Anyone deal w/Urticaria, Trich, Sperm antibodies, Mycoplasma?

[Heatherttc1]

I've been posting on another board re urticaria and fertility and a lady suggested this forum. I hope someone can relate (at least somewhat).
I am 37 and ttc #1, DH's #3 since Jan '04. My ob/gyn found trichomoniasis in September '04 on a wetslide (barely) and said it had been around a long time. Dh and I were treated and a later exam showed no infection present.
I went to my new ob/gyn this month and he ran blood tests. My FSH, TSH, and Prolactin were good. I was concerned about the results of the antisperm test - it said "Sperm antibody" and "See detailed report" underneath The ob/gyn doesn't have the results yet (I got what I did from a print out at the lab when I went in for other tests) so I am anxiously awaiting a phone call
The results of the mycoplasma and ureaplasma tests weren't back yet.
I have also had a painful throat for a very long time along with postnasal drip and sinus pain, and the ENT said I have lumps on the right side of my neck. I also come down with a cold whenever I get really tired and/or stressed.
I tested negative for mono, Chlamydia, Gonorrhea in the past two wks
I have had hives for 3 months. The allergist thinks it's from Amoxicillin I took in November for my sinuses. Another doctor said it wouldn't be from that after all this time but the allergist said it is and it will eventually fade I also get pain on the right side of my chest and in my stomach, and it sometimes rises up my throat and up through my ears. I thought this was angiodema/angiodemia (sp?) but the allergist thinks I have acid reflux (I don't have a bad or acid taste in my throat though).
After researching I think I might have mycoplasma that originated in the genitourinary area and migrated to my throat (I read that mycoplasmas can do this and I also had trich which was found with patients who had mycoplasma). Also, I read that hives can result from this.
Of course, I don't have all my test results in but I have a feeling this is what's going on.
Anyone deal with any of this???
I read that Zithromax and Tetracycline and other protein-inhibiting antibiotics can be used to treat mycoplasma, and that a strong healthy immune system is able to fight off the mycoplasma - often for forever
I am still worried about this antisperm antibody test - and I wonder if that might "go away" once the other things are treated and go away...or if I do have them might I not EVER get rid of them? I did read if the antibody level is low one can still conceive naturally, but usually women have to have IUI or IVF.

[ginnylynne]

Hi Heatherttc1, I don't have any light to shed on your condition but was floored when I read that you're having hives! I've been trying to conceive for about a year now with no luck at all and have also been having major hives that just started in august for no apparent reason. I'm seeing an RE who doesnt seem real interested in the hives but I've thought for a long time that this has to be an immune response of some kind. I've been told that I test positive for anticardiolipin antibodies, prolactin is high, progesterone low and have had 3 miscarraiges all before 8 weeks. Have you been told that mycoplasma can cause hives? I did an internet search but didnt come up with much info, anything you can pass on would be greatly appreciated! Thanks!!!

[Heatherttc1]

Hi! Sorry for your losses.
I have saved tons of info on everything I THINK I could have! It may turn out the hives are related only to the Amoxicillin but I think they have something to do with my immune system being screwed up. I did read things about Mycoplasma and hives...I will have to dig stuff up for you. Mycoplasma can lead to nasal-membrane-throat problems (which I have had for a long time)...even Mycoplasma hominis (originating in the vaginal area and is what I was tested for) can lead to nasal and throat problems.
I am waiting on the ob/gyn to call and the ENT to check my CTs and MRI. This wait is killing me!!!!! Aaaaaarrrggghhhhh!!!!!

I also thought perhaps I have recurrent Strep - I had it bad in 03 and had the flu 3 times that yr and never got 100% better after that - everytime I get rundown I start getting sick- the same symptoms in the same order (feels like the same virus is back) and every day I have pain in my throat. I don't have mono but it sure feels like some virus won't leave me. I should send my old job (quit in Aug) all these bills - I was in good health til I started getting extremely stressed there (it was REALLY bad!!!).
Well I will post what I can dig up! GL and babydust!!!! I would love to get started on curing myself ASAP but since I don't totally know what's going on I can't do much except try to eat healthy/better! I read a post re hives - the girl said she started drinking tons of water and thinks she "flushed" the hives out. Worth a try - at least it might help the immune system a bit. I have a veggie powder my sister gave me but am reluctant to add herbs and things to my body right now til I find out what's up.

[Heatherttc1]

What produces hives?
Mast cell degranulation is the mechanism behind hives. In simple terms, certain little white blood cells are going bonkers and firing histamine. Mast cells fire in response to antigens (invaders, real or perceived) that come into your body either by contact (skin), inhalation or digestion. Antigens are also produced within the body by other factors, such as inflammation or systemic illnesses such as cancer, thyroid disease or lupus.

