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ENDOMETRIOSIS

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Endometriosis is a common condition that affects women during the reproductive years. It occurs when normal tissue from the uterine lining, the endometrium, attaches to organs in the pelvis and begins to grow. This displaced endometrial tissue causes irritation in the pelvis that may lead to pain and infertility. Experts do not know why some women develop endometriosis. During each menstrual period, most of the uterine lining and blood is shed through the cervix and into the vagina. However, some of this tissue enters the pelvis through the fallopian tubes. Women who develop endometriosis may simply be unable to clear the pelvis of these cells.
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AMERICAN SOCIETY FOR REPRODUCTIVE MEDICINE
ENDOMETRIOSIS
A Guide for Patients
PATIENT INFORMATION SERIES

Published by the American Society for Reproductive Medicine under the
direction of the Patient Education Committee and the Publications Committee.
No portion herein may be reproduced in any form without written permission.
This booklet is in no way intended to replace, dictate, or fully define evaluation
and treatment by a qualified physician. It is intended solely as an aid for patients
seeking general information on infertility evaluation, treatment, research, and
related topics.
Copyright 2007 by the American Society for Reproductive Medicine.



AMERICAN SOCIETY FOR REPRODUCTIVE MEDICINE
ENDOMETRIOSIS
A Guide for Patients
A glossary of italicized words is located at the end of this booklet.
INTRODUCTION
Women with endometriosis may experience infertility, pelvic pain, or both. This
booklet will describe options for diagnosing and treating pain or infertility that
may be attributed to endometriosis.
What is Endometriosis?
Endometriosis is a common condition that affects women during the reproductive
years. It occurs when normal tissue from the uterine lining, the endometrium,
attaches to organs in the pelvis and begins to grow. This displaced endometrial
tissue causes irritation in the pelvis that may lead to pain and infertility.
Experts do not know why some women develop endometriosis. During each
menstrual period, most of the uterine lining and blood is shed through the cervix
and into the vagina. However, some of this tissue enters the pelvis through the
fallopian tubes. Women who develop endometriosis may simply be unable to
clear the pelvis of these cells.
Early endometriosis implants look like small, flat patches, blebs or flecks
sprinkled on the pelvic surface. The flecks can be clear, white, brown, red, black
or blue. The severity and course of endometriosis is highly unpredictable. Some
women may have a few endometriosis implants on the surface of the pelvis, the
peritoneum, or pelvic organs, or it may invade the peritoneum and grow as
nodules. Endometriosis may grow on the surface of the ovary as implants or
invade inside the ovary and develop a blood filled cyst called an endometrioma,
or a “chocolate cyst.” Chocolate cysts are so named because over time the blood
they contain darkens to a deep reddish brown color. These cysts may be as small
as a pea or grow to be larger than a grapefruit. Endometriosis may irritate
surrounding tissue and produce internal scar tissue called adhesions. These
adhesions can bind the pelvic organs together, cover them entirely, or involve
nearby intestines. The adhesions may keep the fallopian tube from picking up
the egg from the ovary during ovulation. Endometriosis may also grow into the
walls of the intestine or into the tissue between the vagina and the rectum.
3


Up to 10% of all women may have endometriosis. Many women who have
endometriosis experience few or no symptoms. Some women experience severe
menstrual cramps, chronic pelvic pain, or painful intercourse. In others,
infertility may be the only symptom of endometriosis. Often, endometriosis is
daignosed when a woman has pelvic surgery because of a persistent ovarian cyst
or other reasons. Endometriosis can affect women who have had children, and
can occur in teenagers and young women. Some specialists feel that
endometriosis is more likely to be found in women who have never been
pregnant. Endometriosis may be found in 24% to 50% of women who
experience infertility, and in more than 20% who have chronic pelvic pain.
Endometriosis is classified into one of four stages, I-minimal, II-mild, III-
moderate, and IV-severe, depending on the location, extent, and depth of
endometriosis implants, the presence and severity of adhesions, and presence
and size of ovarian endometriomas. Most women have minimal or mild
endometriosis, which is characterized by superficial implants and mild
adhesions. Nevertheless, this degree of endometriosis is strongly associated with
infertility, dysmenorrhea, and chronic pelvic pain. Moderate and severe
endometriosis is characterized by chocolate cysts and more severe adhesions.
4



