MTHFR Tutorial

[Charity]

I've recently been diagnosed with having the homozygous C677T MTHFR mutation and have found various information on the subject. I was hoping this might help others that are looking for the majority of the information available in one reading...I needed to put together something to send out to my family to ensure they all got tested, so thought I'd share here. I have borrowed much of this from others, so if some sounds familiar, you likely have read it either here or on other forums. Best wishes to those who have recently been diagnosed. For those who have experienced losses, I hope your recent diagnosis and treatment proves to be the answer to your prayers. I am hopeful it's the answer to mine and dh's. All my best!

MTHFR Gene Mutation

What is it?
The gene MTHFR (Methylenetetrahydofolate Reductase) encodes the protein MTHFR. Its job is to convert one form of folate (5,10-Methylenetetrahydofolate) to another form of folate (5-Methyltetrahydrofolate). 5-Methyltetrahydrofolate is used to convert Homocysteine (a "bad" amino acid) to Methionine (a "good" amino acid). Therefore, if MTHFR is not doing its job as well, homocysteine will not be converted to Methionine and will be elevated in plasma. Elevated Homocysteine has been associated with a variety of multi-factorial diseases.

Essentially what this means is that the genes that instruct MTHFR to convert homocysteine to Methionine are mutated and may not be capable of doing this important function. MTHFR is an enzyme that converts Homocysteine to an essential amino acid (Methionine). When the genes are mutated you may be lacking this enzyme. Your Homocysteine levels can possibly climb making the blood clot. Some doctors don't check for the MTHFR mutations and rely only on homocysteine levels. This isn't as reliable as testing for the mutations, because Homocysteine levels fluctuate (if you catch your level on a normal day, you may go undiagnosed).

What Type Do I Have?
With MTHFR, there are two different genes identified for this mutation, and it's possible to be "heterozygous," "compound heterozygous," or "homozygous." The MTHFR gene mutation has varying degrees of possible implications. The order of potential severity from most to least is:
1. C677T & C677T (Two C Copies - C677T Homozygous)
2. C677T & A1298C (One Copy of Each The C & A - Compound Heterozygous)
3. C677T (One C Copy - C677T Heterozygous)
4. A1298C & A1298C (Two A Copies - A1298C Homozygous)
5. A1298C (One A Copy - A1298C Heterozygous)

The MTHFR mutation is fairly common in the general population. Approximately 44% of the population is heterozygous and another approximate 12% are homozygous for the MTHFR mutation. Compound heterozygous and homozygous MTHFR have the highest incidences of being linked to implantation failure, late term miscarriages, specific birth defects and overall vascular health. Whichever type of MTHFR you have, it should not be discounted, particularly if there is a personal or family history of any such incidences.

What Are the Implications?
Any and all of the mutations can affect homocysteine levels, but there is much dispute as to whether elevated homocysteine levels are actually needed in order for MTHFR to cause medical complications. Many other MTHFR patients have normal homocysteine levels; yet have had implantation problems, m/c(s), and/or stillbirth(s) due to clotting problems. So it is important to find out your Homocysteine levels (although again, normal doesn't necessarily mean all is well). This is a serious field and MTHFR is a serious condition, so consulting an expert is wise.

Research shows that high homocysteine levels and/or those with the mutation show a higher propensity for thrombosis (blood clots), arteriosclerosis (hardening of arteries), Alzheimer's, stroke, heart attack, Fibromyalgia, migraines (especially with "Aura" migraines), osteoporotic fractures, bone marrow disorders and for those of child bearing years, it has found to be connected to higher incidences of down's syndrome, spina bifida, other neural tube defects, trisomy, miscarriage, stillbirth, implantation failure, placental abruption, preeclampsia, higher incidences of autism, amongst others. Additionally, if you test positive you may want to have your parents, siblings, and any children you may already have tested, as well. There are a few positives to this disorder. Because folate is necessary for cellular division, there is support that shows having this disorder can actually help keep certain types of cancer cells from multiplying as rapidly, so there are some benefits from having this mutation.

Treatment?
Many doctors prescribe Folgard, which is a prescription vitamin supplement containing high levels of folic acid, B12 and B6. These vitamins are what the body essentially needs to convert Homocysteine to Methionine. To put this into perspective, the average multivitamin contains 400 mcgs , most prenatals have 800mcgs of Folic Acid (200% of the normal daily value). Those that are compound heterozygous and those that are homozygous for the mutation are recommended taking 5 mgs. of Folic Acid/B vitamins (12 times the average multi-vitamin and 6 times more than prenatals). It is also recommended to begin taking a low dose (LD) aspirin (81 mgs) once a day, every day, for the rest of your life.

