Possible Uterine Abnormality Or Immunologic Disorder Causing Four Miscarriages In 32 Year Old: IVF With Surrogate Again?

Question:

Background: I am 32 as is my husband. We had an ectopic pregnancy 10/2005, 8.5 week miscarriage 3/2006, 10 week miscarriage 8/2006, 9 week miscarriage 2/2007 (genetic testing done - female/chromosomally normal), and 9 week miscarriage 8/2007 (male/chromosomally normal).

We had a healthy son via gestational surrogacy with my egg in 2008. During the IVF (in vitro fertilization) procedure for this surrogacy, I only produced 6 eggs and only 1 blastocyte made it to the 5 day transfer as an 8 cell blastocyte. I have Hashimoto's Disease (on medication since 2000), diagnosed with Endometriosis in 2005 (2nd lap in 1/2010 showed it is gone) and diagnosed with Adenomyosis in 1/2010, after which I took Depot Lupron for 4 months.

I have had every genetic test I've heard of and the only issue is one copy of the MTHFR gene. I took 81 ASA and Heperin with my last two pregnancies, and progesteronne with the last four. I even did IVIG with the 5th pregnancy. Two weeks ago I tested my FSH and it was normal. I also had an AMH test and it was 0.2, very low.

My RE has told me that I should try IVF (with me being the carrier) but I'm not sure. I know they are concerned about the number of eggs I have left and the quality of the eggs that are left. What I want to know is if my 2nd through 5th pregnancies could progress to 8-10 weeks with normal hearbeats and the last two we know were chromosomally normal, does this have anything to do with poor egg quality? How could these last two pregnancies test normal but be of poor quality? Is that possible?

Thanks! D. from the U.S.

Answer:

Hello D. from the U.S.,

To answer one of your last questions, since your pregnancies were know to be genetically normal, this is not an indication that you have poor egg quality. Poor egg quality leads to abnormal embryos (genetically) because the chromosomes within are fragile and break during division. It is most likely that you have either an immunologic disorder or a uterine abnormality. The latter might be the case because a surrogate was successful with your eggs.

I don't see any reason for you not to try with your own uterus if you can afford it financially. The only downside is if the uterus is a problem, you will end up miscarrying again and will have spent the money for that IVF cycle. I am not sure that I am convinced that it is a uterine problem, however, because the previous pregnancies progressed as far as they did. I would recommend that you go the gamut with the next in vitro fertilization cycle, using aspirin, heparin and IVIG if you decide to use your own uterus. That may be what it takes. If finances is an issue, then I would recommend that you use a surrogate again.

I know these are tough decisions but your young age, the positives that you have had, in addition to the child you have already had via surrogate two years ago, make your chances for another pregnancy very likely.

Good Luck,

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Program

http://www.montereybayivf.com/

Monterey, California, U.S.A.

IVF Patient With Positive Beta On Immunoglobulins (IVIG) & Has Questions

Question:

Good day Dr Ramirez,

I wrote to you a while ago. We just completed our 3rd IVF (in vitro fertilization cycle) and 2 , 5-day frozen blastocysts were transferred.

I had a blood test on day 10 post transfer and the result was positive. I suffer from rheumatoid arthritis. My doctor gave me 5ml immunoglobulin (integram) on day 2 of my cycle and 5ml again 10 days post transfer. I am also on 600mg cyclogest as well as folic acid , baby asprin, omega 3 & 6 and staminogro.

I am still concerned about the arthritis and worry about the anti bodies - is the immunoglobulin sufficient - what is the protocol, what do you suggest?

My second question is. From the day of the FET I felt this twitch on my left side of my uterus . From 7 days post transfer I have lower back and stomach pains.

Should I worry? I have heard that it is normal for FET patients to get pains and cramps and it is good pains. I have no spotting though. My first beta on day 10 was 198 and my second beta on day 12 was 416 .Can you please advise. Thank you. V.

Answer:

Hello V.,

I believe the immunoglobulin is sufficient from a fertility point of view, but I don't know in regards to the arthritis. You would need to consult a rheumatologist to get the answer to that question.

The pains you are having are probably normal. Many women experience some uterine cramping or pains in the early pregnancy. We call these "growing" pains. Your bHCG levels are good so things look good. At this point, you just have to hope for the best. Congratulations and stay positive!