American Society for Reproductive Medicine: Revised Classification of Endometriosis (1997)
SYMPTOMS OF ENDOMETRIOSIS
Menstrual Cramps
Many women experience mild menstrual cramps, which are considered normal.
When cramping is more severe it is called dysmenorrhea, and may be a
symptom of endometriosis or other types of pelvic pathology such as uterine
fobroids or adenomyosis. Severe cramping may cause nausea, vomiting, or
diarrhea. Primary dysmenorrhea occurs during the early years of menstruation,
tends to improve with age or after childbearing, and is usually not related to
endometriosis. Secondary dysmennorhea occurs later in life and may increase
with age. This may be a warning sign of endometriosis, although some women
with endometriosis feel no cramping at all.
Painful Intercourse
Endometriosis can cause pain during or after intercourse, a condition known as
dyspareunia. Deep penetration can produce pain in an ovary bound by scar
tissue to the top of the vagina. Pain also may be caused by bumping against a
tender nodule of endometriosis behind the uterus or on the uterosacral
ligaments
, which connect the cervix to the sacrum.
5



Infertility
There is a large body of evidence that demonstrates an association between
endometriosis and infertility. Endometriosis can be found in up to 50% of
infertile women. Infertility patients with untreated mild endometriosis conceive
on their own at a rate of 2% to 4.5% per month, compared to a 15% to 20%
monthly fertility rate in normal couples. Infertility patients with moderate and
severe endometriosis have monthly pregancy rates of less than 2%. Even though
endometriosis is strongly associated with infertility, not all women who have
endometriosis are infertile. For example, many women undergoing tubal
sterilization procedures are noted to have endometriosis.
A cause and effect relationship between endometriosis and reduced fertility is
presumed but not proven. It is not known how minimal and mild endometriosis
reduces fertility when there are no adhesions. It is presumed that endometriosis
alters the pelvic environment in subtle but important ways. Theories include
inflammation, altered immune system, hormonal changes, abnormal function of
the fallopian tube, or impaired fertilization and implantation. It is easier to
understand how moderate and severe endometriosis reduces fertility, since major
pelvic adhesions, when present, may prevent the release of eggs, block sperm
entry into the fallopian tube, and prevent the fallopian tube’s ability to pick up
eggs during ovulation.
HOW IS ENDOMETRIOSIS DIAGNOSED?
Endometriosis cannot be diagnosed by symptoms alone. Your physician may
suspect endometriosis if you are having fertility problems, severe menstrual
cramps, pain during intercourse, or chronic pelvic pain. It may also be suspected
when there is a persistent ovarian cyst. Endometriosis is often found in close
family members like a mother or sister. Remember, however, that many women
with endometriosis have no symptoms at all.
Pelvic Exam
Certain findings of a pelvic examination may lead your physician to suspect
endometriosis. The doctor may feel a tender nodule behind the cervix during a
combined vaginal and rectal exam, or the uterus may be tilted back or
retroverted. One or both ovaries may be enlarged or fixed in position.
Occasionally, endometriosis implants may be visible in the vagina or the cervix.
Although your physician may suspect endometriosis, based on your history and
the results of a pelvic exam, surgery is needed to confirm endometriosis.
Laparoscopy
Laparoscopy
is an outpatient surgical procedure that enables the physician to see
the pelvic organs and look for endometriosis. During laparoscopy, a thin camera
called a laparoscope is inserted into the abdomen through a small incision near the
navel. The laparoscope allows the surgeon to see the surface of the uterus, fallopian
tubes, ovaries, and other pelvic organs. For more information on laparoscopy,
please see the ASRM booklet entitled, Laparoscopy and Hysteroscopy.
6



