A Global Survey of Reproductive Specialists to Determine the Clinical Utility of Oxidative Stress Testing and Antioxidant Use in Male Infertility

Abstract

Purpose The use of antioxidants is common practice in the management of infertile patients. However, there are no established guidelines by professional societies on antioxidant use for male infertility. Materials and Methods Using an online survey, this study aimed to evaluate the practice pattern of reproductive specialists to determine the clinical utility of oxidative stress (OS) testing and antioxidant prescriptions to treat male infertility. Results Responses from 1,327 participants representing 6 continents, showed the largest participant representation being from Asia (46.8%). The majority of participants were attending physicians (59.6%), with 61.3% having more than 10 years of experience in the field of male infertility. Approximately two-thirds of clinicians (65.7%) participated in this survey did not order any diagnostic tests for OS. Sperm DNA fragmentation was the most common infertility test beyond a semen analysis that was prescribed to study oxidative stress-related dysfunctions (53.4%). OS was mainly tested in the presence of lifestyle risk factors (24.6%) or sperm abnormalities (16.3%). Interestingly, antioxidants were prescribed by 85.6% of clinicians, for a duration of 3 (43.7%) or 3–6 months (38.6%). A large variety of antioxidants and dietary supplements were prescribed, and scientific evidence were mostly considered to be modest to support their clinical use. Results were not influenced by the physician's age, geographic origin, experience or training in male infertility. Conclusions This study is the largest online survey performed to date on this topic and demonstrates 1) a worldwide understanding of the importance of this therapeutic option, and 2) a widely prevalent use of antioxidants to treat male infertility. Finally, the necessity of evidence-based clinical practice guidelines from professional societies is highlighted.

Telomere Signaling and Maintenance Pathways in Spermatozoa of Infertile Men Treated With Antioxidants: An in silico Approach Using Bioinformatic Analysis

“…Antioxidants are widely used in the treatment of male infertility. A recent global survey reported that 85.6% of physicians involved in the management of male infertility prescribe antioxidants as a part of their treatment regime ( Agarwal et al, 2021a ). Apart from improving the semen parameters, antioxidant intake increases the sperm DNA integrity without any side effects/complications ( Zini et al, 2009 ; Majzoub et al, 2017 ; Arafa et al, 2020 ).…”

“…Antioxidants that counterbalance the increased levels of seminal ROS are widely used in the management of oxidative stress-mediated male infertility ( Agarwal et al, 2021a , b ). Use of antioxidants in treatment of male infertility have shown to improve semen parameters ( Keskes-Ammar et al, 2003 ; Smits et al, 2019 ; Arafa et al, 2020 ).…”

Toxicity of Antioxidant Supplements in Patients with Male Factor Infertility: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…In fact, most systematic reviews and meta-analyses on the topic showed an overall low quality of included studies; therefore, no clear recommendation for antioxidant therapy can be drawn [ 6 , 33 , 34 ]. Nevertheless, in a recent survey, more than 85% of clinicians worldwide stated that they recommend antioxidant therapy in infertile males [ 35 ]. Of note, recent evidence suggests that antioxidant supplements may be harmful and cause unwanted consequences to health [ 36 , 37 , 38 , 39 , 40 ].…”

Oxidative Stress: A Comprehensive Review of Biochemical, Molecular, and Genetic Aspects in the Pathogenesis and Management of Varicocele

“…The use of antioxidants in male infertility has received significant attention due the central role of oxidative stress in many causes of male infertility [ 25 ]. Antioxidants are also reported to be used extensively by urologists and reproductive medicine specialists globally [ 146 ]. Common antioxidants used in clinical practice include vitamin A (carotenes), vitamin C (ascorbic acid), vitamin E (tocopherols), carnitine, N-acetyl-cysteine (NAC) and Co-Enzyme Q 10 (CoQ 10 ), as well as antioxidant co-factors including selenium, zinc, and folic acid [ 25 147 ].…”

“…As oxidative stress is also closely associated with varicocele pathogenesis, there is significant interest in the use of antioxidants in the management of varicocele as a sole therapy or alongside varicocele repair [ 122 ]. In fact, antioxidants for varicocele in clinical practice is reportedly recommended by 39.9% of reproductive medicine specialists [ 146 ]. Antioxidants may also be a non-invasive alternative to consider prior to surgery or more expensive ART management [ 122 ].…”