Global Andrology Forum Clinical Guidelines on Antioxidant Use in the Treatment of Male Infertility

Authors

Ashok Agarwal
Taymour Mostafa
Manaf Al Hashimi
Selahittin Çayan
Edoardo Pescatori
Keerti Singh
Bahadır Şahin
Armand Zini
Eric Chung
Mohamed Arafa
Edmund Ko
Germar-M Pinggera
Ramadan Saleh
Widi Atmoko
Amarnath Rambhatla, Henry Ford HealthFollow
Rossella Cannarella
Ayad Palani
Cevahir Ozer
Mohammed Abdulgabbar Noman
Fotios Dimitriadis
Tuncay Toprak
Erman Ceyhan
Juan Manuel Corral Molina
Manh Truong Nguyen
Tan V Le
Rosadi Putra
Luca Boeri
Murat Gül
Naif Alhathal
Hussein Kandil
Charalampos Thomas
Ayman Rashed
Saleh Binsaleh
Marco Falcone
Niwanda Yogiswara
Andrian Japari
Akhaine Oriazowan Julius
Gökhan Çeker
Nur Dokuzeylül Güngör
Carlo Giulioni
Islam Fathy Soliman Abdelrahman
Quang Nguyen
Gokhan Calik
Abheesh Varma Hegde
Ahmad Tarek Motawi
Satish Pundlik Dipankar
Celeste Manfredi
Akira Tsujimura
Charalampos Konstantinidis
Shedeed Ashour
Essam Aa Nada
Mohamed Al-Marhoon
Mohammed Abu El-Hamd
Moheiddin Alghobary
Nasser Mogharabian
Murtadha Almusafer
Ahmed El-Sakka
Ahmed Abd Elmoaty Khalifa
Selcuk Sarikaya
Nguyen Ho Vinh Phuoc
Noor Kareem Alfatlawy
Lim Tze Ying Benjamin
Ryan Patrick Smith
Hyun Jun Park
Giorgio Ivan Russo
Eser Ördek
Haocheng Lin
Mustafa Kadihasanoglu
Naveen Kumar
Muslim Dogan Deger
Kareim Mohamed Khalafalla
Baris Altay
Siu King Mak
Sadik Görür
Iman Shamohammadi
Murat Dursun
David Pening
Nima Narimani
Mustafa Suat Bolat
Osvaldo Rajmil
Ula Mohmmed Alkawaz
Kaan Aydos
Coşkun Kaya
Walter D Cardona Maya
Athanasios Zachariou
Mesut Berkan Duran
Taras Shatylko
Giancarlo Balercia
Jean De La Rosette
Amr El Meliegy
Barış Saylam
Tuncer Bahçeci
Ozan Efesoy
Elena Eugeni
Birute Zilaitiene
Nazim Gherabi
Oğuzhan Kahraman
Andrea Crafa
Jesus Fernando Solorzano Vazquez
Fahmi Bahar
Emad Abdelraheem Taha
Osama M Selim
Mohamed Saeed Mohamed Hasan
Nicholas N Tadros
Christopher Chee Kong Ho
Emrullah Sogutdelen
Gian Maria Busetto
Sava Micic
Fatih Gokalp
Ehab Jasim Mohammad
Ramazan Asci
Eray Hasirci
Muhammad Ujudud Musa
Praveen Bhimasen Joshi
Ahmed Reda
Chadi Yazbeck
Ricky Adriansjah
Ella Kinzikeeva
Gianmaria Salvio
Tahsin Turunc
Dongsuk Kim
Ranjit Babulal Vishwakarma
Konstantinos Makarounis
Mikhail Ruzaev
Hiva Alipour
Rupin Shah

Document Type

Article

Publication Date

1-1-2026

Publication Title

World J Mens Health

Keywords

Antioxidants; Delphi technique; GRADE approach; Guideline; Male infertility; Surveys and questionnaires

Abstract

PURPOSE: Antioxidant (AOX) therapy has long been investigated for the management of male infertility. It has potential benefits, but persistent controversy affects its broad acceptance and clinical utility. This study aimed to develop standardized, evidence-based guidelines for AOX use by synthesizing the best available evidence and achieving global expert consensus.

MATERIALS AND METHODS: A comprehensive literature review was conducted by senior experts of the Global Andrology Forum (GAF). Additionally, data on the real-life use of oxidative stress (OS) testing and AOX use obtained from the largest global survey of practicing physicians conducted by GAF, which served as a reference point for this study. In phase one, 151 international specialists (>5 years' experience) participated in a modified Delphi process to evaluate AOX therapy in male infertility. Experts reviewed draft statements and rated agreement on a 10-point Likert scale. Statements achieving >80% consensus (with score >7/10) were accepted. The original eight statements were expanded to 19 and finalized into 18. In phase two, 84 senior physicians (>10 years' experience) graded the Delphi-approved statements using the GRADE approach.

RESULTS: Four out of the 18 statements failed to reach consensus and were excluded. Of the final 14 statements, seven (50%) were graded as "Strong" and seven (50%) as "Weak." Current evidence indicates that AOX therapy can reduce OS, improve sperm quality, and potentially enhance reproductive outcomes. However, benefits vary by agent, regimen, and patient population. The guidelines emphasize the need to document OS and to consider underlying factors before initiating AOX therapy, and caution against indiscriminate or prolonged use.

CONCLUSIONS: Developed through a dual-validation process and endorsed by a globally diverse expert panel, these GAF guidelines represent the first standardized, evidence-based guidelines for AOX use in male infertility. By addressing heterogeneity in research and practice, they provide clinicians with practical, safe, and patient-centered recommendations for rational AOX therapy worldwide.

PubMed ID

41508382

ePublication

ePub ahead of print

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