The extent of endometriosis is evaluated during laparoscopy. A clinical
staging system is used to describe the extent of endometriosis, adhesions, and
endometrioma cysts in the ovary. A score of 1-15 indicates minimal or mild
endometriosis, and a score of 16 or higher indicates moderate or severe disease.
The staging system, however, does not correlate well with a woman’s chance of
conceiving with fertility treatment or the degree of pain that she experiences.
Your physician may decide to treat your endometriosis during the
laparoscopy. Additional small incisions allow your physician to insert surgical
instruments. Endometriosis may be coagulated, vaporized, burned or excised,
and scar tissue or ovarian cysts may be removed. During laparoscopy, your
doctor can determine if your fallopian tubes are open by injecting dye through
the cervix into the uterus. If the tubes are open, the dye will flow out the ends of
the fallopian tubes.
Other Diagnostic Procedures
In special cases, your doctor may use special imaging techniques such as
ultrasound, computerized tomography (CT scan), or magentic resonance
imaging (MRI)
to gather more information about your pelvis. These procedures
can identify cysts and help characterize the fluid within an ovarian cyst,
although an endometrioma cyst and a normal corpus luteum cyst may have a
similar appearance. These tests are useful when evaluating women experiencing
infertility and/or chronic pelvic pain.
TREATMENT OF PAIN
Your doctor will consider your symptoms, physical examination, test results, and
your goals and concerns before advising treatment. Women with mild symptoms
may benefit from lifestyle changes, or require no treatment at all. Hormonal
therapy may be suggested when pain interferes with family, work, or daily
activities, since these therapies usually reduce pelvic pain and dyspareunia in
more than 80% of women in whom endometriosis is diagnosed. Since several
effective treatments are available, the choice is made based on side effects and
cost. Hormonal treatments are not effective for large ovarian endometriomas, and
surgery is necessary. Surgery also may be indicated when medical treatment is
unsuccessful or when medical conditions prohibit the use of hormone treatments.
Lifestyle Modifications
Some women have found that their pain is improved by exercise and relaxation
techniques. Although natural supplements have not been shown to reduce
endometriosis-related pain, over-the-counter, non-steroidal, anti-inflammatory
medications, like ibuprofen and naproxen, reduce painful menstrual cramps.
When painful intercourse is a problem, changing positions prevents pain caused
by deep penetration. In spite of these measures, medical treatment is frequently
needed.
7



Hormonal Contraceptives
When used for contraception, birth control pills are taken daily for three weeks,
followed by a week without pills to permit menstrual flow. Birth control pills
often reduce menstrual cramping and pelvic pain that may be associated with
endometriosis.
Birth control pills may also be prescribed continuously without pausing for
menstrual periods. This may be effective when menstrual cramps are still
bothersome despite using birth control pills. Side effects of this approach
include fluid retention and irregular spotting or bleeding. Serious side effects of
birth control pills are very rare and include stroke, vascular problems, and heart
disease. It should also be noted that endometriosis may be diagnosed in women
taking birth control pills, and that birth control pills have never been shown to
prevent the development of endometriosis. No data is currently available
concerning the effect of transdermal contraceptive patches and vaginal
contraceptive rings upon endometriosis.
Progestins
Progestins
are synthetic medications that have progesterone-like activity upon
the endometrium, the uterine lining. Many progestins have been demonstrated to
reduce endometriosis-associated pelvic pain. The most common side effects of
progestin therapy are irregular uterine bleeding, weight gain, water retention,
breast tenderness, headaches, nausea, and mood changes, particularly
depression. Progestins are considerably less expensive than other medications,
and may be prescribed as pills, injections, or the levonorgestrel-containing
intrauterine contraceptive devices (IUDs). Drawbacks of the injectable form
known as depot-medroxyprogesterone acetate (depo Provera) is that it may
inhibit fertility for many months after treatment is discontinued, and that its use
for longer than six months may cause a significant loss of bone mineral density
and place a woman at risk for osteoporosis.
GnRH Analogs
GnRH analogs,
particularly GnRH agonists, cause estrogen levels to fall to
menopausal levels, and menstruation does not occur. These drugs are highly
effective for painful endometriosis. Side effects include menopausal symptoms:
hot flashes, vaginal dryness, and loss of calcium from the bones. The
medications are usually given for six months. Low-dose estrogen-progestin
hormone therapy or progestins alone may be added when prolonged treatment is
needed, or if menopausal symptoms are severe. Calcium supplementation and
exercise are recommended to reduce the loss of bone density that occurs with
therapy. Most bone density loss is temporary and is regained after treatment is
stopped. In a recent comparative trial, GnRH agonist therapy with depot-
leuprolide acetate and progestin therapy with depot medroxyprogesterone
acetate for subcutaneous injection (DMPA-SC) were equally effective in
reducing endometriosis-associated pain; and both medications maintained
8



