ATA, NKa and IVIG - please share.

[Mrs Pea]

Good morning, I am new to this site and I am here bc I am looking for any info about ATA's and IVIG.

I am starting IVF#4 in November and I am excited/nervous/afraid because IVIG has given me true hope once again. I am 37 and I have endo, ridiculously high ATA's and borderline NKa+. We've been TTC'ing for three years and have already had 1xD&C, 2xLAP, 3xIUI, 3xIVF and 1xFET = all BFN. I did have one chemical pregnancy on my own.

I guess I am not sure if I have specific questions - more a need to hear stories good and bad about IVIG experiences. I know IVIG is not a guaranteee just like IVF, but I feel like it just has to work bc we have tried everything else.

I guess I'll ask how many grams did you receive and on which CD?

TIA - Christina

[Tanya T.]

Hi Christina,
WELCOME WELCOME WELCOME!!!!!!! I hope that you can find the support & answers that you are looking for here... And make a few new friends in the process...

My name is Tanya... I am 35yrs old & my husband David is 43yrs old... I wont go into too much detail about my history because it could become a novel if I try... I will say that it took me 14 long years of TTC HELL to finally have success... She is my little miracle... Her name is Cheyenne & she is almost 8 months old now & the absolute joy of my life!!! You can see by my signature at the bottom of this post a bit more about my history...

My success finally came by way of the only doctor in all of Canada who is actively treating reproductive autoimmune dissorder... His name is Dr. Clark... He is not as thourough when it comes to testing & details as some of the other RI's are (such as Dr. Beers & Dr Sher) - But the one thing that I do love about him is that he was always willing to treat his patients empirically, meaning that he treats his patients based on his medical experience & on the patient's medical history & whatever test results are available - rather than specifically on conclusive test results alone... For me, this was the key because I had only one borderline positive aCL (anticardiolipin) test 7yrs earlier & a history of loss. I also could not afford the best testing that was not available in Canada...
Dr. Clark started me on heparin twice a day (5000IU each) & IVIg (40grams) once every 3 weeks... I get IVIg preconception & throughout pregnancy once every 3 weeks... Dr. Clark has seen evidence that has shown that IVIg (in some people) can only last for 3 weeks before the NK cells start acting up again... And because the NK testing is not available in Canada, he preffers to give his patients IVIg once every 3 weeks rather than to base it on a specific time in the womans cycle... Therfore it's in the system constantly & there is no guessing involved... Thisa is a great way to do things (in my opinion) but for most people, it is not financially feasible... IVIg is very expensive & most insurance companies do not cover it... For us gals in Canada (if we can get a doctor to RX it), it's free... It's covered under our general public health care system...

I can tell you that IVIg does work!!! I have Cheyenne to prove that immune treatment works... Every pregnancy I had failed until I got proper treatment... I never had any side effects from it & besides the fact that it takes a few hours to get infused, it's not that bad...

I noticed that you are also aPL (antiphospholipid antibodies) positive "ridiculously high APA's" APA is no longer the medically proper abreviation for antiphospolipid antibodies - it is now aPL (just so that you are aware that they mean the same thing)... Anyway, I hope that your doctor has you on a blood thinner such as heparin, fragmin or lovenox???? You should also be aware that it is extremely important to start the blood thinner on CD6 ------- Do NOT wait until a postive pregnancy test!!!! aPL can distroy an embryo starting at the moment of implantation... If you wait to take your blood thinner, you could (and most likely would) loose any pregnancy that you acheived... I know this from past experience... That along with several medical studies that have proven it...

I wish you all the luck in the world & I hope that your IVF in November is the one that brings you success!!!!
Hugs
Tanya
TTC#1 - 14+ long nightmarish years
Several (12+ early losses < 7 weeks)
1 B/O at 11 weeks
1 viable (after seeing the hb ) loss at 12 weeks - Elijah - our lost angel
DX - immune issues aPL's & NKcells
TX - IVIg, heparin, baby aspirin, progesterone, calcium, iron & prenatal vit.
IUI #1 - Femara & Gonal F May 04- BFN
IUI #2 - Femera & Gonal F Jun 04 - BFP- YIPPEEE!!!
CHEYENNE - our miracle - Born March 7th 05
TTC #2 - IUI Aug. 05-BFN (sperm issues-very unusual)
Next IUI - ?????

[Lauren2005]

Hello and welcome!

