. 2024 Jan;42(1):202-215.

doi: 10.5534/wjmh.230076. Epub 2023 Aug 24.

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

Ashok Agarwal^{1

2}, Ala'a Farkouh¹, Ramadan Saleh^{1

3}, Taha Abo-Almagd Abdel-Meguid Hamoda^{1

4

5}, Gianmaria Salvio^{1

6}, Florence Boitrelle^{1

7

8}, Ahmed M Harraz^{1

9

10

11}, Ramy Abou Ghayda^{1

12}, Parviz Kavoussi^{1

13}, Murat Gül^{1

14}, Tuncay Toprak^{1

15}, Giorgio Ivan Russo^{1

16}, Damayanthi Durairajanayagam^{1

17}, Amarnath Rambhatla^{1

18}, Ponco Birowo^{1

19}, Rossella Cannarella^{1

20

21}, Nguyen Ho Vinh Phuoc^{1

22

23}, Armand Zini^{1

24}, Mohamed Arafa^{1

25

26

27}, Christine Wyns^{1

28}, Kelton Tremellen^{1

29}, Selçuk Sarıkaya^{1

30}, Sheena Lewis^{1

31}, Donald P Evenson^{1

32}, Edmund Ko^{1

33}, Aldo E Calogero^{1

10}, Fahmi Bahar^{1

34}, Marlon Martínez^{1

35}, Rafael F Ambar^{1

36

37}, Giovanni M Colpi^{1

38}, Mustafa Emre Bakircioglu^{1

39}, Ralf Henkel^{1

40

41}, Hussein Kandil^{1

42}, Ege Can Serefoglu^{1

43}, Abdullah Alfakhri^{1

44}, Akira Tsujimura^{1

45}, Alireza Kheradmand^{1

46}, Angelo Marino^{1

47}, Aram Adamyan^{1

48}, Birute Zilaitiene^{1

49}, Cevahir Ozer^{1

50}, Edoardo Pescatori^{1

51}, Paraskevi Vogiatzi^{1

52}, Gian Maria Busetto^{1

53}, Giancarlo Balercia^{1

6}, Haitham Elbardisi^{1

25

26

54}, Hamed Akhavizadegan^{1

55}, Hesamoddin Sajadi^{1

56}, Hisanori Taniguchi^{1

57}, Hyun Jun Park^{1

58

59}, Israel Maldonado Rosas^{1

60}, Mohamed Al-Marhoon^{1

61}, Mohammad Ali Sadighi Gilani^{1

56}, Naif Alhathal^{1

62}, Nguyen Quang^{1

63

64}, Germar-Michael Pinggera^{1

65}, Priyank Kothari^{1

66}, Sava Micic^{1

67}, Sheryl Homa^{1

68}, Tran Quang Tien Long^{1

69}, Wael Zohdy^{1

27}, Widi Atmoko^{1

19}, Wael Ibrahim^{1

70}, Marjan Sabbaghian^{1

56}, Saad Mohammed Abumelha^{1

71}, Eric Chung^{1

72}, Muhammet Rasit Ugur^{1

73}, Mehmet Serkan Ozkent^{1

74}, Osama Selim^{1

27}, Mahsa Darbandi^{1

75

76}, Shinichiro Fukuhara^{1

77}, Mounir Jamali^{1

78}, Jean de la Rosette^{1

79}, Shinnosuke Kuroda²¹, Ryan P Smith^{1

80}, Aykut Baser^{1

81}, Arif Kalkanli^{1

82}, Nicholas N Tadros^{1

83}, Kaan Aydos^{1

84}, Tiago Cesar Mierzwa^{1

85}, Kareim Khalafalla^{1

25

86

87}, Vineet Malhotra^{1

88}, Mohamad Moussa^{1

89

90}, Federica Finocchi^{1

6}, Rinaldo Indra Rachman^{1

19}, Carlo Giulioni^{1

6}, Tomer Avidor-Reiss^{1

91

92}, Oguzhan Kahraman^{1

51}, Gökhan Çeker⁹³, Cătălina Zenoaga-Barbăroșie^{1

94}, Trenton L Barrett^{1

95}, Mehmet Yilmaz^{1

96}, Ates Kadioglu^{1

97}, Sunil Jindal^{1

98}, Huda Omran^{1

99}, Kadir Bocu^{1

100}, Vilvapathy Senguttuvan Karthikeyan^{1

101}, Giorgio Franco^{1

102}, Jesús Fernando Solorzano^{1

60}, Ranjit B Vishwakarma^{1

103}, Eko Arianto^{1

104}, Nicolas Garrido^{1

105}, Divyanu Jain^{1

106}, Nazim Gherabi^{1

107}, Ioannis Sokolakis^{1

108}, Ayad Palani^{1

109}, Gokhan Calik^{1

79}, Deniz Kulaksiz^{1

110}, Vaida Simanaviciene^{1

111}, Mara Simopoulou^{1

112}, Nur Dokuzeylül Güngör^{1

113}, Gideon Blecher^{1

114}, Marco Falcone^{1

115}, Davor Jezek^{1

116}, Mirko Preto^{1

115}, Edouard Amar^{1

117}, Tan V Le^{1

22

23}, Sun Tae Ahn^{1

118}, Andri Rezano^{1

119}, Keerti Singh^{1

120}, Lucia Rocco^{1

121}, Missy Savira^{1

19}, Osvaldo Rajmil^{1

122}, Sara Darbandi^{1

75

76}, Emrullah Sogutdelen^{1

123}, Luca Boeri^{1

124}, Guadalupe Hernández^{1

125}, Lukman Hakim^{1

126}, Yoshiharu Morimoto^{1

127}, Andrian Japari^{1

128}, Nikolaos Sofikitis^{1

129}, Baris Altay^{1

130}, Asli Metin Mahmutoglu^{1

131}, Manaf Al Hashimi^{1

132}, Imad Ziouziou^{1

133}, Christina Anagnostopoulou^{1

134}, Haocheng Lin^{1

