Auto- and alloimmune disease, what can I do in an IVF?

Larissa

2 Posts
Reply Auto- and alloimmune disease, what can I do in an IVF? Posted on: Feb 7, 2011 at 9:11am
Hello Dr. Braverman,

Thank you for this wonderful and helpful website!

I try to be brief, but my story is a little complicated: I am from Germany and now 39 years old. I conceived first without any problems in 2006. Our wonderful little daughter was born in week 27 with 550 g due to intrauterine growth restriction. After her birth it was discovered that I have an inherited coagulation disorder (prothrombin mutation) which probably lead to the placental insufficiency. I also have an autoimmune thyroid disease which was discovered in 2004 (Hashimoto thyroiditis, I take l-thyroxin in an adequate dose, feel fine, but have TPO antibodies. I also have ANA's, which have first been found in 2005).

When I was pregnant again in July 2008, I had to inject Clexane 40 and took Aspirin daily. The pregnancy was monitored very thoroughly. In week 30 suddenly an oligohydramnios had developed and our son had to be delivered. He died on the fourth day. The hospital here in Germany had no idea what the reason was. With the help of Dr. Whitington in Chicago it could be established that he died of neonatal hemochromatosis (NH), a very rare, alloimmune disease in which the immune system of the mother acts against the child’s liver. The risk of recurrence is 93 % due to the immune factor. Dr. Whitington has found that a gestation treatment with IVIG (week 14 to week 35, 1 g/kg per week) is very successful. The results provide an overwhelming endorsement for using IVIG during gestation to prevent severe NH in infants of women at risk ( http://www.pediatrics.org/cgi/content/f ... 007-3107v1 ). I would receive that treatment in the next pregnancy.

For more than a year now we are trying to conceive. Two very short biochemical pregnancies, that was it. My blood has now been checked. It has been found that my NK cell activity is absolutely normal, but that three activating KIR receptors are missing (2DS1, 2DS5 and 3DS1). I have slightly elevated ANA’s and ATA/TPO antibodies. My TSH is fine (below 1). My Anti Mullerian Hormone is very good. No ENAs, no LKM (liver-kidney) antibodies. However, I have not been checked for HLA matching or TH1/TH2 ratio as the doctor here says I conceived twice without any problems. And I had no miscarriages.

When ttc, I always used Prednisolone 5 mg, Aspirin and Clexane 40 as support after ovulation. In the last two natural cycles I even used G-CSF (Granocyte) after ovulation (1 dose per day for five days). Nothing. In the next cycle, I will do an IVF.

I thought about trying IVIG in the IVF cycle. I have the feeling that there is something going on in my body, a kind of autoimmune / alloimmune “disbalance” that is at this stage not completely testable. The reaction of my body to my son supports this. IVIG seems to be the only solution, even if I and my doctors do not know what is going on.

The doctors here in Germany are not very familiar with IVIG. It is all “experimental” to them. Would you recommend IVIG already before IVF transfer or only after a positive pregnancy test? And in what dose? 5 g or 10 g? And then? Once pregnant, I will receive it from week 14 anyway, but I hope that it might help with implantation. It is very expensive here and we have to pay ourselves.
Is Intralipid an option for me? I have the feeling that IVIG would be better in my kind of extreme situation…
Is 5 mg Prednisolone too low? Should I take it already during stimulation or only after the transfer? Do you have any other ideas?

Thank you very much for your feedback, it is very much appreciated.

Dr. Braverman

2005 Posts
Re: Auto- and alloimmune disease, what can I do in an IVF? Posted on: Feb 7, 2011 at 5:33pm
I am very sorry for your loss. Clearly there is an alloimmune component that you need the IVIG for. I would like to see the remainder of your immune testing. and yes it is possible that you need IVIG earlier and doses can range up to 30gm a day over 2 days. Prednisone can be increased as well as many of our patients are on up to 40mg / day, but again only when the immune testing indicates the need. why was the G-CSF used for only 5 days. which center and doctor in Germany treated you?
I would be happy to help you , you would need to call my office and schedule a telephone consultation. I can take care of all remaining testing and give you a management plan with timing and doses of all medications as well.
Dr. Jeffrey Braverman MD FACOG
Medical Director
Braverman Reproductive Immunology P.C.

Larissa

2 Posts
Reply Re: Auto- and alloimmune disease, what can I do in an IVF? Posted on: Feb 8, 2011 at 9:15am
Thank you very much for your quick answer.
I have been tested by Dr. Reichel-Fentz in Heidelberg, who recommended IVIG 10 g after a positive pregnancy test and Granocyte (G-CSF) an day 6,7,8,9, 11 and 14 after ovulation in a normal cycle. I tried this dose of Granocyte in two cycles without success. I have also been in contact with Prof. Würfel in Munich who performed a study on patients with missing KIR-receptors and reported very high pregnancy rates with G-CSF ( http://humrep.oxfordjournals.org/conten ... eq106.full ). Dr. Reichel-Fentz only did the tests, the IVF center is in Cologne. They have absolutely no experience with immune issues, so I handled that separately.

I will now follow your recommendation and will take IVIG before transfer (and again after a positive test). I will also take a higher dose of Prednisolone. Dr. Reichel-Fentz probably recommended only 5 mg as I had no NK cell activity when she tested it. But would it not be possible that this activity goes up after ovulation or once I get pregnant?

As the stimulation in my first IVF cycle has just started, I would like to give it a go first and get back to you for further testing if we have a negative result. I am sure there is still a lot that is missing and am very glad that you can help me.

Dr. Braverman

2005 Posts
Re: Auto- and alloimmune disease, what can I do in an IVF? Posted on: Feb 8, 2011 at 2:54pm
I would not go to higher doses of prednisone without knowing your cytokine levels, it is important to have some degree of inflammation for implantation, and you should really be more certain of what you are treating. I know Dr. Wurfel as he and I are looking to collaborate on the G-CSF study.
I do however agree with treating with IVIG prior to conception. Good luck!
Dr. Jeffrey Braverman MD FACOG
Medical Director
Braverman Reproductive Immunology P.C.