Nutritional Factors in Female Fertility, Part 1 of 2

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As the average reproductive age rises, many turn to natural ways to enhance fertility

The age at which we elect to reproduce has been on the rise for some time. Both men and women are putting parenthood on hold to pursuing a variety of things including their career, financial security, travel and global exploration, and, in general, the search for a purposeful mission in life.

However, the clock held by Father Time keeps ticking.

In females, fertility begins to decline even before 30, and accelerates after 35.^[1] This rapid decline is largely due to the lack of viability of a women’s own oocytes, as we still see a fairly high rate of success until the later 40s with implantation of embryos from donor eggs.^[2] The increasing age at which women seek to give birth has led to a considerable reliance on medicine for reproductive assistance in developing nations: in 2005, approximately 1% of U.S. births were conceived using assisted reproductive technology, and by 2012, the number had increased to 1.5%.^[2],[3]

There actually is a substantial amount of research with nutritional therapies for the various types of female fertility challenges. In Part 1, we look at the research behind essential nutrients, while in Part 2, we take a look at the fat-soluble antioxidants melatonin and CoQ10 as they pertain to female fertility. The research pertaining to male reproductive health is also discussed at length here, offering the reader a comprehensive look at ways to support couples at all levels.

Although all of the essential vitamins and minerals are, by their very essence, necessary for human life and reproduction, particular nutrients rise to the top when we specifically direct our focus at female reproductive health: selenium and folate.

Selenium

Selenium-dependent enzymes have an impact on thyroid function, which is one reason why it is so important for female conception.

In the human body, selenium is necessary for the normal function of 25 different selenium-containing proteins, known as selenoproteins.^[4] A large portion of these selenoproteins are enzymes that catalyze redox reactions, helping our body to maintain antioxidant/oxidant homeostasis. Selenium is necessary for the body to facilitate the many redox reactions involving glutathione, our main water-soluble antioxidant.^[5] Selenium and its redox enzymes have been shown to play an important role in the health and development of both female and male gametes.^[6],[7]

Many of the selenium-dependent enzymes have an impact on thyroid function, which is one reason why it is so important for female conception.^[8],[9] Selenium also plays an important role in immune function. Where fertility is concerned, the data behind selenium is significant for the role it plays in regulating the immune response, that is, its action of putting a “damper” on autoimmunity.^[10] Thyroid autoimmunity is an increasingly common problem and has been shown in numerous studies to increase the likelihood of miscarriage two to three-fold.^[11]

In women suffering from recurrent miscarriages (not known to have thyroid autoimmunity), significantly lower levels of selenium have been shown compared to a population of women who had healthy pregnancies.^[12] Lower levels of selenium have also been shown in the follicular fluid obtained from women with idiopathic infertility, as compared to those for whom tubal issues or male factors were deemed to be the cause of infertility.^[13] Similarly, selenium levels have also been shown to be lower in infertile women with endometriosis or polycystic ovarian syndrome (PCOS) than control women, each of these being additional female populations in which fertility is known to be compromised.^[14],[15]

Multiple clinical studies have shown that selenium supplementation reduces the thyroid autoimmune response.^[16],[17] Selenium has been shown clinically to improve thyroid function post-pregnancy in women with thyroid autoimmunity, significantly reducing the occurrence of both hypothyroidism and post-partum thyroiditis.^[18],[19] Although there have not been studies looking at selenium as a monotherapy in women as an adjunctive to reproductive assistance, positive outcomes with multinutrient combinations including selenium have been seen.^[20],[21] The dose of selenium used in the clinical studies with positive findings varied, but generally is 200 mcg a day or less, and in the form of selenomethionine.

Although we most oft see thyroid autoimmunity in women, modest amounts of selenium also have been shown to have a positive impact on male fertility, likely due to its antioxidant effects.

Folate and folate cycle roadblocks

Studies suggest that more than 400 mcg of folate intake daily is necessary to achieve adequate folate levels for a healthy pregnancy.

Another factor which comes up in discussions of fertility is the folate cycle and factors which affect it. Folate is essential for cellular replication and embryo development, and adequate amounts during pregnancy are necessary to prevent neural tube defects,^[22] among other things.^[23] As a nutrient, folate often is found in supplements and used for food fortification in its most economical form – folic acid. In the body, folic acid is converted through a process of reactions to its active form known as 5-methyltetrahydrofolate (5-MTHF), which is needed for metabolism of homocysteine. Adequate amounts of folic acid and vitamin B12 are necessary for proper homocysteine metabolism while other nutrients also play a role.^[24]

Altered folate and homocysteine metabolism are factors that may contribute to suboptimal fertility in both females and males.^[25] Certain genetic variants of the enzymes involved in these processes may be a contributing factor.^{[26],[27],[28]} When coupled with sub-optimal intake of folate and the other B vitamins, the impact is more significant.

In a population of 269 women going in for in vitro fertilization (IVF) procedures, it was shown that although homocysteine levels were deemed to be appropriate in 69% of the population, only 44% of women had adequate levels of B12 and a mere 12% had adequate red blood cell levels of folate to prevent neural tube defects.^[29] Of the larger group, 125 women reported taking folate as a supplement for an extended period – and of this sub population, still, only about 25% of women were found to have adequate levels of folate.

Another study of women going in for IVF looked a bit more closely at if supplementation with the recommended amount of folate (400 mcg/day) was adequate to achieve folate sufficiency. Although about 75% of the women were taking in the recommended amount of folate for at least three months, only 61% of women were found to have optimal levels.^[30]

A comprehensive 2014 review on the matter suggests increasing the guidelines for folic acid supplementation in pregnancy to 800 mcg/day to overcome hinderances in folate metabolism due to genetic variants,^[31] supplementation of folate in its active form, 5-MTHF, also may circumvent the issue. Folate inadequacy may be a factor that renders one more susceptible to the adverse effects of bisphenol A (BPA) exposure,^[32] a factor in both male and female fertility.^[33]

Fertility challenges can be very difficult for all involved parties. Although our modern era offers numerous medical tools that we can turn to, it is important to remember the nutritional basics. The nutrients discussed herein, the antioxidants discussed in Part 2, and additional supplements that have been researched in the setting of male reproductive health, should offer further hope to the individuals dealing with these challenges.

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