135}, Rupin Shah^{1

103}

Affiliations

¹ Global Andrology Forum, Moreland Hills, OH, USA.
² Cleveland Clinic, Cleveland, OH, USA. agarwaa32099@outlook.com.
³ Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt.
⁴ Department of Urology, King Abdulaziz University, Jeddah, Saudi Arabia.
⁵ Department of Urology, Faculty of Medicine, Minia University, Minia, Egypt.
⁶ Department of Endocrinology, Polytechnic University of Marche, Ancona, Italy.
⁷ Reproductive Biology, Fertility Preservation, Andrology, CECOS, Poissy Hospital, Poissy, France.
⁸ Department of Biology, Reproduction, Epigenetics, Environment, and Development, Paris Saclay University, UVSQ, INRAE, BREED, Jouy-en-Josas, France.
⁹ Urology and Nephrology Center, Mansoura, Egypt.
¹⁰ Department of Surgery, Urology Unit, Farwaniya Hospital, Farwaniya, Kuwait.
¹¹ Department of Urology, Sabah Al Ahmad Urology Center, Kuwait City, Kuwait.
¹² Urology Institute, University Hospitals, Case Western Reserve University, Cleveland, OH, USA.
¹³ Department of Reproductive Urology, Austin Fertility & Reproductive Medicine/Westlake IVF, Austin, TX, USA.
¹⁴ Department of Urology, SelÃ§uk University School of Medicine, Konya, Turkey.
¹⁵ Department of Urology, Fatih Sultan Mehmet Training and Research Hospital, University of Health Sciences, Istanbul, Turkey.
¹⁶ Urology Section, University of Catania, Catania, Italy.
¹⁷ Department of Physiology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia.
¹⁸ Department of Urology, Henry Ford Health System, Vattikuti Urology Institute, Detroit, MI, USA.
¹⁹ Department of Urology, Dr. Cipto Mangunkusumo General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
²⁰ Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
²¹ Department of Urology, Glickman Urological & Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
²² Department of Andrology, Binh Dan Hospital, Ho Chi Minh City, Vietnam.
²³ Department of Urology and Andrology, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam.
²⁴ Department of Surgery, McGill University, Montreal, QC, Canada.
²⁵ Department of Urology, Hamad Medical Corporation, Doha, Qatar.
²⁶ Department of Urology, Weill Cornell Medical-Qatar, Doha, Qatar.
²⁷ Department of Andrology and STDs, Cairo University, Cairo, Egypt.
²⁸ Department of Gynaecology-Andrology, Cliniques Universitaires Saint-Luc, Universitat Catholique de Louvain, Brussels, Belgium.
²⁹ Department of Obstetrics Gynaecology and Reproductive Medicine, Flinders University, Bedford Park, Australia.
³⁰ Department of Urology, Galhane Research and Training Hospital, University of Health Sciences, Ankara, Turkey.
³¹ Examen Lab Ltd., Northern Ireland, UK.
³² SCSA Diagnostics, Brookings, SD, USA.
³³ Department of Urology, Loma Linda University Health, Loma Linda, CA, USA.
³⁴ Andrology Section, Siloam Sriwijaya Hospital, Palembang, Indonesia.
³⁵ Section of Urology, Department of Surgery, University of Santo Tomas Hospital, Manila, Philippines.
³⁶ Department of Urology, Centro Universitario em Saude do ABC, Santo Andre, Brazil.
³⁷ Andrology Group at Ideia Fertil Institute of Human Reproduction, Santo Andre, Brazil.
³⁸ Andrology and IVF Center, Next Fertility Procrea, Lugano, Switzerland.
³⁹ SENSART Clinic, Urology, Fulya, Istanbul, Turkey.
⁴⁰ Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
⁴¹ Department of Medical Bioscience, University of the Western Cape, Bellville, South Africa.
⁴² Fakih IVF Fertility Center, Abu Dhabi, UAE.
⁴³ Department of Urology, Biruni University School of Medicine, Istanbul, Turkey.
⁴⁴ Department of Urology, King Fahad Medical City, Riyadh, Saudi Arabia.
⁴⁵ Department of Urology, Juntendo University Urayasu Hospital, Chiba, Japan.
