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. 2025 Jan;43(1):92-122.
doi: 10.5534/wjmh.230339. Epub 2024 Apr 4.

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

Amarnath Rambhatla  1 , Rupin Shah  2 , Imad Ziouziou  3 , Priyank Kothari  4 , Gianmaria Salvio  5 , Murat Gul  6 , Taha Hamoda  7   8 , Parviz Kavoussi  9 , Widi Atmoko  10 , Tuncay Toprak  11 , Ponco Birowo  10 , Edmund Ko  12 , Mohamed Arafa  13   14   15 , Ramy Abou Ghayda  16 , Vilvapathy Senguttuvan Karthikeyan  17 , Giorgio Ivan Russo  18 , Germar-Michael Pinggera  19 , Eric Chung  20 , Ahmed M Harraz  21   22   23 , Marlon Martinez  24 , Nguyen Ho Vinh Phuoc  25 , Nicholas Tadros  26 , Ramadan Saleh  27 , Missy Savira  10 , Giovanni M Colpi  28 , Wael Zohdy  14 , Edoardo Pescatori  29 , Hyun Jun Park  30   31 , Shinichiro Fukuhara  32 , Akira Tsujimura  33 , Cesar Rojas-Cruz  34 , Angelo Marino  35 , Siu King Mak  36 , Edouard Amar  37 , Wael Ibrahim  38 , Puneet Sindhwani  39 , Naif Alhathal  40 , Gian Maria Busetto  41 , Manaf Al Hashimi  42   43 , Ahmed El-Sakka  44 , Asci Ramazan  45 , Fotios Dimitriadis  46 , Massimiliano Timpano  47 , Davor Jezek  48 , Baris Altay  49 , Daniel Suslik Zylbersztejn  50 , Michael Yc Wong  51 , Du Geon Moon  52 , Christine Wyns  53 , Safar Gamidov  54 , Hamed Akhavizadegan  55 , Alessandro Franceschelli  56 , Kaan Aydos  57 , Nguyen Quang  58   59 , Shedeed Ashour  14 , Adel Al Dayel  60 , Mohammed S Al-Marhoon  61 , Sava Micic  62 , Saleh Binsaleh  63 , Alayman Hussein  8 , Haitham Elbardisi  13   15 , Taymour Mostafa  14 , Jonathan Ramsay  64 , Athanasios Zachariou  65 , Islam Fathy Soliman Abdelrahman  14   66 , Osvaldo Rajmil  67 , Arif Kalkanli  68 , Juan Manuel Corral Molina  69 , Kadir Bocu  70 , Gede Wirya Kusuma Duarsa  71 , Gökhan Çeker  72 , Ege Can Serefoglu  73 , Fahmi Bahar  74 , Nazim Gherabi  75 , Shinnosuke Kuroda  76 , Abderrazak Bouzouita  77 , Ahmet Gudeloglu  78 , Erman Ceyhan  79 , Mohamed Saeed Mohamed Hasan  80 , Muhammad Ujudud Musa  81 , Ahmad Motawi  14 , Chak-Lam Cho  82 , Hisanori Taniguchi  83 , Christopher Chee Kong Ho  84 , Jesus Fernando Solorzano Vazquez  85 , Shingai Mutambirwa  86 , Nur Dokuzeylul Gungor  87 , Marion Bendayan  88   89 , Carlo Giulioni  90 , Aykut Baser  91 , Marco Falcone  47 , Luca Boeri  92 , Gideon Blecher  93   94 , Alireza Kheradmand  95 , Tamilselvi Sethupathy  96 , Ricky Adriansjah  97 , Nima Narimani  98 , Charalampos Konstantinidis  99 , Tuan Thanh Nguyen  100   101   102 , Andrian Japari  103 , Parisa Dolati  104 , Keerti Singh  105   106 , Cevahir Ozer  79 , Selcuk Sarikaya  107 , Nadia Sheibak  108   109 , Ndagijimana Jean Bosco  110 , Mehmet Serkan Özkent  111 , Sang Thanh Le  8   103 , Ioannis Sokolakis  112 , Darren Katz  113   114   115 , Ryan Smith  116 , Manh Nguyen Truong  104   117 , Tan V Le  25   118 , Zhongwei Huang  119 , Muslim Dogan Deger  120 , Umut Arslan  11 , Gokhan Calik  121 , Giorgio Franco  122 , Ayman Rashed  123 , Oguzhan Kahraman  79 , Sotiris Andreadakis  124 , Rosadi Putra  125 , Giancarlo Balercia  5 , Kareim Khalafalla  20   126 , Rossella Cannarella  18 , Anh Đặng Tuấn  127 , Amr El Meliegy  14 , Birute Zilaitiene  128 , Marlene Lizbeth Zamora Ramirez  129 , Filippo Giacone  130 , Aldo E Calogero  18 , Konstantinos Makarounis  