Dealing with the heartbreak of a lost pregnancy can leave many people asking – why? While the answers aren’t always known, there are some cases where the parents’ genetic variants can interact with diet and lifestyle to increase miscarriage risk. This article dives into the MTHFR variants and miscarriage risk – with added information
MTHFR and Miscarriages:
There are quite a few studies showing that women carrying certain MTHFR variant combinations are at a somewhat higher risk for recurrent miscarriages. Almost all of these studies point to a small, yet statistically significant increase in miscarriage risk for women carrying MTHFR variants.[ref][ref]
(Want to learn the basics of MTHFR? Check out this article…)
Recently, I ran across a study that added a new twist to the topic. It turns out that the father’s MTHFR variants can also play a role in recurrent miscarriages.
This makes sense. Both the DNA in the egg and the DNA in the sperm need to be complete and without significant errors in order to become a baby.
Importance of Dad’s MTHFR Variants in miscarriage:
The study from 2015 looked at 225 couples with more than three consecutive pregnancy losses compared with 100 control couples with successful pregnancies. All 225 mothers in the pregnancy loss group carried either compound heterozygous MTHFR C677T and A1298C variants or homozygous C677T or homozygous A1298C. The study defined carrying just one copy (heterozygous) of either C677T or A1298C as being at low risk for miscarriage.
When the researchers looked at the father’s MTHFR variants, they found that in the pregnancy loss group the men were more likely to carry the risk variants.[ref] This backs up the work of other, smaller studies that also found that the male’s MTHFR status combined with the mother’s MTHFR variants does seem to statistically increase the risk of miscarriage.[ref]
There are a couple of things that could be going on here:
First, fathers who carry the MTHFR variants are likely to pass them on to the baby. There are a couple of studies showing that the baby’s MTHFR variants may play a role in miscarriages. On the other hand, there are quite a few studies showing no effect from the baby’s MTHFR gene. Overall, the meta-analyses that combine all the study data tend to show little to no effect on the baby’s MTHFR status, so this is probably not the reason.[ref]
The second possibility of why the father’s MTHFR variants matter could tie in with the fact that men carrying homozygous MTHFR variants are also at a higher overall risk for infertility.
A meta-analysis pooled the results of 20+ studies and showed that men carrying either the homozygous MTHFR C677T or A1298C variants were at a higher risk for infertility (29 – 63% increase). Statistics here… Keep in mind that this is just the increase in the risk of infertility compared to the normal risk. For example, if the risk of male infertility is 1 in 20, a 69% increase would make the risk 1.69 in 20.[ref]
One of the final steps in sperm creation involves methylation of the DNA and packing it up correctly in the nucleus. Decreased methylation cycle nutrients could be affecting this final step in sperm creation. Alternatively, the methylation cycle and the MTHFR variants impact the way the cells deal with oxidative stress. Excessive oxidative stress can also impact and damage the DNA in the sperm. [ref]
Genetic Variants for MTHFR:
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Check your genetic data for rs1801133 (23andMe v4, v5; AncestryDNA):
- G/G: typical *
- A/G: one copy of MTHFR C677T allele (heterozygous), decreased by 40%
- A/A: two copies of MTHFR C677T (homozygous), decreased by 70 – 80%
Members: Your genotype for rs1801133 is —.
Check your genetic data for rs1801131 (23andMe v4, v5; AncestryDNA):
- T/T: typical *
- G/T: one copy of MTHFR A1298C (heterozygous), slightly decreased enzyme function
- G/G: two copies of MTHFR A1298C (homozygous), decreased enzyme by about 20%
Members: Your genotype for rs1801131 is —.
In conception, pregnancy, and throughout life! It is easy to see how prospective moms need to clean up their diets, exercise, and sleep well before getting pregnant, but I think these studies are a good reminder that prospective fathers need to pay attention to their own health as well!
Eating more folate:
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Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.