⁴⁶ Department of Urology, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
⁴⁷ Reproductive Medicine Unit, ANDROS Day Surgery Clinic, Reproductive Medicine Unit, Palermo, Italy.
⁴⁸ IVF Department, Astghik Medical Center, Yerevan, Armenia.
⁴⁹ Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
⁵⁰ Department of Urology, Faculty of Medicine, Baskent University, Ankara, Turkey.
⁵¹ Andrology and Reproductive Medicine Unit, Gynepro Medical, Bologna, Italy.
⁵² Andromed Health & Reproduction, Fertility & Reproductive Health Diagnostic Center, Athens, Greece.
⁵³ Department of Urology and Renal Transplantation, University of Foggia, Policlinico Riuniti, Foggia, Italy.
⁵⁴ Department of Urology, College of Medicine, Qatar University, Doha, Qatar.
⁵⁵ Department of Urology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.
⁵⁶ Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
⁵⁷ Department of Urology and Andrology, Kansai Medical University, Hirakata, Osaka, Japan.
⁵⁸ Department of Urology, Pusan National University School of Medicine, Busan, Korea.
⁵⁹ Medical Research Institute of Pusan National University Hospital, Busan, Korea.
⁶⁰ IVF Laboratory, CITMER Reproductive Medicine, Mexico City, Mexico.
⁶¹ Division of Urology, Department of Surgery, Sultan Qaboos University, Muscat, Sultanate of Oman.
⁶² King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
⁶³ Center for Andrology and Sexual Medicine, Viet Duc University Hospital, Hanoi, Vietnam.
⁶⁴ Department of Urology, Andrology and Sexual Medicine, University of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam.
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 Department of Andrology, Uromedica Polyclinic, Belgrade, Serbia.
⁶⁸ Department of Biosciences, University of Kent, Canterbury, UK.
⁶⁹ Department of Obstetrics and Gynecology, Hanoi Obstetric and Gynecology Hospital, Hanoi, Vietnam.
⁷⁰ Department of Surgery, School of Medicine, Taylor's University, Subang Jaya, Selangor, Malaysia.
⁷¹ Division of Urology, Department of Surgery, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
⁷² Department of Urology, University of Queensland, Princess Alexandra Hospital, Brisbane QLD, Australia.
⁷³ IVF Michigan, Bloomfield Hills, MI, USA.
⁷⁴ Department of Urology, Konya City Hospital, Konya, Turkey.
⁷⁵ Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran.
⁷⁶ Gene Therapy and Regenerative Medicine Research Center, Hope Generation Foundation, Tehran, Iran.
⁷⁷ Department of Urology, Graduate School of Medicine, Osaka University, Osaka, Japan.
⁷⁸ Department of Urology, Mohammed V Military Hospital, Rabat, Morocco.
⁷⁹ Department of Urology, Istanbul Medipol University, Istanbul, Turkey.
⁸⁰ Department of Urology, University of Virginia School of Medicine, Charlottesville, VA, USA.
⁸¹ Department of Urology, Bandirma Onyedi Eylül University, Balikesir, Turkey.
⁸² Department of Urology, Taksim Education and Research Hospital, Istanbul, Turkey.
⁸³ Division of Urology, Southern Illinois University, Springfield, IL, USA.
⁸⁴ Department of Urology, Ankara University, Ankara, Turkey.
⁸⁵ Androlab, Fertility Clinic, Curitiba, PR, Brazil.
⁸⁶ Department of Urology, University of Texas McGovern Medical School, Houston, TX, USA.
⁸⁷ Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.
⁸⁸ Department of Urology, SCM Clinic and Hospital, New Delhi, India.
⁸⁹ Department of Urology, Lebanese University, Beirut, Lebanon.
⁹⁰ Department of Urology, Al Zahraa Hospital, UMC, Lebanon.
⁹¹ Department of Biological Sciences, University of Toledo, Toledo, OH, USA.
⁹² Department of Urology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH, USA.
⁹³ Department of Urology, Başakşehir Çam and Sakura City Hospital, Istanbul, Turkey.