You might have had a chance to read this thread about my recent (very good) IVIg experience. The end result is that my NK cell activity was lowered from 27.9% to 17%!!! Hooray!!!

http://www3.fertilethoughts.com/foru...d.php?t=362999

Lauren

[Mrs Pea]

Tanya - wow, thanks so much for sharing your story! And KUDOS to you for sticking it out - it all paid off! I find it more and more difficult to keep up the pace. I have ATA's which are anti-thyroid-antibodies but no APA's / aPL's that I know of yet. Your doc sounds fantastic. I am at a new clinic here in Germany and immune treatments for IVF are really quite new. I am supposed to get 15g of IVIG on the day of ER and do a 5 day transfer. I am worried bc the more I read the more I feel I should have more and earlier. But, my NK's went fro 13.5% to 5% just on prednisone alone so I don't need a high dose, but I am concerned about the timing. I may have a delay of this cycle anyway bc my thyroid just went wacky again - my TSH was way high although my FT3 and FT4 are ok. I should know more later this week. I took my last BCP today!

Lauren - wow, I am excited for you! You had the perfect reaction - had you tried prednsione alone for NKcells?
I read through your link - good luck with beta!!!

Anyone with ATA's???

[BC-Tabithalyn]

Mrs. Pea... as requested here is the whole thyroid article that has for some reason never been updated at Dr.Beer's site but which led me into the world of repro. immun. and my own success with DS... good luck and keep us posted on your upcoming cycle and any test/treatment you will get...

Thyroid Disorders and Reproductive Problems of Miscarriage, Implantation Failure and In Vitro Fertilization Failure
Alan E. Beer, MD
Professor of Microbiology and Immunology, Professor of Obstetrics and Gynecology, Director of Reproductive Medicine, Finch University of Health Sciences/The Chicago Medical School, N. Chicago, Illinois; E-mail: beerdoc@aol.com.
Contents
I. Introduction
II. Symptoms of Hyperthyrodism
III. Symptoms of Hypothyroidism
IV. Immune Changes
V. Treatment of the Autoimmunity Associated with Thyroid Conditions
VI. Outcome Statistics of Treatment
VII. A New Disease? Multiorgan Autoimmune Endocrinopathy
I. Introduction A

Thyroid disorders are 5-10 times more common in women than in men. The reason for this has not been understood until recently when it was shown that the immune problems that can cause infertility, implantation failures, in vitro fertilization (IVF) failures and infertility could also damage the thyroid gland. In fact many fertile women who deliver a live born infant subsequently develop thyroid disorders and suffer secondary infertility. Doctors have long accepted the fact that thyroid disorders as well as other autoimmune conditions are far more common in women than in men but have had very little science to underpin the reasons for this. Autoimmune thyroid disease is a term that encompasses Graves' disease, Graves' orbitopathy, Hashimoto's thyroiditis and post partum thyroiditis.
Thyroid abnormalities can be detected by doing a thyroid panel that consists of
 TSH Thyroid Stimulating Hormone 0.4-5.5
 T-3 Uptake Short Acting Thyroid Hormone 22-35
T-4 (Thyroxine) Total Long Acting Thyroid Hormone 4.5 - 12.5
 Free T 4 Index (T-7) 1.4 - 3.8
When the thyroid is overactive, called Hyperthyroidism, the TSH may be high or low, and the T-3 and T 4 are high. When the thyroid is underactive (Hypothyroidism), the TSH is high and the T-3 and the T-4 are low. The conditions are often referred to as Graves' Disease (Hyperthyroidism or overactive thyroid) and Hashimoto's Thyroiditis (Hypothyroidism or underactive thyroid).
The treatment for the Hyperthyroidism consists of drugs to suppress the overactive condition. These are Propylthiouracil( PTU), and in some women Radioactive Iodide which causes thyroid ablation. Sometimes the PTU drug is be taken prior to and during pregnancy. Occasionally this condition has its onset during pregnancy or in the immediate post partum period. Some women develop nodules or goiters and need to have surgery to correct this.
The treatment for Hypothyroidism consists of thyroid hormone replacement. These drugs are usually very much like T-3 and or T-4 or both. They are taken daily to prevent the symptoms and body changes associated with this condition.

