Fertility | MTHFR

Are you having a harder time conceiving than you expected? Have you weathered the deep devastation of pregnancy loss? Are you wanting to understand more of your health before you take the plunge and try to conceive?

Then I want to talk with you about MTHFR.

MTHFR stands for methylenetetrahydrofolate reductase (now you see why it's just, MTHFR) which is an enzyme required to activate folate. Folate is an essential nutrient required for so many cellular reactions, particularly cellular metabolism in DNA, RNA and protein function all of which are incredibly important in conception and the magical process of growing a human. How well the MTHFR enzyme functions can play a role in the entire conception process: DNA replication, ovarian function, sperm health and embryo development. 

Before getting too deep into this big topic, I want to briefly breakdown what genetic polymorphisms or single nucleotide polymorphisms (SNPs) are. If this is confusing, feel free to skip!

Genetic polymorphisms are measurable variations in the DNA chain. Genetics are the code for a particular reaction to happen in the body. These kind of genetic variants (like MTHFR) code for an enzyme to make a biochemical reaction happen in the body.

Polymorphisms are not a mutation. A mutation is a permanent change to the DNA strand that changes what the gene codes for. A variant (as in the case of MTHFR) discusses a change in the type of protein on a DNA strand that can impact how well the enzyme works. Genetic polymorphisms can turn enzymes on faster, slower or have little effect on how the enzyme works naturally. A single nucleotide polymorphism (SNP) is just one alteration in the protein used in the DNA code.

This kind of genetic information is very helpful in looking functionally at health because we can see what possible underlying root cause imbalances may be contributing to hormone metabolism, nutrient status, symptoms of ADHD, anxiety, depression, and much more.

This can be confusing, so hang with me. 

There are thousands of genetic polymorphisms in our bodies, and yet we walk about much of our lies without knowing. These variants become adaptable. BUT - in the case of fertility when we’re looking to ensure all the details of body’s function are well nourished, we can look to some genetic polymorphisms to know how best to support the individual or couple. 

Delayed conception

Healthy levels of folate are needed for cellular differentiation and DNA replication. This influences hormone production and metabolism as well. MTHFR variants have been correlated with diminished ovarian function. Multiple studies have found that men with MTHFR variants who take B9 (folate) and B12 supplements show notable improvement in semen parameters for fertility. This brings us back to the essential requirements of the body in making DNA for healthy conception.

Folate deficiency can compromise fertility by impairing the development of oocytes, preparation of endometrial lining to receive fertilized egg, implantation of the embryo and pregnancy outcomes. 

Pregnancy loss 

Research over the years has found a correlation with recurrent miscarriage in patients who have MTHFR variants. The mechanism for this is not entirely clear, but some literature describes the integrity of blood vessels supplying placenta formation, cellular division or proper cellular metabolism as possible causes. 

Another possible contributing factor is elevated levels of homocysteine in the blood. Homocysteine is a protein that can be inflammatory for the blood vessels when elevated. People who have variants of MTHFR are more likely to have higher homocysteine and may be at greater risk of pregnancy loss. And while most research is done on patients with female bodies, there is also mention of male influence here too. 

Preparing for a healthy pregnancy

There is so much that can be supported here! Remember: a genetic variant is not a mutation, it is not a sentence for health conditions or continued trouble conceiving. It is information we can gather and use to support your healthiest self in preparation for a healthy pregnancy and baby!

The #1 thing you can do to support your genetic health and fertility journey right now:

Eat foods high in natural folate: 

  • Dark leafy greens 

  • Nuts, seeds

  • Beans, legumes

  • Avocados

Avoid enriched foods and supplements with folic acid*:

  • Most processed foods

  • Breads, cereal, pastas, crackers, baked goods, pizza, etc. that have enriched or fortified flour in the ingredient list

Additional ways to support MTHFR during fertility:

  • take a well balanced prenatal supplement that includes methylfolate* (B9), methylcobalamin* (B12), choline, vitamin B6. Ask your provider for their individualized recommendation for your body’s needs

  • take good care of your digestive system and support your microbiome with diverse, plant-based foods. If you have ongoing digestive symptoms, consider a work up for the root cause

  • try to reduce inflammation in your body as high inflammation can directly impact methylation and fertility

  • limit environmental, chemical exposures to things like BPA, pesticides, lead, mercury, phthalates and mold

  • soften stress as elevated maternal stress can impact fetal development and epigenetics

* If you have tried a supplement with active folate in it (rather than folic acid) and have noticed insomnia, increased anxiety or other symptoms it is highly likely you have other SNPs that are impacting your methylation. I encourage comprehensive testing and working closely with a provider to best support your beautiful body’s needs. MTHFR is not the only genetic SNP that can impact fertility.

