Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations (2025)

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.

Original language	English
Pages (from-to)	202-215
Number of pages	14
Journal	The World Journal of Men's Health
Volume	41
Issue number	1
DOIs	https://doi.org/10.5534/wjmh.230076
Publication status	Published - Jan 2024

Keywords

Delphi method
Diagnostic test
DNA fragmentation
Infertility
male
Survey

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.5534/wjmh.230076

Cite this

APA
Author
BIBTEX
Harvard
Standard
RIS
Vancouver

Agarwal, A., Farkouh, A., Saleh, R., Hamoda, T. A. A. A. M., Salvio, G., Boitrelle, F., Harraz, A. M., Ghayda, R. A., Kavoussi, P., Gül, M., Toprak, T., Russo, G. I., Durairajanayagam, D., Rambhatla, A., Birowo, P., Cannarella, R., Phuoc, N. H. V., Zini, A., Arafa, M., ... Shah, R. (2024). Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations. The World Journal of Men's Health, 41(1), 202-215. https://doi.org/10.5534/wjmh.230076

Agarwal, Ashok ; Farkouh, Ala’a ; Saleh, Ramadan et al. / Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility : A Global Survey, Current Guidelines, and Expert Recommendations. In: The World Journal of Men's Health. 2024 ; Vol. 41, No. 1. pp. 202-215.

@article{c7649e07842f4458bad59fab6b9f9d0c,

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

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 = "Delphi method, Diagnostic test, DNA fragmentation, Infertility, male, Survey",

author = "Ashok Agarwal and Ala{\textquoteright}a Farkouh and Ramadan Saleh and Hamoda, {Taha Abo Almagd Abdel Meguid} and Gianmaria Salvio and Florence Boitrelle and Harraz, {Ahmed M.} and Ghayda, {Ramy Abou} and Parviz Kavoussi and Murat G{\"u}l and Tuncay Toprak and Russo, {Giorgio Ivan} and Damayanthi Durairajanayagam and Amarnath Rambhatla and Ponco Birowo and Rossella Cannarella and Phuoc, {Nguyen Ho Vinh} and Armand Zini and Mohamed Arafa and Christine Wyns and Kelton Tremellen and Sel{\c c}uk Sarıkaya and Sheena Lewis and Evenson, {Donald P.} and Edmund Ko and Calogero, {Aldo E.} and Fahmi Bahar and Marlon Mart{\'i}nez and Ambar, {Rafael F.} and Colpi, {Giovanni M.} and Bakircioglu, {Mustafa Emre} and Ralf Henkel and Hussein Kandil and Serefoglu, {Ege Can} and Abdullah Alfakhri and Akira Tsujimura and Alireza Kheradmand and Angelo Marino and Aram Adamyan and Birute Zilaitiene and Cevahir Ozer and Edoardo Pescatori and Paraskevi Vogiatzi and Busetto, {Gian Maria} and Giancarlo Balercia and Haitham Elbardisi and Hamed Akhavizadegan and Hesamoddin Sajadi and Hisanori Taniguchi and Park, {Hyun Jun} and Rosas, {Israel Maldonado} and Mohamed Al-Marhoon and Gilani, {Mohammad Ali Sadighi} and Naif Alhathal and Nguyen Quang and Pinggera, {Germar Michael} and Priyank Kothari and Sava Micic and Sheryl Homa and Long, {Tran Quang Tien} and Wael Zohdy and Widi Atmoko and Wael Ibrahim and Marjan Sabbaghian and Abumelha, {Saad Mohammed} and Eric Chung and Ugur, {Muhammet Rasit} and Ozkent, {Mehmet Serkan} and Osama Selim and Mahsa Darbandi and Shinichiro Fukuhara and Mounir Jamali and {de la Rosette}, Jean and Shinnosuke Kuroda and Smith, {Ryan P.} and Aykut Baser and Arif Kalkanli and Tadros, {Nicholas N.} and Kaan Aydos and Mierzwa, {Tiago Cesar} and Kareim Khalafalla and Vineet Malhotra and Mohamad Moussa and Federica Finocchi and Rachman, {Rinaldo Indra} and Carlo Giulioni and Tomer Avidor-Reiss and Oguzhan Kahraman and G{\"o}khan {\c C}eker and C{\u a}t{\u a}lina Zenoaga-Barb{\u a}roșie and Barrett, {Trenton L.} and Mehmet Yilmaz and Ates Kadioglu and Sunil Jindal and Huda Omran and Kadir Bocu and Karthikeyan, {Vilvapathy Senguttuvan} and Giorgio Franco and Solorzano, {Jes{\'u}s Fernando} and Vishwakarma, {Ranjit B.} and Eko Arianto and Nicolas Garrido and Divyanu Jain and Nazim Gherabi and Ioannis Sokolakis and Ayad Palani and Gokhan Calik and Deniz Kulaksiz and Vaida Simanaviciene and Mara Simopoulou and G{\"u}ng{\"o}r, {Nur Dokuzeyl{\"u}l} and Gideon Blecher and Marco Falcone and Davor Jezek and Mirko Preto and Edouard Amar and Le, {Tan V.} and Ahn, {Sun Tae} and Andri Rezano and Keerti Singh and Lucia Rocco and Missy Savira and Osvaldo Rajmil and Sara Darbandi and Emrullah Sogutdelen and Luca Boeri and Guadalupe Hern{\'a}ndez and Lukman Hakim and Yoshiharu Morimoto and Andrian Japari and Nikolaos Sofikitis and Baris Altay and Mahmutoglu, {Asli Metin} and {Al Hashimi}, Manaf and Imad Ziouziou and Christina Anagnostopoulou and Haocheng Lin and Rupin Shah",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 Korean Society for Sexual Medicine and Andrology.",