⁹⁴ Department of Genetics, Faculty of Biology, University of Bucharest, Bucharest, Romania.
⁹⁵ Department of Urology, Perth Urology Clinic, Murdoch, WA, Australia.
⁹⁶ Asklepios Klinik Triberg, Urology, Triberg, Germany.
⁹⁷ Section of Andrology, Department of Urology, Istanbul University, Istanbul, Turkey.
⁹⁸ Department of Andrology and Reproductive Medicine, Jindal Hospital, Meerut, India.
⁹⁹ Molecular Genetics Department, Pulse Health Training Center, Manama, Bahrain.
¹⁰⁰ Department of Urology, Silopi State Hospital, Sirnak, Turkey.
¹⁰¹ Andrology Unit, Department of Urology, Apollo Hospitals, Greams Road, Chennai, India.
¹⁰² Department of Urology, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
¹⁰³ Division of Andrology, Department of Urology, Lilavati Hospital and Research Centre, Mumbai, India.
¹⁰⁴ Department of Surgery, Prof. Dr. R.D. Kandou Central General Hospital, Manado, Indonesia.
¹⁰⁵ IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain.
¹⁰⁶ Department of Obstetrics and Gynecology, Jaipur Golden Hospital, New Delhi, India.
¹⁰⁷ Department of Medicine, University of Algiers 1, Algiers, Algeria.
¹⁰⁸ 2nd Department of Urology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
¹⁰⁹ Research Centre, University of Garmian, Kalar, Iraq.
¹¹⁰ Department of Obstetrics and Gynecology, University of Health Sciences Kanuni Training and Research Hospital, Trabzon, Turkey.
¹¹¹ Fertility Centre, Northway Medical Centre, Vilnius, Lithuania.
¹¹² Department of Physiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
¹¹³ Department of Obstetrics and Gynecology, Reproductive Endocrinology and IVF Unit, School of Medicine, Bahcesehir University, Istanbul, Turkey.
¹¹⁴ Department of Surgery, School of Clinical Sciences, Monash University, Melbourne, Australia.
¹¹⁵ Department of Urology, Molinette Hospital, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, University of Turin, Torino, Italy.
¹¹⁶ Reproductive Tissue Bank, Department for Transfusion Medicine and Transplantation Biology, University Hospital Zagreb, Zagreb, Croatia.
¹¹⁷ American Hospital of Paris, Paris, France.
¹¹⁸ Department of Urology, Korea University College of Medicine, Seoul, Korea.
¹¹⁹ Department of Biomedical Sciences, Division of Cell Biology, Faculty of Medicine, Universitas Padjadjaran, Sumedang, West Java, Indonesia.
¹²⁰ Department of Preclinical and Health Sciences, Faculty of Medical Sciences, The University of the West Indies, Cave Hill Campus, St Michael, Barbados, Italy.
¹²¹ Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, Caserta, Italy.
¹²² Department of Andrology, Fundacio Puigvert, Barcelona, Spain.
¹²³ Department of Urology, Bolu Abant Izzet Baysal University, Bolu, Turkey.
¹²⁴ Department of Urology, IRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
¹²⁵ IVF Department, CITMER Reproductive Medicine, Puebla, Mexico.
¹²⁶ Department of Urology, Faculty of Medicine, Universitas Airlangga Teaching Hospital, Surabaya, Indonesia.
¹²⁷ Department of Urology, HORAC Grand Front Osaka Clinic, Osaka, Japan.
¹²⁸ Department of Urology, Fertility Clinic, Telogorejo Hospital, Central Java, Indonesia.
¹²⁹ Department of Urology, Ioannina University School of Medicine, Ioannina, Greece.
¹³⁰ Department of Urology, Ege University, Izmir, Turkey.
¹³¹ Departmant of Medical Biology, Faculty of Medical, Yozgat Bozok University, Yozgat, Turkey.
¹³² Department of Urology, Burjeel Hospital, Abu Dhabi, UAE.
¹³³ Department of Urology, University Hospital of Souss Massa, Massa, Morocco.
¹³⁴ Unit of Reproductive Medicine, EmbryoART, Leto Maternity Hospital, Athens, Greece.
¹³⁵ Department of Urology, Peking University Third Hospital, Beijing, China.

