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1. Controversy and Consensus on Indications for Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations

Author

Agarwal, A, Farkouh, A, Saleh, R, Abdel-Meguid Hamoda, TA-A, Harraz, AM, Kavoussi, P, Arafa, M, Salvio, G, Rambhatla, A, Toprak, T, Gül, M, Phuoc, NHV, Boitrelle, F, Birowo, P, Ghayda, RA, Cannarella, R, Kuroda, S, Durairajanayagam, D, Zini, A, Wyns, C, Sarikaya, S, Tremellen, K, Mostafa, T, Sokolakis, I, Evenson, DP, Henkel, R, Zohdy, W, Chung, E, Ziouziou, I, Falcone, M, Russo, GI, Al-Hashimi, M, Calogero, AE, Ko, E, Colpi, G, Lewis, S, Serefoglu, EC, Bahar, F, Martinez, M, Nguyen, Q, Ambar, RF, Bakircioglu, ME, Kandil, H, Mogharabian, N, Sabbaghian, M, Taniguchi, H, Tsujimura, A, Sajadi, H, Ibrahim, W, Atmoko, W, Vogiatzi, P, Gunes, S, Gilani, MAS, Roychoudhury, S, Güngör, ND, Hakim, L, Adriansjah, R, Kothari, P, Jindal, S, Amar, E, Park, HJ, Long, TQT, Homa, S, Karthikeyan, VS, Zilaitiene, B, Rosas, IM, Marino, A, Pescatori, E, Ozer, C, Akhavizadegan, H, Garrido, N, Busetto, GM, Adamyan, A, Al-Marhoon, M, Elbardisi, H, Dolati, P, Darbandi, M, Darbandi, S, Balercia, G, Pinggera, G-M, Micic, S, Ho, CCK, Moussa, M, Preto, M, Zenoaga-Barbăroșie, C, Smith, RP, Kosgi, R, Rosette, JDL, El-Sakka, AI, Abumelha, SM, Mierzwa, TC, Ong, TA, Banihani, SA, Bowa, K, Fukuhara, S, Boeri, L, Danacıoğlu, YO, Gokalp, F, Selim, OM, Cho, C-L, Tadros, NN, Ugur, MR, Ozkent, MS, Chiu, P, Kalkanli, A, Khalafalla, K, Vishwakarma, RB, Finocchi, F, Andreadakis, S, Giulioni, C, Çeker, G, Ceyhan, E, Malhotra, V, Yilmaz, M, Timpano, M, Barrett, TL, Kim, SHK, Ahn, S-T, Giacone, F, Palani, A, Duarsa, GWK, Kadioglu, A, Gadda, F, Zylbersztejn, DS, Aydos, K, Kulaksız, D, Gupte, D, Calik, G, Karna, KK, Drakopoulos, P, Baser, A, Kumar, V, Molina, JMC, Rajmil, O, Ferreira, RH, Leonardi, S, Avoyan, A, Sogutdelen, E, Franco, G, Ramsay, J, Ramirez, L, Shah, R, Global Andrology Forum, Agarwal, Ashok, Farkouh, Ala'A, Saleh, Ramadan, Abdel-Meguid Hamoda, Taha Abo-Almagd, Harraz, Ahmed M, Kavoussi, Parviz, Arafa, Mohamed, Salvio, Gianmaria, Rambhatla, Amarnath, Toprak, Tuncay, Gül, Murat, Phuoc, Nguyen Ho Vinh, Boitrelle, Florence, Birowo, Ponco, Ghayda, Ramy