Jarrett Fertility Group > Endometriosis

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Overview: Endometriosis

Every month when a woman has a period, the cells that line the uterus, known as the endometrium, are shed in the menstrual flow. Some small portion of this combination of blood and endometrial cells may also pass out through the fallopian tubes into the abdominal cavity. This is termed retrograde menstruation. There are other theories as to how endometriosis develops, and this scenario certainly cannot explain all cases of endometriosis. It is, however, the most widely held theory and does explain all but the most unusual cases of endometriosis.

Most of the time, the body's natural defense systems attack and destroy these cells before they can begin to grow. However, for reasons that are not clear, this is not always the case. In certain individuals, these endometrial cells actually implant on structures in the abdominal cavity and begin to grow. This is endometriosis: the presence of viable endometrial cells in places other than the uterine cavity. Then, each month when the normal hormonal changes result in a menstrual period, much the same change occurs in the endometriosis. A small amount of bleeding occurs from the endometriosis cells. This is very irritating to the body, and as a result of this, scarring occurs around the endometriosis. Most often this is a progressive process, with a small additional amount of bleeding and scarring occurring every month.

Once the endometrial cells begin to grow in the abdominal cavity, they are known as implants. Implants can occur on any structure, including the ovaries, fallopian tubes, bladder, bowel and on the lining of the abdominal cavity (known as the peritoneum ). The area behind the uterus, between it and the rectum, is known as the cul-de-sac, and this is the most common site for endometriosis. Implants may appear as small, clear or red, fluid-filled sacs, or most commonly, as dark brown or black areas. It is the collection of old blood in the implants that gives them this appearance. Some scarring is typical around the implants, and can be very localized or, at times, quite severe. When endometriosis develops in the ovaries, large cysts full of old blood, known as chocolate cysts or endometriomas , may result.

Although in some individuals endometriosis may cause no symptoms, it is typically associated with two problems: difficulty conceiving and pain. The pain may be present as extremely painful menstrual periods. In the presence of endometriosis, the pain with the periods, known as dysmenorrhea , often becomes worse as one gets older. Pain with intercourse is not uncommon in women with endometriosis, and there may even be pain that persists throughout the month but is worse during periods. Not everyone with endometriosis has pain; in fact, there is little correlation between the amount of endometriosis an individual has and the amount of pain she experiences. Sometimes a single, small implant may cause excruciating pain, while someone with severe disease may be pain free.

The association of endometriosis with difficulty conceiving has long been known, and research has demonstrated many different ways in which endometriosis interferes with normal conception. Endometrial implants are irritating to the body, and as a result of this, the body produces, among other things, a group of substances known as prostaglandins . Prostaglandins have been shown to alter not only the maturation and development of the egg within the ovary, but also the release of the egg from the ovary. The ability of the tube to function normally may also be impaired. Whereas in nature's way the tube is poised and ready to pick up an egg if one appears on the surface of the ovary, in the presence of endometriosis the tube may be A lazy or A floppy. Not only is the overall tone of the tube decreased, but the fimbria, which are responsible for egg pickup, may end up being very far from the ovary itself. The combination of these factors may make it very difficult for the tube to pick the egg up off the surface of the ovary. Thus, even if ovulation does occur, the egg may not get into the fallopian tube. Endometrial implants also result in the increased production and increased activation of a group of cells known as macrophages . Macrophages are part of the body's natural defense system and can be visualized as little A Pac-men, actively attacking and destroying any cells that they encounter. One of the groups of cells that macrophages attack and destroy more than normal in women with endometriosis are the sperm, thus making it more difficult for the sperm to reach and fertilize the egg. The macrophages may also interfere with tubal function, ovarian function, and perhaps even early embryo development. Finally, endometriosis produces other substances that may impair implantation. It is important to keep in mind the number and variety of ways endometriosis affects fertility, particularly when discussing the ways of treating endometriosis.

Diagnosing Endometriosis

It is not clear why endometriosis occurs in some individuals and not in others, but about ten to twenty percent of all reproductive-age females have been found to have endometriosis. In women with infertility, this number may be as high as thirty to fifty percent. Factors associated with the development of endometriosis include delayed childbearing, long periods of uninterrupted menstrual cycles, abnormal pelvic anatomy and stress. Many other factors have been associated with the development of endometriosis and there is even a genetic factor, meaning that one may inherit an increased likelihood of developing this process if a close relative has it.