II. Symptoms of Hyperthyrodism
GENERAL
Nervousness Heat intolerance Fatigue
EYES
Dry gritty sensation
Conjunctiva! injection
Lid edema
Decreased visual acuity
CARDIOVASCULAR
Palpitations Shortness of breath Angina
GASTROINTESTINAL
Hunger
Diarrhea
Hyperdefecation
SKIN
Sweating Leg swelling Hair loss Itching
NEUROMUSCULAR
Weakness Periodic paralysis
REPRODUCTIVE

Irregular menses Premature menopause Infertility Implantation Failure Miscarriage
PSYCHOLOGICAL
Restlessness
Anxiety
Decreased concentration
Irritability
III. Symptoms of Hypothyroidism A
GENERAL
Goiter
Solitary nodule
Neck or jaw pain
Temperature changes, low fever with low body temperature
in-between
Weight gain
Thin hair
Coarse hair
Puffy face
Low energy levels
Infertility
Miscarriages
Implantation failure
PREGNANCY COMPLICATIONS
Intrauterine growth retardation

Neonatal thyroid dysfunction
Prematurity
Unexplained intrauterine fetal death
Abnormal slow heart rate of baby
Preterm labor
Preeclampsia
Reduced weight gain
Heart failure
IV. Immune Changes A
It is known that the onset of both of these diseases of the thyroid gland can be induced by an autoimmunity response in the women against thyroglobulin. Thyroglobulin is produced by the thyroid gland to be the vehicle that carries the thyroid hormone from the gland into the blood stream where it becomes active in controlling the metabolism of the body. Many women have an antibody against thyroglobulin and this can transiently produce hyperthyroidism and then an underactive thyroid gland. The thyroid cells are very active cells and endowed with many mitochondria. The mitochondria are the batteries or energy sources of the cell so that it can continue to produce the thyroid hormone requirements for life. Inside the mitochondria are peroxidases that are part of the energy system. Some women also make an antibody or autoimmunity against the peroxidases as well as to the mitochondria themselves (microsomes). These antibodies cause inflammation in the thyroid gland and greatly disturb thyroid function. This process also activates the Natural Killer Cells of the CD 56+ variety and the CD 19+5+ variety. The Natural Killer cells that are CD 56+ produce TNF (Tumor Necrosis Factor) that causes further damage to the thyroid and to other organs including the embryo, the lining of the womb and the placental cells that attach the baby to the uterus. (See Natural Killer (NK) Cell Embryo Toxic /Assay for the Consumer and Antibodies to Hormones and Neurotransmitters.)

The CD 19+5+ cells produce antibodies to a variety of hormones including Estradiol, FSH, LH, Progesterone and HC. It has recently been shown that they are also capable of producing antibodies to Neurotransmitters including Endorphins, Enkaphlins and Serotonin. These neurotransmitters are important in ovarian and uterine function. Women with antibodies to these neurotransmitters often stimulate poorly during an ovulation induction cycle, suffer premature menopause (see Antibodies to Hormones and Neurotransmitters and Intravenous Immunoqiobulin & (IMIG): Dream Or Reality?) and have poor uterine lining responses and blood flow responses to the lining of the uterus (endometrium) as the uterus models itself for successful implantation and pregnancy (see Uterine Biophysical Profile).
Treatment of the hyperthyroid or hypothyroid conditions does not change nor improve the autoimmunity directed against the thyroid gland. Treated women still suffer poor stimulation cycles, infertility, IVF failures, implantation failures, donor egg failures and miscarriages. Diagnosis and treatment of the autoimmunity involving activated natural killer cells and antibodies to hormones and neurotransmitters are necessary. Immune treatment is also necessary before a successful pregnancy is realized in most women. This treatment must be given preconception. Many women require three months of preconception treatment before it is safe to begin a cycle of conception. The treatment must continue for at least 10 weeks into the pregnancy. By 10 weeks of pregnancy, natural processes associated with pregnancy are strongly "up and running" and the autoimmune dangers caused by the CD 56+ natural killer cells and the CD 19+5+ cells are past. Many women have a very hard time believing this and are very resistant to stopping any of the medications that have allowed them to progress to this point in their pregnancies.
* * * IMPORTANT IMPORTANT IMPORTANT * * *

All women with reproductive problems should have a THYROID PANEL and ANTIBODIES TO THYROID COMPONENTS mentioned above. If there is an overactive or underactive thyroid condition identified, then further autoimmune tests are necessary as described for women with reproductive failure. These are
 ANA* (CPT 86038)
 APTT,PTT* (CPT 85730)
 LUPUS ANTICOAGULANT ANTIBODY* (CPT 85300)
 THYROID PANEL* (CPT 80091)
 ANTITHYROID ANTIBODIES* (CPT 86376, 86800)
 SERUM IMMUNOGLOBULINS* (CPT 82784)
 LEUKOCYTE ANTIBODY DETECTION ASSAY (CPT 86021)
 ANTIPHOSPHOLIPID ANTIBODIES (CPT 86147)
 DQ ALPHA FEMALE AND MALE TESTING (CPT 86816)
 ANTI DNA/HISTONE ANTIBODIES (CPT 86225)