Abou, Cannarella, Rossella, Kuroda, Shinnosuke, Durairajanayagam, Damayanthi, Zini, Armand, Wyns, Christine, Sarikaya, Selcuk, Tremellen, Kelton, Mostafa, Taymour, Sokolakis, Ioanni, Evenson, Donald P, Henkel, Ralf, Zohdy, Wael, Chung, Eric, Ziouziou, Imad, Falcone, Marco, Russo, Giorgio I, Al-Hashimi, Manaf, Calogero, Aldo E, Ko, Edmund, Colpi, Giovanni, Lewis, Sheena, Serefoglu, Ege Can, Bahar, Fahmi, Martinez, Marlon, Nguyen, Quang, Ambar, Rafael F, Bakircioglu, Mustafa Emre, Kandil, Hussein, Mogharabian, Nasser, Sabbaghian, Marjan, Taniguchi, Hisanori, Tsujimura, Akira, Sajadi, Hesamoddin, Ibrahim, Wael, Atmoko, Widi, Vogiatzi, Paraskevi, Gunes, Sezgin, Gilani, Mohammad Ali Sadighi, Roychoudhury, Shubhadeep, Güngör, Nur Dokuzeylül, Hakim, Lukman, Adriansjah, Ricky, Kothari, Priyank, Jindal, Sunil, Amar, Edouard, Park, Hyun Jun, Long, Tran Quang Tien, Homa, Sheryl, Karthikeyan, Vilvapathy Senguttuvan, Zilaitiene, Birute, Rosas, Israel Maldonado, Marino, Angelo, Pescatori, Edoardo, Ozer, Cevahir, Akhavizadegan, Hamed, Garrido, Nicola, Busetto, Gian Maria, Adamyan, Aram, Al-Marhoon, Mohamed, Elbardisi, Haitham, Dolati, Parisa, Darbandi, Mahsa, Darbandi, Sara, Balercia, Giancarlo, Pinggera, Germar-Michael, Micic, Sava, Ho, Christopher Chee Kong, Moussa, Mohamad, Preto, Mirko, Zenoaga-Barbăroșie, Cătălina, Smith, Ryan P, Kosgi, Raghavender, Rosette, Jean de la, El-Sakka, Ahmed I, Abumelha, Saad Mohammed, Mierzwa, Tiago Cesar, Ong, Teng Aik, Banihani, Saleem A, Bowa, Kasonde, Fukuhara, Shinichiro, Boeri, Luca, Danacıoğlu, Yavuz Onur, Gokalp, Fatih, Selim, Osama Mohamed, Cho, Chak-Lam, Tadros, Nicholas N, Ugur, Muhammet Rasit, Ozkent, Mehmet Serkan, Chiu, Peter, Kalkanli, Arif, Khalafalla, Kareim, Vishwakarma, Ranjit B, Finocchi, Federica, Andreadakis, Sotiri, Giulioni, Carlo, Çeker, Gökhan, Ceyhan, Erman, Malhotra, Vineet, Yilmaz, Mehmet, Timpano, Massimiliano, Barrett, Trenton L, Kim, Shannon Hee Kyung, Ahn, Sun-Tae, Giacone, Filippo, Palani, Ayad, Duarsa, Gede Wirya Kusuma, Kadioglu, Ate, Gadda, Franco, Zylbersztejn, Daniel Suslik, Aydos, Kaan, Kulaksız, Deniz, Gupte, Deepak, Calik, Gokhan, Karna, Keshab Kumar, Drakopoulos, Panagioti, Baser, Aykut, Kumar, Vijay, Molina, Juan Manuel Corral, Rajmil, Osvaldo, Ferreira, Raphael H, Leonardi, Sofia, Avoyan, Armen, Sogutdelen, Emrullah, Franco, Giorgio, Ramsay, Jonathan, Ramirez, Liliana, Shah, Rupin, and Rocco, Lucia

