
  30. 30. Department of Urology, Galhane Research and Training Hospital, University of Health Sciences, Ankara, Turkey
  31. 31. Examen Lab Ltd., United Kingdom
  32. 32. SCSA Diagnostics, Brookings, SD, United States
  33. 33. Department of Urology, Loma Linda University Health, Loma Linda, CA, United States
  34. 34. Andrology Section, Siloam Sriwijaya Hospital, Palembang, Indonesia
  35. 35. Section of Urology, Department of Surgery, University of Santo Tomas Hospital, Manila, Philippines
  36. 36. Department of Urology, Centro Universitario em Saude do ABC, Santo Andre, Brazil
  37. 37. Andrology Group, Ideia Fertil Institute of Human Reproduction, Santo Andre, Brazil
  38. 38. Andrology and IVF Center, Next Fertility Procrea, Lugano, Switzerland
  39. 39. SENSART Clinic, Urology, Fulya, Istanbul, Turkey
  40. 40. Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
  41. 41. Department of Medical Bioscience, University of the Western Cape, Bellville, South Africa
  42. 42. Fakih IVF Fertility Center, Abu Dhabi, United Arab Emirates
  43. 43. Department of Urology, Biruni University School of Medicine, Istanbul, Turkey
  44. 44. Department of Urology, King Fahad Medical City, Riyadh, Saudi Arabia
  45. 45. Department of Urology, Juntendo University Urayasu Hospital, Chiba, Japan
  46. 46. Department of Urology, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  47. 47. Reproductive Medicine Unit, ANDROS Day Surgery Clinic, Reproductive Medicine Unit, Palermo, Italy
  48. 48. IVF Department, Astghik Medical Center, Yerevan, Armenia
  49. 49. Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
  50. 50. Department of Urology, Faculty of Medicine, Baskent University, Ankara, Turkey
  51. 51. Andrology and Reproductive Medicine Unit, Gynepro Medical, Bologna, Italy
  52. 52. Andromed Health & Reproduction, Fertility & Reproductive Health Diagnostic Center, Athens, Greece
  53. 53. Department of Urology and Renal Transplantation, University of Foggia, Policlinico Riuniti, Foggia, Italy
  54. 54. Department of Urology, College of Medicine, Qatar University, Doha, Qatar
  55. 55. Department of Urology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
  56. 56. Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
  57. 57. Department of Urology and Andrology, Kansai Medical University, Osaka, Hirakata, Japan
  58. 58. Department of Urology, Pusan National University School of Medicine, Busan, South Korea
  59. 59. Medical Research Institute, Pusan National University Hospital, Busan, South Korea
  60. 60. IVF Laboratory, CITMER Reproductive Medicine, Mexico City, Mexico
  61. 61. Division of Urology, Department of Surgery, Sultan Qaboos University, Muscat, Oman
  62. 62. King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  63. 63. Center for Andrology and Sexual Medicine, Viet Duc University Hospital, Hanoi, Viet Nam
  64. 64. Department of Urology, Andrology and Sexual Medicine, University of Medicine and Pharmacy, Vietnam National University, Hanoi, Viet Nam
  65. 65. Department of Urology, Innsbruck Medical University, Innsbruck, Austria
  66. 66. Department of Urology, Topiwala National Medical College, B.Y.L Nair Ch Hospital, Mumbai, India
  67. 67. Department of Andrology, Uromedica Polyclinic, Belgrade, Serbia
  68. 68. Department of Biosciences, University of Kent, Canterbury, United Kingdom
  69. 69. Department of Obstetrics and Gynecology, Hanoi Obstetric and Gynecology Hospital, Hanoi, Viet Nam
  70. 70. Department of Surgery, School of Medicine, Taylor’s University, Selangor, Subang Jaya, Malaysia
  71. 71. Division of Urology, Department of Surgery, King Abdulaziz Medical City, Riyadh, Saudi Arabia
  72. 72. Department of Urology, University of Queensland, Princess Alexandra Hospital, Brisbane, QLD, Australia
  73. 73. IVF Michigan, Bloomfield Hills, MI, United States
  74. 74. Department of Urology, Konya City Hospital, Konya, Turkey
  75. 75. Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran
  76. 76. Gene Therapy and Regenerative Medicine Research Center, Hope Generation Foundation, Tehran, Iran
  77. 77. Department of Urology, Graduate School of Medicine, Osaka University, Osaka, Japan
  78. 78. Department of Urology, Mohammed V Military Hospital, Rabat, Morocco
  79. 79. Department of Urology, Istanbul Medipol University, Istanbul, Turkey
  80. 80. Department of Urology, University of Virginia School of Medicine, Charlottesville, VA, United States
  81. 81. Department of Urology, Bandirma Onyedi Eylul University, Balikesir, Turkey
  82. 82. Department of Urology, Taksim Education and Research Hospital, Istanbul, Turkey
  83. 83. Division of Urology, Southern Illinois University, Springfield, IL, United States
  84. 84. Department of Urology, Ankara University, Ankara, Turkey
  85. 85. Androlab, Fertility Clinic, Curitiba, Brazil
  86. 86. Department of Urology, University of Texas McGovern Medical School, Houston, TX, United States
