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MTHFR and Pregnancy Success


Can You Have a Successful Pregnancy with MTHFR?

MTHFR and Pregnancy Success


Recent research has shown that an MTHFR mutation may increase the risk of complications during pregnancy. It’s also been suggested that MTHFR may explain why some women have recurrent miscarriages.


While more research is pending, this information will no doubt have many women with MTHFR wondering if they can have a successful pregnancy.


The MTHFR gene codes the enzyme required for metabolizing folate. While most people with MTHFR can obtain enough folate from their diet to make up for this impaired metabolism, the body’s needs for folate are much greater during pregnancy. As a result, women with an MTHFR polymorphism may be at a higher risk of complications or birth defects due to lack of folate.


Folate is crucial for proper DNA synthesis and repair, control of gene expression, and many other biological processes of fundamental importance for cell division and embryo development.


Impaired folate metabolism can also lead to elevated levels of homocysteine, which has been linked to recurrent miscarriage. It’s for this reason that women who have had multiple miscarriages are often advised to undergo testing for folate levels or hyperhomocysteinemia.


The good news is that yes, it is possible to have a successful pregnancy with an MTHFR mutation. It’s just a matter of taking the right nutrients.


This article will explain the risks associated with different MTHFR variants during pregnancy, how these risks can be minimized, and the most effective folate supplements that pregnant mothers can take.


How Can You Have a Successful Pregnancy with MTHFR?


Folate is crucial to fetal development, which is why taking the correct form of folate prior to conception and during pregnancy can significantly improve your chances of a successful pregnancy.


Folic acid supplements are often prescribed by doctors, and also used in fortified foods and many prenatal multivitamins. However, the MTHFR mutation impairs the body’s ability to methylate the synthetic folic acid into a usable form. This mutation may also interfere with nutrient status of other B vitamins, including B12.


The solution is to source a prenatal vitamin that contains methylated folate, referred to as 5-MTHF or 5-methyl-tetra-hydro-folate. A methylated B12 should also be included.


Can an MTHFR Mutation Cause Infertility?


Several studies have suggested that MTHFR genetic mutations may be associated with male infertility because of its effect on spermatogenesis; however, results are largely inconsistent. MTHFR appears not to affect female fertility: one study showed that the C677T mutation was found in 49.2% of fertile women, and in 58.5% of infertile women, which the study authors conclude was not statistically significant.


A meta-analysis of 37 studies found that the MTHFR C677T mutation was a risk factor for male infertility in patients with azoospermia (no sperm in the ejaculate) and oligoasthenoteratozoospermia (low number of sperm). This was especially high in Asian men.


Another meta-analysis in 2015 also suggested that the MTHFR 677C>T polymorphism is associated with an enhanced risk of male infertility, with the authors suggesting that this may be due to a deficiency in folate and vitamin B12.


Recurrent Miscarriage with MTHFR


Recurrent miscarriage is most often defined as three or more consecutive spontaneous fetal losses.

 

A 1997 study showed that a homozygous MTHFR gene mutation increased the risk of miscarriage more than three-fold. More recently, a significant association was seen between MTHFR C677T polymorphism and the number of miscarriages, with study authors concluding that the higher the number of miscarriages, the higher the presence of the MTHFR mutation.


A 2019 study found that the 1298AC and 677CT/1298AC (composite heterozygous) genotypes were both risk factors for unexplained recurrent pregnancy loss. The risk was highest in women with two mutations of A1298C and C677T, with the incidence increasing six-fold. The authors suggested that supplementation with “folic acid and other corresponding measures” would be necessary to reduce the risk of pregnancy loss.


The Role the MTHFR Gene Plays in Pregnancy

The Role the MTHFR Gene Plays in Pregnancy


A mutation of the MTHFR gene affects the body’s ability to process folate, which is especially problematic during pregnancy.

 

Folate is absolutely crucial for the proper DNA replication involved in a baby’s development. It is an essential factor for the growing placental tissue, acts as a substrate for the metabolism of several amino acids, and is required for the transmethylation pathway. MTHFR also plays a part in the control of gene expression by DNA methylation during the first trimester of pregnancy.

 

Folate deficiencies can lead to health issues for both mother and the fetus. Mothers are at a higher risk of anemia or peripheral neuropathy, while the fetus is more likely to suffer congenital abnormalities.

 

It has been noted that many studies suggest hyperhomocysteinemia, homozygous MTHFR gene mutations, and folate deficiency to be likely risk factors for recurrent miscarriage, fetal death, blood clotting disorders in pregnancy, neural tube defects, and congenital cardiac issues, along with many other placental diseases.

 

Reduced MTHFR enzyme activity decreases the conversion of homocysteine into methionine, resulting in higher levels of homocysteine in the blood.