Besides histamine, mast cells also fire heparin, chrondroitin sulfates, neutral proteases, acid hydrolases and other enzymes. On the surface of these mast cells are little receptors for IgE (immunoglobulin E antibody). Think Velcro®. When an antigen comes into the body it "sticks" to the IgE receptors. When the mast cell gets loaded it starts firing its weapons(degranulating) and it encourages other mast cells as well as other inflammatory cells (basophils and leukotrienes) to fire also.

As the mast cells fire, they release histamine. Histamine and other mast cell byproducts cause
vasodilation (where the capillaries increase in diameter), which in turn causes the blood vessels to leak fluid into surrounding tissues. The histamine infusion into the tissues produces hives.
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What causes CU?
CU can be caused by a great many different things. Generally, chronic urticaria is either autoimmune (a primary autoimmune disease all its own) or a symptom of something, it is just a matter of finding what that something is. Approximately half of CU cases are autoimmune.

CU may be related to an autoimmune problem such as lupus, thyroid disease, or multiple sclerosis. It may be an allergic reaction to something (although if the hives are chronic this is unlikely). If you have had hives for longer than six weeks, you may not discover the cause. This doesn't mean you should stop looking for the cause, but knowing this can help you focus on managing your symptoms and living with the condition on a daily basis.
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How can I figure out the cause of my CU?
If you want to pursue finding the cause, keep in mind it may take a long time to pinpoint, and it probably won't be easy to do. And you may never find the underlying cause. You will have to be your own detective and advocate to find it. If it means changing doctors, so be it. Listen to your body and keep a detailed diary of what goes into your body, what you are exposed to, and what your symptoms are like each day. A pattern may emerge. Several people with mastocytosis/mast cell activation syndrome have also reported that their symptoms began with an 'event' or trauma, like that seen in autoimmunity.
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How do I find out if it's autoimmune?
One of the first tests you should have is something called the autologous serum skin test (ASST). This test is still not widely available, so it may take some hunting around to find a local clinic or hospital that offers the test. The ASST involves taking a sample of your blood, spinning it down in a centrifuge to separate the serum, and then injecting the serum back into your arm. A wheal/flare response to the injection is considered positive for autoimmune CU.

Some things many people with autoimmune disease have in common:

For women, a worsening of symptoms during periods
Remissions during pregnancy
Development of other autoimmune diseases
Family history of various autoimmune problems (one family member may have rheumatoid arthritis, another may have thyroid disease, still another may have endometriosis)
Onset of symptoms with an event or trauma such as accident, illness, surgery, or infection within approximately 6 months—something that kicks the immune system into high gear.
If you've experienced any of these, you may indeed have autoimmune CU, and this warrants further investigation.
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What if I am not autoimmune?
Here are a few things to consider:

Can you take aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs)? If not, you may be salicylate sensitive. Salicylates are the active ingredient in aspirin, and are found in all plant matter to some extent (fruits, vegetables, herbal supplements, etc). If you find that taking aspirin makes your hives worse, you may have discovered your cause. This is also true if you cannot tolerate other NSAIDs such as Ibuprofen or Aleve, because they are cross-reactive with salicylates. A low salicylate diet may help.
A few people have found that a yeast-elimination program (diet and medications) has helped reduce their flares.
You may be sensitive to additives or dyes or preservatives. Again, you have to be your own detective. Pay attention to what is happening, and your body may give you clues.
Have you had a complete thyroid workup? It seems to be quite common that people with several autoimmune diseases also have thyroid trouble. If you have a thyroid disorder, you may find that the CU improves with appropriate thyroid medications.
Have you ever had a root canal done? Some people in our group have had CU go away after being treated for infected root canalled teeth.
Do you have any other possible sources of infection? Potential culprits are kidney infections, sinus infections and gallbladder infection.
Hepatitis B and C have also been implicated in CU.
Have you been tested for other autoimmune conditions? While the majority of autoimmune CU is a primary illness, hives can also be a symptom of some other autoimmune diseases, such as lupus. The most common screening test is ANA, which looks for some specific autoimmune diseases, such as lupus. However, it is possible to have a negative ANA and still be autoimmune. A diagnosis is made based on a combination of symptoms and lab results. One excellent starting place to learn more about autoimmune diseases is the American Autoimmune Related Diseases Association website.
Do you have any other symptoms besides hiving? Stomach problems, slow healing, sinus problems, headaches, normally low temperature (less than 98) or low blood pressure, anything at all, whether you think it is related or not? The more you know about your symptoms and the medications you are currently taking, the better able you will be to manage your CU.
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How can CU be controlled?
The principal approach is to control mast cells, by controlling either the IgE stimulation or the histamine being leaked. Granted, this treats the symptom and not the cause, but until a cause is determined, it is in your best interest to try to gain some control over the symptoms. It's a matter of working with your doctor to find the right combination of medications for you.

