What you should know about IMMUNE ISSUES

[Lauren2005]

Hi Everyone,

You may (or may not) know me as one of the women here who constantly encourages people to look into the field of reproductive immunology (RI). This is a different, and often competing, field than reproductive endocrinology (RE).

If you are "unexplained," this means that the RE field did everything it could and can offer you no anwers. Please consider immune issues and the RI field.

Red flags for immune issues include:

- 3 or more failed IVF's or 1 failed IVF under age 35
- 3 or more chem pg's
- 1 or more m/c's with normal pathology
- "unexplained" dx
- endometriosis, especially stage I or II, even if it's been removed
- extensive use of antibiotics earlier in life
- cold/sore throat/flu-like symptoms after ovulation, IUI, egg transfer
- achy/restless legs/knees after ovulation, IUI, egg transfer
- known autoimmune disorders (you or family members)
- family history of heart attack, stroke, Alzheimer's, DVT (do the thrombophilia panel and also check for antiphospholipid antibodies)
- m/c(s), followed by chem pg(s), followed by BFN's
- there are many more.

Here is an interesting article from a recent edition of a magazine formerly known as "Infertility Times."

If any of this sounds familiar, or if you're just curious, please check out the "immune issues" bb and/or the Yahoo immunology group listed at the very end.

Best wishes, ladies!!
Lauren

Article from Achieving Families Magazine
http://www.achievingfamilies.com/

Pages 18-22
September/October 2005 edition

"SimplyComplex: The Immune System Reproduction and Making Sense (and
Use) of Science"

By Tracy Morris

About 20 percent of couples who seek help for their inability to
conceive are handed the devastating diagnosis of "unexplained
infertility." Another emotionally jarring diagnostic label, that of
recurrent miscarriage" (also called recurrent pregnancy loss or RPL,)
is given to a smaller but significant percentage of people trying to
have a baby. RPL usually describes patients who have conceived but
lost pregnancies three times or more.

Both sets of patients those who have unexplained infertility and
those with RPL — may benefit from looking into a highly specialized
branch of reproductive medicine: the field of reproductive immunology.

The Immune System: It's Everywhere Now

If you grew up in the 1970's or later, you may not be aware of just
how recent our growth in knowledge is about the human body's immune
system. In fact, the term "immune system" only originated in the late
1960's, even though the groundwork for its study had been laid over
150 years earlier by British scientist Edward Jenner. The development
of immunology as a field of research and treatment has paralleled the
expansion in our holistic understanding of the body.

Unlike most other fields of medicine in which physicians become very
specifically trained in a particular, chosen system, for example, the
cardiac system, the study of immunology and its application in
clinical practice can find its way into virtually any realm of
medical specialty.

As Dr. Benjamin Rivnay, Vice President and Lab Director of Repromedix
Corporation, puts it, "There is no significant address for immune
related problems. It's a system that is not confined to a single
organ or even a set of organs, such as in the case of, say, the
kidneys or the cardiac system."

Just as immunology warrants an encompassing view of the human body
and its functions, says Rivnay, the condition of infertility is often
the result of multiple aspects. `Some infertility," the scientist
explains, "may be traced to a specific situation, such as a gene
defect. Some examples of that are Gaucher's disease or cystic
fibrosis. But for many patients, this ability to pinpoint a cause
simply is not feasible." Accordingly, the American Society for
Reproductive Immunology, founded in 1981, includes among its diverse
membership molecular biologists, microbiologists, geneticists,
pediatricians, infectious disease specialists, animal scientists, and
more, in addition to the expected OB/Gyns and endocrinologists.


Immunology 101 —More Than You Want to Know

The term "immune system" refers to all the components in your body
that work toward defending it against harmful entities. It would be
impossible to learn about the entire immune system through a single
magazine article (although you can find a lot of great details in
Hildy Silverman's article, "Your Own Worst Enemy: Autoimmune
Disorders and Infertility", from the June 2004 issue of
inFertility Times magazine.)