  87. 87. Department of Urology, MD Anderson Cancer Center, Houston, TX, United States
  88. 88. Department of Urology, SCM Clinic and Hospital, New Delhi, India
  89. 89. Department of Urology, Lebanese University, Beirut, Lebanon
  90. 90. Department of Urology, Al Zahraa Hospital, UMC, Lebanon
  91. 91. Department of Biological Sciences, University of Toledo, Toledo, OH, United States
  92. 92. Department of Urology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH, United States
  93. 93. Department of Urology, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
  94. 94. Department of Genetics, Faculty of Biology, University of Bucharest, Bucharest, Romania
  95. 95. Department of Urology, Perth Urology Clinic, Murdoch, WA, Australia
  96. 96. Asklepios Klinik Triberg, Urology, Triberg, Germany
  97. 97. Section of Andrology, Department of Urology, Istanbul University, Istanbul, Turkey
  98. 98. Department of Andrology and Reproductive Medicine, Jindal Hospital, Meerut, India
  99. 99. Molecular Genetics Department, Pulse Health Training Center, Manama, Bahrain
  100. 100. Department of Urology, Silopi State Hospital, Sirnak, Turkey
  101. 101. Andrology Unit, Department of Urology, Apollo Hospitals, Greams Road, Chennai, India
  102. 102. Department of Urology, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy
  103. 103. Division of Andrology, Department of Urology, Lilavati Hospital and Research Centre, Mumbai, India
  104. 104. Department of Surgery, Prof. Dr. R.D. Kandou Central General Hospital, Manado, Indonesia
  105. 105. IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigacion Sanitaria La Fe (IIS La Fe), Valencia, Spain
  106. 106. Department of Obstetrics and Gynecology, Jaipur Golden Hospital, New Delhi, India
  107. 107. Department of Medicine, University of Algiers 1, Algiers, Algeria
  108. 108. 2nd Department of Urology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
  109. 109. Research Centre, University of Garmian, Kalar, Iraq
  110. 110. Department of Obstetrics and Gynecology, University of Health Sciences, Kanuni Training and Research Hospital, Trabzon, Turkey
  111. 111. Fertility Centre, Northway Medical Centre, Vilnius, Lithuania
  112. 112. Department of Physiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
  113. 113. Department of Obstetrics and Gynecology, Reproductive Endocrinology and IVF Unit, School of Medicine, Bahcesehir University, Istanbul, Turkey
  114. 114. Department of Surgery, School of Clinical Sciences, Monash University, Melbourne, Australia
  115. 115. Department of Urology, Molinette Hospital, Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino, University of Turin, Torino, Italy
  116. 116. Reproductive Tissue Bank, Department for Transfusion Medicine and Transplantation Biology, University Hospital Zagreb, Zagreb, Croatia
  117. 117. American Hospital of Paris, Paris, France
  118. 118. Department of Urology, Korea University College of Medicine, Seoul, South Korea
  119. 119. Department of Biomedical Sciences, Division of Cell Biology, Faculty of Medicine, Universitas Padjadjaran, West Java, Sumedang, Indonesia
  120. 120. Department of Preclinical and Health Sciences, Faculty of Medical Sciences, The University of the West Indies, Cave Hill Campus, St Michael, Barbados
  121. 121. Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, Caserta, Italy
  122. 122. Department of Andrology, Fundacio Puigvert, Barcelona, Spain
  123. 123. Department of Urology, Bolu Abant Izzet Baysal University, Bolu, Turkey
  124. 124. Department of Urology, IRCCS Fondazione Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy
  125. 125. IVF Department, CITMER Reproductive Medicine, Puebla, Mexico
  126. 126. Department of Urology, Faculty of Medicine, Universitas Airlangga Teaching Hospital, Surabaya, Indonesia
  127. 127. Department of Urology, HORAC Grand Front Osaka Clinic, Osaka, Japan
  128. 128. Department of Urology, Fertility Clinic, Telogorejo Hospital, Central Java, Indonesia
  129. 129. Department of Urology, Ioannina University School of Medicine, Ioannina, Greece
  130. 130. Department of Urology, Ege University, Izmir, Turkey
  131. 131. Departmant of Medical Biology, Faculty of Medical, Yozgat Bozok University, Yozgat, Turkey
  132. 132. Department of Urology, Burjeel Hospital, Abu Dhabi, United Arab Emirates
  133. 133. Department of Urology, University Hospital of Souss Massa, Massa, Morocco
  134. 134. Unit of Reproductive Medicine, EmbryoART, Leto Maternity Hospital, Athens, Greece
  135. 135. Department of Urology, Peking University Third Hospital, Beijing, China

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


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. Copyright © 2023 Korean Society for Sexual Medicine and Andrology.
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