Because skin contains receptors for H1 and H2, treatment frequently involves taking both an H1 and H2 antihistamine.

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What are H1 and H2?
Mast cells release 3 known types of histamine, H1, H2, H3. It is believed there are also H4 and H5 histamine. Skin has receptors at least for H1 and H2. Airways have receptors for H1, the gastrointestinal (GI) tract has receptors for H2, and the brain is believed to have H3
receptors.

The H1 drugs are those commonly thought of as antihistamines, such as Zyrtec, Benadryl, Claritin, Allegra, and Atarax. The H2's are normally thought of as ulcer medications, but are actually histamine 2 blockers. Zantac, Pepcid, Axid and Tagamet are the most common.
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What other treatments are there?
Some people also benefit from the tricyclic antidepressant Doxepin. For CU, it is prescribed at a much lower dose than for depression, and works as both an H1 and H2 blocker.

Still others find that drugs like Gastrocrom, Zyflo and Accolate help. Gastrocrom can also be made into a cream that helps the itching for many people.

Ephedrine sulphate or inhaled epinephrine can help some symptoms, especially for those with mast cell disease. Inhaled epi (Primatene Mist) is also used by some shockers as a first line of defense during anaphylaxis.

Another drug some people respond to is Procardia (which is actually a heart medication).

If your hives are due to autoimmunity, immunosuppressant drugs such as colchicine or Imuran (Azathioprine) may help.

And if you have ever experienced symptoms of anaphylatic shock (especially drop in blood pressure, throat swelling/tightness, trouble breathing), an Epipen® (emergency shot of epinephrine)—best to have at least two—is a MUST.
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Will I have to stay on these medications forever?
You may find that over time, the drugs you are taking aren't as effective. Talk to your doctor about switching to something else, or changing the combinations you are taking.
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What can I do for immediate relief of itching?
Here is a list of a few things that may help you. Before you slather your whole body with any of these, test it on a small area of skin away from your face, preferably for about three days. Many people are more reactive to any new substance when they are in a flare, so be cautious!

Cromolyn cream is something you can make yourself using any form of cromolyn (Gastrocrom, Nasalcrom, Intal or cromolyn eyedrops). The recipe for it was developed by a nurse and pharmacist who are both mastocytosis sufferers, and many people swear by it.
In a pinch, you can spray some Nasalcrom directly on an especially itchy spot of skin for instant relief.
MSM lotion or cream works very well for the itching for some people.
Other lotions and creams that have helped many include Sarna™ Lotion, Aveeno™ Lotion in the green bottle, Aveeno™ Oatmeal Bath, tea tree gel, and several other lotions which contain menthol.
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Are there any natural remedies for CU?
A number of people with CU have experienced relief using a variety of natural treatments. the list of possible treatments and remedies is quite long and results have been variable. Remember that many people with CU are very sensitive to certain chemicals, such as salicylates, and some of these chemicals may be found in natural remedies. Always proceed with caution when trying any new treatment, and collaborate with your medical professional.

Note: This post to the Urticaria Yahoo group reviews several possibilities. (You must be a member of the group to open this link. )

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How can I help manage my own care?
Every time you see your doctor, ask for a photocopy of every test and his notes. This is your right as a patient. If you have to change doctors, get a second opinion, or try to keep the facts straight, having your own file will help.

If you find a medical journal article about a kind of hiving you think might be the same as yours, copy it and take it to your doctor. He has to include it in your medical file at your request—another of your rights as a patient.
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How can I live with this?
Never give up. You are going to be either your best friend or your worst enemy in this thing. Sometimes that choice will be made daily, hourly or by the minute. And take a look at our Useful Information pages for some practical help.

The ICUS email list is a wonderful support group where you will find many others who may be able to help and will certainly listen to your joys and sorrows.
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[Heatherttc1]

In about half of patients with chronic idiopathic hives, the explanation is that body's immune system is, in a sense, overactive. The urticaria represents an "autoimmune" phenomenon - the immune system (which is charged with fighting off infection) is attacking the normal tissue of the body and causing inflammation. One example of an autoimmune disease is rheumatoid arthritis (inflammation of the joints). HOWEVER, having "autoimmune" chronic hives DOES NOT mean that a given patient will end up with another autoimmune disease. Even though, we know certain hive sufferers have an autoimmune problem causing their rash, there is not presently any specific treatment for them besides the usual medications for urticaria. In the other half of patients whose chronic hives are not autoimmune in nature, medical science has no idea what is causing their misery.

So, in the great majority of patients with chronic hives, there is really no exposure (drug, food, insect, chemical) to blame for the urticaria. The patient must understand and accept this for their ideal management. Basically, all that needs to be done is treat the hives. The main treatment of hives is antihistamines, and they will work if they are used properly. Common reasons for lack of effectiveness of antihistamines are 1) the particular antihistamine used is not strong enough 2) the antihistamine is not used in a high enough dose 3) the antihistamines are not continued for a long enough period.

