I am in shock (children mentioned)

[LMKH]

I am in so much shock right now.

I have lost my last 4 pregnancies. I asked for a loss panel but was told everything has been tested for that can be tested for that would be appropriate to me. This means, because I already have children, certain tests were skipped.

Turns out..I have MTHFR. I just got the results.

I have lost so many babies because I was not tested earlier. I am torn between being happy to know, and crying because of my babies I lost because of me. I am both..crying and sad, yet happy that this can be treated and I have a chance.

I was never told what type of MTHFR, how can I find out?

[Charity]

LMKH...Congratulations on your dx! And I'm so sorry for your losses. I know all to well what you're feeling. I had the same revelation in August. My babies were gone, because my body was failing me and due to RE ignorance in not testing me (and me actually being turned away when asking for testing)...Very frustrating, painful and yet hopeful at the same time.

The way you can find out is to either call the doctor/nurse and ask them to read you the lab results, fax you a copy of them, or to mail you a copy of your results. I actually asked for all my results to be mailed to me when they were received, and that's how I found out was by reading the lab report myself. I had the result and the internet...That's the only way I figured out what I had. You will be told you are either heterozygous for a single copy of the A1298C mutation, heterozygous for a single copy of the C677T mutation, compound heterozygous with a single copy of the A1298C and C677T mutations, homozygous for 2 copies of the A1298C mutation or homozygous for 2 copies of the C677T mutation. Depending upon the results, the higher your risks. Though, since you have already had 4 m/c's, it's pretty clear that you're being affected by this mutation.

The main thing at this stage is to be treated going forward, kiddo...You should definitely have your Homocysteine, folic acid, B12 & B6 levels checked. I have been dx'ed with two copies of the C677T mutation, and I had all the tests done. I had been treating myself for these before being dx'ed through the extra vitamins, prenatals, and low dose aspirin I was taking for ttc. So, I was fortunate to have all my levels check out. However, I notified my family that they are at risk, as well. My mom had her Homocysteine checked and had dangerous levels of 19 when she should be under 13. She already suffered a massive heart attack a few years ago, so she is definitely being treated for it now and is upset wondering if she could have prevented her heart attack had she known about this years ago. And the death of her mom, her sister's strokes, her brother and sisters' deaths, etc...Very frustrating this isn't being taken more seriously by doctor's when looking at family histories.

You might want to get the rest of the thromobophilia panel run if you want to make sure there are no other clotting disorders or genetic mutations. While this will not likely change the treatment you receive since you've already had several losses, it would be wise to make sure that you yourself are being treated properly, not only as it relates to ttc but for your own long-term health. You take care hon, and please don't blame yourself. You had no control over this and it's a genetic mutation just like any other disease that a family carries. I don't blame you for your frustration with the medical field, though, that I have a hard time accepting too. But please don't blame yourself. Okay? Take care hon, and see this as a new beginning. That's what you have to embrace and hold onto. We can't change the past, but can look forward to those future babies. They're going to be so loved. (((Hugs)))

[LMKH]

Based on your post..I ran to the doctors office and just got a copy of my bloodwork minutes before they closed. It says I have 1 copy of heterozygous c677t mutation.

Should I have my husband tested too?

I have 2 children with autism spectrum disorders. Is this related? I saw it was related to autism.

[Charity]

LMKH...It certainly does have some ties in many studies, but most are not conclusive based on the sample size. At this stage, the only reason I would have your other children tested is to make sure they're being treated for it (additional folic acid, B6, B12 & low dose aspirin), but it's likely there will be no other treatment advised. With having only one copy but having so many m/c's, I would highly recommend getting tested for any others you have not yet been tested for. It could be carried onto your existing children, and I would hate for you to not be treated if there are others. It just seems like there might be, LMKH...Some women only have the single copy and yet have as difficult time with the clotting aspect of MTHFR, but more often then not, they have other contributing factors. Just get healthy kiddo! That next baby is a keeper, so you get yourself in proper health, and you'll be fine...Take care...

[LMKH]

What would the other testing be? Because there area lot of things listed on here that I was tested for. Would it be more extensive testing on the MTHFR? I was going to have my dh tested for it too.

Also..I had a general chromosome analysis, as did my dh. I had a whole list of things like lupus and leiden something. I would have to have the blood work in front of me to tell you which was tested. But I didn't know if there was anything else you had in mind. You have been a great help already. Thanks so much!

[Charity]

LMKH...Here's some information from a lab website that does Immunological testing...It's pretty good, so thought it was worth posting...I would also recommend having your ANA, APA, LA done as well. Here's a link to the panel order form for this lab, that I used as a guide to request the tests from my general practitioner. My RE refused to do testing, as they were not equipped to do so at their lab. However, when I had wanted some testing done on my dh's sperm, they were more than willing to work with an outside lab to get these tests done. Ironic, that when it's a field they are in direct competition with (Reproductive Immunology), they suddenly don't do that testing and aren't willing to act as a go-between to have the testing done elsewhere. Ticked me off, as you can probably tell from my tone. But it was probably a good thing, since these were submitted without the infertility diagnosis, since they came from my GP and I got all the testing covered. Yeah! Here's the link to their order form that gives the test names and panels that you might consider having done. Good luck hon...If you have coverage, then I would say that it might be good to have the testing done, but if it's simply to determine if your children are at risk, unless you were both homozygous it's hard to determine what combination would fall onto your children. http://www.millenova.com/tests/reqform.pdf

