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1. Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations

Author

Rupin Shah, Amarnath Rambhatla, Widi Atmoko, Marlon Martinez, Imad Ziouziou, Priyank Kothari, Nicholas Tadros, Nguyen Ho Vinh Phuoc, Parviz Kavoussi, Ahmed Harraz, Gianmaria Salvio, Murat Gul, Taha Hamoda, Tuncay Toprak, Ponco Birowo, Edmund Ko, Mohamed Arafa, Ramy Abou Ghayda, Vilvapathy Senguttuvan Karthikeyan, Ramadan Saleh, Giorgio Ivan Russo, Germar-Michael Pinggera, Eric Chung, Missy Savira, Giovanni M. Colpi, Wael Zohdy, Edoardo Pescatori, Hyun Jun Park, Shinichiro Fukuhara, Akira Tsujimura, Cesar Rojas-Cruz, Angelo Marino, Siu King Mak, Edouard Amar, Wael Ibrahim, Puneet Sindhwani, Naif Alhathal, Gian Maria Busetto, Manaf Al Hashimi, Ahmed El-Sakka, Asci Ramazan, Fotios Dimitriadis, Massimiliano Timpano, Davor Jezek, Baris Altay, Daniel Suslik Zylbersztejn, Michael YC Wong, Du Geon Moon, Christine Wyns, Safar Gamidov, Hamed Akhavizadegan, Alessandro Franceschelli, Kaan Aydos, Vinh Nguyen Quang, Shedeed Ashour, Adel Al Dayel, Mohamed S. Al-Marhoon, Sava Micic, Saleh Binsaleh, Alayman Hussein, Haitham Elbardisi, Taymour Mostafa, Emad Taha, Jonathan Ramsay, Athanasios Zachariou, Islam Fathy Soliman Abdelrahman, Osvaldo Rajmil, Arif Kalkanli, Juan Manuel Corral Molina, Kadir Bocu, Gede Wirya Kusuma Duarsa, Gokhan Ceker, Ege Can Serefoglu, Fahmi Bahar, Nazim Gherabi, Shinnosuke Kuroda, Abderrazak Bouzouita, Ahmet Gudeloglu, Erman Ceyhan, Mohamed Saeed Mohamed Hasan, Muhammad Ujudud Musa, Ahmad Motawi, Cho Chak-Lam, Hisanori Taniguchi, Christopher Chee Kong Ho, Jesus Fernando Solorzano Vazquez, Shingai Mutambirwa, Nur Dokuzeylul Gungor, Marion Bendayan, Carlo Giulioni, Aykut Baser, Marco Falcone, Luca Boeri, Gideon Blecher, Alireza Kheradmand, Tamilselvi Sethupathy, Ricky Adriansjah, Nima Narimani, Charalampos Konstantinidis, Tuan Thanh Nguyen, Andrian Japari, Parisa Dolati, Keerti Singh, Cevahir Ozer, Selcuk Sarikaya, Nadia Sheibak, Ndagijimana Jean Bosco, Mehmet Serkan Özkent, Sang Thanh Le, Ioannis Sokolakis, Darren Katz, Ryan Smith, Manh Nguyen Truong, Tan V. Le, Zhongwei Huang, Muslim Dogan Deger, Umut Arslan, Gokhan Calik, Giorgio Franco, Ayman Rashed, Oguzhan Kahraman, Sotiris Andreadakis, Rosadi Putra, Giancarlo Balercia, Kareim Khalafalla, Rossella Cannarella, Anh Đặng Tuấn, Amr El Meliegy, Birute