Most Allergists prefer to try the new non-sedating antihistamines first. If that doesn't eliminate the hives, some doctors will either increase the dose, or add another sedating-type of antihistamine at night (hydroxyzine and the anti-depressant doxepin are particularly strong antihistamines). It is important that high doses are tried - an example being a total of 100 to 200mg of hydroxzine per day.

If that doesn't work, some doctors may try a short course of cortisone/steroid-type pills (for example, a "dose pack" or 5 days of prednisone) to clear the hives completely. Then the patient can maintain the effect with the much safer antihistamines, since steroids have significant side effects if used long term.

One important issue for patients taking strong antihistamines at high doses is sedation. Fortunately, most patients will become less affected by sedation after they have taken the drug regularly for a while.

There are other medications that may be added to the antihistamines, but these are non-standard therapies. That is, there is not a lot of good scientific information supporting their use. However, if the hives are not responding to high doses of antihistamines, most allergists will consider trying them. Examples are anti-acid pills (e.g. Zantac(TM)), dapsone (an antibiotic), sulfasalazine (a drug for inflammatory bowel disease), nifedipine (a blood pressure medicine), Accolate(TM)(an asthma drug), colchicine (a drug for gout), and several others. Unfortunately, none of these drugs have turned out to be a panacea for those with antihistamine-resistant hives.

The important thing is that the patient is given enough medication (antihistamines, perhaps in conjunction with other drugs) to suppress the hives. Whatever amount and type of medication works, experts say that patients with chronic hives should remain on that particular regimen, taking the drugs every day, whether or not they have the hives on any given day. The idea is that you are preventing the hives from breaking out. Some doctors suggest that medications should be continued for long periods - perhaps even a month after the hives have disappeared. Again, the exception to this are the cortisone/steroid-type medications, which should only be used for short periods initially to quiet down the urticaria.

There is some good news for patients with hives. The statistics are that more than 50% of cases of hives will be spontaneously resolve in about 6 months. More and more patients resolve with time, so that by a few years, most patients are cured.

In summary, the great majority of cases of chronic hives (urticaria) have no cause. When initially seen by a doctor, the patient with hives should get a good history and physical exam along with a few blood and urine tests (and possibly some allergy tests). If no cause is found, the patient must work closely with their doctor to find a medication regimen that suppresses the hives until they resolve on their own.

[Heatherttc1]

Mycoplasma, chlamydia and ureaplasma can infect your eyes, throat, nose, lungs, vagina, bladder, urinary tube, prostate, colon and joints.

You can get it in your lungs when an infected person coughs in your face or in your genitals and urinary tract when an infected person has sexual relations with you. You may feel like there is a hair in your urinary tube, you may have terrible burning on urination, absolute misery when your bladder is full, spotting between periods, a feeling that you have to urinate all the time, pain on intercourse or you may have no symptoms at all.

The only way to diagnose mycoplasma infections is to order special test such as PCR which are not available to practicing physicians. For many, the only way to find if they are infected with mycoplasma, chlamydia or ureaplasma is to take certain antibiotics for several weeks or months and see if they feel better. However, the next time they go back to their sexual partner, they become infected again. If your doctor cannot diagnose the cause of a chronic cough, urinary tract infection or sore throat, you may be cured when you and your sexual partner take azithromycin, minocycline or a quinolone antibiotic for several weeks or months.

[Heatherttc1]

Category 5 Immunological Problems
Introduction
Chapter 1: CD 56+ Natural Killer Cells
Chapter 2: CD 19+ 5+ B Cells (1)
Chapter 3: CD 19+ 5+ B Cells (2)
Introduction
There are 30 different types of lymphocytes (CD designations) that make up the immune system. A balanced functioning of these white blood cells keeps a person healthy. Two of these cell types can cause infertility, implantation failures and miscarriages (see diagram below). Women are born with these cell types. In some women, they increase in numbers and activity and result in reproductive failures.

The Immune System
has 30 Different Kinds
of Lymphocytes

Two Types Can
Damage Pregnancies

Antibodies to Hormones
(Chapter 2)
Tumor Necrosis
Factor Alpha
(Chapter 1) Antibodies to Neurotransmitters
(Chapter 2)


Types of white blood cells include the following:

TH-2 ("T Helper 2")
The response is a balanced correct response during pregnancy (Category 1).


TH-1 ("T Helper 1")
The response is a cyto-toxic autoimmune response that can lead to infertility, implantation failure and miscarriage (categories 2, 3, 4 and 5).


CD3, CD4, CD8
Control production of blocking antibody response; a correct response.


CD19+ 5+
Produce antiphospholipid antibodies (Category 2) and anti-DNA and histone antibodies (Category 3). It also produces antisperm antibodies.