PMID: 37635341
PMCID: PMC10782128
DOI: 10.5534/wjmh.230076

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

Ashok Agarwal et al. World J Mens Health. 2024 Jan.

. 2024 Jan;42(1):202-215.

doi: 10.5534/wjmh.230076. Epub 2023 Aug 24.

Authors

Affiliations

¹ Global Andrology Forum, Moreland Hills, OH, USA.
² Cleveland Clinic, Cleveland, OH, USA. agarwaa32099@outlook.com.
³ Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt.
⁴ Department of Urology, King Abdulaziz University, Jeddah, Saudi Arabia.
⁵ Department of Urology, Faculty of Medicine, Minia University, Minia, Egypt.
⁶ Department of Endocrinology, Polytechnic University of Marche, Ancona, Italy.
⁷ Reproductive Biology, Fertility Preservation, Andrology, CECOS, Poissy Hospital, Poissy, France.
⁸ Department of Biology, Reproduction, Epigenetics, Environment, and Development, Paris Saclay University, UVSQ, INRAE, BREED, Jouy-en-Josas, France.
⁹ Urology and Nephrology Center, Mansoura, Egypt.
¹⁰ Department of Surgery, Urology Unit, Farwaniya Hospital, Farwaniya, Kuwait.
¹¹ Department of Urology, Sabah Al Ahmad Urology Center, Kuwait City, Kuwait.
¹² Urology Institute, University Hospitals, Case Western Reserve University, Cleveland, OH, USA.
¹³ Department of Reproductive Urology, Austin Fertility & Reproductive Medicine/Westlake IVF, Austin, TX, USA.
¹⁴ Department of Urology, SelÃ§uk University School of Medicine, Konya, Turkey.
¹⁵ Department of Urology, Fatih Sultan Mehmet Training and Research Hospital, University of Health Sciences, Istanbul, Turkey.
¹⁶ Urology Section, University of Catania, Catania, Italy.
¹⁷ Department of Physiology, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Selangor, Malaysia.
¹⁸ Department of Urology, Henry Ford Health System, Vattikuti Urology Institute, Detroit, MI, USA.
¹⁹ Department of Urology, Dr. Cipto Mangunkusumo General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
²⁰ Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
²¹ Department of Urology, Glickman Urological & Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
²² Department of Andrology, Binh Dan Hospital, Ho Chi Minh City, Vietnam.
²³ Department of Urology and Andrology, Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam.
²⁴ Department of Surgery, McGill University, Montreal, QC, Canada.
²⁵ Department of Urology, Hamad Medical Corporation, Doha, Qatar.
²⁶ Department of Urology, Weill Cornell Medical-Qatar, Doha, Qatar.
²⁷ Department of Andrology and STDs, Cairo University, Cairo, Egypt.
²⁸ Department of Gynaecology-Andrology, Cliniques Universitaires Saint-Luc, Universitat Catholique de Louvain, Brussels, Belgium.
²⁹ Department of Obstetrics Gynaecology and Reproductive Medicine, Flinders University, Bedford Park, Australia.
³⁰ Department of Urology, Galhane Research and Training Hospital, University of Health Sciences, Ankara, Turkey.
³¹ Examen Lab Ltd., Northern Ireland, UK.
³² SCSA Diagnostics, Brookings, SD, USA.
³³ Department of Urology, Loma Linda University Health, Loma Linda, CA, USA.
³⁴ Andrology Section, Siloam Sriwijaya Hospital, Palembang, Indonesia.
³⁵ Section of Urology, Department of Surgery, University of Santo Tomas Hospital, Manila, Philippines.
³⁶ Department of Urology, Centro Universitario em Saude do ABC, Santo Andre, Brazil.
³⁷ Andrology Group at Ideia Fertil Institute of Human Reproduction, Santo Andre, Brazil.
³⁸ Andrology and IVF Center, Next Fertility Procrea, Lugano, Switzerland.
³⁹ SENSART Clinic, Urology, Fulya, Istanbul, Turkey.
⁴⁰ Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
⁴¹ Department of Medical Bioscience, University of the Western Cape, Bellville, South Africa.
⁴² Fakih IVF Fertility Center, Abu Dhabi, UAE.
⁴³ Department of Urology, Biruni University School of Medicine, Istanbul, Turkey.