Follow-Up Question:

Thank you so much for your reply. Do I understand correctly that the dosage of the immunoglobulin that I got is sufficient for the duration of the whole pregnancy and I don't need to get additional imunoglobulin again? The reason why I ask is that I had a miscarriage 7 years ago ( a natural cycle without any meds)- due to the antibodies of the athritis and I am concerned that it might happen again.

Follow-Answer:

Hello Again,

Because the use of Immunoglobulin in IVF is controversial, there are no set protocols or dosages. Therefore, I cannot comment on the dosage or times of delivery. In my experience, however, it is given at the beginning of the cycle, after the transfer and if pregnant again at that time. I would recommend that you look up the Reproductive Immunology Associates website (www.rialab.com/ivf_immunotherapy.php). They are immunologists that have geared their practice specifically to reproductive issues. They will have more specific information regarding the use of immunoglobulins. They will also answer email questions.

Good Luck,

Edward J. Ramirez, M.D., FACOG

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF Programwww.montereybayivf.com

Monterey, California, U.S.A.

Twitter with me at @montereybayivf and follow me on Facebook at http://bit.ly/9Iw9oV

43 yr. old Trying To Conceive Needs High Stim Protocol

Question:

My Medical History: TTC 4.5 yrs. (3.5 with RE) Many IUI's & IVF's. 3 chemical pregnancies - 2 with IUI 1 with IVF. AMA - 43ys young.

Had a Coagulation Panel done - Mutation found -

heterozygous MTHFR C677T

Results negative for Factor V mutation

Factor II DNA Analysis

Results WNL for

ANA

APA

Lupus anticoagulant

Homocystein

Elevated levels for

Protein C Functional (187)

Factor II Activity (133)

Plasminogen (161)

B2 Glycoprotein (low positive)

Do I need to supplement my prenatal with extra folic acid and b vitamins? Baby aspirin? If so - can I just add extra supplements or do I need an Rx for something like Folgard?

Could this be the reason for all of my failed IUI's, IVF's and chemicals? Before finally agreeing to do this testing, my RE kept telling me that immune issues are too controversial and that the risks of their treatment outweighed their assumed potential benefits. I don't know what his thoughts are now as I couldn't get a Dr. callback for 3 weeks.

Many thanks, Dr. Ramirez, for so graciously donating your time in answering our questions! Your services are invaluable! Oh, yes - I am located on the east coast.

Answer:

I'm afraid I am in agreement with your RE, although for slightly different reasons. We do know that the immune system does contribute to miscarriages, although I am not sure that is the problem that you have. There are definitely some very controversial treatments, such as IVIG, which are very expensive and have not been shown to be of benefit in multiple studies. However, the alternative, which I try with all my patients is low dose aspirin (81 mg) per day, progesterone (injections and suppositories) and low dose heparin 2000 U twice per day. This regimen has been shown to help with recurrent miscarriages and is very low risk. That is why I use it. I have had some successful pregnancies in patients with recurrent miscarriages using this cocktail.

However, although you are still very young in my book, your fertility age may be the basic problem. You have shown that you can get pregnant. The problem is an egg problem. It is what I call "age related egg factor." We know that because a woman is born with all her eggs, and they age with her, and the lifetime of the eggs are about 43 years old, they deteriorate with time and age. This deterioration causes internal problems in the egg, including fragile chromosomes. This leads to bad embryos that either don't progress in their development, don't implant or end in miscarriage. There is a 40% chance of miscarriage with each pregnancy in your age group. Chromosomal abnormalities is probably the major reason for your losses.

There are only two ways to mitigate this increased risk: you can keep trying until you are successful (and hopefully you will be eventually) as long as your ovaries are still functioning well, or you can do preimplantation genetic testing (PGD) to identify the normal embryos prior to transfer (however, keep in mind that this is a new experimental technology, is very expensive, and does lower the implantation rate because of the "injury" to the embryo.).

I think that if you were to present to me, I would continue to recommend IVF with a high stimulation protocol and put you on my cocktail. I don't necessarily recommend PGD. I think nature will take care of that. The key would be to keep trying if you are determined to have a baby. There have been successes in your age group but time is running out for you.

I hope this helps,

Edward J. Ramirez, M.D.

Executive Medical Director

The Fertility and Gynecology Center

Monterey Bay IVF program

http://www.montereybayivf.com/