Antioxidants and Fertility

What is Oxidative Stress?

Cells in our body are working all the time. As a natural by-product of the normal metabolism of oxygen, Free Radicals are produced. These include: Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS).

A free radical can be defined as an atom or molecule containing one or more unpaired electrons in valency shell or outer orbit and is capable of independent existence. The odd number of electron(s) of a free radical makes it unstable, short lived and highly reactive. Because of their high reactivity, they can abstract electrons from other compounds to attain stability. Thus the attacked molecule loses its electron and becomes a free radical itself, beginning a chain reaction cascade which finally damages the living cell.

Oxidative stress happens when production of free radicals is higher than the cells’ ability to eliminate them. This may result in significant damage to cell structures.

What Causes Oxidative Stress?

Generation and elimination of Free Radicals are balanced under normal conditions. Homeostasis disturbances may be provoked by diverse internal and external factors.
Exogenous causes are:

• Environmental pollution
• Smoking
• Alcohol
• Poor nutrition, diet high in fat, sugar and processed foods
• Obesity
• Infections
• Exposure to radiation
• Pesticides or industrial chemicals
• Medications (eg, cyclosporine, gentamycin, and bleomycin)

It is thought that oxidative stress can cause male and female subfertility, and antioxidants are thought to reduce the damage caused by oxidative stress.

Oxidative Stress & Female Fertility

Oxidative Stress has a direct effect on the oocyte, embryo, and implantation. Oxidative stress is also associated with conditions such as endometriosis, hydrosalpinxes, polycystic ovary syndrome (PCOS), and unexplained subfertility.

The benefits for female fertility include improved blood circulation in the endometrium, lowered hyperandrogenism, decreased insulin resistance, fertile cervical mucus, and an influence on prostaglandin synthesis and steroidogenesis.

More research is needed but:

• among subfertile women with an expected live birth rate of 20%, the rate among women using antioxidants would be between 26% and 43%.
• among subfertile women with an expected clinical pregnancy rate of 22%, the rate among women using antioxidants would be between 27% and 33%.

Oxidative Stress & Male Fertility

Over the years, it has been proven that subfertile men, have higher levels of ROS and lower levels of antioxidants in their semen. Spermatozoa themselves are a major source of ROS, and physiologic levels of ROS are needed for several sperm functions. However, spermatozoa are more vulnerable than other body cells when it comes to damage due to the overproduction of ROS.

More research is needed, but:

• Live birth rates: if the chance of a live birth following placebo or no treatment is assumed to be 5%, the chance following the use of antioxidants is estimated to be between 10% and 31%.
• Clinical pregnancy rate: if the chance of clinical pregnancy following placebo or no treatment is assumed to be 6%, the chance following the use of antioxidants is estimated at between 11% and 28%.
• There was insufficient evidence to show whether there was a difference in miscarriage rates between the antioxidant and placebo or no treatment groups.

Different Types of Antioxidants

To prevent oxidative damage or stress, the body has developed a natural antioxidant defence mechanism. Antioxidants can directly inactive oxidative stress, and repair the damage.

Research has been done to look into the effect of antioxidant supplementation.

1) Inositol

Inositol is considered part of B group, but not a true vitamin.

Evidence in PCOS

• It has been shown to play different roles in the physiology and treatment of PCOS.
• It can restore spontaneous ovarian activity, and consequently fertility, in most patients with PCOS.

Evidence in IVF outcomes

• Significantly improved clinical pregnancy rate and abortion rate
• There were no significant difference in total oocytes retrieved, MII stage oocytes retrieved, stimulation days, and E2 peak level.

2) Vitamin C

Female Fertility

• Found in the cytosol of oocyte, extracellular fluid.
• Its supplementation is in practice to treat luteal phase defects and recurrent abortions.

Male Fertility

As its concentration increases in seminal plasma, it prohibits DNA damage.

3) Vitamin E

Female Fertility

• Not found to have any benefit

Male Fertility

• Inhibits the production of ROS
• two-month treatment with 1gr vitamin E and C improved ICSI success rate in patients with sperm DNA damage and reduced the level of DNA damage in these individuals
• daily supplement of selenium (200 μg) in combination with vitamin E (400 IU) for at least 100 days, resulted in 52.6% total improvement in sperm motility, morphology, or both, and 10.8% spontaneous pregnancy in comparison with no treatment.

