Infertility plagues couples intent on having children, with a global prevalence of 15%. In 50% of cases, fertility is linked to male factors.

Li KP, Yang XS, Wu T. The effect of antioxidants on sperm quality parameters and pregnancy rates for idiopathic male infertility: a network meta-analysis of randomized controlled trials. Front Endocrinol (Lausanne). 2022;13:13:810242.

 

 

Much evidence points to oxidative stress as a principal player in male infertility. Consequently, antioxidants may improve sperm parameters, according to the experts.

 

Male oxidative stress infertility

 

In 2019, a group of international researchers proposed the concept of male oxidative stress infertility (MOSI), referring to men with abnormal semen characteristics and oxidative stress. One potential clinical biomarker for this condition is oxidation-reduction potential. This metric considers concentrations of both oxidants and reductants.

Agarwal A, Parekh N, Panner Selvam MK, et al. Male oxidative stress infertility (MOSI): proposed terminology and clinical practice guidelines for management of idiopathic male infertility. World J Mens Health. 2019;37(3):296–312.

 

Either leukocytes or abnormal/immature spermatozoa produce seminal reactive oxygen species (ROS). These ROS are a byproduct of metabolic pathways, as well as resulting from cytosolic and plasma membrane oxidases and ATP production at the level of sperm cell mitochondria. 

“Small quantities of ROS are required to ensure normal cellular physiological functions, including spermatogenesis and various sperm functions preceding fertilization, such as capacitation and acrosome reaction,” the researchers wrote. “When ROS levels increase to a pathological level, the body uses dietary and endogenously produced antioxidants to bring the system back to homeostasis.”

Elevated oxidative stress can also contribute to sperm genotoxic and mutagenic byproducts, which can raise the  disease risk in the offspring.

 

Role of supplements

 

Results of a recent network meta-analysis underscored the effects of various antioxidants on sperm quality and pregnancy rates in patients with idiopathic male infertility.

Li KP, Yang XS, Wu T. The effect of antioxidants on sperm quality parameters and pregnancy rates for idiopathic male infertility: a network meta-analysis of randomized controlled trials. Front Endocrinol (Lausanne). 2022;13:13:810242.

 

Investigators included 23 RCTs (n=1,917) representing 10 types of antioxidants. Overall, L-carnitine, L-carnitine+L-acetylcarnitine, coenzyme-Q10 (CoQ10), ω-3 fatty acid, and selenium were most effective in improving sperm quality parameters.

Other research supports the use of the following doses in reversing OS-related sperm dysfunction and enhancing pregnancy rates: folic acid (0.5 mg), selenium (200 mg), vitamin E (400 mg), carnitines (500–1000 mg), vitamin C (500–1000 mg), CoQ10 (100–300 mg), NAC (600 mg), zinc (25–400 mg),  and lycopene (6–8 mg). These antioxidants can be used either as monotherapy or combined therapy.

Dimitriadis F, Borgmann H, Struck JP, et al. Antioxidant supplementation on male fertility—a systematic review. Antioxidants (Basel). 2023;12(4):836.

 

 

Length of treatment

 

A global survey of 1,327 reproductive specialists from 88 countries indicated that 85.6% routinely prescribed oral antioxidants. In total, 43.7% of these clinicians prescribed these supplements for 3 months, whereas 38.6% prescribed them for between 3 and 6 months.

Agarwal A, Finelli R, Panner Selvam MK, et al. A global survey of reproductive specialists to determine the clinical utility of oxidative stress testing and antioxidant use in male infertility. World J Mens Health. 2021;39(3):470–488.

 

Researchers publishing in Fertility and Sterility sought to clarify the optimum duration of antioxidant therapy in male infertility.

Kuroda S, Agarwal A, Saleh R, et al. Antioxidant therapy for male infertility–3 month or 6 months: which is better? Fertil Steril. 2021;116(3;Suppl E352).

 

Antioxidants reviewed included vitamins C and E, L-carnitine, folic acid, CoQ10, zinc, and selenium.

Taken together, these results seem to suggest that there’s little reason to continue antioxidant supplementation past 3 months if there is no improvement in sperm quality. However, the authors note, other studies have demonstrated a non-statistical trend toward improvement in sperm parameters when treatment duration approaches 6 months. 

The authors concluded: “It may be argued that the uncertainty surrounding the effectiveness of [antioxidant] therapy in male infertility is attributed, at least in part, to their use for insufficient durations. On the other hand, a concern exists for the potential risk(s) associated with the uncontrolled use of [antioxidant] therapy for extended periods of time.”