For those undergoing fertility treatments, often times the treatment includes Lovenox (low molecular weight heparin) or Heparin (both are anti-coagulants) during the cycle. If you have a history of implantation failure or early miscarriage, it is becoming more acceptable to use the protocol established by the well-respected Reproductive Immunologist Dr. Beers by beginning Lovenox (40mg/once a day) on cycle day 6 and continuing throughout the cycle. If pregnancy is confirmed, this dosage is likely increased (Typically up to 40mg/twice a day, but potentially higher doses are prescribed dependent upon blood work results since homocysteine levels tend to increase with pregnancy) and usage continues throughout your pregnancy. Approximately two to four weeks prior to birth, the patient is converted to Heparin and continues to take an anti-coagulant for another 6 weeks postpartum (typically switched back to Lovenox). During that time, you will typically be directed to take additional Calcium and Vitamin D, as anti-coagulants can cause bone loss (Heparin more so than Lovenox). Some doctors will recommend a bone scan after use is discontinued to ensure there are no bone density issues. While being treated with an anti-coagulant, you will typically be asked to discontinue taking the 81 mg. baby aspirin since the anti-coagulants will replace the need for the thinning property of the LD aspirin. The FDA has placed Lovenox in the pregnancy category B. Lovenox is not expected to be harmful to an unborn baby. It is not known whether Lovenox passes into breast milk or if it could harm a nursing baby. Do not use Lovenox without telling your doctor if you are breast-feeding a baby. However, many doctors believe it is fine to breastfeed for the 6 weeks postpartum while still receiving Lovenox.

[JenX]

Wow Thanks! I'm going to print this out....do they really up your dose of lovenox after pregnancy...I expected to stay at 40 cause I thought that was typical...

[domino]

Amazing!! I think I almost understood that. Thank you!

[LemonadeGlugger]

Thank you, loved how you wrote it up. Will send to family. I'm diagnosed as homozygous C.

[Charity]

Xtgirl...Yes, they usually do raise the Lovenox after positive pregnancy test. Homocysteine levels have a tendency to rise with pregnancy, so that's the reason for the increased dosage. It's more precautionary than anything else, but I would rather take a little more than needed than not enough...You hang in there hon, and we'll all be getting our BFPs before you know it!

DietPepsiGal...Good luck on your upcoming beta this Friday...Have everything crossed fro you, kid!

[Ruth41]

Charity,

Well done. I am hetero for the MTHFR gene mutation and have a healthy baby boy (now 17 months old) thanks to Lovenox and Dr. Beer. I took 40 mg of Lovenox during my entire pregnancy and must say I am surprised about the increase in dosage to DOUBLE that. That was not Dr. Beer's protocol when he was alive and I was pregnant. Can you please confirm where you found that info? I did deliver a full term extremely healthy baby with no clotting in the placenta/umbilical cord, so the 40 mg obviously did the trick. I would be hesitant to up that dosage unless there is overwhelming evidence that more is necessary as Lovenox does have it's downside. At 40 mg a day, I had almost daily nosebleeds for 4 months at the end of my pregnancy. Also, being so anticoagulated can be dangerous in the event of even the smallest accident; I"m not just talking a car accident. I barely knicked myself with a razor in my second trimester and it took over an hour to stop the bleeding with pressure and ice. I almost went to the ER, it was so unnerving. Also, bruising is another issue while anticoagulated.

So, hence my concern over the 2x a day Lovenox recommendation you are stating. It is a wonder drug to MTHFR women, but should be used with caution. And FYI, my IVF doctor wanted me on Lovenox from 1 day post retrieval as it increases circulation in the uterus which is good for implantation.

I had 6 pregnancy losses before having my son and I owe it all to my doctor and Lovenox. Worth every painful shot.

Ruth

[Charity]

Ruth...Let me preface by saying that by no means was my post "recommendations" for treatment. These are just protocols and treatments others have experienced in the past, as they've posted on several forums throughout the internet "world"...These protocols are coming from laymen (lay-women) and being posted by a lay-woman on non-medical forums, so by no means are necessary for the safe treatment of MTHFR mutation.

I have gone back and searched the internet and have found several women who are on Lovenox 2x daily at the dosage noted, and only being afflicted with MTHFR (no other clotting disorders). There are others that are on the single dosage, as you've noted, and have had great success. I personally know others that are only on low dose aspirin, and have had success after numerous m/c's. I can only assume that just as there are many varying medical histories, varying degrees of MTHFR, and varying doctors' recommendations/opinions, it would only lend itself to there being as equally varying degrees of treatment and dosages of anti-coagulants. I'm sure much is related to an individuals' homocysteine levels during pregnancy, as well. Some women don't have significant increases, whereas others body chemistry is completely different and do experience higher levels.