131 , Sunil Jindal  132 , Bac Nguyen Hoai  133 , Ravi Banthia  134 , Marcelo Rodriguez Peña  135 , Dharani Moorthy  136 , Aram Adamyan  137 , Deniz Kulaksiz  138 , Hussein Kandil  139 , Nikolaos Sofikitis  65 , Ciro Salzano  140 , Andreas Jungwirth  141 , Surendra Reddy Banka  142 , Tiago Cesar Mierzwa  143 , Tahsin Turunç  144 , Divyanu Jain  145 , Armen Avoyan  138 , Pietro Salacone  146 , Ateş Kadıoğlu  147 , Chirag Gupta  148 , Haocheng Lin  149 , Iman Shamohammadi  150 , Nasser Mogharabian  151 , Trenton Barrett  152 , Yavuz Onur Danacıoğlu  153 , Andrea Crafa  18 , Salima Daoud  154 , Vineet Malhotra  155 , Abdulmalik Almardawi  156 , Osama Mohamed Selim  14 , Mohamad Moussa  157   158 , Saeid Haghdani  159 , Mesut Berkan Duran  160 , Yannic Kunz  19 , Mirko Preto  47 , Elena Eugeni  161   162 , Thang Nguyen  138 , Ahmed Rashad Elshahid  123 , Seso Sulijaya Suyono  163 , Dyandra Parikesit  164 , Essam Nada  27 , Eduardo Gutiérrez Orozco  165 , Florence Boitrelle  88   89 , Nguyen Thi Minh Trang  102 , Mounir Jamali  166 , Raju Nair  167 , Mikhail Ruzaev  168 , Franco Gadda  92 , Charalampos Thomas  99 , Raphael Henrique Ferreira  169 , Umit Gul  170 , Serena Maruccia  171 , Ajay Kanbur  172   173 , Ella Kinzikeeva  174 , Saad Mohammed Abumelha  156 , Raghavender Kosgi  175 , Fatih Gokalp  176 , Mohammad Ayodhia Soebadi  177 , Gustavo Marquesine Paul  178 , Hesamoddin Sajadi  179 , Deepak Gupte  180 , Rafael F Ambar  143 , Emrullah Sogutdelen  181 , Karun Singla  182 , Ari Basukarno  183 , Shannon Hee Kyung Kim  184 , Mohammad Ali Sadighi Gilani  179 , Koichi Nagao  185 , Sakti Ronggowardhana Brodjonegoro  186 , Andri Rezano  187   188 , Mohamed Elkhouly  189 , Rossella Mazzilli  190 , Hasan M A Farsi  7 , Hung Nguyen Ba  191 , Hamed Alali  184 , Dimitrios Kafetzis  192 , Tran Quang Tien Long  193 , Sami Alsaid  14 , Hoang Bao Ngoc Cuong  194 , Knigavko Oleksandr  195 , Akhmad Mustafa  97 , Herik Acosta  196 , Hrishikesh Pai  197 , Bahadır Şahin  198 , Eko Arianto  199 , Colin Teo  200 , Sanjay Prakash Jayaprakash  17 , Rinaldo Indra Rachman  10 , Mustafa Gurkan Yenice  153 , Omar Sefrioui  201 , Shivam Priyadarshi  202 , Marko Tanic  203 , Noor Kareem Alfatlaw  204 , Fikri Rizaldi  187 , Ranjit B Vishwakarma  2 , George Kanakis  205 , Dinesh Thomas Cherian  206 , Joe Lee  207 , Raisa Galstyan  208 , Hakan Keskin  80 , Janan Wurzacher  19 , Doddy Hami Seno  209 , Bambang S Noegroho  97 , Ria Margiana  199   210   211   212 , Qaisar Javed  213 , Fabrizio Castiglioni  214 , Raman Tanwar  215 , Ana Puigvert  87   216 , Coşkun Kaya  217 , Medianto Purnomo  218 , Chadi Yazbeck  219 , Azwar Amir  220 , Edson Borges  221 , Marina Bellavia  28 , Isaac Ardianson Deswanto  10 , Vinod Kv  222 , Giovanni Liguori  223 , Dang Hoang Minh  59 , Kashif Siddiqi  224 , Fulvio Colombo  29 , Armand Zini  225 , Niket Patel  226 , Selahittin Çayan  227 , Ula Al-Kawaz  228 , Maged Ragab  229 , Guadalupe Hernández Hebrard  230 , Jean de la Rosette  121 , Ozan Efesoy  229 , Ivan Hoffmann  231   232 , Thiago Afonso Teixeira  233   234   235 , Barış Saylam  227 , Daniela Delgadillo  85 , Ashok Agarwal  236 ; Global Andrology Forum
Affiliations

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

Amarnath Rambhatla et al. World J Mens Health. 2025 Jan.