Subjects
Male infertility, Practice guideline, Delphi method, DNA fragmentation, Survey, Sperm
Abstract

PURPOSE: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations. MATERIALS AND METHODS: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus. RESULTS: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing. CONCLUSIONS: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians.

Published
2023

2. Global Practice Patterns and Variations in the Medical and Surgical Management of Non-Obstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations.

Author

Rambhatla A, Shah R, Ziouziou I, Kothari P, Salvio G, Gul M, Hamoda T, Kavoussi P, Atmoko W, Toprak T, Birowo P, Ko E, Arafa M, Ghayda RA, Karthikeyan VS, Russo GI, Pinggera GM, Chung E, Harraz AM, Martinez M, Phuoc NHV, Tadros N, Saleh R, Savira M, Colpi GM, Zohdy W, Pescatori E, Park HJ, Fukuhara S, Tsujimura A, Rojas-Cruz C, Marino A, Mak SK, Amar E, Ibrahim W, Sindhwani P, Alhathal N, Busetto GM, Al Hashimi M, El-Sakka A, Ramazan A, Dimitriadis F, Timpano M, Jezek D, Altay B, Zylbersztejn DS, Wong MY, Moon DG, Wyns C, Gamidov S, Akhavizadegan H, Franceschelli A, Aydos K, Quang N, Ashour S, Al Dayel A, Al-Marhoon MS, Micic S, Binsaleh S, Hussein A, Elbardisi H, Mostafa T, Ramsay J, Zachariou A, Abdelrahman IFS, Rajmil O, Kalkanli A, Molina JMC, Bocu K, Duarsa GWK, Çeker G, Serefoglu EC, Bahar F, Gherabi N, Kuroda S, Bouzouita A, Gudeloglu A, Ceyhan E, Hasan MSM, Musa MU, Motawi A, Cho CL, Taniguchi H, Ho CCK, Vazquez JFS, Mutambirwa S, Gungor ND, Bendayan M, Giulioni C, Baser A, Falcone M, Boeri L, Blecher G, Kheradmand A, Sethupathy T, Adriansjah R, Narimani N, Konstantinidis C, Nguyen TT, Japari A, Dolati P, Singh K, Ozer C, Sarikaya S, Sheibak N, Bosco NJ, Özkent MS, Le ST, Sokolakis I, Katz D, Smith R, Truong MN, Le TV, Huang Z, Deger MD, Arslan U, Calik G, Franco G, Rashed A, Kahraman O, Andreadakis S, Putra R, Balercia G, Khalafalla K, Cannarella R, Tuấn AĐ, El Meliegy A, Zilaitiene B, Ramirez MLZ, Giacone F, Calogero AE, Makarounis K, Jindal S, Hoai BN, Banthia R, Peña MR, Moorthy D, Adamyan A, Kulaksiz D, Kandil H, Sofikitis N, Salzano C, Jungwirth A, Banka SR, Mierzwa TC, Turunç T, Jain D, Avoyan A, Salacone P, Kadıoğlu A, Gupta C, Lin H, Shamohammadi I, Mogharabian N, Barrett T, Danacıoğlu YO, Crafa A, Daoud S, Malhotra V, Almardawi A, Selim OM, Moussa M, Haghdani S, Duran MB, Kunz Y, Preto M, Eugeni E, Nguyen T, Elshahid AR, Suyono SS, Parikesit D, Nada E, Orozco EG, Boitrelle F, Trang NTM, Jamali M, Nair R, Ruzaev M, Gadda F, Thomas C, Ferreira RH, Gul U, Maruccia S, Kanbur A, Kinzikeeva E, Abumelha SM, Kosgi R, Gokalp F, Soebadi MA, Paul GM, Sajadi H, Gupte D, Ambar RF, Sogutdelen E, Singla K, Basukarno A, Kim SHK, Gilani MAS, Nagao K, Brodjonegoro SR, Rezano A, Elkhouly M, Mazzilli R, Farsi HMA, Ba HN, Alali H, Kafetzis D, Long TQT, Alsaid S, Cuong HBN, Oleksandr K, Mustafa A, Acosta H, Pai H, Şahin B, Arianto E, Teo C, Jayaprakash SP, Rachman RI, Yenice MG, Sefrioui O, Priyadarshi S, Tanic M, Alfatlaw NK, Rizaldi F, Vishwakarma RB, Kanakis G, Cherian DT, Lee J, Galstyan R, Keskin H, Wurzacher J, Seno DH, Noegroho BS, Margiana R, Javed Q, Castiglioni F, Tanwar R, Puigvert A, Kaya C, Purnomo M, Yazbeck C, Amir A, Borges E, Bellavia M, Deswanto IA, Kv V, Liguori G, Minh DH, Siddiqi K, Colombo F, Zini A, Patel N, Çayan S, Al-Kawaz U, Ragab M, Hebrard GH, de la Rosette J, Efesoy O, Hoffmann I, Teixeira TA, Saylam B, Delgadillo D, and Agarwal A

Abstract

Purpose: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA., Materials and Methods: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process., Results: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit., Conclusions: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines., Competing Interests: The authors have nothing to disclose., (Copyright © 2025 Korean Society for Sexual Medicine and Andrology.)

Published
2025
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3. Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations.

