There are quite a few studies showing that women carrying certain MTHFR variant combinations are at a somewhat higher risk for miscarriage, but I recently 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.
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 a low risk for miscarriage.
When the researchers looked at the fathers MTHFR variants, they found that in the pregnancy loss group the men were more likely to carry the risk variants.[study] 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.[study]
How to check your MTHFR variants on 23andMe
Check your 23andMe results for rs1801133 for the MTHFR C677T:
- G/G: normal (wildtype)
- A/G: one copy of C677T allele (heterozygous), MTHFR efficiency reduced by 40%
- A/A: two copies of C677T (homozygous), MTHFR efficiency reduced by 70 – 80%
Check your 23andMe results for rs1801131 for the MTHFR A1298C:
- T/T: normal (wildtype)
- G/T: one copy of A1298C allele (heterozygous), MTHFR efficiency reduced
- G/G: two copies of A1298C (homozygous), MTHFR efficiency reduced
There are a couple of things that could be going on here:
First, fathers who carry the MTHFR variants are likely passing them on to the baby. There are a couple of studies showing that the baby’s MTHFR variants may play a role in miscarriages, but there are other studies showing no effect from the baby’s MTHFR gene. Overall, the meta-studies tend to show little to no effect from the baby’s MTHFR status, so this is probably not the reason.[study]
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 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 the 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.[study]
Dads matter – 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!
MTHFR variants (read more here) increase the need for ensuring adequate folate consumption. This means leafy green veggies, legumes, and other organic food sources of folate need to be eaten daily. If you won’t make the necessary dietary changes, there are methyl folate supplements as well. A quality B12 is also important, and many people find it convenient to take a B-complex to cover all the bases. Here is one that I like: Jarrow B-Right. But you may find other options that are a better fit for you.
This may be a ‘talk to your doctor’ situation if you have a physician working with you on family planning. I know – telling some guys to talk to a doctor is like banging your head against the wall, but if recurrent miscarriages or infertility are a problem, this really may be a time to get some professional help.
I didn’t find any specific studies looking at men supplementing with folate for recurrent miscarriage, but there are studies showing that it is effective for women. One recent (small) study found that 5mg of methyl folate along with B6 and B12 decreased the risk of miscarriage.[study]
Please note that methyl folate is likely the better form of supplemental folate vs. folic acid,[study] but that some studies show that a folate-rich diet is as effective as either methyl folate or folic acid. [study] One reason for methyl folate instead of folic acid is that there have been several recent studies linking high doses of folic acid to things like an increased risk of allergies[ study] and some epigenetic changes that are a bit of an unknown.[study]
Studies on miscarriage risk for women carrying MTHFR variants:
- Association of Methylenetetrahydrofolate Reductase C677T and A1298C Gene Polymorphisms With Recurrent Pregnancy Loss in Syrian Women.
- Comparison of two preventive treatments for patients with recurrent miscarriages carrying a C677T methylenetetrahydrofolate reductase mutation: 5-year experience.
- Association between the MTHFR C677T polymorphism and recurrent pregnancy loss: a meta-analysis.