MTHFR: What is it and how does it affect your fertility?

MTHFR: What is it and how does it affect your fertility?

Ever since scientists and doctors have started to understand the impact of metabolism and genetic makeup on health, they have been diligently working towards early identification and prompt treatment of disorders arising from metabolic imbalance and genetic mutations. As simple as our body might look on the outside, a lot of enzymes and proteins that mediate various processes are active round the clock to regulate the functioning of the bodily systems. One such important enzyme is MTHFR, which stands for methylene-tetrahydrofolate reductase. This enzyme is important for converting folate from our diet into its active form 5-methylene tetrahydrofolate (5-MTHF). 5-MTHF is crucial in regulating hormones, body energy, detoxification, fertility, mental health and several other important functions. With the rising conception-failure rates, MTHFR has been found to be playing some important roles in successful and healthy pregnancies. Read on to know more about how this enzyme helps you in making your dream of becoming a parent come true.

MTHFR

How does MTHFR affect fertility in women?

MTHFR is beneficial for women wanting to naturally conceive or get artificial fertilisation done through a procedure called in vitro fertilisation (IVF). Studies have shown that folate deficiency and/or a mutation in the MTHFR gene can have a negative impact on your fertility. The most common variants of MTHFR gene mutation are C677T and A1298C. These mutations and folate deficiency can lead to an increased risk of recurrent miscarriages, foetal growth retardation in the uterus, premature births, implantation failure and so on. Let’s take a look at what MTHFR does for regulating fertility.

How does MTHFR affect fertility in women

Improves the functioning of ovaries, your egg-producing organs

5-MTHF helps in the conversion of homocysteine, a type of amino acid, to methionine. Methionine is further involved in protein synthesis and methylation of proteins and DNA, which are crucial for gene expression in the foetus. Studies have shown that when homocysteine is in range in the fluid of the follicles where the eggs (oocytes) develop, it improves the ovarian reserve and quality of egg cells or oocytes and embryos. The ovarian reserve is the capacity of an ovary to produce egg cells, which are required for successful fertilisation. During follicular development, if the blood homocysteine level is high, the cells start dying, which can finally lead to degeneration of the follicles. High homocysteine levels (more than 14.7 μmol/L) can also reduce the quality of the developing embryo and the oocytes retrieved for IVF.

Prevents developmental defects in the foetus

The MTHFR enzyme derived from folate breakdown in the body plays a crucial role in the development of the foetus. A deficiency of folate before conception or a mutated MTHFR gene results in the development of neural defects, such as spina bifida. In spina bifida, the development of the spine and spinal cord of the foetus are adversely affected, which results in a gap in the spine. Adequate folate intake or supplementation during the preconception period can reduce the incidence of neural tube defects by 60%.

Promotes healthy cell production in the uterus

As we’ve mentioned before, MTHFR helps in cell division, tissue growth, and protein and DNA synthesis. Any polymorphisms in the MTHFR gene or a deficiency of folate in diet can result in abnormal cell divisions in the uterus and cervix, which are also known as uterine and cervical dysplasia, respectively. Dysplasia in the reproductive tract tissues can cause repeated miscarriages or even failure to conceive altogether. High folate level can prevent this from happening.

Healthy Cell Production in the Uterus

Reduces the chances of miscarriages and other pregnancy-related outcomes

When folate metabolism is faulty or there is folate deficiency in the body, the levels of homocysteine rise in the blood. High homocysteine levels have been found to be associated with an increased risk of blood clot formation, a condition called thrombophilia. A high homocysteine level has also been found to contribute to 5-10% of all thrombotic episodes. Because of this condition, clot formation can occur at the implantation site, which can cut off the nutrient supply to the embryo from the uterine wall. This is true for both natural conception and IVF, resulting in implantation failure and miscarriages along with other adverse outcomes, such as preeclampsia, intrauterine growth retardation (IUGR), stillbirth and abruption in the placenta.

Regulates hormones

A good balance of reproductive hormones is necessary for maintaining reproductive health and fertility. In the presence of a variant of the MTHFR gene in the body, especially the MTHFR 677T variant, the level of follicle-stimulating hormone (FSH) rise, estradiol concentrations go down and the count of egg cells or oocytes retrieved is reduced in women with ovarian hyperstimulation (an exaggerated response to fertility medications or excess hormones used to stimulate egg growth).