Author

Shah R, Rambhatla A, Atmoko W, Martinez M, Ziouziou I, Kothari P, Tadros N, Phuoc NHV, Kavoussi P, Harraz A, Salvio G, Gul M, Hamoda T, Toprak T, Birowo P, Ko E, Arafa M, Ghayda RA, Karthikeyan VS, Saleh R, Russo GI, Pinggera GM, Chung E, Savira M, Colpi GM, Zohdy W, Pescatori E, Park HJ, Fukuhara S, Tsujimura A, Rojas-Cruz C, Marino A, Mak SK, Amar E, Ibrahim W, Sindhwani P, Alhathal N, Busetto GM, Al Hashimi M, El-Sakka A, Ramazan A, Dimitriadis F, Timpano M, Jezek D, Altay B, Zylbersztejn DS, Wong MY, Moon DG, Wyns C, Gamidov S, Akhavizadegan H, Franceschelli A, Aydos K, Quang VN, Ashour S, Al Dayel A, Al-Marhoon MS, Micic S, Binsaleh S, Hussein A, Elbardisi H, Mostafa T, Taha E, Ramsay J, Zachariou A, Abdelrahman IFS, Rajmil O, Kalkanli A, Molina JMC, Bocu K, Duarsa GWK, Ceker G, Serefoglu EC, Bahar F, Gherabi N, Kuroda S, Bouzouita A, Gudeloglu A, Ceyhan E, Hasan MSM, Musa MU, Motawi A, Chak-Lam C, Taniguchi H, Ho CCK, Vazquez JFS, Mutambirwa S, Gungor ND, Bendayan M, Giulioni C, Baser A, Falcone M, Boeri L, Blecher G, Kheradmand A, Sethupathy T, Adriansjah R, Narimani N, Konstantinidis C, Nguyen TT, Japari A, Dolati P, Singh K, Ozer C, Sarikaya S, Sheibak N, Bosco NJ, Özkent MS, Le ST, Sokolakis I, Katz D, Smith R, Truong MN, Le TV, Huang Z, Deger MD, Arslan U, Calik G, Franco G, Rashed A, Kahraman O, Andreadakis S, Putra R, Balercia G, Khalafalla K, Cannarella R, Tuấn AĐ, El Meliegy A, Zilaitiene B, Ramirez MLZ, Giacone F, Calogero AE, Makarounis K, Jindal S, Hoai BN, Banthia R, Peña MR, Moorthy D, Adamyan A, Kulaksiz D, Kandil H, Sofikitis N, Salzano C, Jungwirth A, Banka SR, Mierzwa TC, Turunç T, Jain D, Avoyan A, Salacone P, Kadıoğlu A, Gupta C, Lin H, Shamohammadi I, Mogharabian N, Barrett T, Danacıoğlu YO, Crafa A, Daoud S, Malhotra V, Almardawi A, Selim OM, Moussa M, Haghdani S, Duran MB, Kunz Y, Preto M, Eugeni E, Nguyen T, Elshahid AR, Suyono SS, Parikesit D, Nada E, Orozco EG, Boitrelle F, Trang NTM, Jamali M, Nair R, Ruzaev M, Gadda F, Thomas C, Ferreira RH, Gul U, Maruccia S, Kanbur A, Kinzikeeva E, Abumelha S, Quang N, Kosgi R, Gokalp F, Soebadi MA, Paul GM, Sajadi H, Gupte D, Ambar RF, Sogutdelen E, Singla K, Basurkano A, Kim SHK, Gilani MAS, Nagao K, Brodjonegoro SR, Rezano A, Elkhouly M, Mazzilli R, Farsi HMA, Ba HN, Alali H, Kafetzis D, Long TQT, Alsaid S, Cuong HBN, Oleksandr K, Mustafa A, Acosta H, Pai H, Şahin B, Arianto E, Teo C, Jayaprakash SP, Rachman RI, Yenice MG, Sefrioui O, Paghdar S, Priyadarshi S, Tanic M, Alfatlawy NK, Rizaldi F, Vishwakarma RB, Kanakis G, Cherian DT, Lee J, Galstyan R, Keskin H, Wurzacher J, Seno DH, Noegroho BS, Margiana R, Javed Q, Castiglioni F, Tanwar R, Puigvert A, Kaya C, Purnomo M, Yazbeck C, Amir A, Borges E, Bellavia M, Deswanto IA, V VK, Liguori G, Minh DH, Siddiqi K, Colombo F, Zini A, Patel N, Çayan S, Al-Kawaz U, Ragab M, Hebrard GH, Hoffmann I, Efesoy O, Saylam B, and Agarwal A

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: 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 countries were analyzed descriptively, with a Delphi process used for expert recommendations., Results: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia 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. Differentiation 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: 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., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

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

Author

Agarwal A, Farkouh A, Saleh R, Hamoda TAA, 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, Maldonado Rosas I, Al-Marhoon M, Sadighi Gilani MA, 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, Metin Mahmutoglu A, Al Hashimi M, Ziouziou I, Anagnostopoulou C, Lin H, and Shah R

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., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Published
2024
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5. Does Varicocele Repair Improve Conventional Semen Parameters? A Meta-Analytic Study of Before-After Data.