 NATURAL KILLER CELL ASSAY (FULL PANEL) WITH TJ6
(CPT 88180, 86353,86849)
 IMMUNOPATHOLOSY OF PLACENTAL TISSUE
If you had a D and C at the time of a pregnancy loss and had pathological evaluation of the tissue, the slides and the paraffin blocks should be sent to me for immunopathology. From this evaluation I can determine why the pregnancy failed and if it failed because of the immunological problems described above. The five categories of immune problems that can lead to infertility and reproductive failure can be determined even before blood testing is done. (See Immunological Evaluation and Monitoring.) It does not matter if the paraffin blocks are from the first or the last pregnancy that is lost. We find the damage in the first pregnancy lost by women that have been evaluated by me after they have lost four or more pregnancies. In my experience the immune problems worsen with each pregnancy that is lost and with each cycle that is unsuccessful. The paraffin blocks and the slides are saved by the pathology department that evaluated your pregnancy losses. Instructions are available in the document The Importance of Pathological Evaluation of Pregnancies that Terminated in Spontaneous Miscarriage.
V. Treatment of the Autoimmunity Associated with Thyroid Conditions A
The autoimmunity associated with thyroid disorders that leads to infertility and reproductive failure have been mentioned above and elsewhere on this web site.
Lymphocyte Immune Therapy (LIT). Lymphocyte immune therapy was introduced by me many years ago as a treatment for recurrent miscarriages. Since then, LIT has been utilized for prolonging transplant survival of recipients of kidney transplants. It has proved beneficial as a treatment for patients with diabetes mellitus, rheumatoid arthritis, autoimmune encephalomyelitis and autoimmune thyroiditis. Studies in progress show that LIT also provide protection against HIV infection of lymphocytes of the host being immunized.

The immune system is balanced between two responses - TH-1 (autoimmune) and TH-2 (normal and not autoimmune). Most individuals have a good balance; however women with autoimmunity have moved the balance towards the TH-1 response and autoimmune diseases and infertility and reproductive failure are far more common. The LIT produces antibodies against T cells and B cells which can be measured (leukocyte antibody detection assay or cross match) and these antibodies have a strong function in "downregulating" autoimmune responses as well as decreasing the killing power of activated Natural Killer Cells discussed above. In my experience, this is the first line of therapy for women with immune infertility and reproductive failure mediated by Natural Killer Cells. (See A Consumer's Guide for Lymphocyte Immune Therapy.)
Intravenous Immunoglobulin & (IVIS). IVI is described elsewhere on this site (see Intravenous Immunoglobulin & (IVI6)1. Dream Or Reality?). IVIS is a pure solution of IgG molecules (gamma globulins) that is prepared from many donors, washed, cleaned, reassembled and is free of viruses past present and future. It is prepared just like the gamma globulin RhoGam or Anti-D Immunoglobulin that is manufactured to give to pregnant and postpartum women who are Rh negative and have delivered an Rh positive baby. This gammaglobulin (IVTS) prevents the woman from developing the antibody that causes the Rh disease problem of babies. This antibody keeps the woman's immune system balanced at a TH-2 level and prevents her from developing the wrong immune response called TH-1. It is nearly 100% effective.
The need for IVIG treatment is determined by the natural killer cell assay. If the cytotoxicity or killing power against placental cells is too high in this assay, IVIG is added to the test tubes to determine how much is needed to suppress the reactivity to below 15%. This is then translated into a dose. It is given preconception usually no later than cycle day 6 and repeat NK testing is done to determine if the IVIS given to the patient is working in her system. This is done 48 hour to 7 days after the dose is administered. If more is needed there is time to administer it before the time of pregnancy implantation. Giving the IV1G with a positive pregnancy test in women with activated autoimmunity is not nearly as effective. In my experience the cytotoxicity of natural killer cells must be suppressed before implantation to be successful.

