Infertility, defined as the inability to conceive after 12 months of trying, affects both men and women and can be attributed to numerous factors. For men, infertility may arise from issues like low sperm count, poor motility, or abnormal sperm shape. Women may experience infertility due to ovulation disorders, hormonal imbalances, or structural issues within the reproductive organs. However, one of the most crucial yet often overlooked factors contributing to infertility is genetics. Genetic variations can have a profound effect on fertility, and understanding these variations can unlock new solutions for overcoming infertility challenges. In recent years, the field of nutrigenetics—how genetic variations influence responses to nutrition—has emerged as a key player in addressing infertility. By identifying specific genetic variants linked to fertility issues, couples can receive personalized nutritional and lifestyle recommendations that significantly improve their chances of conception.

Male and female infertility: the genetic component

Both male and female infertility have genetic underpinnings. For men, gene mutations or variants affecting sperm production, function, or motility can lead to infertility. In women, fertility can be compromised by genetic variations that affect hormonal balance, ovarian function, and egg quality. Nutrigenetics aims to bridge the gap between genetic predisposition and practical interventions by providing targeted solutions. Genetic testing plays a pivotal role in identifying these predispositions, offering couples a clearer understanding of their infertility and a pathway to overcoming it through personalized approaches.

Genetic testing for infertility: key genes to consider

  • MTHFR (Methylenetetrahydrofolate Reductase): variants in the MTHFR gene can affect folate metabolism, leading to elevated homocysteine levels, which can impair fertility. In women, this may increase the risk of recurrent miscarriages or implantation issues, while in men, it can negatively impact sperm quality.

  • FSHR (Follicle-Stimulating Hormone Receptor): variants in the FSHR gene can impair ovarian function in women, leading to ovulatory disorders. In men, these variants may reduce sperm production.

  • ESR1 (Estrogen Receptor 1): mutations in the ESR1 gene can disrupt estrogen signaling, which is critical for maintaining a healthy uterus and supporting pregnancy. In men, estrogen imbalances can affect sperm health.

  • CYP19A1 (Aromatase): this gene influences the conversion of androgens to estrogens. Variants in CYP19A1 can lead to hormonal imbalances in both men and women, affecting fertility.

  • Y Chromosome Microdeletions (Male-specific): Y chromosome deletions are a common cause of male infertility, particularly in men with reduced sperm production or azoospermia (no sperm).

  • BMP15 (Bone Morphogenetic Protein 15): variants in BMP15 affect egg maturation and ovarian function, leading to infertility, particularly in women experiencing premature ovarian failure.

Supplementation recommendations for infertility based on genetic variations

  • MTHFR and folate supplementation: individuals with MTHFR gene variants often have difficulty processing synthetic folic acid, leading to elevated homocysteine levels. It is recommended that these individuals take methylated folate (L-methylfolate) instead of folic acid. Methylated folate bypasses the metabolic blocks caused by MTHFR variants and ensures adequate folate levels, which are crucial for cell division, egg health, sperm quality, and reducing the risk of miscarriage.

  • Vitamin B12 and B6: along with methylated folate, supplementing with methylcobalamin (active Vitamin B12) and pyridoxal-5-phosphate (active Vitamin B6) can help lower homocysteine levels. These vitamins work synergistically to support DNA synthesis and healthy reproductive function, especially in individuals with MTHFR mutations.

  • Coenzyme Q10 (CoQ10): CoQ10 is a powerful antioxidant that supports mitochondrial function, which is essential for egg and sperm health. Supplementation with CoQ10 has shown to improve egg quality in women with aging-related infertility and has also been beneficial for men with poor sperm motility and morphology.

  • Omega-3 fatty acids: omega-3 fatty acids, particularly DHA and EPA, support hormonal balance and reduce inflammation, improving both male and female fertility. Studies have shown that Omega-3 supplementation can enhance sperm motility in men and improve egg quality and uterine health in women.

  • Zinc: zinc plays a key role in sperm production and testosterone levels in men. It also supports proper ovarian function and egg health in women. Zinc deficiency is often linked to infertility, making supplementation vital for those with low levels.

  • Vitamin D: vitamin D is essential for maintaining healthy hormone levels in both men and women. Studies have shown that women with adequate vitamin D levels are more likely to conceive and have a successful pregnancy. Men with sufficient Vitamin D levels also tend to have better sperm quality.

  • Inositol (Myo-Inositol and D-Chiro inositol): inositol, particularly the combination of myo-inositol and D-chiro inositol, is effective in improving ovarian function and egg quality in women with polycystic ovary syndrome (PCOS). It is also beneficial in restoring hormone balance in women with insulin resistance, which is a common cause of infertility.

Real-life example: MTHFR and infertility

The MTHFR gene has been a focal point in numerous infertility case studies. In one such case, a woman experiencing recurrent miscarriages underwent genetic testing and discovered she had a mutation in the MTHFR gene, specifically the C677T variant. This mutation was causing elevated homocysteine levels, which can interfere with placental development. By switching to a methylated form of folate (L-methylfolate) and supplementing with B vitamins, her homocysteine levels normalized, and she was able to conceive and carry a healthy pregnancy to term.

In another case, a man diagnosed with poor sperm motility and morphology was found to have the same MTHFR variant. His fertility specialist recommended supplementation with methylated folate, CoQ10, and omega-3 fatty acids. Within months, his sperm quality improved, and his partner successfully conceived through natural conception.

Other gene-based success stories

  • Y Chromosome microdeletions: a man diagnosed with azoospermia due to Y chromosome microdeletions successfully fathered a child through intracytoplasmic sperm injection (ICSI) after undergoing genetic testing and targeted fertility treatment.

  • FSHR variants: a woman with ovarian dysfunction due to an FSHR variant received personalized hormonal therapy. Genetic testing allowed her to tailor her treatment more precisely, leading to a successful pregnancy after months of struggling with infertility.

Conclusion: the role of genetic testing and nutrigenetics in overcoming infertility

Genetic testing is transforming the way we approach infertility. By identifying specific gene variants, such as MTHFR, FSHR, or Y chromosome deletions, couples can take targeted actions to improve their fertility. Nutrigenetics offers a holistic approach by incorporating genetic insights into personalized nutritional and supplementation strategies. These interventions can address the root causes of infertility, helping couples to overcome their fertility challenges and achieve their dream of starting a family.

References

Rietveld, C. A., et al. (2017). Impact of MTHFR gene polymorphisms on female infertility: A systematic review and meta-analysis. Fertility and Sterility, 108(3), 481-491.
Krausz, C., et al. (2015). Genetics of male infertility: From research to clinic. Reproduction, 150(5), R159-R174.
Gromoll, J., et al. (2000). Follicle-stimulating hormone receptor gene mutations and reproductive disorders. European Journal of Endocrinology, 143(5), 585-596.
Di Pasquale, E., et al. (2004). BMP15 mutations associated with ovarian failure. American Journal of Human Genetics, 75(1), 106-111.
Stanger, O. (2002). Physiology of folic acid in health and disease. Current Drug Metabolism, 3(2), 211-223.