 

Hyperhomocysteinaemia can be caused by enzyme deficiencies related to MTHFR and a subsequent lack of cofactors required for methionine metabolism (vitamins B6, B12, and folic acid).


How an MTHFR Mutation Affects Developing Embryos


Folate deficiency has been associated with a higher risk of folate-dependent functions required for DNA synthesis and repair, control of gene expression, and many other biological processes involved in cell division and embryo development.

 

MTHFR mutations are associated with an increased risk of aneuploid pregnancy. This study found that parental MTHFR genotypes had a higher risk of aneuploid embryos (embryos with too many or too few chromosomes), indicating that MTHFR may affect rates of chromosome abnormality.


Another study involving women with and without MTHFR polymorphisms showed that 94.7% of the women in the MTHFR group had pregnancies with chromosomal abnormalities.


Abnormal folate metabolism in MTHFR mutations can lead to improper DNA methylation, resulting in abnormal gene expression and DNA strand breaks. Studies in mice affected by MTHFR showed growth defects and the appearance of congenital malformations through several generations.


What About MTHFR Variants?


Some research suggests that different variants have different effects on pregnancy. The activity of the MTHFR enzyme is reduced by 35% in people who are 677CT carriers (heterozygosity) and by 70% among 677TT carriers (homozygosity).

 

Homozygosity for C677T is associated with elevated homocysteine in some individuals, especially in those with low folate. However, one study found that the C677T MTHFR mutation was not a risk predictor in women with a history of early or late recurrent miscarriage.

 

In another study, the 1298C allele was found to be significantly higher in miscarriages involving fetal chromosomal aneuploidy than the 1298AA genotype. There was no association between miscarriage with fetal chromosomal aneuploidy and other polymorphisms. This study also suggested that 1298AC polymorphism may be an independent risk factor for miscarriage with chromosomal abnormalities.


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Possible Fetal Development Disorders

Possible Fetal Development Disorders

  • Behavioral disorders (e.g, autism)
  • Neural tube defects
  • Metabolic defects
  • Mitochondrial disorders
  • Congenital heart defects
  • Cleft palate/cleft lip


Numerous studies have reported associations of MTHFR polymorphisms with an array of conditions including autism and fetal neural tube defects.

 

MTHFR polymorphisms that disrupt folate metabolism may increase the risk of neural tube defects. However, study results are mixed.  Significant 5-MTHF deficiency has  been associated with metabolic defects, specific mitochondrial disorders, and cerebral problems.

 

Congenital malformations among babies born to parents with MTHFR mutations include neural tube defects (NTD), cleft lip or cleft palate, and congenital heart defects. In this study, the most common malformations were NTD (25.3%) and cardiac anomalies (25.3%). Around 90% of babies with NTDs in the study included patients with reduced MTHFR activity.

 

However, some researchers have noted given the high prevalence of the MTHFR polymorphisms and the low frequency of neural tube defects, they suggested that the polymorphisms alone were unlikely to have a significant role in causing neural tube defects.


While there may be some increased risk of neural tube defects in those with the homozygous 677C>T variant, the exact level of risk is still uncertain. Folate supplementation may be more important: population-level fortification with folate led to a significant drop in neural tube defects by about 70%.


Folate is crucial for pregnancy success

Prevention Through Supplementation


Folate is crucial for pregnancy success. This nutrient is especially important during the first few weeks of a fetus' development, which is often before a woman discovers she’s pregnant.


Folate deficiency has been associated with greater risk of infertility, miscarriage, development abnormalities, and other negative pregnancy outcomes.


Numerous studies show a strong link between an impaired folate cycle, and consequently altered metabolic pathways, and the ability to conceive and carry a pregnancy to term. However, those with MTHFR polymorphisms C677T and A1298C and who suffered repeated miscarriages improved the chances of pregnancy to term by supplementing with 5-MTF.


Folate-containing multivitamin supplements have also been shown to reduce the risk of NTD recurrence in women with a previously affected pregnancy. Supplements containing vitamin B12, a co-factor in folate one-carbon metabolism, may further reduce the frequency of NTDs


It is recommended that folic acid be avoided by couples experiencing infertility. However, 5-MTHF bypasses the MTHFR block and is therefore an effective treatment. It also avoids potential adverse effects of the Unmetabolized Folic Acid (UMFA) syndrome, which has its own adverse effects.


Women who are trying to conceive should look for a prenatal supplement containing methylated folate.


One of the best methylfolate supplements for those with MTHFR mutations is Methyl-Life® Methylated Multivitamin. The Methyl-Life® range has been created by a team of natural health experts and contains the purest, most stable, and most potent of four of the world’s industry-leading patented L-Methylfolates. It is also suitable for vegans and those with cardiovascular risks.


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