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 The
endometrium, or uterine lining, is the surface where the embryo implants to
develop into a fetus, and, eventually a baby. The exact process and nature of
embryo implantation are not fully understood, but we are continually gaining
information about the essential ingredients. As with most of our collection of
knowledge, it remains a work in progress.
For many years, we evaluated the crude appearance of the endometrium, under a
microscope, to evaluate the change in appearance after exposure to
progesterone. There is a progressive change in the microscopic structure from
the time of ovulation until the next menstrual flow. In normal ovulatory
cycles, with normal endometrial response, the changes are very predictable. The
well trained physician, with careful inspection, could determine how many days
after ovulation the biopsy to obtain the specimen was done. The process of
evaluating the endometrium for proper response to progesterone is called
endometrial dating. If the microscopic appearance was that of an earlier date,
by greater than 2 days, we defined the condition as a luteal phase defect.
Luteal phase defects have been associated with poor fertility rates and
increased miscarriage rates.
The problem with the endometrial dating is that it is crude and subjective.
When highly skilled and trained observers were given the same specimen to
review at various times, their evaluations were not always consistent. Variance
between observers was even more common. We needed a better method to determine
if the endometrium is being adequately prepared for embryo implantation. To
that goal, many centers have been conducting research projects to better
understand the mechanism operative in normal implantation.
Part of our new understanding is related to the mechanisms by which the cells
of our bodies stick together, instead of falling apart, leaving us a puddle of
individual cells. The "glue" which holds our cells together is a family of
"adhesion molecules" which are located on cell surfaces. In the endometrium,
three of these molecules seem to be regulated by progesterone. They all appear
and disappear at varying times after ovulation, or administration of
progesterone. One of these 3 adhesion molecules seems to be a good marker for
endometrial receptivity. It is called avb3 integrin.
There appear to be 3 conditions which impair the expression of this adhesion
molecule. Low progesterone levels, dilated fallopian tube(s), and endometriosis
have all been incriminated. We have a clinical assay for avb3 integrin in the
endometrium. To perform the assay, it requires that we perform an endometrial
biopsy a week after ovulation, or progesterone administration, if ovulation
does not occur. Using ultrasound, I monitor follicle growth starting on cycle
day 12 and look for follicle rupture 48 hours after we identify a follicle of
adequate size to rupture. I add progesterone supplementation, to eliminate a
low progesterone level as a concern. We have already done an HSG, to be sure
that the tubes are not dilated. One week after ovulation, we do an endometrial
biopsy and send the specimen to the lab which can perform the assay. The lab
requires you send a check for $425 with your specimen. We will provide you with
the information you will, predictably, need to obtain reimbursement from your
insurance company. The laboratory tells us that insurance reimbursement is
good.
If you have poor expression of the target integrin, we must assume you have, at
least, minimal endometriosis, and your potential for embryo implantation is
poor. The treatment I will recommend is laparoscopy for surgical treatment of
endometriosis, then 3 months of medical suppression of endometriosis.
There are two medications we will use to suppress your microscopic
endometriosis. The first is Lupron. Lupron will be given as a depot injection,
once a month for the three months of treatment. It stops the pituitary gland
from stimulating the ovaries, and creates a medical, reversible,
menopause. Since endometriosis has the enzyme which makes estrogens, aromatase,
we must suppress aromatase activity with Femara. Femara is marketed to treat
women with breast cancer, and our use in this treatment protocol is "off
label". You will take one Femara pill a day for the duration of the protocol.
The treatment described seems to provide us with an interval of time when there
will be adequate expression of your avb3 integrin. Immediately after treatment,
I recommend we begin our stimulation of your ovaries, in an effort to achieve a
pregnancy. We do not know how long our window of adequate integrin expression
will be open.
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Recurrent Pregnancy Loss
Ovulation Disorder
Endometriosis
Tubal Disease
Cervical Factor
Immunological Factor
Unexplained Infertility
Gene Abnormalities
Polycystic Ovary Syndrome
Endometrium
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