I understand the seriousness of using anti-coagulants, and that's a great point to restate here. Especially considering there is medical evidence that supports anti-coagulants, as well as low dose aspirin, can cause miscarriages. So please know that this is simply information that I came across during my many readings. Also, my reference to Dr. Beers was only with regard to the beginning Lovenox on cd6. This was of particular interest to me, as many RE's prefer only to start Lovenox with a positive pregnancy test. However, there is evidence to support MTHFR can cause implantation failure, so a positive HPT could never be achieved. That's the only reason for my particular investigation into that area, and consequential posting of it to my family.

The rest of the information regarding the use of anti-coagulants is not taken directly from Dr. Beers' treatments. Interestingly, I just moved to another RE, and had my consult on Friday. My new RE knew Dr. Beers personally and is aware of his work. Some he respected and other he feels was questionable as to it's necessity (i.e. significant number of tests at high dollars that resulted in no change in treatment). So, I am with a more conservative RE, who has agreed that Lovenox could be useful in my specific situation, with my degree of MTHFR, with my medical history, and the benefits outweigh the risks, FOR ME, at this stage.

Thank you for bringing up a very good point, and I do not want to give the impression that I am "recommending" any of the information or treatments I posted. This was simply information I found on the subject in my searches.

[loved2life]

FYI...I am homozygous for C677T and did follow Dr. Beer's protocol...40mg every day of Lovenox from cycle day 6 until positive pregnancy test...then increased to 40mg twice daily until a week prior to c section. I know have a happy, healthy 2.5 yr old boy!!!!

[Charity]

Congratulations on your success and miracle ds, Loved2Life...It's so encouraging to hear a success story on the protocol I'm planning on following next month.

I have been torn on the use of Heparin over Lovenox. I know there are bone loss issues that can result from long-term use of Heparin, but the costs are phenomenally different. I'm just worried that if the first cycle isn't a success, that with just one IUI cycle between meds and procedures, I wouldn't be able to afford another cycle. It's getting as costly as 1/3 of an IVF cycle was for me...Just thinking of going with Heparin for that reason alone, allowing me a few more cycles this year, and then if I do get a BFP, I would be able to switch over to the Lovenox, as I believe my insurance would cover it at that stage. Before pregnancy, it's deemed fertility treatment, so is not covered, but after pregnancy, would be medically necessary. I've already started taking extra Vitamin D3. Your thoughts between the two? Anyone else? Thanks for any support and any opinions/suggestions anyone can offer...

[laurelavenue]

Some background: I am 41 years old and have experienced 8 miscarriages in the past 3 years. All except one were before 7 weeks. The last one - two months ago - was at 7.5 weeks, after we saw the heartbeat on ultrasound.

I did also have one successful pregnancy (yay!) in 2007, and I have three much older children. We would love to have just one more baby.

After the first three early miscarriages in 2006, I was diagnosed as compound heterozygous for the MTHFR genetic mutations C677T and A1298C. I also carry the PAI (-675) 4g/5g genotype.

After this diagnosis, I was put on Metanx and baby aspirin. Taking these meds, I was able to carry my next pregnancy to term. Since giving birth to my daughter in July 2007, I have had several more early miscarriages, all while taking the baby aspirin and Metanx.

Neither the perinatologist I have seen, nor my regular OB believes I need any type of injectable blood thinner. They do not see a relationship between my recurrent losses and my genetic thrombophilia issues. This is because when my homocysteine and PAI levels are checked right after a positive pregnancy test, they are normal. Yet time after time, I go on to miscarry after being told my levels look fine.

I am at a normal weight and am in good health. My husband and I have been checked for chromosomal anomalies and are both fine. I do tend to have low progesterone in pregnancy, and have taken prometrium as soon as pregnancy tests come back positive. I took it before all my losses, and I also took it with my one successful pregnancy in recent years.

My OB now has me taking a first round of clomid - even though I am clearly ovulating, since I keep getting pregnant - to try to improve my hormone levels at the time of implantation. However, I continue to believe that perhaps the reason I keep miscarrying within the first few weeks of pregnancy is related to the MTHFR and PAI issues. SInce I have now had two competent doctors assure me this is NOT the case and I do NOT need blood thinners, I am really wondering whom I should consult next.

Thanks for reading my long history. I welcome and and all feedback and suggestions.