Pregnancy

Production of blood cells

The blood cells in the body largely comprise red blood cells (RBCs), white blood cells (WBCs) and platelets. While RBCs are responsible for carrying oxygen to different body tissues, WBCs and platelets are involved in fighting against infections. The MTHFR enzyme and folate are vital to protein synthesis and cell division and a deficiency of either of the two can result in abnormal blood cell production along with reduced functioning of the blood cells. This may further result in reduced oxygen supply to the reproductive organs, inadequate tissue growth, anaemia and low immunity. All these factors are crucial to prevent adverse pregnancy outcomes.

How does MTHFR affect fertility in men?

The role of MTHFR is not only limited to pregnancy but also to male fertility. 8% of the men in the reproductive age group have been reported to seek counselling for problems related to infertility. Studies have shown that MTHFR C677T mutation is associated with an increased risk of male infertility. Let’s discuss how MTHFR affects male fertility.

Improves the generation of sperm

For a successful conception or pregnancy, not only the ovarian reserve but the sperm count is equally important. Sperm are produced in good quantity with adequate cell division, sufficient protein synthesis and unaltered methylation of DNA. All of these processes are directly associated with folate metabolism and the MTHFR gene. In a study where men were given folate supplementation for 26 weeks, the total sperm count was found to be increased. Therefore, maintaining the recommended dietary folate level is of utmost importance for ensuring the production of adequate sperm quantity. Though further research is ongoing to confirm this hypothesis, the current evidence suggests that folate and semen health are correlated.

How to Improves the Generation of Sperm

Improves sperm quality

Quantity and quality go hand in hand when it comes to successful fertilisation of the egg and sperm. To increase the chances of fertilisation with the right sperm, both quality and motility of the sperm need to be taken care of. Studies have shown that in the presence of folate deficiency or MTHFR gene mutations, excessive reactive oxygen species (ROS) are produced along with aberrant methylation processes. As a result, the process of DNA repair, replication, transcription, etc. get altered or become defective. Production of sperm with low quality DNA and reduced motility will prevent fertilisation from happening or cause genetic defects in the embryo, such as Down’s syndrome. Early detection of the MTHFR gene mutation can help bring down these issues related to male fertility.

Conclusion

Understanding the effect of MTHFR and genes supporting its function can help identify fertility issues beforehand. Addressing these issues in both men and women during the preconception phase can help couples enjoy safe and happy parenthood. Therefore, going for MTHFR gene test along with supplementary folate are key to successful conception. We have been creating life-changing experiences for couples by addressing their methylation issues head-on.

References

  1. Thaler CJ. Folate Metabolism and Human Reproduction. Geburtshilfe Frauenheilkd. 2014;74(9):845-851.
  2. Ocal P, et al. The association between homocysteine in the follicular fluid with embryo quality and pregnancy rate in assisted reproductive techniques. J Assist Reprod Genet. 2012;29(4):299-304.
  3. Rosen MP, et al. Methylenetetrahydrofolate reductase (MTHFR) is associated with ovarian follicular activity. Fertil Steril. 2007 Sep;88(3):632-8.
  4. Liu K, et al. Role of genetic mutations in folate-related enzyme genes on Male Infertility. Sci Rep. 2015;5:15548.
  5. Murto T, et al. Folic acid supplementation and IVF pregnancy outcome in women with unexplained infertility. Reprod Biomed Online. 2014 Jun;28(6):766-72.
  6. Gunes S, et al. Chapter 2 – Genetic Variations and Male Infertility. Reproductomics. 2018;21-45
  7. Enciso M, et al. Polymorphisms in the MTHFR gene influence embryo viability and the incidence of aneuploidy. Hum Genet. 2016 May;135(5):555-568.
  8. Zeng S, et al. MTHFR C677T polymorphism is associated with follicle-stimulating hormone levels and controlled ovarian hyperstimulation response: a retrospective study from the clinical database. Fertil Steril. 2019 May;111(5):982-990.e2.
  9. Gupta N, et al. Significant impact of the MTHFR polymorphisms and haplotypes on male infertility risk. PLoS One. 2013;8(7):e69180. Published 2013 Jul 18.
  10. Gong M, et al. MTHFR 677C>T polymorphism increases the male infertility risk: a meta-analysis involving 26 studies. PLoS One. 2015;10(3):e0121147. Published 2015 Mar 20.
  11. Murto T, et al. Folic acid supplementation and methylenetetrahydrofolate reductase (MTHFR) gene variations in relation to in vitro fertilization pregnancy outcome. Acta Obstet Gynecol Scand. 2015 Jan;94(1):65-71.

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