For a complete glossary of immunology related terms, see

http://repro-med.net/glossary.php

on the website of the Alan E. Beer Center for Reproductive Immunology
and Genetics.

It should be noted at this point that, while it is helpful to break
down the related terms to make learning about them easier, the truth
is that all of these components work together in a very complicated
mix of constant stimulus-response interactions. The best situation
for a body to be in immunologically is to have all systems ready to
go and functioning well. There are some checks and balances built in,
fortunately, to keep a minimal level of protection going even when
one or more of the components aren't working well. There are also, as
most of us know, some disease circumstances that can add up to an
illness-causing or even life-threatening break in the system.

Diseases of the immune system might be over-simplified as resulting
from either too little (immunodeficiency) or too much response.

Immunology 201 —What You Really Need to Know

Immunodeficiency is a condition in which a body is not adequately
defending itself against invaders. A well-known example is AIDS
(acquired immune deficiency syndrome), and there a number of other
immunity-debilitating diseases that are either congenital or
acquired. Some medical treatments, particularly chemotherapy and
those for organ transplant patients, actively work to induce
immunodeficiency as part of the therapy.

At the other end of immunity's continuum, a body's immune responses
may over-react, essentially battling against "good" cells it has
mistaken for invaders. "Autoimmune disorders" is the term used to
refer to these conditions.

Common examples of autoimmune disorders include

• lupus

• Type 1 diabetes mellitus

• rheumatoid arthritis

• psoriasis

• Sjogren's syndrome

• multiple sclerosis

• inflammatory bowel diseases such as Crohn's and ulcerative colitis

• myasthenia gravis

• scleroderma

• thyroid diseases such as Hashimoto's and Grave's

• Addison's disease

What causes immune conditions to occur?

Some, such as AIDS, are caused by viral infection. Some are medically-
induced, such as by chemotherapy. Many are passed down through
families, genetically. The exact causes of many immune disorders have
simply not yet been nailed down by science. Some of these diseases
can lie dormant and without symptoms until certain environmental
factors (for example, nutrition, stress, body fat) kick-start them
into doing their damage.

Where do these conditions occur, which body parts are affected?

Because, as Dr. Rivnay puts it, "Most of the immune system `happens'
in the blood," virtually any organ can be impacted by immune diseases.

How are immune diseases treated?

Essentially, disorders of the immune system are chronic (meaning they
continue indefinitely) and progressive (meaning they get worse over
time if un-challenged), so treatment is often confined to tackling
the symptoms of the disease, not the root cause. For example, insulin
injections may regulate blood sugar for diabetics, but it does not
end their diabetes. For those with immunodeficient conditions,
experimental medicines may be available to try and "crank up" the
body's immune system. Similarly, immunity-suppressing drugs are being
investigated for use in "turning down" autoimmune responses.

Connecting Immunology of Reproduction

How the whole concept of immunology factors into conception and
pregnancy is almost as complicated as the immune system itself. A
woman's body may actively work against pregnancy as if the conceptus —
the unique creation resulting from combination of an egg cell and
sperm cell were an invader. It's generally understood that in order
for a genetically unique person to begin and continue growing within
a woman s body, some very intricate temporary readjustments must be
made by the mother's immune system. When these adjustments go awry,
either as the result of a pre-existing condition in the mother or
because the presence of the conceptus has activated an immune
response, the result can be infertility, primarily due to
implantation problems and recurrent early miscarriage.

Fortunately for people who are trying to conceive and need more hope,
the past three decades have seen tremendous growth in the diagnosis
and treatment of immune-related fertility problems. The past decade
in particular, Rivnay says, has seen an explosion in research that
explores "the interface between systems such as coagulation and
immunology or the endocrine system and immunology."