⁴⁴ Department of Urology, King Fahad Medical City, Riyadh, Saudi Arabia.
⁴⁵ Department of Urology, Juntendo University Urayasu Hospital, Chiba, Japan.
⁴⁶ Department of Urology, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
⁴⁷ Reproductive Medicine Unit, ANDROS Day Surgery Clinic, Reproductive Medicine Unit, Palermo, Italy.
⁴⁸ IVF Department, Astghik Medical Center, Yerevan, Armenia.
⁴⁹ Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
⁵⁰ Department of Urology, Faculty of Medicine, Baskent University, Ankara, Turkey.
⁵¹ Andrology and Reproductive Medicine Unit, Gynepro Medical, Bologna, Italy.
⁵² Andromed Health & Reproduction, Fertility & Reproductive Health Diagnostic Center, Athens, Greece.
⁵³ Department of Urology and Renal Transplantation, University of Foggia, Policlinico Riuniti, Foggia, Italy.
⁵⁴ Department of Urology, College of Medicine, Qatar University, Doha, Qatar.
⁵⁵ Department of Urology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.
⁵⁶ Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
⁵⁷ Department of Urology and Andrology, Kansai Medical University, Hirakata, Osaka, Japan.
⁵⁸ Department of Urology, Pusan National University School of Medicine, Busan, Korea.
⁵⁹ Medical Research Institute of Pusan National University Hospital, Busan, Korea.
⁶⁰ IVF Laboratory, CITMER Reproductive Medicine, Mexico City, Mexico.
⁶¹ Division of Urology, Department of Surgery, Sultan Qaboos University, Muscat, Sultanate of Oman.
⁶² King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
⁶³ Center for Andrology and Sexual Medicine, Viet Duc University Hospital, Hanoi, Vietnam.
⁶⁴ Department of Urology, Andrology and Sexual Medicine, University of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam.
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 Department of Andrology, Uromedica Polyclinic, Belgrade, Serbia.
⁶⁸ Department of Biosciences, University of Kent, Canterbury, UK.
⁶⁹ Department of Obstetrics and Gynecology, Hanoi Obstetric and Gynecology Hospital, Hanoi, Vietnam.
⁷⁰ Department of Surgery, School of Medicine, Taylor's University, Subang Jaya, Selangor, Malaysia.
⁷¹ Division of Urology, Department of Surgery, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
⁷² Department of Urology, University of Queensland, Princess Alexandra Hospital, Brisbane QLD, Australia.
⁷³ IVF Michigan, Bloomfield Hills, MI, USA.
⁷⁴ Department of Urology, Konya City Hospital, Konya, Turkey.
⁷⁵ Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran.
⁷⁶ Gene Therapy and Regenerative Medicine Research Center, Hope Generation Foundation, Tehran, Iran.
⁷⁷ Department of Urology, Graduate School of Medicine, Osaka University, Osaka, Japan.
⁷⁸ Department of Urology, Mohammed V Military Hospital, Rabat, Morocco.
⁷⁹ Department of Urology, Istanbul Medipol University, Istanbul, Turkey.
⁸⁰ Department of Urology, University of Virginia School of Medicine, Charlottesville, VA, USA.
⁸¹ Department of Urology, Bandirma Onyedi Eylül University, Balikesir, Turkey.
⁸² Department of Urology, Taksim Education and Research Hospital, Istanbul, Turkey.
⁸³ Division of Urology, Southern Illinois University, Springfield, IL, USA.
⁸⁴ Department of Urology, Ankara University, Ankara, Turkey.
⁸⁵ Androlab, Fertility Clinic, Curitiba, PR, Brazil.
⁸⁶ Department of Urology, University of Texas McGovern Medical School, Houston, TX, USA.
⁸⁷ Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.
⁸⁸ Department of Urology, SCM Clinic and Hospital, New Delhi, India.
⁸⁹ Department of Urology, Lebanese University, Beirut, Lebanon.
⁹⁰ Department of Urology, Al Zahraa Hospital, UMC, Lebanon.
⁹¹ Department of Biological Sciences, University of Toledo, Toledo, OH, USA.
⁹² Department of Urology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH, USA.
