Utility of Antioxidants in the Treatment of Male Infertility: Clinical Guidelines Based on a Systematic Review and Analysis of Evidence

Ashok Agarwal; Kristian Leisegang; Ahmad Majzoub; Ralf Henkel; Renata Finelli; Manesh Kumar Panner Selvam; Nicholas Tadros; Neel Parekh; Edmund Y Ko; Chak Lam Cho; Mohamed Arafa; Marco G Alves; Pedro Fontes Oliveira; Juan G Alvarez; Rupin Shah

doi:10.5534/wjmh.200196

Utility of Antioxidants in the Treatment of Male Infertility: Clinical Guidelines Based on a Systematic Review and Analysis of Evidence

World J Mens Health. 2021 Apr;39(2):233-290. doi: 10.5534/wjmh.200196. Epub 2021 Jan 15.

Authors

Ashok Agarwal¹, Kristian Leisegang², Ahmad Majzoub^{3

4

5}, Ralf Henkel^{3

6

7}, Renata Finelli³, Manesh Kumar Panner Selvam³, Nicholas Tadros⁸, Neel Parekh⁹, Edmund Y Ko¹⁰, Chak Lam Cho^{11

12}, Mohamed Arafa^{3

4

13}, Marco G Alves¹⁴, Pedro Fontes Oliveira¹⁵, Juan G Alvarez¹⁶, Rupin Shah¹⁷

Affiliations

¹ American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA. agarwaa@ccf.org.
² School of Natural Medicine, Faculty of Community and Health Sciences, University of the Western Cape, Bellville, South Africa.
³ American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA.
⁴ Department of Urology, Hamad Medical Corporation, Doha, Qatar.
⁵ Department of Urology, Weill Cornell Medicine - Qatar, Doha, Qatar.
⁶ Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
⁷ Department of Medical Bioscience, University of the Western Cape, Bellville, South Africa.
⁸ Division of Urology, Southern Illinois University School of Medicine, Springfield, IL, USA.
⁹ Department of Urology, Cleveland Clinic, Cleveland, OH, USA.
¹⁰ Department of Urology, Loma Linda University, Loma Linda, CA, USA.
¹¹ Department of Surgery, Union Hospital, Hong Kong.
¹² S. H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong, Hong Kong.
¹³ Andrology Department, Cairo University, Giza, Egypt.
¹⁴ Department of Anatomy & Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
¹⁵ QOPNA & LAQV, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
¹⁶ Centro Androgen, La Coruña, Spain and Harvard Medical School, Boston, MA, USA.
¹⁷ Department of Urology, Lilavati Hospital and Research Centre, Mumbai, India.

Abstract

It is widely accepted that oxidative stress plays an important role in the pathophysiology of male infertility and that antioxidants could have a significant role in the treatment of male infertility. The main objectives of this study are: 1) to systematically review the current evidence for the utility of antioxidants in the treatment of male infertility; and 2) propose evidence-based clinical guidelines for the use of antioxidants in the treatment of male infertility. A systematic review of the available clinical evidence was performed, with articles published on Scopus being manually screened. Data extracted included the type of antioxidant used, the clinical conditions under investigation, the evaluation of semen parameters and reproductive outcomes. The adherence to the Cambridge Quality Checklist, Cochrane Risk of Bias for randomized controlled trials (RCTs), CONSORT guidelines and JADAD score were analyzed for each included study. Further, we provided a Strength Weakness Opportunity Threat (SWOT) analysis to analyze the current and future value of antioxidants in male infertility. Of the 1,978 articles identified, 97 articles were included in the study. Of these, 52 (53.6%) were uncontrolled (open label), 12 (12.4%) unblinded RCTs, and 33 (34.0%) blinded RCTs, whereas 44 (45.4%) articles tested individual antioxidants, 31 (32.0%) a combination of several products in variable dosages, and 22 (22.6%) registered antioxidant products. Based on the published evidence, we 1) critically examined the necessity of additional double-blind, randomized, placebo-controlled trials, and 2) proposed updated evidence-based clinical guidelines for antioxidant therapy in male infertility. The current systematic review on antioxidants and male infertility clearly shows that antioxidant supplementation improves semen parameters. In addition, it provides the indications for antioxidant treatment in specific clinical conditions, including varicocele, unexplained and idiopathic male infertility, as well as in cases of altered semen quality.

Keywords: Antioxidants; Oxidative stress; Practice guideline; Semen analysis; Sperm maturation.

Publication types

Review

Grants and funding

500000105879/American Center for Reproductive Medicine/United States of America