Author

Cannarella R, Shah R, Hamoda TAA, Boitrelle F, Saleh R, Gul M, Rambhatla A, Kavoussi P, Toprak T, Harraz AM, Ko E, Çeker G, Durairajanayagam D, Alkahidi N, Kuroda S, Crafa A, Henkel R, Salvio G, Hazir B, Darbandi M, Bendayan M, Darbandi S, Falcone M, Garrido N, Kosgi R, Sawaid Kaiyal R, Karna K, Phuoc NHV, Birowo P, Colpi GM, de la Rosette J, Pinggera GM, Nguyen Q, Zini A, Zohdy W, Singh R, Saini P, Glina S, Lin H, Mostafa T, Rojas-Cruz C, Arafa M, Calogero AE, Dimitriadis F, Kothari P, Karthikeyan VS, Okada K, Chiba K, Kadıoglu A, Altay B, Turunc T, Zilaitiene B, Gokalp F, Adamyan A, Katz D, Chung E, Mierzwa TC, Zylbersztejn DS, Paul GM, Sofikitis N, Sokolakis I, Malhotra V, Brodjonegoro SR, Adriansjah R, Tsujimura A, Amano T, Balercia G, Ziouziou I, Deswanto IA, Martinez M, Park HJ, Bakırcıoglu ME, Ceyhan E, Aydos K, Ramsay J, Minhas S, Al Hashimi M, Ghayda RA, Tadros N, Sindhwani P, Ho CCK, Rachman RI, Rodriguez Pena M, Motawi A, Ponnusamy AK, Dipankar S, Amir A, Binsaleh S, Serefoglu EC, Banthia R, Khalafalla K, Basukarno A, Bac NH, Singla K, Ambar RF, Makarounis K, Priyadarshi S, Duarsa GWK, Atmoko W, Jindal S, Arianto E, Akhavizadegan H, El Bardisi H, Shoshany O, Busetto GM, Moussa M, Jamali M, Al-Marhoon MS, Ruzaev M, Farsi HMA, Mutambirwa S, Lee DS, Kulaksiz D, Cheng YS, Bouzouita A, Sarikaya S, Kandil H, Tsampoukas G, Farkouh A, Bowa K, Savira M, Mogharabian N, Le TV, Harjanggi M, Anh DT, Long TQT, Soebadi MA, Hakim L, Tanic M, Ari UC, Parikh FR, Calik G, Kv V, Dorji G, Rezano A, Rajmil O, Tien DMB, Yuan Y, Lizarraga-Salas JF, Eze B, Ngoo KS, Lee J, Arslan U, and Agarwal A

Abstract

Purpose: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles., Materials and Methods: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies)., Results: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129-0.278; p<0.001; I²=83.62%, Egger's p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474-1.706; p<0.001; I²=97.86%, Egger's p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526-2.121; p<0.001; I²=97.88%, Egger's p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318-1.968; p<0.001; I²=98.65%, Egger's p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%-2.153%; p<0.001; I²=98.97%, Egger's p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%-1.759%; p<0.001; l2=97.98%, Egger's p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%-1.211%; p<0.001; I²=97.87%, Egger's p=0.1864., Conclusions: The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