4) Carnitine

Female Fertility

• L-carnitine (LC) is a naturally occurring compound and also a semi-essential vitamin like substance required for human metabolism.
• While both L-carnitine (LC) and acetyl L-carnitine (ALC) have their applications in improving female fertility, ALC is preferred for its better antioxidant properties and LC for amelioration of energy supply to the cells.

• Several studies found that both LC and ALC supplementation improves disorders such as polycystic ovary syndrome and amenorrhea.
• Carnitines are reported to increase gonadotropins and sex hormone levels as well as improve oocyte health.
• Effects of LC on endometriosis are still a matter of debate.

5) Coenzyme Q10 (CoQ10)

CoQ10 also known as ubiquinone is an antioxidant.

Female Fertility

• CoQ10 could improve the response of the ovaries to stimulation in women undergoing in vitro fertilization (IVF). The pregnancy rate was higher in women who used CoQ10.

Male Fertility

• After 6 months of CoQ10 therapy, sperm motility was improved.
• 28 week treatment with ubiquinone led to improvement in sperm density, sperm motility and sperm morphology.
• A meta-analysis showed that supplementing infertile men with CoQ10 does not increase live birth or pregnancy rates, but there is a global improvement in sperm parameters such as sperm concentration and motility and CoQ10 concentration in semen.

6) Zinc
Zinc is the second most abundant metal in the body after iron.

Female Fertility

• Women who had lower zinc had a longer time to pregnancy.
• Disrupted growth of cells.
• Smaller egg cells early in development.
• Deterioration of oocyte quality.
• Problems with development of somatic cells.
• Impaired the egg cell's ability to properly divide (meiosis), a necessary step before successful fertilization can occur.

Male Fertility

• It has been shown that zinc supplementation normally protects the spermatozoa against bacteria and also prevents damage to chromosomes.
• Zinc plays an important role in testicular development and sperm maturation.
• Decreased levels of zinc in the semen were associated with reduced sperm fertilization capacity.
• Patients who received 5 mg of folic acid and 66 mg of zinc for 26 weeks reported improving sperm concentration.
• 2 zinc sulphate capsules (220 mg per capsule) per day for 3 months. Results showed that the volume of semen, progressive sperm motility percentage and total normal sperm count increased.

7) Selenium
Female Fertility

• Levels are increased in large healthy follicles and might perform a vital antioxidant function during later growth and the proliferation of follicles.
• The follicular fluid and serum proteins were protected from oxidative injury when aged women were supplemented with micronutrients ahead of IVF cycles.
• Significant increase in good quality oocytes.
• Significantly improved embryonic quality.
• No significant improvement in follicle number, oocyte maturation or quality of vitrified embryos.

Male Fertility

• Selenium is an essential trace element in formation of sperm and testosterone.
• Selenium supplementation improved sperm counts, concentration, motility and morphology as well as sperm concentration.
• There is significantly increase in sperm count, motility, viability, normal sperm morphology, and ejaculate volume of infertile men compared after treatment with selenium.

8) N-acetyl-cysteine

• Polycystic ovary syndrome (PCOS) is associated with low-quality oocytes.
• Improvement in oocytes and embryo quality.
• Improvement in pregnancy and ovulation rate.
• Higher odds of having a live birth, getting pregnant, and ovulation.
• Unsure if better than metformin.
• We concluded that NAC improves oocyte and embryo quality and could be administered as an alternative to metformin in patients with PCOS.

9) Multi-antioxidant supplementation

• There are combinations of antioxidants available.
• Make sure you don’t take several medications with the same substances to avoid taking too much of a particular substance.

Impryl

• Impryl leverages the physiologic antioxidant system to achieve a better oxy-redox balance within the control of the natural cellular homeostasis.
• Its formula contains all the substances required for the activation of antioxidant defenses in the absence of any substance with direct antioxidant activity.
• It is made from activated micro-nutrients that help every cell within the human body, from the biggest (eggs) to the smallest (sperm).
• These micronutrients have been clinically proven to significantly improve live birth rates for men and women who had previously been struggling to get pregnant.