⁹³ Department of Urology, Başakşehir Çam and Sakura City Hospital, Istanbul, Turkey.
⁹⁴ Department of Genetics, Faculty of Biology, University of Bucharest, Bucharest, Romania.
⁹⁵ Department of Urology, Perth Urology Clinic, Murdoch, WA, Australia.
⁹⁶ Asklepios Klinik Triberg, Urology, Triberg, Germany.
⁹⁷ Section of Andrology, Department of Urology, Istanbul University, Istanbul, Turkey.
⁹⁸ Department of Andrology and Reproductive Medicine, Jindal Hospital, Meerut, India.
⁹⁹ Molecular Genetics Department, Pulse Health Training Center, Manama, Bahrain.
¹⁰⁰ Department of Urology, Silopi State Hospital, Sirnak, Turkey.
¹⁰¹ Andrology Unit, Department of Urology, Apollo Hospitals, Greams Road, Chennai, India.
¹⁰² Department of Urology, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
¹⁰³ Division of Andrology, Department of Urology, Lilavati Hospital and Research Centre, Mumbai, India.
¹⁰⁴ Department of Surgery, Prof. Dr. R.D. Kandou Central General Hospital, Manado, Indonesia.
¹⁰⁵ IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain.
¹⁰⁶ Department of Obstetrics and Gynecology, Jaipur Golden Hospital, New Delhi, India.
¹⁰⁷ Department of Medicine, University of Algiers 1, Algiers, Algeria.
¹⁰⁸ 2nd Department of Urology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
¹⁰⁹ Research Centre, University of Garmian, Kalar, Iraq.
¹¹⁰ Department of Obstetrics and Gynecology, University of Health Sciences Kanuni Training and Research Hospital, Trabzon, Turkey.
¹¹¹ Fertility Centre, Northway Medical Centre, Vilnius, Lithuania.
¹¹² Department of Physiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
¹¹³ Department of Obstetrics and Gynecology, Reproductive Endocrinology and IVF Unit, School of Medicine, Bahcesehir University, Istanbul, Turkey.
¹¹⁴ Department of Surgery, School of Clinical Sciences, Monash University, Melbourne, Australia.
¹¹⁵ Department of Urology, Molinette Hospital, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, University of Turin, Torino, Italy.
¹¹⁶ Reproductive Tissue Bank, Department for Transfusion Medicine and Transplantation Biology, University Hospital Zagreb, Zagreb, Croatia.
¹¹⁷ American Hospital of Paris, Paris, France.
¹¹⁸ Department of Urology, Korea University College of Medicine, Seoul, Korea.
¹¹⁹ Department of Biomedical Sciences, Division of Cell Biology, Faculty of Medicine, Universitas Padjadjaran, Sumedang, West Java, Indonesia.
¹²⁰ Department of Preclinical and Health Sciences, Faculty of Medical Sciences, The University of the West Indies, Cave Hill Campus, St Michael, Barbados, Italy.
¹²¹ Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, Caserta, Italy.
¹²² Department of Andrology, Fundacio Puigvert, Barcelona, Spain.
¹²³ Department of Urology, Bolu Abant Izzet Baysal University, Bolu, Turkey.
¹²⁴ Department of Urology, IRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
¹²⁵ IVF Department, CITMER Reproductive Medicine, Puebla, Mexico.
¹²⁶ Department of Urology, Faculty of Medicine, Universitas Airlangga Teaching Hospital, Surabaya, Indonesia.
¹²⁷ Department of Urology, HORAC Grand Front Osaka Clinic, Osaka, Japan.
¹²⁸ Department of Urology, Fertility Clinic, Telogorejo Hospital, Central Java, Indonesia.
¹²⁹ Department of Urology, Ioannina University School of Medicine, Ioannina, Greece.
¹³⁰ Department of Urology, Ege University, Izmir, Turkey.
¹³¹ Departmant of Medical Biology, Faculty of Medical, Yozgat Bozok University, Yozgat, Turkey.
¹³² Department of Urology, Burjeel Hospital, Abu Dhabi, UAE.
¹³³ Department of Urology, University Hospital of Souss Massa, Massa, Morocco.
¹³⁴ Unit of Reproductive Medicine, EmbryoART, Leto Maternity Hospital, Athens, Greece.
¹³⁵ Department of Urology, Peking University Third Hospital, Beijing, China.