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.

Keywords: Azoospermia; Hypogonadism; Infertility, male; Semen; Sperm retrieval.

PubMed Disclaimer

Conflict of interest statement

The authors have nothing to disclose.

Figures

Fig. 1
Fig. 1. Geographical distribution of respondents. The number of respondents is shown in brackets after the name of each country. The map is color-coded according to the number of respondents in each country.
Fig. 2
Fig. 2. Years of practice of the respondents.
Fig. 3
Fig. 3. The number of new couples evaluated per week by the respondents.
Fig. 4
Fig. 4. Characteristics of NOA patients who are offered hormonal therapy. NOA: non-obstructive azoospermia.
Fig. 5
Fig. 5. Duration of hormonal therapy before sperm retrieval in NOA patient. NOA: non-obstructive azoospermia.
Fig. 6
Fig. 6. Evaluation of the effect of hormonal therapy before sperm retrieval. LH: luteinizing hormone, FSH: follicle-stimulating hormone, T: testosterone, T/E2: testosterone to estradiol ratio.
Fig. 7
Fig. 7. Hormonal therapy before sperm retrieval in hypergonadotropic NOA patient. NOA: non-obstructive azoospermia, HCG: human chorionic gonadotropin, FSH: follicle-stimulating hormone, HMG: human menopausal gonadotropin.
Fig. 8
Fig. 8. Hormonal therapy before sperm retrieval in eugonadotropic NOA patient. NOA: non-obstructive azoospermia, HCG: human chorionic gonadotropin, FSH: follicle-stimulating hormone, HMG: human menopausal gonadotropin.
Fig. 9
Fig. 9. Advice for patient with NOA due to exogenous testosterone. NOA: non-obstructive azoospermia, HCG: human chorionic gonadotropin, FSH: follicle-stimulating hormone, HMG: human menopausal gonadotropin.
Fig. 10
Fig. 10. Proportion of respondents who prescribe exogenous testosterone therapy when a man with NOA has a low testosterone level and is yet to undergo sperm retrieval. NOA: non-obstructive azoospermia, HCG: human chorionic gonadotropin, LH: luteinizing hormone, SERM: selective estrogen receptor modulators
Fig. 11
Fig. 11. Frequency performing mTESE for NOA cases. mTESE: microdissection testicular sperm extraction, NOA: non-obstructive azoospermia.
Fig. 12
Fig. 12. Overall surgical sperm retrieval rate in men with NOA. mTESE: microdissection testicular sperm extraction, NOA: non-obstructive azoospermia.
Fig. 13
Fig. 13. General acceptability of mTESE in your practice. mTESE: microdissection testicular sperm extraction, OA: obstructive azoospermia, NOA: non-obstructive azoospermia
Fig. 14
Fig. 14. Sperm retrieval rate in patients with Klinefelter syndrome.
Fig. 15
Fig. 15. Working place of laboratory team during surgical sperm retrieval.
Fig. 16
Fig. 16. Time needed by embryologist to look for sperm before declaring absence of sperm in retrieved samples at the time of mTESE. mTESE: microdissection testicular sperm extraction.
Fig. 17
Fig. 17. Preference of sperm during mTESE for ICSI. mTESE: microdissection testicular sperm extraction, ICSI: intracytoplasmic sperm injection, IVF: in vitro fertilization.
Fig. 18
Fig. 18. Testicular biopsy for histopathology at the time of surgical sperm retrieval.
Fig. 19
Fig. 19. Genetic conditions to perform surgical sperm retrieval in patients with NOA. mTESE: microdissection testicular sperm extraction, cTESE: conventional testicular sperm extraction, NOA: non-obstructive azoospermia, AZF: azoospermia factor.
Fig. 20
Fig. 20. Microsurgical varicocelectomy in case of large varicocele associated with NOA. NOA: non-obstructive azoospermia.
Fig. 21
Fig. 21. Conditions to recommend surgery for a varicocele associated with NOA. NOA: non-obstructive azoospermia, FSH: follicle-stimulating hormone.
Fig. 22
Fig. 22. Treatment option for patient with genetic abnormality as well as clinical varicocele and NOA. AZF: azoospermia factor, NOA: non-obstructive azoospermia.
