Update on 6/24/2021: Women are finding this article to be extremely useful. Please read this article fully. Evaluate the list of genetic variations and order genetic testing with your healthcare professional. It’s not just about MTHFR. There are more to evaluate. Details below.
UPDATE on 2/13/2012: This is no longer a theory as current research supports it. This research has yet to be published. First, read my theory below and then I will provide the proof.
This theory is born out of wondering why some women are experiencing recurrent pregnancy loss, have had all sorts of laboratory and physical tests done yet the only thing that shows up is a heterozygous A1298C MTHFR mutation OR a heterozygous C677T mutation along with a normal homocysteine level.
What do women typically hear as recommendations when having heterozygous MTHFR mutations along with normal homocysteine levels?
We don’t see risk associated with heterozygous MTHFR mutations when homocysteine levels are fine. Heterozygous A1298C (or C677T) is a mild and common mutation seen in the population. No treatment is necessary.
Researchers, geneticists and doctors do not appear to be considering the fact that a developing baby is made from two sets of genes:
The Mother’s AND The Father’s MTHFR Genes and the Odds of Inheritance:
If the mother is heterozygous A1298C and the husband is also carrying a heterozygous A1298C mutation – then the likelihood of baby having two copies of A1298C mutations exists.
In fact, the likelihood is at least 25% that baby can be homozygous A1298C.
Let’s look at another scenario:
Mother has a heterozygous A1298C mutation and the father has a heterozygous C677T mutation.
The likelihood that the developing baby has a compound heterozygous mutation is at least a 25% reality.
Compound heterozygous MTHFR mutation is also not great to have as the MTHFR mutation has significantly reduced function. The function of the MTHFR gene is at 50% capacity when one has a heterozygous A1298C mutation and a heterozygous C677T mutation.
I’m not going to begin explaining the reality of a homozygous A1298C or homozygous C677T father.
Research does state this:
…combined MTHFR mutations likely carry a selective disadvantage and contribute to decreased fetal viability, especially during times of folate insufficiency…. This study provides evidence that the combined effects of multiple mutations on phenotype, particularly in the case of common polymorphisms, are not restricted to intergenic interactions. The recognition that combined MTHFR genotypes may influence pregnancy outcomes further demonstrates both the clinical significance of this gene and the potential protective role of folate sufficiency.
That said, it is best to proactively treat for MTHFR mutations in all its forms because the baby may carry more than just the mother’s MTHFR mutation – but the father’s MTHFR mutation as well.
Doctors must test the future father’s genes for MTHFR mutations and understand the potential risk to developing baby. Then take the necessary precautions for the woman (and baby) by supplementing or prescribing properly.
Doesn’t this explain why so many women with heterozygous MTHFR mutations still miscarry – at least in part?
Obviously there can be other causes here as well for miscarriage – but let’s keep it focused to MTHFR.
How to address MTHFR mutations and pregnancy:
- Future mother and father: Get an MTHFR genetic test plus identify important genetic variations such as COMT, GST, GPX, MTHFD1, DHFR and over 100 others in a comprehensive 100+ page report.
- Future mother: Get tested for MMA, S-adenosylhomocysteine and homocysteine (only focusing on MTHFR here. Obviously other testing and physicals need to be done).
- Take appropriate action to ensure a safer pregnancy.
UPDATE on 2/13/2012: I found the research and it is not yet even published – it is that new.
Results of the study:
The overall, heterozygous and/or homozygous point mutations in FVL – FVR2, ApoE2, PAI-1, MTHFR C677T – A1298C, and ACE genes were associated with recurrent pregnancy loss (RPL). There was no meaningful association between RPL and other studied genes.
Current results showed that RPL is related to combined parental (not only maternal) thrombophilic gene mutations. 
If you have recurrent pregnancy loss or are considering becoming pregnant, then I highly recommend you ask your doctor to test you AND your partner for the genes:
- FVL – FVL2
The research by Ozdemir proves the point that genetics from the father and mother must be considered in recurrent pregnancy loss.
Whether heterozygous MTHFR by itself causes recurrent pregnancy loss is still to be debated; however, when combined with the above mutations, the effect is clear.
I need you to Tweet, Share, Like, Email, Print, Post on Forums – do everything you can think of to get this article in the hands of those who need to read it.
This article can save the lives of babies every year. Add the ability to help potential parents avoid the devastating loss of their baby.
Health care needs to be more aware of prevention. This is a classic example of why.
Read this article on MTHFR and Pregnancy to optimize your pregnancy and your future child!
 Isatolo et al, Neonatal and Fetal Methylenetetrahydrofolate Reductase Genetic Polymorphisms: An Examination of C677T and A1298C Mutations, American Journal of Human Genetics
 Ozdemir et al, Recurrent Pregnancy Loss and Its Relation to Combined Parental Thrombophilic Gene Mutations, Genetic Testing and Molecular Biomarkers