CD56+, CD57+
Are natural killer cells.


Please see A Guide to Interpreting the Results of the Reproductive Immunophenotype for more information on lymphocytes.

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[Heatherttc1]

Immunology May Be Key To Pregnancy Loss
Until the last decade, there was little a couple could do if they suffered from recurrent pregnancy losses. Miscarriages that couldn't be attributed to chromosomal defects, hormonal problems or abnormalities of the uterus were labeled "unexplained," and couples would continue to get pregnant, only to suffer time and again as they lost their babies. New research, however, indicates that as many as 80 percent of "unexplained" losses may the attributable to immunological factors-and some new therapies are enabling up to 80 percent of those affected to carry a baby to term.

About 15 to 20 percent of all pregnancies result in miscarriage, and the risk of pregnancy loss increases with each successive pregnancy loss. For example, in a first pregnancy the risk of miscarriage is 11 to 13 percent. In a pregnancy immediately following that loss, the risk of miscarriage is 13 to 17 percent. But the risk to a third pregnancy after two successive losses nearly triples to 38 percent.

Many doctors do not begin testing for the cause of pregnancy loss until after three successive miscarriages. However, because the risk of loss to a third pregnancy after two successive miscarriages is so high, the American College of Obstetrics and Gynecologists (ACOG) now recommends testing after a second loss-especially for women over the age of 35.

There are two major reasons for recurrent spontaneous abortion (RSA), or miscarriage. One is that there is something wrong with the pregnancy itself, such as a chromosomal abnormality, that curtails embryonic development. (A fertilized ovum is an embryo until 10 weeks gestation, and a fetus thereafter. Most miscarriages, though not all, occur between six and eight weeks, with expulsion taking place four weeks later, between 10 and 12 weeks.)

The best way to find out if the pregnancy itself is the problem is to test the chromosomes of the aborted embryo. While in many cases this is not an option, requesting genetic testing after a dilation and curettage (D&C) for a missed abortion can often give couples some definitive answers about what went wrong. An alternative is genetic testing for the couple, called "karyotyping." This involves a blood test for each partner so that both sets of chromosomes can be evaluated for abnormalities which may cause RSA, or which may be passed on to children.

The other cause of RSA, and the category into which immunological problems fall, is an environmental barrier to pregnancy-something wrong with he environment in which the pregnancy grows. In addition to immunological problems, other possible environmental causes of pregnancy loss are hormonal (not enough of necessary hormones to sustain the pregnancy) and anatomic (such as structural abnormalities of the uterus).

Anatomic problems may be detected with a hysterosalpinogram, hysteroscopy or hysterosonogram. Assessment of the hormonal environment looks at hormone levels and uterine response at the expected time of ovulation and implantation, usually through an endometrial biopsy or high level ultrasound examination.

The final way to determine an environmental cause of multiple miscarriage is through immunologic testing.

Immune System

The immune system, one of the most intricate and complex systems in the body, functions as the first line of defense against disease. It works by identifying proteins as normal or foreign. The immune response to a foreign protein is to neutralize or destroy the antigen. An antigen is a protein marker on the surface of a cell that identifies the cell as "self" or "nonself" An antigen can cause the production of antibodies. Antibodies are complex compounds made by the white blood cells (WBCs) that combine with specific antigens to destroy or control bacterial infections. As bacteria enter the body, WBCs produce antibodies to provide protection against illness.

Immune Causes of Recurrent Pregnancy Loss

The immunologic causes for pregnancy loss and implantation failure are the result of abnormalities in antibody responses. These responses fall into two categories: autoimmune and alloimmune.

Contributions to a pregnancy represent the pairing of genes from both man and woman. Autoimmune represents the immunologic response of the mother to a pregnancy ("self-immune" problems). Autoimmune disorders that can cause rejection of a pregnancy mean the woman is rejecting her own proteins-in other words, treating them like they are an invading illness. Autoantibodies are antibodies which attack one's own antigens.

Alloimmune problems indicate a mother's response to the man's genetic contribution to the pregnancy ("other-immune" problems). Alloimmune disorders are the rejection of a protein from the man. Both kinds of immune disorders can be determined with blood tests.

AUTOIMMUNE FACTORS

There are four different autoimmune problems that can cause RSA. A woman may have one or more of these underlying problems: antiphospholipid antibodies; antithyroid antibodies, antinuclear antibodies and lupus-like anticoagulant. Thirty percent of women with "unexplained" RSA will test positive for an autoimmune problem.

Antiphospholipid Antibodies

In pregnancy, phospholipids act like a sort of glue that holds the dividing cells together, and are necessary for growth of the placenta into the wall of the uterus. Phospholipids also filternourishment from the mother's blood to the baby, and in turn, filter the baby's waste back through the placenta.

