Male infertility testing Reactive oxygen species and antioxidant capacity

Elevated reactive oxygen species (ROS) levels have been associated with abnormal semen parameters and male infertility. The impact of ROS on fertilization rates and pregnancy remains controversial.

Edmund Y. Ko, M.D., Edmund S. Sabanegh, M.D., Ashok Agarwal, Ph.D.

Volume 102, Issue 6, Pages 1518-1527

Reactive oxygen species (ROS) are an integral component of sperm developmental physiology, capacitation, and function. Elevated ROS levels, from processes such as infection or inflammation, can be associated with aberrations of sperm development, function, and fertilizing capacity. We review the impact of ROS on sperm physiology, its place in infertility evaluation, the implications for reproductive outcomes, and antioxidant therapy. Our systematic review of PubMed literature from the last 3 decades focuses on the physiology and etiology of ROS and oxidative stress (OS), evaluation of ROS, and antioxidants. ROS is normally produced physiologically and is used to maintain cellular processes such as sperm maturation, capacitation, and sperm-oocyte interaction. When ROS production exceeds the buffering capacity of antioxidants, OS occurs and can have a negative impact on sperm and fertility. ROS and antioxidant capacity testing can potentially add additional prognostic information to standard laboratory testing for the infertile male, although its role as standard part of an evaluation has yet to be determined. Elevated ROS levels have been implicated with abnormal semen parameters and male infertility, but the impact of ROS on fertilization rates and pregnancy is controversial. This is partly because of the lack of consensus on what type of patients may be suitable for ROS testing and assay standardization. Routine ROS testing for the infertile male is not currently recommended.

  • Jason Kovac

    In my experience, most couples are already on “antioxidant” therapy when they come to visit the male infertility specialist. One question for the authors would be when do they actually use ROS testing? I would agree with dr. samplaski… testing does not directly alter management. So how does one justify doing an expensive test that doesn’t really serve any benefit? Perhaps in the context of deciding when to fix a varicocele? If the patient has really high ROS and a varicocele, repair might be suggested at an earlier time?

  • Thanks for the questions and comments Dr. Quaas and Dr. Samplaski.
    To date, it is unknown how many laboratories offer ROS testing. This is due mainly to the cost of the testing.
    In regards to the etiology – any pathology or environmental exposure that results in increased DNA fragmentation (i.e. varicocele, local testicular infection like epididymitis or orchitis, STI, systemic infection, smoking, external radiation, chemotherapy, radiation, or etc.) can increase ROS levels and increase the oxidative stress in the system.

    Most practitioners would just start their infertile males with semen abnormalities on some sort of antioxidant / vitamin regimen to try to increase the oxidant capacity within the system to buffer the presumed oxidative stress levels.

  • This is a fascinating review by Ko et al. How many laboratories actually offer ROS testing and what is the most commonly used test in practice? Also, is it known whether certain patient characteristics (eg smoking) make a patient more likely to have abnormal ROS testing?

  • msamplaski

    This well-conducted review reinforces what most male fertility experts already practice: that while ROS are bad for sperm, testing does not change management. These men will have an assessment for modifiable factors and be started on emperic antioxidant therapy, and otherwise managed in with progressive ART. While ROS are compelling, and likely play a role in male fertility, at present routine testing is not warranted.

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