Zilaitiene, Marlene Lizbeth Zamora Ramirez, Filippo Giacone, Aldo E. Calogero, Konstantinos Makarounis, Sunil Jindal, Bac Nguyen Hoai, Ravi Banthia, Marcelo Rodriguez Peña, Dharani Moorthy, Aram Adamyan, Deniz Kulaksiz, Hussein Kandil, Nikolaos Sofikitis, Ciro Salzano, Andreas Jungwirth, Surendra Reddy Banka, Tiago Cesar Mierzwa, Tahsin Turunç, Divyanu Jain, Armen Avoyan, Pietro Salacone, Ateş Kadıoğlu, Chirag Gupta, Haocheng Lin, Iman Shamohammadi, Nasser Mogharabian, Trenton Barrett, Yavuz Onur Danacıoğlu, Andrea Crafa, Salima Daoud, Vineet Malhotra, Abdulmalik Almardawi, Osama Mohamed Selim, Mohamad Moussa, Saeid Haghdani, Mesut Berkan Duran, Yannic Kunz, Mirko Preto, Elena Eugeni, Thang Nguyen, Ahmed Rashad Elshahid, Seso Sulijaya Suyono, Dyandra Parikesit, Essam Nada, Eduardo Gutiérrez Orozco, Florence Boitrelle, Nguyen Thi Minh Trang, Mounir Jamali, Raju Nair, Mikhail Ruzaev, Franco Gadda, Charalampos Thomas, Raphael Henrique Ferreira, Umit Gul, Serena Maruccia, Ajay Kanbur, Ella Kinzikeeva, Saad Abumelha, Nguyen Quang, Raghavender Kosgi, Fatih Gokalp, Mohammad Ayodhia Soebadi, Gustavo Marquesine Paul, Hesamoddin Sajadi, Deepak Gupte, Rafael F. Ambar, Emrullah Sogutdelen, Karun Singla, Ari Basurkano, Shannon Hee Kyung Kim, Mohammad Ali Sadighi Gilani, Koichi Nagao, Sakti Ronggowardhana Brodjonegoro, Andri Rezano, Mohamed Elkhouly, Rossella Mazzilli, Hasan M. A. Farsi, Hung Nguyen Ba, Hamed Alali, Dimitrios Kafetzis, Tran Quang Tien Long, Sami Alsaid, Hoang Bao Ngoc Cuong, Knigavko Oleksandr, Akhmad Mustafa, Herik Acosta, Hrishikesh Pai, Bahadır Şahin, Eko Arianto, Colin Teo, Sanjay Prakash Jayaprakash, Rinaldo Indra Rachman, Mustafa Gurkan Yenice, Omar Sefrioui, Smit Paghdar, Shivam Priyadarshi, Marko Tanic, Noor Kareem Alfatlawy, Fikri Rizaldi, Ranjit B. Vishwakarma, George Kanakis, Dinesh Thomas Cherian, Joe Lee, Raisa Galstyan, Hakan Keskin, Jana Wurzacher, Doddy Hami Seno, Bambang S. Noegroho, Ria Margiana, Qaisar Javed, Fabrizio Castiglioni, Raman Tanwar, Ana Puigvert, Coşkun Kaya, Medianto Purnomo, Chadi Yazbeck, Azwar Amir, Edson Borges, Marina Bellavia, Isaac Ardianson Deswanto, Vinod K V, Giovanni Liguori, Dang Hoang Minh, Kashif Siddiqi, Fulvio Colombo, Armand Zini, Niket Patel, Selahittin Çayan, Ula Al-Kawaz, Maged Ragab, Guadalupe Hernández Hebrard, Ivan Hoffmann, Ozan Efesoy, Barış Saylam, and Ashok Agarwal