Still, there are many reproductive experts of the highest caliber who
minimize the prevalence of infertility, including RPL, that stems
from immune system issues. As a result, some practitioners may not be
willing to discuss possible options for immunology testing or
resulting treatment protocols. Many will only refer their patients
for this more specialized testing after several miscarriages.
Laypeople usually find themselves more bewildered after trying to
find out the facts themselves by reading professional studies, which
range from supportive to dismissive of the questions regarding
immunology and infertility.

The good news is that a pioneer in the treatment of immunology-based
infertility and miscarriage, Dr. Alan E. Beer, believes that "the
debate is totally over" between scientists and clinicians who are all
eager to assist their patients yet want to avoid instilling false
hope or futile costs.

Clearing the Confusion

When asked why he thinks patients are still able to find completely
conflicting studies on whether or not reproductive immunology will
provide their family-building answers, Dr. Beer, a past president of
the American Society for Reproductive Immunology and a practicing
OB/Gyn who has spent his entire academic career looking at the
intersection between immunology and infertility, says simply that "We
were dealing with such a focused part of immunology that was
incredibly complicated, so that physicians didn't really have the
tools or the background to understand a lot of what was being
written."

"But it's totally clear now," Beer elaborates hopefully, "I think
that all reproductive endocrinologists would now agree that too much
tumor necrosis factor (TNF) alpha, produced by natural killer cells,
paralyzes the embtyo. It doesn't kill the embryo, it causes
inactivation of the DNA within the embryo so that within two hours,
these cells stop growing and dividing."

Dr. Rivnay wonders, "When will people [who are comparing research
studies] stop looking for high levels of incidence in infertility to
gauge significance? Infertility in itself is too multi-factorial to
have such expectations.

Dr. Beer cites his own and others' research as indicating that the
problem found in patients with RPL is actually worse in patients with
IVF failures and primarily for those who experienced primary
infertility. "These individuals have elevations in natural killer
cells that they're born with. They've also produced NK cells that
they're not born with and that are the same kind found in patients
with rheumatoid arthritis. In our patients, though, these cells
migrate to the uterus, where the cells wait to damage an embryo as
soon it appears. If the levels of TNF-alpha production is above 40
(on the assay), then I know it routinely damages DNA in the eggs she
produces so that any embryos she creates via IVF are likely of poor
quality."

More good news Beer and his staff have seen treatment for the above-
described condition, which is merely one of many that can occur
within a woman's immune system, result in healing within just under
18 weeks. The specific testing in these cases have been:

• the NK assay

• Th-1, Th-2 Intracellular Cytokine assay Those are just a couple of
the many tests that can now be administered for diagnostic purposes.
There are only a handful of labs in the U.S. that specialize in
reproductive immunology testing, and all have become adept at working
in partnership with a patient's own fertility practitioner,
regardless of location. Treatment depends on the issue determined by
testing to be the cause of either conception, implantation, or
pregnancy problems. Some cases can be effectively managed through the
use of donor gametes or embryos, PGD with IVF, common blood thinning
agents (such heparin and aspirin), and intravenous immunoglobulin
(IVIg) therapy, among others.

So should anyone who wants to get pregnant inquire about these very
specialized diagnostic tests, or is the more common course of trying
to conceive, seeing what happens, and then seeking specialty care the
better route?

While many current reproductive Immunology tests are diagnostic in
scope, meaning that they seek something that is going wrong right
now, others are being developed that are predictive. An example is
the Embryo Toxic Factor test, which Dr. Rivnay describes "will look
at the potential for maternal immune response during pregnancy.

Dr. Beer recommends that anyone who is even slightly concerned can
start by taking his free "informational immunological self-tests"
online, beginning at

www.repro-med.net/tests/stest.php

Reproductive Immunology Testing for All?

"All of the immunity disorders," says Beer, "have at their basis the
activated natural killer cells." That's not to say that anyone with
immunity-related diseases will invariably have fertility or pregnancy
problems, but their chances are higher.