year = "2024",

month = jan,

doi = "10.5534/wjmh.230076",

language = "English",

volume = "41",

pages = "202--215",

journal = "The World Journal of Men's Health",

issn = "2287-4208",

publisher = "Korean Society for Sexual Medicine and Andrology",

number = "1",

}

Agarwal, A, Farkouh, A, Saleh, R, Hamoda, TAAAM, Salvio, G, Boitrelle, F, Harraz, AM, Ghayda, RA, Kavoussi, P, Gül, M, Toprak, T, Russo, GI, Durairajanayagam, D, Rambhatla, A, Birowo, P, Cannarella, R, Phuoc, NHV, Zini, A, Arafa, M, Wyns, C, Tremellen, K, Sarıkaya, S, Lewis, S, Evenson, DP, Ko, E, Calogero, AE, Bahar, F, Martínez, M, Ambar, RF, Colpi, GM, Bakircioglu, ME, Henkel, R, Kandil, H, Serefoglu, EC, Alfakhri, A, Tsujimura, A, Kheradmand, A, Marino, A, Adamyan, A, Zilaitiene, B, Ozer, C, Pescatori, E, Vogiatzi, P, Busetto, GM, Balercia, G, Elbardisi, H, Akhavizadegan, H, Sajadi, H, Taniguchi, H, Park, HJ, Rosas, IM, Al-Marhoon, M, Gilani, MAS, Alhathal, N, Quang, N, Pinggera, GM, Kothari, P, Micic, S, Homa, S, Long, TQT, Zohdy, W, Atmoko, W, Ibrahim, W, Sabbaghian, M, Abumelha, SM, Chung, E, Ugur, MR, Ozkent, MS, Selim, O, Darbandi, M, Fukuhara, S, Jamali, M, de la Rosette, J, Kuroda, S, Smith, RP, Baser, A, Kalkanli, A, Tadros, NN, Aydos, K, Mierzwa, TC, Khalafalla, K, Malhotra, V, Moussa, M, Finocchi, F, Rachman, RI, Giulioni, C, Avidor-Reiss, T, Kahraman, O, Çeker, G, Zenoaga-Barbăroșie, C, Barrett, TL, Yilmaz, M, Kadioglu, A, Jindal, S, Omran, H, Bocu, K, Karthikeyan, VS, Franco, G, Solorzano, JF, Vishwakarma, RB, Arianto, E, Garrido, N, Jain, D, Gherabi, N, Sokolakis, I, Palani, A, Calik, G, Kulaksiz, D, Simanaviciene, V, Simopoulou, M, Güngör, ND, Blecher, G, Falcone, M, Jezek, D, Preto, M, Amar, E, Le, TV, Ahn, ST, Rezano, A, Singh, K, Rocco, L, Savira, M, Rajmil, O, Darbandi, S, Sogutdelen, E, Boeri, L, Hernández, G, Hakim, L, Morimoto, Y, Japari, A, Sofikitis, N, Altay, B, Mahmutoglu, AM, Al Hashimi, M, Ziouziou, I, Anagnostopoulou, C, Lin, H & Shah, R 2024, 'Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations', The World Journal of Men's Health, vol. 41, no. 1, pp. 202-215. https://doi.org/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. / Agarwal, Ashok; Farkouh, Ala’a; Saleh, Ramadan et al.
In: The World Journal of Men's Health, Vol. 41, No. 1, 01.2024, p. 202-215.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility

AU - Quang, Nguyen

AU - Pinggera, Germar Michael

AU - Kothari, Priyank

AU - Micic, Sava

AU - Homa, Sheryl

AU - Long, Tran Quang Tien

AU - Zohdy, Wael

AU - Atmoko, Widi

AU - Ibrahim, Wael

AU - Sabbaghian, Marjan

AU - Abumelha, Saad Mohammed

AU - Chung, Eric

AU - Ugur, Muhammet Rasit

AU - Ozkent, Mehmet Serkan

AU - Selim, Osama

AU - Darbandi, Mahsa

AU - Fukuhara, Shinichiro

AU - Jamali, Mounir

AU - de la Rosette, Jean

AU - Kuroda, Shinnosuke

AU - Smith, Ryan P.

AU - Baser, Aykut

AU - Kalkanli, Arif

AU - Tadros, Nicholas N.

AU - Aydos, Kaan

AU - Mierzwa, Tiago Cesar

AU - Khalafalla, Kareim

AU - Malhotra, Vineet

AU - Moussa, Mohamad

AU - Finocchi, Federica

AU - Rachman, Rinaldo Indra

AU - Giulioni, Carlo

AU - Avidor-Reiss, Tomer

AU - Kahraman, Oguzhan

AU - Çeker, Gökhan

AU - Zenoaga-Barbăroșie, Cătălina

AU - Barrett, Trenton L.

AU - Yilmaz, Mehmet

AU - Kadioglu, Ates

AU - Jindal, Sunil

AU - Omran, Huda

AU - Bocu, Kadir

AU - Karthikeyan, Vilvapathy Senguttuvan

AU - Franco, Giorgio

AU - Solorzano, Jesús Fernando

AU - Vishwakarma, Ranjit B.

AU - Arianto, Eko

AU - Garrido, Nicolas

AU - Jain, Divyanu

AU - Gherabi, Nazim

AU - Sokolakis, Ioannis

AU - Palani, Ayad

AU - Calik, Gokhan

AU - Kulaksiz, Deniz

AU - Simanaviciene, Vaida

AU - Simopoulou, Mara

AU - Güngör, Nur Dokuzeylül

AU - Blecher, Gideon

AU - Falcone, Marco

AU - Jezek, Davor

AU - Preto, Mirko

AU - Amar, Edouard

AU - Le, Tan V.

AU - Ahn, Sun Tae

AU - Rezano, Andri

AU - Singh, Keerti

AU - Rocco, Lucia

AU - Savira, Missy

AU - Rajmil, Osvaldo

AU - Darbandi, Sara

AU - Sogutdelen, Emrullah

AU - Boeri, Luca

AU - Hernández, Guadalupe

AU - Hakim, Lukman

AU - Morimoto, Yoshiharu

AU - Japari, Andrian

AU - Sofikitis, Nikolaos

AU - Altay, Baris

AU - Mahmutoglu, Asli Metin

AU - Al Hashimi, Manaf

AU - Ziouziou, Imad

AU - Anagnostopoulou, Christina

AU - Lin, Haocheng

AU - Shah, Rupin

PY - 2024/1

Y1 - 2024/1

N2 - 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.

AB - 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.

KW - Delphi method

KW - Diagnostic test

KW - DNA fragmentation

KW - Infertility

KW - male

KW - Survey

UR - http://www.scopus.com/inward/record.url?scp=85173813215&partnerID=8YFLogxK

U2 - 10.5534/wjmh.230076

DO - 10.5534/wjmh.230076

M3 - Article

C2 - 37635341

AN - SCOPUS:85173813215

SN - 2287-4208

VL - 41

SP - 202

EP - 215

JO - The World Journal of Men's Health

JF - The World Journal of Men's Health

IS - 1

ER -

Agarwal A, Farkouh A, Saleh R, Hamoda TAAAM, Salvio G, Boitrelle F et al. Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations. The World Journal of Men's Health. 2024 Jan;41(1):202-215. doi: 10.5534/wjmh.230076