If a woman tests positive for any one of variety of antiphospholipid antibodies (APA), it indicates the presence of an underlying process that can cause recurrent pregnancy loss. The antibodies themselves do not cause miscarriage, but their presence indicates that an abnormal autoimmune process will likely interrupt the ability of the phospholipids to do their job, putting the woman at risk for miscarriage, second trimester loss, intrauterine growth retardation (IUGR) and pre-eclampsia.

While testing for anticardiolipins (cardiolipins are a kind of phospholipid) is standard in some infertility clinics, this test alone cannot identify the presence of all underlying autoimmune processes that causes RSA. A panel of tests for antibodies to six additional phospholipids is recommended to determine the presence of APA. Testing positive for one or more kind of antiphospholipid antibodies indicates the woman has the immune response that can causes RSA. (See the full range of APA tests in the accompanying chart.)

The markers tested for each of seven phospholipids include IgM, IgG and IgA. These are circulating immunoglobulins (proteins that ward off potential harmful invaders). In some patients, measuring these 21 markers can identify elevations of immunoglobulins to unknown proteins, and signal some as-yet-unidentified process exists that can trigger RSA.

About four percent of women with recurrent miscarriage test positive for lupus-like anticoagulant, and nine percent of individuals diagnosed with SLE have a positive lupus anticoagulant test, or activated partial thromboplastin time (APTT). APTT is an adequate screening test for lupus-like anticoagulant antibodies, but there is a high incidence of false positives. Women who have a positive APTT should also have more specific tests, such as Kaolin clotting time, Russel viper venom assay and the platelet neutralization assay a to confirm the presence of lupus anticoagulant antibody activity. And, since some women do not test positive until they are pregnant or have suffered a pregnancy loss, repeat testing during early pregnancy is highly recommended when there is a history of RSA.

Because some circumstances can cause false positives for these tests, it is important to determine persistent positive levels by repeating the tests in six to eight weeks.

The live birth rate for a patient with untreated APA ranges from 11 percent to 20 percent. Individuals with recurrent pregnancy loss and/or implantation failure, venous or arterial, thrombosis, thrombocytopenia, elevated APTT or a circulating lupus-like anticoagulant are among those at risk for development of APA. Also at risk may be women experiencing infertility associated with endometriosis, premature ovarian failure, multiple failed in-vitro fertilization, and unexplained infertility. With treatment, the live birth rate for women with APA increases to 70 to 80 percent.

Antinuclear Antibodies

Antinuclear antibodies react against normal components of the cell nucleus. They can be present in a number of immunologic diseases, including: systemic lupus erythematosus (SLE or Lupus), progressive systemic sclerosis, Sjorgen's syndrome, scleroderma polymyositis, dermatomyositis and in persons taking hydralazine and procainamide or isoniazid. In addition, ANA is present in some normal individuals or those who have collagen vascular diseases. The presence of ANA indicates there may be an underlying autoimmune process that affects the development of the placenta and can lead to early pregnancy loss.

Histones are proteins which combine with the DNA of the cell nucleus to govern the development of tissues. Histones are the smallest building blocks of DNA. Antibodies to these histones mean the mother is developing an immunity to histone components of DNA. The mechanism by which ANA cause pregnancy loss is not known. (See the accompanying chart for specific ANA tests.)

Antithyroid Antibodies

Women with thyroid antibodies face double the risk of miscarriage as women without them. Increased levels of thyroglobulin and thyroid microsomal (thyroid peroxidase) autoantibodies show a relationship in an increased miscarriage rate, and as many as 31 percent of women experiencing RSA are positive for one or both antibodies. Chances of a loss in the first trimester of pregnancy increase to 20 percent, and there is also an increased risk of post-partum thyroid dysfunction. Therefore, antithyroid antibody testing should be routine in women with a history of two or more losses or thyroid irregularities.

It is important to note that when only the hemagglutination blood test is used, one out of five women with thyroid antibodies will not be correctly screened. More sensitive tests, enzyme linked immunosorbant assays (ELISAs), or gel agglutination tests, have become the standard for thyroid antibodies associated with recurrent pregnancy loss.

Autoimmune Treatments

Treatments for autoimmune risk factors include preconception administration of low-dose heparin (an anticoagulant produced naturally by the body), aspirin and prednisone (a steroid to decrease inflammation ). Heparin is administered (at 5,000 10,000 units) every 12 hours, subcutaneously, and is used to treat women with APA syndrome and to combat possible clotting problems. Prednisone (40-60 mg. per day) is given to decrease autoantibody levels, provide blood-thinning and anti-inflammatory reactions, and reduce the risk of clotting. Aspirin is a prostaglandin inhibitor which decreases agglutination of the platelets (clotting), and has some anti-inflammatory action.