The term "red flag" can be heard frequently when talking about
immunology. As it relates to conception and miscarriage, it is
interchangeable women who already know that they have certain immune-
based or related disorders might expect to have higher chances of
fertility problems, while on the other hand, otherwise healthy (or at
least, undiagnosed) women might consider their infertility
experiences to be possible signals that an underlying immunology
condition may be present. Beer and others have said that if a person
has failed three or more IVF cycles, there is a very high likelihood
(Beer cites up to 70 percent) that immune issues are a factor.

Scientist Rivnay agrees that overall knowledge of the immune system
has been difficult to introduce into medical clinics, for a variety
of reasons. He states a recognition of the need to control costs, for
one thing. As such, he agrees that across-the-board testing of all
pregnant women for some conditions that may only turn up positive in
one percent of the population is, well, over the top. On the other
hand, he uses the following road-trip analogy to express testing
benefits:

"If you're going on a long car journey, and you find at the outset
that your brake lights aren't working, you look into the cause of the
problem and fix it before

beginning the journey You'll want to examine all possible causes of
the broken light. is it just a burned-out bulb or are the brakes not
working properly? If you simply change the bulb — the easiest and
most immediately visible problem you might miss a piece of the puzzle
that is so important it impacts your entire trip.

In short, you cannot say with assurance that you know the entire
system is functioning if you have only looked at one component of the
system. Such assumptions can be detrimental in their impact on your
journey's goals."

"There's no guesswork in this business," Beer says confidently. "If a
problem exists, we can find it, and the chances of it being corrected
vary by age." His Center's success rates range from a mw of 17
percent for women who are between age 43 and 46 to a high of 78
percent for 30 to 35 year olds. Unlike many infertility practices,
Beer and his colleagues around the world have

focused on older hopeful moms who have already experienced a number
of failed pregnancies. Soon, Beer will be presenting what he knows
with the help of co-author Julia Kantecki, in patient-friendly
language, with an upcoming book appropriately called, "Is Your Body
Baby-Friendly?"

Beer says everything he espouses in the book tentatively
subtitled "Unexplained infertility, unexplained miscarriage,
unexplained IVF failure -explained for the first time ever: An
insight into the field of reproductive immunology by Alan E. Beer" —
will be backed up by references to soothe any lingering critics.

For the thousands of individuals and couples haunted by the uneasy
limbo of the unexplained, answers to their mysteries will be long
overdue.

The following laboratories will be happy to answer your detailed
Reproductive Immunology testing questions:

The Alan E. Beer Center for Reproductive Immunology &
Genetics

repro-med.net

Millenova Immunology Laboratories

millenova.com

Nora LLC

www.multiplemiscarriage.com

Repromedix Corporation

repromedix.com

You can also find patient-based support here:

Yahoo Reproductive Immunology Support

http://health.groups.yahoo.com/group/immunologysupport

[Daviso]

Thank you Lauren...

Do you know if insurance would normally cover testing for immune issues or is that considered IF related and therefore you would need IF coverage of some kind?!

[Lauren2005]

I have NO coverage for IF but my insurance covered every penny of the immune testing. I'm sure this varies based on the plan, but I literally didn't pay a cent.

Hope that's helpful!
Lauren

P.S. I very, very highly recommend doing immune testing through Dr. Alan Beer (mentioned in the article above.) Not only does he code all the testing as "autoimmune disorder" but his testing is also the most comprehensive in the nation. Most of his patients have never met him; they do the tests locally and he consults with them by phone. He provides a complete protocol starting pre-conception and ending six weeks after delivery. I'm lucky enough to live half an hour away from his office, so I've met him and know his staff quite well. http://www.repro-med.net

P.P.S. I am on my second cycle ttc since my immune dx and tx. Due to my aggressive endometriosis, I'll be doing IVF this cycle. Ordinarily Dr. Beer recommends natural cycles (even to people who have had multiple failed IVF's including with donor eggs!) The man is a miracle worker.

[Daviso]

Thanks for all your info, Lauren...

DH and I have already started talking about looking into it...

[Lauren2005]

Best wishes to you!!!


Lauren