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

Author

Farkouh A, Agarwal A, Hamoda TAA, Kavoussi P, Saleh R, Zini A, Arafa M, Harraz AM, Gul M, Karthikeyan VS, Durairajanayagam D, Rambhatla A, Boitrelle F, Chung E, Birowo P, Toprak T, Ghayda RA, Cannarella R, Phuoc NHV, Dimitriadis F, Russo GI, Sokolakis I, Mostafa T, Makarounis K, Ziouziou I, Kuroda S, Bendayan M, Kaiyal RS, Japari A, Simopoulou M, Rocco L, Garrido N, Gherabi N, Bocu K, Kahraman O, Le TV, Wyns C, Tremellen K, Sarikaya S, Lewis S, Evenson DP, Ko E, Calogero AE, Bahar F, Martinez M, Crafa A, Nguyen Q, Ambar RF, Colpi G, Bakircioglu ME, Henkel R, Kandil H, Serefoglu EC, Alarbid A, Tsujimura A, Kheradmand A, Anagnostopoulou C, 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, Maldonado Rosas I, Al-Marhoon M, Sadighi Gilani MA, Alhathal N, Pinggera GM, Kothari P, Mogharabian N, Micic S, Homa S, Darbandi S, Long TQT, Zohdy W, Atmoko W, Sabbaghian M, Ibrahim W, Smith RP, Ho CCK, de la Rosette J, El-Sakka AI, Preto M, Zenoaga-Barbăroșie C, Abumelha SM, Baser A, Aydos K, Ramirez-Dominguez L, Kumar V, Ong TA, Mierzwa TC, Adriansjah R, Banihani SA, Bowa K, Fukuhara S, Rodriguez Peña M, Moussa M, Ari UÇ, Cho CL, Tadros NN, Ugur MR, Amar E, Falcone M, Santer FR, Kalkanli A, Karna KK, Khalafalla K, Vishwakarma RB, Finocchi F, Giulioni C, Ceyhan E, Çeker G, Yazbeck C, Rajmil O, Yilmaz M, Altay B, Barrett TL, Ngoo KS, Roychoudhury S, Salvio G, Lin H, Kadioglu A, Timpano M, Avidor-Reiss T, Hakim L, Sindhwani P, Franco G, Singh R, Giacone F, Ruzaev M, Kosgi R, Sofikitis N, Palani A, Calik G, Kulaksız D, Jezek D, Al Hashmi M, Drakopoulos P, Omran H, Leonardi S, Celik-Ozenci C, Güngör ND, Ramsay J, Amano T, Sogutdelen E, Duarsa GWK, Chiba K, Jindal S, Savira M, Boeri L, Borges E, Gupte D, Gokalp F, Hebrard GH, Minhas S, and Shah R

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., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

Published
2023
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7. Controversy and Consensus on Indications for Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

Author

Agarwal A, Farkouh A, Saleh R, Abdel-Meguid Hamoda TA, Harraz AM, Kavoussi P, Arafa M, Salvio G, Rambhatla A, Toprak T, Gül M, Phuoc NHV, Boitrelle F, Birowo P, Ghayda RA, Cannarella R, Kuroda S, Durairajanayagam D, Zini A, Wyns C, Sarikaya S, Tremellen K, Mostafa T, Sokolakis I, Evenson DP, Henkel R, Zohdy W, Chung E, Ziouziou I, Falcone M, Russo GI, Al-Hashimi M, Calogero AE, Ko E, Colpi G, Lewis S, Serefoglu EC, Bahar F, Martinez M, Nguyen Q, Ambar RF, Bakircioglu ME, Kandil H, Mogharabian N, Sabbaghian M, Taniguchi H, Tsujimura A, Sajadi H, Ibrahim W, Atmoko W, Vogiatzi P, Gunes S, Sadighi Gilani MA, Roychoudhury S, Güngör ND, Hakim L, Adriansjah R, Kothari P, Jindal S, Amar E, Park HJ, Long TQT, Homa S, Karthikeyan VS, Zilaitiene B, Maldonado Rosas I, Marino A, Pescatori E, Ozer C, Akhavizadegan H, Garrido N, Busetto GM, Adamyan A, Al-Marhoon M, Elbardisi H, Dolati P, Darbandi M, Darbandi S, Balercia G, Pinggera GM, Micic S, Ho CCK, Moussa M, Preto M, Zenoaga-Barbăroșie C, Smith RP, Kosgi R, de la Rosette J, El-Sakka AI, Abumelha SM, Mierzwa TC, Ong TA, Banihani SA, Bowa K, Fukuhara S, Boeri L, Danacıoğlu YO, Gokalp F, Selim OM, Cho CL, Tadros NN, Ugur MR, Ozkent MS, Chiu P, Kalkanli A, Khalafalla K, Vishwakarma RB, Finocchi F, Andreadakis S, Giulioni C, Çeker G, Ceyhan E, Malhotra V, Yilmaz M, Timpano M, Barrett TL, Kim SHK, Ahn ST, Giacone F, Palani A, Duarsa GWK, Kadioglu A, Gadda F, Zylbersztejn DS, Aydos K, Kulaksız D, Gupte D, Calik G, Karna KK, Drakopoulos P, Baser A, Kumar V, Molina JMC, Rajmil O, Ferreira RH, Leonardi S, Avoyan A, Sogutdelen E, Franco G, Ramsay J, Ramirez L, and Shah R

