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Impact of Antioxidant Therapy on Natural Pregnancy Outcomes and Semen Parameters in Infertile Men: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Agarwal A 1 , Cannarella R 2 , Saleh R 3 , Harraz AM 4 , Kandil H 5 , Salvio G 6 Show all authors , Boitrelle F 7 , Kuroda S 8 , Farkouh A 9 , Rambhatla A 10 , Zini A 11 , Colpi G 12 , Gül M 13 , Kavoussi P 14 , Hamoda TAA 15 , Ko E 16 , Calik G 17 , Toprak T 18 , Pinggera GM 19 , Park HJ 20 , Ghayda RA 21 , Minhas S 22 , Busetto GM 23 , Bakırcıoğlu ME 24 , Kadioglu A 25 , Chung E 26 , Russo GI 27 , Calogero AE 2 , Ambar RF 28 , Jayasena CN 29 , Shah R 30

Affiliations 

  • 1 American Center for Reproductive Medicine, Global Andrology Forum, Moreland Hills, OH, USA. agarwaa32099@outlook.com
  • 2 Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
  • 3 Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Sohag University, Sohag, Egypt
  • 4 Department of Urology, Mansoura University Urology and Nephrology Center, Mansoura, Egypt
  • 5 Fakih IVF Fertility Center, Abu Dhabi, UAE
  • 6 Department of Endocrinology, Polytechnic University of Marche, Ancona, Italy
  • 7 Reproductive Biology, Fertility Preservation, Andrology, CECOS, Poissy Hospital, Poissy, France
  • 8 Glickman Urological & Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
  • 9 American Center for Reproductive Medicine, Global Andrology Forum, Moreland Hills, OH, USA
  • 10 Department of Urology, Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI, USA
  • 11 Division of Urology, Department of Surgery, McGill University, Montreal, QC, Canada
  • 12 Next Fertility Procrea, Lugano, Switzerland
  • 13 Department of Urology, Selcuk University School of Medicine, Konya, Turkey
  • 14 Austin Fertility & Reproductive Medicine/Westlake IVF, Austin, TX, USA
  • 15 Department of Urology, King Abdulaziz University, Jeddah, Saudi Arabia
  • 16 Department of Urology, Loma Linda University Health, Loma Linda, CA, USA
  • 17 Department of Urology, Faculty of Medicine, Istanbul Medipol University, Istanbul, Turkey
  • 18 Department of Urology, Fatih Sultan Mehmet Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
  • 19 Department of Urology, Medical University Innsbruck, Innsbruck, Austria
  • 20 Department of Urology, Pusan National University School of Medicine, Busan, Korea
  • 21 Urology Institute, University Hospitals, Case Western Reserve University, Cleveland, OH, USA
  • 22 Division of Surgery, Department of Surgery and Cancer, Imperial College, London, UK
  • 23 Department of Urology and Organ Transplantation, University of Foggia, Ospedali Riuniti of Foggia, Foggia, Italy
  • 24 SENSART Clinic, Istanbul, Turkey
  • 25 Section of Andrology, Department of Urology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
  • 26 Department of Urology, Princess Alexandra Hospital, University of Queensland, Brisbane, Australia
  • 27 Urology Section, University of Catania, Catania, Italy
  • 28 Department of Urology, Centro Universitario em Saude do ABC, Santo André, Brazil
  • 29 Department of Reproductive Endocrinology and Andrology, Imperial College London, London, UK
  • 30 Division of Andrology, Department of Urology, Lilavati Hospital and Research Centre, Mumbai, India
World J Mens Health, 2023 Jan;41(1):14-48.
PMID: 36102104 DOI: 10.5534/wjmh.220067

Abstract

PURPOSE: Seminal oxidative stress (OS) is a recognized factor potentially associated with male infertility, but the efficacy of antioxidant (AOX) therapy is controversial and there is no consensus on its utility. Primary outcomes of this study were to investigate the effect of AOX on spontaneous clinical pregnancy, live birth and miscarriage rates in male infertile patients. Secondary outcomes were conventional semen parameters, sperm DNA fragmentation (SDF) and seminal OS.

MATERIALS AND METHODS: Literature search was performed using Scopus, PubMed, Ovid, Embase, and Cochrane databases. Only randomized controlled trials (RCTs) were included and the meta-analysis was conducted according to PRISMA guidelines.

RESULTS: We assessed for eligibility 1,307 abstracts, and 45 RCTs were finally included, for a total of 4,332 infertile patients. We found a significantly higher pregnancy rate in patients treated with AOX compared to placebo-treated or untreated controls, without significant inter-study heterogeneity. No effects on live-birth or miscarriage rates were observed in four studies. A significantly higher sperm concentration, sperm progressive motility, sperm total motility, and normal sperm morphology was found in patients compared to controls. We found no effect on SDF in analysis of three eligible studies. Seminal levels of total antioxidant capacity were significantly higher, while seminal malondialdehyde acid was significantly lower in patients than controls. These results did not change after exclusion of studies performed following varicocele repair.

CONCLUSIONS: The present analysis upgrades the level of evidence favoring a recommendation for using AOX in male infertility to improve the spontaneous pregnancy rate and the conventional sperm parameters. The failure to demonstrate an increase in live-birth rate, despite an increase in pregnancy rates, is due to the very few RCTs specifically assessing the impact of AOX on live-birth rate. Therefore, further RCTs assessing the impact of AOX on live-birth rate and miscarriage rate, and SDF will be helpful.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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