Aspirin therapy, sometimes in concert with heparin and prednisone in severe cases), can increase blood flow to the placenta by inhibiting the tendency for clotting in women with abnormal levels of autoantibodies. Because of complications of pregnancy are significantly higher with prednisone, however, it is usually recommended for women who do not respond to aspirin and heparin therapy.

Another successful method for treatment of autoimmune factors is intravenous immunoglobulin (IVIg), a process which infuses the mother with antibodies from thousands of donors in the general population. The basic effect of IVIg is like neutralizing a large military force (the mother's dangerous antibodies) armed with weapons. The army is still present after administering the IVIg, but it is disarmed. The donor immunoglobulin keeps the attacking antibodies busy and away from the developing fetus.

Among women with the combined problems of APA and elevated NK cells who achieve pregnancy with preconception treatment, the subsequent live birth rate is about 70 percent. The initial treatment of choice is usually low-dose heparin and aspirin therapy because obstetrical complications, such as preterm birth, premature rupture of the membrane and gestational diabetes, are more common with prednisone. IVIg, while very effective, is also quite costly --- roughly $10-30,000 for treatments throughout pregnancy ($39 to $145 per gram, depending on the distributor). However, among women for whom pregnancy loss occurred even with preconception use of heparin and aspirin, IVIg remains an alternative that may allow them to carry a pregnancy to term.

ALLOIMMUNE FACTORS

There are two possible reasons that women with alloimmune problems lose their pregnancies in miscarriage: Either her immune system does not recognize the pregnancy, or she develops an abnormal immunologic response to the pregnancy.

Successful pregnancy has been associated with the presence of circulating "blocking antibodies." These are antibodies that are formed by a woman's immune system when she is pregnant, and they "mask," or disguise the pregnancy so it is not recognized as "foreign." Pregnancies that end with RSA have been associated with the absence of these blocking antibodies.

Recently, an antigen identified as R80K has been identified on the surface of syncytiotrophoblasts, the outer layer of cells covering of the chorionic villi of the placenta. These cells are in contact with maternal blood. R80K is a kind of protein marker to which the blocking antibodies respond during a successful pregnancy. The antibodies to this antigen react in a specific way to the antigens from the father's genetic material in the developing embryo, and thus create the protective, blocking antibodies.

For some women who lack the blocking antibodies, immunization with their husband's white blood cells may be an effective treatment. However, a leukocyte antibody detection assay (LAD) should be performed prior to initiating this treatment.

Also, IVIg treatment may be effective for some women who lack blocking antibodies because the immunoglobulin, which comes from thousands of donors, appear to contain small amounts of antibodies to R80K.

Leukocyte Antibody Detection Assay

Performed after a series of suspected losses when a woman is not pregnant, the Leukocyte antibody detection (LAD) test indicates a woman's physiologic response to pregnancy. Women who test for high levels of leukocyte antibodies have a history of carrying pregnancies longer than women who exhibit low levels. Women who have low levels of leukocyte antibodies generally had pregnancies that ended by week 12, or their immune systems did not respond to the stimulus of pregnancy by creating blocking antibodies. Only women with low levels of LAD are candidates for immunization with their husbands' white blood cells (leukocytes), so it is recommended that this assay be done prior to initiating an immunization protocol.

Natural Killer Cells

WBCs that belong to the innate or primitive group of cells that kill anything perceived as foreign . They kill abnormal invaders, including virally-affected cells. Some types of NK cells produce a substance called tumor necrosis factor (TNF), which might be described as your body's version of chemotherapy, and is toxic to a developing fetus. Patients who have high levels of these cells are at risk for implantation failure and miscarriage.

The proportion of NK cells is determined by a reproductive immunophynotype (RIP) test, which looks for cells that have the CD56+ marker. An NK (CD56+) cell range above 12 percent is abnormal. A patient with high NK cell activity will respond very well to intravenous immunoglobulin (IVIg) therapy. In fact, the live birth rate with preconception IVIg is more than 90 percent, compared to 20 percent without treatment.

Embryo Toxicity

Cells make proteins called cytokines. Different cytokines do different things. Some stimulate growth of cells, some inhibit growth. The proinflammatory cytokines stimulate inflammatory response, while others inhibit inflammatory response of cells. The embryo toxicity assay (ETA) is looking for cytokines which kill embryos.

Embryotoxic factors have been identified in as many as 60 percent of women with recurrent, unexplained miscarriage, and also reported among women endometriosis-associated infertility.

For the ETA, blood serum from the woman is incubated with mouse embryos. If the embryos die, a toxin (to the embryo) cytokine is present. IVIg therapy controls these cytokines and allows a pregnancy to progress.

Alloimmune Treatment

For a women who exhibits low levels of LAD, immunization with her husband's white blood cells results in about a 10 percent increase in the chance of live birth (to 60 percent) over the live birth rate without treatment. And risk of complications for these women, such as intrauterine growth retardation (IUGR), preterm birth and birth defects, are generally diminished with treatment.

