Understanding oxidative and reductive stress in male fertility
While a standard semen analysis looks at count, movement, and shape, it doesn't always explain why conception is not occurring. There can be many other factors at play that don’t show up in a standard semen analysis and one of the major causes of impaired sperm quality is oxidative stress.
The balance: Oxidative vs. reductive stress
In healthy semen, there is a natural balance between Reactive Oxygen Species (ROS) and the body’s antioxidant defences, this is critical for sperm health and function.
Oxidative stress (OS) occurs when ROS production outweighs the available antioxidants which can lead to sperm DNA fragmentation and reduced fertilising potential.
Reductive stress refers to an imbalance in the opposite direction to oxidative stress where there is an excess of antioxidants in the semen - often due to excess or over supplementation of antioxidants. This "reductive stress" can be just as detrimental to fertility as oxidative stress.
Recent data indicates that up to 15% of men with "normal" semen parameters experience these hidden imbalances, which a standard semen analysis cannot detect.
The impact on fertility outcomes
Research consistently shows that an imbalance in seminal oxidative stress levels is associated with:
• Decreased rates of fertilisation and embryo development.
• Lower clinical pregnancy and live birth rates.
• In some cases, an increased risk of miscarriage.
Common triggers
Physical/Medical: Varicocele, infections, high fever, diabetes, obesity, and advanced age.
Environmental: Heat exposure (tight clothing, sedentary desk work, hot baths), pollutants, and smoking.
Lifestyle: Poor diet, certain prescribed medicines and drug use and extended periods of sexual abstinence.
Triggers for reductive stress can be driven by over-supplementation of antioxidants, but can also be influenced by chronic endurance exercise or certain medical conditions.
How the MiOXSYS test works
Testing for Oxidative-Reduction Potential (ORP) provides a more comprehensive picture of a man’s fertility potential if used in conjunction with a standard semen analysis and other diagnostic tests.
At testhim we use the MiOXSYS system, a validated electrochemical tool that measures the static Oxidation-Reduction Potential (sORP). By placing a small amount of semen on a sensor, the device measures the transfer of electrons between oxidants and antioxidants. This provides a snapshot of the current oxidative state in your semen. Future developments of the test may also allow us to measure the levels of antioxidants within the seminal fluid.
Interpreting the report
The test provides specific thresholds to guide your clinical management.
≤1.34 mV/106 sperm/mL - Normal value indicating good sperm fertilising potential, fertilisation and blastocyst formation rates, and pregnancy
>1.34 mV/106 sperm/mL - High oxidative stress that may warrant further investigation and treatment
The statistically significant ORP threshold for subfertility has been established at >1.34 mV/106 sperm/ml.
Clinical management and treatment
The advantage of identifying oxidative stress levels is that they are often reversible. Based on your results, a specialist may recommend:
Lifestyle modifications: Weight loss, smoking cessation, dietary advice and temperature management (avoiding heated seats/hot baths).
Ejaculatory frequency: Reduce time of abstinence and increasing the frequency of ejaculation can reduce the time sperm are exposed to ROS, often improving pregnancy outcomes.
Medical intervention: Treatment of underlying infections with antibiotics or surgical repair of a varicocele.
Targeted nutrition: Using the test results to "right-size" antioxidant intake, ensuring you are treating a deficiency without causing reductive stress.
Summary
Oxidative stress testing in conjunction with other investigations offers a more comprehensive look at your fertility potential. By identifying these invisible barriers, we can create a more targeted treatment plan to improve your chances of a healthy, ongoing pregnancy.
References
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Agarwal A, Bui AD (2017); Oxidation-reduction potential as a new marker for oxidative stress: Correlation to male infertility. Investig Clin Urol 58: 385-399
Agarwal A, Henkel R, Sharma R, Tadros NN, Sabanegh E (2018); Determination of seminal oxidation-reduction potential (ORP) as an easy and cost-effective clinical marker of male infertility. Andrologia 50(3). doi: 10.1111/and.12914. Epub 2017 Oct 23.
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Dimitriadis F, Tsounapi P, Zachariou A, Kaltsas A, Sokolakis I, Hatzichristodoulou G, Symeonidis EN, Kotsiris D, Gabales MR, Vlachopoulou E, Takenaka A, Sofikitis N (2021); Therapeutic effects of micronutrient supplements on sperm parameters: Fact or fiction? Curr Pharm Des 27: 2757-2769
Henkel R (2024); Antioxidant paradox. In: Andreescu S, Henkel R, Khelfi A (eds.); Biomarkers of Oxidative Stress – Clinical Aspects of Oxidative Stress. Springer Nature Switzerland, Cham, Switzerland, pp. 349-360
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