The understanding of how thyroid disorders can lead to infertility and reproductive failure problems and the development of newer treatments represents a huge milestone in Obstetrics and Gynecology. It is discouraging none the less that the same Obstetrical and Gynecological community that pioneered other preventive treatments such as prevention of the Rh factor problem are very hesitant to believe that other TH-1 responses can cause infertility, implantation failure or even pregnancy losses. This is in part due to the fact that infertile couples are hesitant to submit themselves to studies that involve placebo therapies. This has limited the number of double blind studies that doctors demand before they will accept a therapy or even a new idea. To learn about the effectiveness of LIT therapy on down regulation of Natural Killer Cells, see Natural Killer Cell Cytotoxicity and Paternal Lymphocyte Immunization in Women with Recurrent Spontaneous Abortions.
VI. Outcome Statistics of Treatment A
We have had the opportunity to study 35 couples who had been through 10 stimulated intrauterme insemination cycles and failed all 10 of these. These couples then went to IVF centers and experienced 4 cycles and failed each cycle. They were rejected from their programs and of course were dejected. They all came to me for immune evaluation. All 35 women were category 5 women with activated Natural Killer Cells and many with antibodies to hormones and neurotransmitters. All received therapy that consisted of lymphocyte immune therapy and I VIS therapy until the autoimmunity involving the CD 56+ and the CD 19+5+ cells was controlled. In many women this required three months of therapy before trying again.
They all returned to a cycle of conception. Some returned to IVF, others returned to ovarian stimulation with intrauterine inseminations. 60% of the women in each group became pregnant the next cycle of conception following the immune treatment. In the ovarian stimulation, intrauterine insemination group 85% of these delivered a live born child and 15% experienced a chemical pregnancy again. In the IVF group 50% delivered a live born and 50% had a chemical pregnancy again. In this latter IVF group we found that the very high levels of Estradiol achieved in an IVF cycle often resulted in bone marrow stimulation with elevation of the very CD 56+ and CD 19+5+ cells we had suppressed at the beginning of the cycle. This troublesome complication (often seen in women with antithyroid antibodies and thyroid dysfunction) is under study at the present time. We are asking if it may not be better to go through the cycle, harvest and fertilize the eggs and then freeze them for a subsequent cycle of frozen transfer. The medications used in a frozen transfer cycle do not stimulated the autoimmunity described above.
VII. A New Disease? Multiorgan Autoimmune Endocrinopathy A

Infertility, IVF failures, implantation failures and recurrent pregnancy losses in women with autoimmune thyroid problems may just be symptoms of an autoimmune disorder that affects many organs. Infertility is the symptom of the autoimmune disease not the disease itself. Many insurance companies that have denied payment of treatment or testing because it was infertility reconsider and pay when the diagnosis is an autoimmune disorder. Much of my time is spent writing letters of medical necessity for patients of mine who have suffered refusal of payment. (See The Reproductive Immunology Patient's 6uide to Insurance Reimbursement.)

It is now clear to me that the problem is an autoimmune one that can affect the way the ovary responds to stimulation medications, the way the uterus models itself for implantation, the secureness with which the embryo attaches and the processes which involve the development of the placenta that feeds the baby. The reproductive system is rebelling just like the thyroid gland has rebelled and been damaged by the autoimmunity. Although double blind studies of this hypothesis are not available at present and may never be, the data in hand (some discussed above) offer great hope for those abused and stricken with infertility that has been unexplained to the present.
/All readers of this document who have a thyroid condition or family with a history of thyroid problems should be on the alert that failure may be your portion if the immune situation is not evaluated and treated before you embarking on parenthood. You should question your health care provider long and hard if suggestions are made to proceed quickly with reproductive efforts of any kind before complete thyroid evaluation is done. If a thyroid condition is established the patient has the right to demand that an autoimmune evaluation by a competent reproductive immunologist be done to determine if immune therapy of they type mentioned above may be necessary. (See Immunological Self Tests.)

regards, Ally

[Tanya T.]

Hi Christina,
I just wanted to appologize - I see now that you were saying you have ATA's & not aPL's (I must have just read it wrong)... Possibly because aPL's are kind of my specialty... I am sorry for not reading what you were saying more closely... How embarrassing!!! Good luck with your cycle...

Hugs
Tanya

[Lauren2005]

Originally Posted by Mrs Pea

Lauren - wow, I am excited for you! You had the perfect reaction - had you tried prednsione alone for NKcells?

Hello, and thanks!! Prednisone hasn't been part of my protocol... I'm glad it worked so well for you, though! I wish I could be more helpful about ATA's. I see that Ally has provided some great info.

Cheers,
Lauren

[Mrs Pea]

Lauren - I am so sorry about the neg but I see you are getting right back on the horse - good luck!!!

Tanya - no worries! I am asking of my aPL's have been tested when I go in for my intital b/w and u/s - thanks for the tip!

Ally - thanks so much for posting that article. I will be a Dr. Beer patient if we need it when we move back to the states, that's for sure.

I hope to start stims this week - my TSH needs to cooperate though. Sheesh! Christina