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Not As Easy as A, B, C

By Team RMI on March 18, 2016

An Extra Boost?

Antioxidants are by far the most studied supplement in reproductive medicine.  Reactive oxygen species (ROS) are a natural byproduct of oxygen metabolism, and can be formed endogenously (internally) by cells upon conversion of energy into a usable form, as well as exogenously (externally) through exposure to smoke/tobacco, radiation, and other environmental pollutants. Although ROS play a role in several natural reproductive processes such as ovulation, there is a growing body of literature which suggests that an excess may also have negative impacts on reproductive ageing, oocyte maturation and fertilization, and embryo development (Agarwal, 2005).  Because of this, several researchers have hypothesized that the use of antioxidants may mitigate these negative effects and in turn lead to a higher chance for pregnancy and treatment success in infertile couples.

Unfortunately, there are no commercially available assays which test levels of oxidative stress in the female reproductive tract, making clinical evaluation of the effectiveness and benefit of treatment challenging.  As such, the literature is limited and the conclusions less than clear.  Examples of anti-oxidants which have been studied include Vitamins A, C, E, Coenzyme Q10, Melatonin, Vitamin B 12, L-arginine, Myo-inositol, Vitamin D, and Selenium.  Available fertility blend supplements contain a varying combination of vitamins and anti-oxidants.  Given the general clean safety history of dietary supplements, Food and Drug Administration (FDA) approval is not required; ultimately, this means that it is not compulsory for manufacturers to test their products for safety and effectiveness, which may lead to uneven quality within the products.  However, manufacturers are still required to comply with general FDA guidelines, and if adverse effects are reported, they are immediately investigated by the FDA. 

Data Dilemmas

A recent review of nearly 30 studies revealed no significant improvement in the chance for live birth or clinical pregnancy following antioxidant use, however the limitations in individual study design, quality, and size make the overall conclusion one which is based on poor quality data (Showell 2013).  Additionally, although no benefit could be drawn, no increased risk for adverse effects in users of antioxidants was seen, although again the data was limited.  This is key when considering benefit versus risk.

While the science behind antioxidants and their role in improving both fertility and outcomes from fertility treatment is still under investigation, there is certainly biologic plausibility to a potential benefit of their use.  In my own Chicago based practice, I may recommend the use of certain supplements or antioxidants based on a patient’s history.  Yet, at the end of the day, we are in need of more data exploring the use of antioxidants in couples with infertility, and as such, couples considering the use of nutritional supplements should discuss this with their physician prior to use.


Agarwal A, Gupta S, Sharma RK. Role of oxidative stress in female reproduction. Reprod Biol Endocrinol 2005; 3: 28
Showell M, Brown J, Clarke J, Hart RJ.  Antioxidants for female subfertility.  Cochrane Database Syst Rev.  2013 Aug 5; 8

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