Subjects
azoospermia, diagnosis, guideline, infertility, male, surveys and questionnaires, Medicine, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Purpose: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. Materials and Methods:Materials and Methods: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 coun-tries were analyzed descriptively, with a Delphi process used for expert recommendations. Results:Results: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoosper-mia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differ-entiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. Conclusions:Conclusions: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

Published
2024
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2. Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations

Author

Ashok Agarwal, Ala’a Farkouh, Ramadan Saleh, Taha Abo-Almagd Abdel-Meguid Hamoda, Gianmaria Salvio, Florence Boitrelle, Ahmed M. Harraz, Ramy Abou Ghayda, Parviz Kavoussi, Murat Gül, Tuncay Toprak, Giorgio Ivan Russo, Damayanthi Durairajanayagam, Amarnath Rambhatla, Ponco Birowo, Rossella Cannarella, Nguyen Ho Vinh Phuoc, Armand Zini, Mohamed Arafa, Christine Wyns, Kelton Tremellen, Selçuk Sarıkaya, Sheena Lewis, Donald P. Evenson, Edmund Ko, Aldo E. Calogero, Fahmi Bahar, Marlon Martínez, Rafael F. Ambar, Giovanni M. Colpi, Mustafa Emre Bakircioglu, Ralf Henkel, Hussein Kandil, Ege Can Serefoglu, Abdullah Alfakhri, Akira Tsujimura, Alireza Kheradmand, Angelo Marino, Aram Adamyan, Birute Zilaitiene, Cevahir Ozer, Edoardo Pescatori, Paraskevi Vogiatzi, Gian Maria Busetto, Giancarlo Balercia, Haitham Elbardisi, Hamed Akhavizadegan, Hesamoddin Sajadi, Hisanori Taniguchi, Hyun Jun Park, Israel Maldonado Rosas, Mohamed Al-Marhoon, Mohammad Ali Sadighi Gilani, Naif Alhathal, Nguyen Quang, Germar-Michael Pinggera, Priyank Kothari, Sava Micic, Sheryl Homa, Tran Quang Tien Long, Wael Zohdy, Widi Atmoko, Wael Ibrahim, Marjan Sabbaghian, Saad Mohammed Abumelha, Eric Chung, Muhammet Rasit Ugur, Mehmet Serkan Ozkent, Osama Selim, Mahsa Darbandi, Shinichiro Fukuhara, Mounir Jamali, Jean de la Rosette, Shinnosuke Kuroda, Ryan P. Smith, Aykut Baser, Arif Kalkanli, Nicholas N. Tadros, Kaan Aydos, Tiago Cesar Mierzwa, Kareim Khalafalla, Vineet Malhotra, Mohamad Moussa, Federica Finocchi, Rinaldo Indra Rachman, Carlo Giulioni, Tomer Avidor-Reiss, Oguzhan Kahraman, Gökhan Çeker, Cătălina Zenoaga-Barbăroșie, Trenton L. Barrett, Mehmet Yilmaz, Ates Kadioglu, Sunil Jindal, Huda Omran, Kadir Bocu, Vilvapathy Senguttuvan Karthikeyan, Giorgio Franco, Jesús Fernando Solorzano, Ranjit B. Vishwakarma, Eko Arianto, Nicolas Garrido, Divyanu Jain, Nazim Gherabi, Ioannis Sokolakis, Ayad Palani, Gokhan Calik, Deniz Kulaksiz, Vaida Simanaviciene, Mara Simopoulou, Nur Dokuzeylül Güngör, Gideon Blecher, Marco Falcone, Davor Jezek, Mirko Preto, Edouard Amar, Tan V. Le, Sun Tae Ahn, Andri Rezano, Keerti Singh, Lucia Rocco, Missy Savira, Osvaldo Rajmil, Sara Darbandi, Emrullah Sogutdelen, Luca Boeri, Guadalupe Hernández, Lukman Hakim, Yoshiharu Morimoto, Andrian Japari, Nikolaos Sofikitis, Baris Altay, Asli Metin Mahmutoglu, Manaf Al Hashimi, Imad Ziouziou, Christina Anagnostopoulou, Haocheng Lin, and Rupin Shah

Subjects
delphi method, diagnostic test, dna fragmentation, infertility, male, survey, Medicine, Diseases of the genitourinary system. Urology, RC870-923
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.

Published
2024
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3. Controversy and Consensus on the Management of Elevated Sperm DNA Fragmentation in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations

Author

Ala’a Farkouh, Ashok Agarwal, Taha Abo-Almagd Abdel-Meguid Hamoda, Parviz Kavoussi, Ramadan Saleh, Armand Zini, Mohamed Arafa, Ahmed M. Harraz, Murat Gul, Vilvapathy Senguttuvan Karthikeyan, Damayanthi Durairajanayagam, Amarnath Rambhatla, Florence Boitrelle, Eric Chung, Ponco Birowo, Tuncay Toprak, Ramy Abou Ghayda, Rossella Cannarella, Nguyen Ho Vinh Phuoc, Fotios Dimitriadis, Giorgio I. Russo, Ioannis Sokolakis, Taymour Mostafa, Konstantinos Makarounis, Imad Ziouziou, Shinnosuke Kuroda, Marion Bendayan, Raneen Sawaid Kaiyal, Andrian Japari, Mara Simopoulou, Lucia Rocco, Nicolas Garrido, Nazim Gherabi, Kadir Bocu, Oguzhan Kahraman, Tan V. Le, Christine Wyns, Kelton Tremellen, Selcuk Sarikaya, Sheena Lewis, Donald P. Evenson, Edmund Ko, Aldo E. Calogero, Fahmi Bahar, Marlon Martinez, Andrea Crafa, Quang Nguyen, Rafael F. Ambar, Giovanni Colpi, Mustafa Emre Bakircioglu, Ralf Henkel, Hussein Kandil, Ege Can Serefoglu, Abdullah Alarbid, Akira Tsujimura, Alireza Kheradmand, Christina Anagnostopoulou, Angelo Marino, Aram Adamyan, Birute Zilaitiene, Cevahir Ozer, Edoardo Pescatori, Paraskevi Vogiatzi, Gian Maria Busetto, Giancarlo Balercia, Haitham Elbardisi, Hamed Akhavizadegan, Hesamoddin Sajadi, Hisanori Taniguchi, Hyun Jun Park, Israel Maldonado Rosas, Mohamed Al-Marhoon, Mohammad Ali Sadighi Gilani, Naif Alhathal, Germar-Michael Pinggera, Priyank Kothari, Nasser Mogharabian, Sava Micic, Sheryl Homa, Sara Darbandi, Tran Quang Tien Long, Wael Zohdy, Widi Atmoko, Marjan Sabbaghian, Wael Ibrahim, Ryan P. Smith, Christopher Chee Kong Ho, Jean de la Rosette, Ahmed I. El-Sakka, Mirko Preto, Cătălina Zenoaga-Barbăroșie, Saad Mohammed Abumelha, Aykut Baser, Kaan Aydos, Liliana Ramirez-Dominguez, Vijay Kumar, Teng Aik Ong, Tiago Cesar Mierzwa, Ricky Adriansjah, Saleem A. Banihani, Kasonde Bowa, Shinichiro Fukuhara, Marcelo Rodriguez Peña, Mohamad Moussa, Umut Çağın Ari, Chak-Lam Cho, Nicholas N. Tadros, Muhammet Rasit Ugur, Edouard Amar, Marco Falcone, Frederic Romain Santer, Arif Kalkanli, Keshab Kumar Karna, Kareim Khalafalla, Ranjit B. Vishwakarma, Federica Finocchi, Carlo Giulioni, Erman Ceyhan, Gökhan Çeker, Chadi Yazbeck, Osvaldo Rajmil, Mehmet Yilmaz, Baris Altay, Trenton L. Barrett, Kay Seong Ngoo, Shubhadeep Roychoudhury, Gianmaria Salvio, Haocheng Lin, Ates Kadioglu, Massimiliano Timpano, Tomer Avidor-Reiss, Lukman Hakim, Puneet Sindhwani, Giorgio Franco, Rajender Singh, Filippo Giacone, Mikhail Ruzaev, Raghavender Kosgi, Nikolaos Sofikitis, Ayad Palani, Gokhan Calik, Deniz Kulaksız, Davor Jezek, Manaf Al Hashmi, Panagiotis Drakopoulos, Huda Omran, Sofia Leonardi, Ciler Celik-Ozenci, Nur Dokuzeylül Güngör, Jonathan Ramsay, Toshiyasu Amano, Emrullah Sogutdelen, Gede Wirya Kusuma Duarsa, Koji Chiba, Sunil Jindal, Missy Savira, Luca Boeri, Edson Borges, Deepak Gupte, Fatih Gokalp, Guadalupe Hernández Hebrard, Suks Minhas, and Rupin Shah

Subjects
delphi method, disease management, dna fragmentation, male infertility, practice guideline, survey, Medicine, Diseases of the genitourinary system. Urology, RC870-923
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.

Published
2023
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