MTHFR Infertility

It is a defect of the MTHFR (Methylenetetrahydrofolate reductase) gene, known as MTHFR C677T and A1298. MTHFR is a gene in the body that plays a key role in the proper function of many body systems. Let’s learn more about how this relates to folic acid utilization…

To begin, it is important to know that the MTHFR gene resides in each and every cell in the body. It is responsible for utilizing folic acid and producing the most active form of folate called methylfolate. People with the variant MTHFR C667T have a 40 – 60% decreased ability to produce methylfolate.

In the body, methylfolate starts an innumerable amount of critical enzymatic reactions. This impacts the body’s ability to produce a compound known as s-adenosylmethionine, SAMe for short. The body needs SAMe to produce CoQ10, carnitine and creatine, all of which play a critical role in the body’s ability to reproduce, not to mention maintain a variety of other body systems.

MTHFR C677T gene defect contributes to elevated homocysteine levels, which are commonly linked to recurrent miscarriages, as well as the other pregnancy related risks I spoke of previously.

One by-product of SAMe is homocysteine. Methylfolate and methylcobalamin help to convert harmful homocysteine into the beneficial methionine, which in turn helps to produce SAMe, in a cycle that is never ending, as long at the body is producing methylfolate. In the case of MTHFR gene defect, homocysteine levels may rise to harmful levels due to the impaired ability to produce adequate amounts of methylfolate; impacting your ability to conceive, or harming an otherwise healthy pregnancy.

Other concerns with this wheel are that the body will poorly convert homocysteine to the powerful antioxidant glutathione, which helps protect the body from free radical damage. People with compromised antioxidant levels are more susceptible to oxidative damage due to stress and environmental toxins, thus increasing the risk for toxin build-up. In addition, people with MTHFR gene defect may have lower levels of SAMe, which has been shown to increase the development of depression and postpartum depression. SAMe is also plays an important role in immune system function, growth, repair and maintenance of cells, and is anti-inflammatory. All of these play a role in reproductive function and proper development of a baby in pregnancy.

If you have been struggling to get pregnant, have experienced recurrent miscarriages or any of the other pregnancy related issues I mentioned previously, schedule an appointment with your doctor for a MTHFR genetic test and blood homocysteine level. This should be done before you try to get pregnant again.

Results Matter – Heterozygous or Homozygous?

There are different variations of the MTHFR gene defect. There are people with heterozygous (1 copy of C677T, passed on from one parent) and homozygous (2 copies of C677T, passed on from both parents) MTHFR mutations. Those with homozygous MTHFR C677T are often advised to take their folate requirements more seriously. Homozygous individuals need to avoid synthetic folic acid (see below for more info on this), they require more methylfolate supplementation than heterozygous individuals do, and their blood thinning requirements are greater, especially where a woman’s ability to get pregnant and carry to term is concerned. Before a successful pregnancy can be achieved, these considerations must be addressed.

Although at first it feels quite scary and hopeless to be diagnosed with a genetic defect, this one is quite common. Fortunately there are things you can do at home to increase your chances of natural conception, carrying a healthy pregnancy to term, preventing postpartum depression and protecting your health overall, since MTHFR gene defect impacts many areas of health.

Folate rich foods include spinach, lentils, papaya, grapefruit, walnuts and asparagus.

• Eat organic, this will help reduce overall toxic load.

• Avoid supplementing with synthetic folic acid, choose a whole food preconception multivitamin like Fertile Woman One Daily while trying to conceive and then switch to a whole food prenatal multivitamin like Baby and Me Multivitamin through pregnancy and breastfeeding. You may also want to ask your doctor about special prenatal vitamins that contain methylated folate or folinic acid.

• Eat a diet rich in naturally occurring folate, such as uncooked dark leafy green vegetables, lentils, beans, liver, and avocado. For a list of folate rich foods, click here…

• Avoid processed foods that are fortified with synthetic folic acid (homozygous), or strictly limit them (heterozygous).

• Consider supplementing with carnitine, CoQ10 Ubiquinol, cod liver oil, probiotics and an antioxidant blend. These can all be found in our online store.

• At each meal, eat a variety of whole foods and be sure to include a protein.

• Make sure all the B vitamins you supplement are from a whole food source and provide the methylated form (active). For vitamin B6 this would be Pyridoxal 5-Phosphate or P5P; for Vitamin B12 this is methylcobalamin.

• Avoid regularly consuming both black and green tea, as they may inhibit folic acid absorption.

• Avoid antacids, these inhibit folic acid absorption as well

• For vegans, it is important to speak with your doctor about supplementing with the following, in addition to the above; methylcobalamin (active form of vitamin B12) and choline.

The mechanism for this concern actually comes from multiple consequences of a mutatedMTHFR enzyme.  Developing embryos may be adversely affected by toxic levels of homocysteine that result from MTHFR mutations. Altered DNA methylation may also have direct negative effects on gene expression and DNA synthesis. The main concerns here are neural tube defects and other midline defects such as cleft palate, although they are not the only ones.  Noteworthy research includes a study from Ireland showing that 26% of all neural tube defects were related to either the homozygous or heterozygous MTHFR mutations (Kirke, P. et al.  BMJ. 2004;328:1535-1536)

Additionally, a 2.6-fold increase in the frequency of the MTHFR C677T polymorphism has been observed in the mothers of Down Syndrome patients in South India (Cyril, C. et al. Indian J Hum Genet. 2009; 15(2): 60-64).

A very recent meta-analysis supports the association between recurrent pregnancy loss (RPL) and the C677T genotype in Asians, although this association was not found in Caucasians (Wu, X. Genet Test Mol Biomarkers. 2012 Feb 7).

Congenital heart disease (CHD) in children has also been linked to MTHFR gene mutations in either the mother or the child, although a complete analysis and conclusion is still unclear.  One of the more recent studies however, did find a clear relationship between CHD and MTHFR mutations (Garcia-Fragoso, L. et al.  Int J Genet Mol Biol.  2010; 2(3): 43–47).

The authors note that, “The prevalence of the TT polymorphism was higher in mothers (22%) than in controls (10%). Compound heterozygosity for both polymorphisms was 3.7 times more common in children with CHD than in the newborn controls. Mothers of children with CHD were more likely to be compound heterozygotes”

An interesting question in relation to embryonic development is whether it is the MTHFR mutation in the mother or in the developing child that is the critical determinant in the development of congenital defects. At IVF PHOENIX, we believe that both mutations play a role, particularly in the unexplained or recurrent miscarrying group of patients.

If you have tested positive for MTHFR gene mutation, I highly recommend learning more from Dr. John Couvaras. He thinks outside the box, provides a wealth of information and is helpful at directing people to support.

Significant roles of a properly functioning MTHFR enzyme include nucleic acid biosynthesis, neurotransmitter synthesis, and production of signaling molecules important for regulating embryonic development