Fig. 23
Fig. 23. Surgery for subclinical varicocele in NOA patient without other pathology present. NOA: non-obstructive azoospermia.
Fig. 24
Fig. 24. Proportion of sperm recovery in the ejaculate of NOA men following varicocele repair. NOA: non-obstructive azoospermia.
Fig. 25
Fig. 25. Imaging targeted testicular biopsies in NOA. NOA: non-obstructive azoospermia.
Fig. 26
Fig. 26. Innovations to increase sperm retrieval rate during mTESE. mTESE: microdissection testicular sperm extraction.
Fig. 27
Fig. 27. Fine needle aspiration (FNA) mapping prior to sperm retrieval procedure.
Fig. 28
Fig. 28. Planning TESA vs cTESE vs mTESE in men with NOA. TESA: testicular sperm aspiration, cTESE: conventional testicular sperm extraction, mTESE: microdissection testicular sperm extraction, NOA: non-obstructive azoospermia.
Fig. 29
Fig. 29. Clinical situations where mTESE is significantly superior to cTESE. mTESE: microdissection testicular sperm extraction, cTESE: conventional testicular sperm extraction, NOA: non-obstructive azoospermia, FSH: follicle-stimulating hormone.
Fig. 30
Fig. 30. Waiting period to perform mTESE after a failed cTESE in men with NOA. mTESE: microdissection testicular sperm extraction, cTESE: conventional testicular sperm extraction, NOA: non-obstructive azoospermia.
Fig. 31
Fig. 31. Period of waiting to perform mTESE after successful mTESE in men with NOA. mTESE: microdissection testicular sperm extraction, NOA: non-obstructive azoospermia.
Fig. 32
Fig. 32. Period of waiting to perform mTESE after failed mTESE. mTESE: microdissection testicular sperm extraction.
Fig. 33
Fig. 33. Procedure for man with NOA and bilaterally symmetrical testes if no sperm found on one side during mTESE. NOA: non-obstructive azoospermia, mTESE: microdissection testicular sperm extraction.
Fig. 34
Fig. 34. The highest FSH level to surgically obtain sperm in NOA. FSH: follicle-stimulating hormone, NOA: non-obstructive azoospermia.
Fig. 35
Fig. 35. Preimplantation genetic testing of embryos in couples doing IVF/ICSI when sperm have been retrieved with mTESE in men with 47XXY. IVF: in vitro fertilization, ICSI: intracytoplasmic sperm injection, mTESE: microdissection testicular sperm extraction.
Fig. 36
Fig. 36. Treatment before sperm retrieval procedure in NOA patients. NOA: non-obstructive azoospermia.
Fig. 37
Fig. 37. Use of testicular MRI prior to sperm retrieval procedures in patients with the majority of the respondents (285, 86.9%) consider MRI useful in clinical practice, whereas 43 (13.1%) consider it as an experimental instrument. MRI: magnetic resonance imaging, NOA: non-obstructive azoospermia.
Fig. 38
Fig. 38. The biggest advancement in the treatment of NOA over the next 10 years. NOA: non-obstructive azoospermia.
Fig. 39
Fig. 39. The strength weakness, opportunities, and threat (SWOT) analysis.
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References

    1. Jarow JP, Espeland MA, Lipshultz LI. Evaluation of the azoospermic patient. J Urol. 1989;142:62–65. - PubMed
    1. Mazzilli F, Rossi T, Delfino M, Sarandrea N, Dondero F. Azoospermia: incidence, and biochemical evaluation of seminal plasma by the differential pH method. Panminerva Med. 2000;42:27–31. - PubMed
    1. Wosnitzer M, Goldstein M, Hardy MP. Review of azoospermia. Spermatogenesis. 2014;4:e28218. - PMC - PubMed
    1. Gudeloglu A, Parekattil SJ. Update in the evaluation of the azoospermic male. Clinics (Sao Paulo) 2013;68(Suppl 1):27–34. - PMC - PubMed
    1. Eysenbach G. Improving the quality of Web surveys: the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) J Med Internet Res. 2004;6:e34. Erratum in: doi: 10.2196/jmir.2042. - PMC - PubMed