Abstract

Purpose: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations., Materials and Methods: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus., Results: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing., Conclusions: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

Published
2023
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8. Consensus and Diversity in the Management of Varicocele for Male Infertility: Results of a Global Practice Survey and Comparison with Guidelines and Recommendations.

Author

Shah R, Agarwal A, Kavoussi P, Rambhatla A, Saleh R, Cannarella R, Harraz AM, Boitrelle F, Kuroda S, Hamoda TAA, Zini A, Ko E, Calik G, Toprak T, Kandil H, Gül M, Bakırcıoğlu ME, Parekh N, Russo GI, Tadros N, Kadioglu A, Arafa M, Chung E, Rajmil O, Dimitriadis F, Malhotra V, Salvio G, Henkel R, Le TV, Sogutdelen E, Vij S, Alarbid A, Gudeloglu A, Tsujimura A, Calogero AE, El Meliegy A, Crafa A, Kalkanli A, Baser A, Hazir B, Giulioni C, Cho CL, Ho CCK, Salzano C, Zylbersztejn DS, Tien DMB, Pescatori E, Borges E, Serefoglu EC, Saïs-Hamza E, Huyghe E, Ceyhan E, Caroppo E, Castiglioni F, Bahar F, Gokalp F, Lombardo F, Gadda F, Duarsa GWK, Pinggera GM, Busetto GM, Balercia G, Cito G, Blecher G, Franco G, Liguori G, Elbardisi H, Keskin H, Lin H, Taniguchi H, Park HJ, Ziouziou I, de la Rosette J, Hotaling J, Ramsay J, Molina JMC, Lo KL, Bocu K, Khalafalla K, Bowa K, Okada K, Nagao K, Chiba K, Hakim L, Makarounis K, Hehemann M, Rodriguez Peña M, Falcone M, Bendayan M, Martinez M, Timpano M, Altan M, Fode M, Al-Marhoon MS, Sadighi Gilani MA, Soebadi MA, Gherabi N, Sofikitis N, Kahraman O, Birowo P, Kothari P, Sindhwani P, Javed Q, Ambar RF, Kosgi R, Ghayda RA, Adriansjah R, Condorelli RA, La Vignera S, Micic S, Kim SHK, Fukuhara S, Ahn ST, Mostafa T, Ong TA, Takeshima T, Amano T, Barrett T, Arslan U, Karthikeyan VS, Atmoko W, Yumura Y, Yuan Y, Kato Y, Jezek D, Cheng BK, Hatzichristodoulou G, Dy J, Castañé ER, El-Sakka AI, Nguyen Q, Sarikaya S, Boeri L, Tan R, Moussa MA, El-Assmy A, Alali H, Alhathal N, Osman Y, Perovic D, Sajadi H, Akhavizadegan H, Vučinić M, Kattan S, Kattan MS, Mogharabian N, Phuoc NHV, Ngoo KS, Alkandari MH, Alsuhaibani S, Sokolakis I, Babaei M, King MS, Diemer T, Gava MM, Henrique R, Silva RSE, Paul GM, Mierzwa TC, Glina S, Siddiqi K, Wu H, Wurzacher J, Farkouh A, Son H, Minhas S, Lee J, Magsanoc N, Capogrosso P, Albano GJ, Lewis SEM, Jayasena CN, Alvarez JG, Teo C, Smith RP, Chua JBM, Jensen CFS, Parekattil S, Finelli R, Durairajanayagam D, Karna KK, Ahmed A, Evenson D, Umemoto Y, Puigvert A, Çeker G, and Colpi GM

Abstract

Purpose: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility., Materials and Methods: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological Association [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field., Results: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the responses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identified where no guidelines are available., Conclusions: This study is the largest global survey performed to date on the clinical management of varicocele for male infertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical practice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

Published
2023
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