Thrombophilia is defined as a predisposition for thrombosis. Increased thrombosis can result from defects in coagulation, fibrinolysis, platelet aggregation and endothelial damage. About 40% of patients with thrombosis are inherited. Inherited thrombophilias have been associated with early and late recurrent pregnancy loss as a result of uteroplacental microvascular thrombosis and hypoperfusion. Obstetrical complications such as intrauterine growth retardation, placental abruption as well as preeclampsia have also been related to abnormal placental vasculature. Genetic thrombophilia are suspected to account for about 30% of these obstetrical complications. Poor pregnancy outcomes are associated with maternal thrombophilia but may also be associated with fetal thrombophilia by inheritance of maternal and paternal thrombophilic genes.

Successful pregnancy requires fibrin polymerization to stabilize the placental basal plate as well as to prevent excess fibrin deposition in placental vessels and intravillous spaces. Thus, a balance between coagulation and fibrinolysis is mandatory to ensure successful pregnancy outcome as early as implantation. Coagulation factors linked to reproductive disorders include mutations of Factor V, Factor II and Factor XIII. Factor V mutations associated with reproductive problems have included G1691A (von Leiden), H1299R (R2) and Y1702C. Factor V von Leiden and Factor II prothrombin mutation G20210A are twice as common among women experiencing recurrent first trimester pregnancy loss and are suspected of tripling the risk of late fetal loss. The mechanism of loss is through generation of thrombin. Thrombin converts fibrinogen to fibrin. Fibrinogen is a protein with 3 polypeptide chains. A mutation in the b chain (-455G1A) has been associated with thrombosis. Fibrin is stabilized by cross-linking polymers under the influence of Factor XIII. One of the variations in the Factor XIII A gene, the Val34Leu polymorphism, has been correlated with thrombosis. Women who are homozygous for Factor XIII mutations also have a high risk for recurrent spontaneous abortion.

Increased thrombosis can result from a defect in fibrinolysis as well as coagulation. The main cause of defective fibrinolysis is an increase in plasmin activator inhibitor (PAI 1) concentrations. PAI 1 is induced by insulin and is increased in patients with polycystic ovary syndrome (PCOS) associated with insulin resistance. Clotting problems associated with increased PAI 1 may cause abnormal uterine artery blood flow, thus contributing to miscarriage associated with PCOS.

Thrombosis can also result from increased platelet aggregation and endothelial cell damage. Human platelet activator 1 (HPA-1) is part of the thrombosis system involved in platelet aggregation. It is a member of the integrin family. The integrin b3 gene encodes glycoprotein IIIa (GP IIIa) which is part of GP IIb/IIIa complex when activated interacts with fibrinogen to cross-link platelets to one another and causes platelet aggregation. Two allelic forms of GPIIIa have been identified (PLA1 and PLA2). The A2 form has been associated with increased thrombosis. Endothelial damage leading to thrombosis can be caused by hyperhomocysteinemia or antiphospholipid antibodies. Methylenetetrahydrofolate reductase (MTHFR) catalyzes remethylation of homocysteine to methionine. Several mutations in the MTHFR gene, C677T and A1298C, leads to hyperhomocysteinemia via decreased enzyme activity. Hyperhomocysteinemia is a major risk factor for both arterial and venous thrombolic disease. Individuals homozygous for the MTHFR gene are at increased risk for thrombosis and pregnancy related disorders. The risk of embryonic and fetal loss is increased if the MTHFR gene mutation is combined with additional thrombophilic factors. Disturbance of maternal and fetal homocysteine metabolism has also been implicated in a decrease in incidence of dizygotic twinning and an increase in fetal neural tube defects.



Indication for Testing
All individuals with a history of thrombosis and all women experiencing recurrent embryonic loss, fetal loss, severe pre-eclampsia, placenta abruptio, or intrauterine growth retardation should be tested for thrombophilic risk factors.



Detection Method
The Thrombophilia Panel includes testing for the following mutations:

Factor VY 1702
Factor V G1691A (Leiden)
Factor V H1299R (R2)
Factor II Prothrombin G20210A
B-Fibrinogen-455 G>A
Factor XIII V34L
PAI I 4G/5G
HPAI a/bHuman Platelet Glycoprotein (PLAI/PLA2)
MTHFR C677T
MTHFR A1298C
Gene mutations are detected by DNA probes and gel electrophoreses.

[LMKH]

I think I had that. Here is the list of what I had

Protein C and S profile, Russel Venom (DRVVT), Antithrombin III activity, Cardiolipin Antibodies (anticardiolipin IGG, IGM, IGA), Prothrombin G20210A, Factor V Leiden, that is all in addition to the MTHFR. There were some other tests done previously and I do not have copies of those.

Does this sound like it all?

[Charity]

There are the other Factor V's beyond Leiden and the Factor II, and there are the APA, ANA & LA that you will probably also want to take a look at...These last three aren't genetic, but are relative to you specifically...I'm sure there are others, and the link I gave you will give you a good feel for what you would want to make sure have been done to date...Did you check that out? Give it a shot...It will probably help...