And remember, you’ve got this. Your body is SO wise and capable.

XO,

Dr. Stang

If you’re looking for a comprehensive and functional approach to your hormones + fertility, you’re in the right place.

Uncovering the root cause of hormone imbalances + optimizing fertility health is the core of my work. If you’re ready for clarity about how best to balance your hormones and prepare for a pregnancy, learn more about my approach + highly successful strategy.

Resources: 

  1. Zarfeshan Fard Y, Kooshkaki O, Kordi Tammandani D, Anani Sarab G. Investigation of the association between C677T polymorphism of the MTHFR gene and plasma homocysteine level in recurrent fetal miscarriage. J Obstet Gynaecol Res. 2019;45(8):1442‐1447. doi:10.1111/jog.13989

  2. Servy EJ, Jacquesson-Fournols L, Cohen M, Menezo YJR. MTHFR isoform carriers. 5-MTHF (5-methyl tetrahydrofolate) vs folic acid: a key to pregnancy outcome: a case series. J Assist Reprod Genet. 2018;35(8):1431‐1435. doi:10.1007/s10815-018-1225-2

  3. Serapinas D, Boreikaite E, Bartkeviciute A, Bandzeviciene R, Silkunas M, Bartkeviciene D. The importance of folate, vitamins B6 and B12 for the lowering of homocysteine concentrations for patients with recurrent pregnancy loss and MTHFR mutations. Reprod Toxicol. 2017;72:159‐163. doi:10.1016/j.reprotox.2017.07.001

  4. Najafipour R, Moghbelinejad S, Aleyasin A, Jalilvand A. Effect of B9 and B12 vitamin intake on semen parameters and fertility of men with MTHFR polymorphisms. Andrology. 2017;5(4):704‐710. doi:10.1111/andr.12351

  5. Servy EJ, Jacquesson-Fournols L, Cohen M, Menezo YJR. MTHFR isoform carriers. 5-MTHF (5-methyl tetrahydrofolate) vs folic acid: a key to pregnancy outcome: a case series. J Assist Reprod Genet. 2018;35(8):1431‐1435. doi:10.1007/s10815-018-1225-2

  6. Cornet D, Cohen M, Clement A, et al. Association between the MTHFR-C677T isoform and structure of sperm DNA. J Assist Reprod Genet. 2017;34(10):1283‐1288. doi:10.1007/s10815-017-1015-2

  7. Zhu Y, Wu T, Ye L, Li G, Zeng Y, Zhang Y. Prevalent genotypes of methylenetetrahydrofolate reductase (MTHFR) in recurrent miscarriage and recurrent implantation failure. J Assist Reprod Genet. 2018;35(8):1437‐1442. doi:10.1007/s10815-018-1205-6

  8. Kim JY, Kim JW, Sung SR, Park JE, Shim SH, Cha DH. Impact of RFC1, MTHFR, and MTHFD1 polymorphism on unexplained pregnancy loss (UPL): comparative analysis of maternal and fetal components using mother-abortus paired samples. Eur J Obstet Gynecol Reprod Biol. 2018;231:152‐157. doi:10.1016/j.ejogrb.2018.09.017

  9. D'Elia PQ, dos Santos AA, Bianco B, Barbosa CP, Christofolini DM, Aoki T. MTHFR polymorphisms C677T and A1298C and associations with IVF outcomes in Brazilian women. Reprod Biomed Online. 2014;28(6):733‐738. doi:10.1016/j.rbmo.2014.02.005

  10. Cornet D, Clement A, Clement P, Menezo Y. High doses of folic acid induce a pseudo-methylenetetrahydrofolate syndrome. SAGE Open Med Case Rep. 2019;7:2050313X19850435. Published 2019 May 17. doi:10.1177/2050313X19850435

Kelsey Stang