clinical improvement for 12 months following the end of treatment. DMPC-SC
was associated with less bone loss and fewer hot flashes than depot-leuprolide.
Danazol
Danazol
, a medication that is similar to male hormones, is also highly effective for
endometriosis pain. Common side effects may include water retention, acne,
irregular vaginal bleeding, muscle cramps, and temporarily reduced breast size.
Uncommon, but irreversible side effects include deepening of the voice and growth
of facial or body hair. Danazol is less frequently used to treat endometriosis today
than 20 years ago because medications such as GnRH agonists are equally
effective, but have a more favorable side effect profile that danazol.
Surgery for Pain
Surgical treatment of endometriosis is often performed when endometriosis is
diagnosed. During laparoscopy, the doctor may remove adhesions,
endometriosis nodules, and ovarian cysts. Laparoscopy is often used to treat
recurrent endometriosis when the goal is to preserve future fertility. Sometimes
the severity of endometriosis is such that major surgery is advised to remove
endometriosis and adhesions. Ovarian cystectomy is superior to cyst drainage
for treating pain and prevention of recurrent cysts.
Overall, fertility-preserving endometriosis surgery improves pain for 60% to
80% of women. After surgery, medical therapy may be needed to control
symptoms of endometriosis since 40% to 80% of women experience recurrent
pain symptoms within two years of surgery. Recurrent symptoms occur within
five to 10 years in more than 50% of women after completing a six-month
course of medical treatment. Long-term management of endometriosis-related
pain is usually necessary.
Hysterectomy, with removal of the ovaries, is an effective approach after
childbearing is completed. This surgery provides final relief from endometriosis-
related pain in more than 90% of women. In contrast, if one or both ovaries are
preserved, there is a much greater chance that symptoms will recur, and
additional surgery will be required. If needed, low-dose hormone therapy
reduces hot flashes and menopausal symptoms that occur after hysterectomy
with bilateral removal of the ovaries.
Pregnancy
Although it has not been proven that pregnancy is therapeutic, endometriosis
often regresses during pregnancy. The hormonal environment produced by
pregnancy may inhibit the condition. However, endometriosis often returns
some time after pregnancy. A woman must carefully consider her immediate and
long-term goals before choosing pregnancy as a treatment for endometriosis.
9



Team Approach to Pain
Some women continue to experience severe pain in spite of hormonal and
surgical treatments. When pain persists, a multidisciplinary "team" approach
may be helpful. This approach combines the expertise of a group of specialist
physicians at a "pain center," along with mental health specialists, counselors
and physical therapists. Nerve blocks, acupuncture, or other treatments may be
beneficial.
Investigational Drug Treatments for Endometriosis
A number of new drugs are under research and development for endometriosis.
Antiprogestins, such as mifespristone and onapristone, have had success in small
studies. These medications work by modulating the estrogen and progesterone
receptors in endometriosis implants and cause atrophy of endometriosis.
Selective estrogen receptor modulators (SERMs) may be effective by virtue of
their antiestrogen effect. Raloxifene is the SERM that currently shows some
promise. In contrast, tamoxifen, another SERM, may cause endometriosis to
worsen. Aromatase inhibitors, medications that inhibit aromatase, an enzyme
that is required for estrogen synthesis, have had success in small studies and
case reports. Anastrazole and letrozole are two examples of aromatase inhibitors
undergoing investigation. Leukotriene antagonists theoretically will improve
dysmenorrhea by modulating the activity of leukotrienes, immune chemicals
that contribute to inflammation and pain. Other immune modulators are under
investigation in animal models as potential therapies for endometriosis. These
include loxoribine, levamisole, interleukin-12, and interferon-a-2b.
TREATMENT OF INFERTILITY
The entire infertility evaluation should be completed before considering treatment
for endometriosis. For infertile women with suspected minimal or mild
endometriosis, a decision must be made whether to perform laparoscopy before
starting treatments to enhance fertility. Clearly, factors such as a woman's age,
duration of infertility, and pelvic pain must be considered. Other infertility factors
may co-exist and impact success rates and treatment outcome. If pain also is a
concern, laparoscopy and surgical treatment seem prudent. In addition,
laparoscopy and possible laparotomy are recommended when moderate or severe
endometriosis is suspected, if no other cause for infertility has been found.
Surgery for Infertility
Laparoscopic treatment of minimal and mild endometriosis has been associated
with a small but significant improvement in pregnancy rates. In the largest study
to date, 29% of women who had their endometriosis treated conceived over nine
months, in contrast to only 17% of women whose endometriosis was diagnosed,
but not treated during laparoscopy. Although this is a modest treatment benefit,
it suggests that there is a period of enhanced fertility after laparoscopic treatment
10

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