PMID: 37635341
PMCID: PMC10782128
DOI: 10.5534/wjmh.230076

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.

Keywords: DNA fragmentation; Delphi method; Diagnostic test; Infertility, male; Survey.

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Conflict of interest statement

The authors have nothing to disclose.

Figures

Fig. 1. Complete survey methodology. The complete survey consisted of 64 questions on SDF clinical practices divided into five sections: demographics, indications for SDF testing, technical aspects of SDF testing, management of elevated SDF, and barriers in incorporating SDF into clinical practice. A total of 18 recommendations were made as follows: seven for indications for SDF testing, ten for management of infertile men with elevated SDF, and one for technical aspects of SDF testing. Passing criteria for the Delphi method was set at >80% scoring the recommendation ≥7 in agreement. SDF: sperm DNA fragmentation, GAF: global andrology forum.

**Fig. 2. SDF assays ordered by the respondents. SDF: sperm DNA fragmentation.**

Fig. 3. Factors determining the choice of SDF assay. Respondents were allowed to select more than one answer. The percentage for each answer was calculated by dividing the number of respondents who had selected it by the total number of respondents who had answered this question (n=420). SDF: sperm DNA fragmentation.

**Fig. 4. Thresholds used for interpretation by the respondents. SDF: sperm DNA fragmentation.**

**Fig. 5. Recommended abstinence period before SDF testing. SDF: sperm DNA fragmentation.**

Fig. 6. Factors that limit the ability of responding practitioners to order SDF testing. Respondents were allowed to select more than one answer. The percentage for each answer was calculated by dividing the number of respondents who had selected it by the total number of respondents who had answered this question (n=394). SDF: sperm DNA fragmentation.

Fig. 7. Opinion on SDF evaluation for infertile men. The percentage for each answer was calculated by dividing the number of respondents who had selected it by the total number of respondents who had answered this question (n=396). SDF: sperm DNA fragmentation, ART: assisted reproductive technology, RPL: recurrent pregnancy loss, IMI: idiopathic male infertility, UMI: unexplained male infertility.

Fig. 8. Reasons for delay in incorporating SDF into clinical practice. The percentage for each answer was calculated by dividing the number of respondents who had selected it by the total number of respondents who had answered this question (n=394). SDF: sperm DNA fragmentation.

Fig. 9. Reasons why SDF should be incorporated more into clinical practice. The percentage for each answer was calculated by dividing the number of respondents who had selected it by the total number of respondents who had answered this question (n=393). SDF: sperm DNA fragmentation, ART: assisted reproductive technology.

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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

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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

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