Immunization can also be performed with seminal plasma vaginal capsules, inserted twice weekly from preconception to the 28th week of pregnancy. There is about a 15 percent increase in the live birth rate with this treatment compared to no treatment.

IVIg is also an effective, though more costly, treatment for women with low LAD levels. Research shows that there is a 28 percent increased live birth rate among women in this category who received IVIg, compared to women given a placebo.

For women with elevated LAD levels, IVIg is the recommended treatment. The dosage is 500 mg. per kg (2.2 lbs.) of weight per month. When treatment is started prior to conception and continued through 28 weeks of gestation, the overall success rate of IVIg is 70 percent. IVIg is also recommended for treatment of elevated circulating natural killer (CD56+) cells, circulating embryotoxins and unexplained recurrent miscarriage.

SUMMARY

As much as 40 percent of unexplained infertility may be the result of immune problems, as are as many as 80 percent of "unexplained" pregnancy losses. Unfortunately for couples with immunological problems, their chances of recurrent loss increase with each successive pregnancy.

Certainly, couples with RSA (two or more) would benefit from the full range of available immunological testing, especially if a woman is older than 35. And, because immune problems are often the cause implantation failure, couples with good embryos that fail to implant during IVF procedures are also good candidates for immunological screening.

Medical researchers have begun to pay attention to the problems of recurrent pregnancy loss, and ongoing genetic and immunologic research will continue to improve the diagnosis and treatment of this heartbreaking problem.

contd...

[Heatherttc1]

The following chart includes the full range of Autoimmune and Alloimmune Risk Tests and their "normal" ranges as conducted by Dr. Coulam at the Center for Human Reproduction in Chicago, Ill. Other labs and doctors may use different norms. The full range of tests is about $1,300.

Autoimmune Risk Tests

Antiphospholipid Antibodies (APA) Each of three markers, IgM, IgG and IgA, are tested for the following phospholipids, for a total of 21 different markers.



Anti-Phospholipid Antibodies (APA) IgM IgG IgA
Anticardiolipin (ACA) .131 - .173 .209 - .254 .192-.212
Phosphoethanolamine .362 - .478 088 - .222 .046-.073
Phosphoinositol .136 - .178 .175 - .236 .093-.122
Phosphatidic Acid .137 - .214 .104 - .132 .131-.155
Phosphogylcerol .168 - .242 .143 - .185 .102-.139
Phosphoserine .101 - .134 .082 - .188 .123-.143
Phosphocholine .152 - .198 .131 - .170 .092-.219
Alloimmune Risk Tests
Natural Killer Cells

Reproductive Immunophynotype (RIP) 3-12%

Leukocyte Antibody Detection (LAD) >10%

Embryo Toxicity Assay (ETA). <37% Artesia

Lupus - LikeAntibodies
Lupus-like Anticoagulant Antibodies (APA) 33.5 - 44.5 seconds
Kaolin ClottingTime 33.5 - 44.5 seconds
Platelet Neutralization Assay 33.5 - 44.5 seconds
Dilute Russel viper Venom Time 33.5 - 44.5 seconds


Antithyroid Antibodies (ATA) Antinuclear Antibodies (ANA)
Thyroglobulin <1:7 ssDNA 99
dsDNA 89
Sm 40
RNP 83
SSA 91
SSB 73
Histone 96
Sci-70 32

Thyroid microsomal (thyroid peroxidase) autoantibodies <1:72
ELISAs Gel agglutination tests <1:72

[ginnylynne]

WOW!!! Thanks for all the information, that is fantastic!! I hope your tests for mycoplasma come back negative because everything I have read about this infection is not good! I think I must also have a problem with sperm antibodies because both post coital tests I've had done said the sperm were dead once they hit my mucus. My RE has said that DH and I are basically "allergic" to eachother and has said the next step is IUI. But since I do test postive for anticardiolipin antibodies, my thinking is that its all related somehow and would make sense to me if my body is attacking his sperm as a foreign invader. Unfortunantly my RE isnt big on explaining anything she tests for or explaining results, so I feel very much in the dark. I know what you mean about sending your old job your Dr. bills! I firmly believe that the high stress job I have is making everything 100 times worse! I was also a very healthy person until I had my 3rd miscarraige this past June, then it all seemed to fall apart. Now I'm so fatigued all the time, my thinking feels a little foggy, I have these hives that won't quit and I just feel bad all the time, like I'm half sick every day. Have been to Dr.s' til I'm blue in the face and it still feels like no body can give me a concrete answer about whats wrong with me. I'm so tired of it!! I do believe though that when your immune system is messed up, there's no way you'r e going to feel good, I would think it's "normal" to feel sick. Baby dust to you and thanks again!