Immune Protocol concerns


3 Posts
Reply Posted on: Dec 11, 2012 at 5:56am
Dear Dr Braverman, I am hoping you can help me and provide some reassurance and advice.

I am currently one week into my 2ww.

I am 42 and only started ttc last April with a donor partner/friend, 31 no children. We were successful on our first mild protocol IVF with a top grade embryo but I miscarried at 5 weeks, believed to be a blighted ovum. Second IVF a couple of months later resulted in a BFN. I then took the decision to change clinics but before I had my first natural cycle IVF I fell pregnant naturally, the one time we thought we would give it a go. Given I have one blocked fallopian tube I was thrilled. Unfortunately this pregnancy was lost at 6 weeks. I then went through a number of rounds of natural cycle IVF to obtain a single embryo each time to eventually get a number of embryo's ready for transfer. In all 4 cycles an egg was obtained, fertilised and resulted in great-good embryo, all of which were frozen. We also decided to try one more time naturally in-between this and again I fell pregnant, this time I got as far as being able to see a yolk sac at week six but no heart beat at week 7 and subsequently miscarried. I decided on this occasion to have a D&C but the result was unfortunately inconclusive coming back as normal female.

With this history in advance of the FET I decided to get some further tests done. I went to a specialist clinic/RI for this as my IVF clinic does not do all the level 2 tests.

Up to this point all my results have come back normal except for MTHFR Heter C677t.

My donor partners sperm tests have always come back strong.

All day 3 hormones have always been well within range – FSH tends to run between 3-6
AMH - 3.7
ANA – normal
Factor V ledien – normal
Level one Thrombophilia screen – normal
Protein C – normal
APA – not tested
Karyotyping - normal

Subsequent RI tests results:

NK Assay Panel – done one week after last miscarriage in August 2012
50:1 15.3
25:1 7.6
12.5:1 3.3

%CD3 82.3
%CD19 7.6
%CD 56 9.9
%of CD19+ cells, CD5+ 6.6

TNF-a:IL-10 53.3
IFN-g:IL-10 32.8

LAD test – result just back this week, post ET

T cells IgM+ 7
T cells IgG+ 1
B cells IgM+ 15.7
Bcells igG+ 3.7

KIR test – result just back this week, post ET

Inhibitory 2DL1, 2DL3, 2DL4, 3DL1, 3DL2, 3DL3
Activating 2DS4*00103,2DS4*003/4/6/7/8/9

(The only test I believe I have not had done is the DQ Alpha – my partner is in the states and I am in the UK, so although he has come over for treatment and trips he has not been over since the immune tests were advised).

On the back of these immune results the RI I went to recommended the treatment protocol of humira pre ET and then steroids, intralipids and clexane. He has a very good reputation and although I did do some preliminary research on humira I trusted him and went ahead. After 2 injections of humira my TNF was down to 45 and he recommended I take a further two injections ahead of ET. I did not get my NK's retested and have not had any further TNF tests.

This brings us to the beginning of Dec this year. I did another natural cycle IVF in the hope of getting a further embryo to add to the collection but for the first time ever I got an empty zona. The hospital was reassuring and said it is quite common and not indicative of any issue that would prevent going ahead with transfer this month with the frozen embryo's. I did have the personal concern whether the humira may have affected the egg quality, as I only finished the last injection mid November, but decided to go ahead with the FET. Out of the 4 frozen embies 3 survived and were transferred a week ago.

I had one intralipid 5 days before ET and after seeing a further RI for a second opinion he also recommended one IVIg along with the IL's which I had done 6 days before ET. He said he would have also recommended the humira for high TH1 as the first RI had.

The first RI recommended 25mg prednisolone, the second RI recommended 40mg and my IVF hospital recommends 20mg. I have stuck with 25mg.
All have recommended clexane at 40mg daily which I have been doing.
As well as estrogen support, and progesterone gel and progesterone injections.

Having done more research this last week, not perhaps the best thing to do, I have since got myself into a bit of a state on this protocol and annoyed at myself for taking the humira without perhaps doing more research or consulting further, as well as being convinced to take an IVIg infusion on top of the intralipids. Having since read humira and over suppression of the immune system can cause implantation issues I am worried that I have perhaps been given too aggressive a treatment protocol. I appreciate that this may all still work out as I am still in the 2WW but if it doesn't I'm at a loss as to what to do next. I have since read that some women have had trouble conceiving after taking humira.

I am sceptical about LIT as I understand that unless you have had a full term pregnancy the LAD tests will always come back negative.
The KIR result I have just had back today and would appreciate your help in interpreting and any treatment advice if required.

If I get a BFP my thoughts are to continue with steroids at 25mg, clexane, progesterone gel and injections and intralipids at 4,8 and 12 weeks. Any advice here again would be much appreciated.

I appreciate that this is a very long post and I would be happy to arrange a phone consultation wiht you if easier.

Many thanks

Dr. Braverman

2026 Posts
RE: Immune Protocol concerns Posted on: Dec 11, 2012 at 6:14am
yes indeed, I would call and arrange a phone consult, try and email all of your immune results so I have them. There are so many facets to immune control and sometimes its just not clear on the surface and we have to really dig deep to find the casue of yoru failures. Poly Pharmacy is a common occurence when things are not going right , but too much sometimes becomes the cause of the problem.
Dr. Jeffrey Braverman MD FACOG
Medical Director
Braverman Reproductive Immunology P.C.


3 Posts
Reply RE: Immune Protocol concerns Posted on: Dec 11, 2012 at 9:08am
Thank you so much Dr Braverman for your wonderfully fast response. I will go ahead and arrange a telephone consultation with you. I'll wait until the outcome of my 2ww unless you think there is a benefit of talking earlier?

Thank you again.


Dr. Braverman

2026 Posts
RE: Immune Protocol concerns Posted on: Dec 11, 2012 at 9:16am
I would try to make it now as it might not be until after your 2WW that we have availability.
Dr. Jeffrey Braverman MD FACOG
Medical Director
Braverman Reproductive Immunology P.C.


3 Posts
Reply RE: Immune Protocol concerns Posted on: Dec 13, 2012 at 6:48am
Hello Dr Braverman, I have requested a consultation and have been told you unfortunatley have nothing until 15th January.

Since my first getting in touch with your via this forum, I have had my KIR results back and I'd be very grateful, given it will be a few weeks until I can speak to you, if you could interpret them for me.:



If it looks like I am misisng the relevant receptors is neuprogen the only treatment or does steroids/ivig/iL's have any effect?

Many thanks inadvance for your ongoing time in answering my concerns.


Dr. Braverman

2026 Posts
RE: Immune Protocol concerns Posted on: Dec 13, 2012 at 8:14am
KIR issues lead to failure to deactivate NK cells so there are other treatments here as well. Yes IL/ prednisone and even IVIG are other options. I havent gone over your case in detail yet so clinical history may also play a part in our decision on how to treat you.
Dr. Jeffrey Braverman MD FACOG
Medical Director
Braverman Reproductive Immunology P.C.