The physician can often suspect endometriosis on the basis of a history and physical exam. A history of progressively worsening pain with the menstrual periods is suggestive. A history of cramping that begins two to three days before the onset of menstrual bleeding is also common with endometriosis, as is deep dyspareunia (pain with deep penetration at the time of intercourse). During the physical exam, the physician may be able to feel endometriosis, particularly if it is in the cul-de-sac. Endometriosis is not visible by ultrasound unless there is ovarian involvement; endometriomas are visible by ultrasound. If significant endometriosis is present, the combination of a history, pelvic exam and ultrasound will reveal it.

There are tremendous variations in the amount of endometriosis an individual may have. The American Society for Reproductive Medicine has developed a grading system for quantifying the amount of endometriosis present. While there are many limitations to this system of classification, it does provide a means for comparing the extent of endometriosis from patient to patient and may be useful in prognosticating about the chances of conceiving. The only way to definitively diagnose endometriosis is by visualizing the process at the time of surgery. At the time of laparoscopy, the surgeon notes the endometriosis present and any adhesions or scarring that may have formed as a result of the endometriosis. These findings are then recorded on the classification sheet and a score assigned. That score is then used to determine the grade of disease, ranging from mild to extensive.

Medical Therapies

Before discussing any form of medical therapy, it is important to stress that there is no medical therapy that cures endometriosis. All forms of medical therapy must be seen as means of temporarily suppressing the process only, not as ways of curing it.

Endometrial implants are dependent on cyclic hormonal function, such as occurs in a normal menstrual cycle. All forms of medical therapy are aimed at disrupting cyclic hormone production and creating a state in which the hormones are constant from day to day. When estrogen and progesterone are steady from day to day over a prolonged period of time, endometriosis typically does not progress, and may even regress. There are two normal physiological states in a woman's life during which her hormones are essentially constant from day to day C pregnancy and menopause. Medical therapies aim to simulate one of these states.

Pseudopregnancy

In the majority of women, endometriosis improves during pregnancy. During pregnancy, ovulation stops and relatively constant, high levels of estrogen and progesterone are present. One can simulate these high constant levels of hormones, or create a state of A pseudopregnancy, @ by the use of birth control pills. The birth control pills suppress ovulation and result in a steady state of relatively high hormone levels, just as is seen in pregnancy. To effect this pseudopregnancy, the pill must be taken continuously. In other words, a pill is taken every day without ever stopping for a week or without taking the A sugar pills @ at the end of the pack. Thus, no periods will occur because a hormonally active pill is being taken every day, and a steady hormone state is achieved. For women who can take the pill, this is a perfectly safe way to do so. Because of the balance of the hormones in the pill, the lining of the uterus does not build up while on continuous therapy, and if anything, it actually thins out. There is no need to have a period each month while on the pill. If the pill is being used to treat or suppress endometriosis, having a period each month will probably render the pill far less effective because of the bleeding and resulting changes in the endometrial implants.

Pseudomenopause

Suppressing Ovarian Function

There are basically two types of medications available for creating a state of pseudomenopause. The first of these is danocrine (Danazol). This is an attenuated, or altered, male hormone. When taken in adequate doses, it results in suppression of the ovaries such that they temporarily stop functioning. This combination of decreased female hormone levels and increased male hormone levels accounts for much of the effectiveness of danocrine in suppressing endometriosis. Danocrine has been around for years and for a long time was the most commonly used form of medical suppression. It does, however, have many unpleasant side effects, including menopausal symptoms such as hot flashes and vaginal dryness. In addition, side effects related to the fact that it is a derivative of a male hormone, such as weight gain, increased muscle mass, hirsutism (increased hair growth) and muscle cramps limit the acceptability of danocrine. With the availability of the GnRH agonists, danocrine is not widely used to treat endometriosis at this time.

Suppressing Pituitary Production

The GnRH agonists are a class of medications that can temporarily suppress the ability of the pituitary to produce LH and FSH. If the pituitary does not produce LH and FSH, the ovaries receive no stimulation and therefore stop producing hormones. Thus, once again, a temporary state of menopause is achieved. The most commonly used form of this therapy is the depo, or long-acting, form of leuprolide acetate, known as Depo-Lupron. An injection of this medication given once a month results in very effective suppression of the ovaries. The major side effects associated with this medication are menopause-related ones, specifically hot flashes and vaginal dryness. In some individuals, these side effects may be severe. Although it may somewhat limit the overall effectiveness of the therapy, small doses of estrogen may be administered along with the Depo-Lupron. A minimal dose of estrogen makes this therapy very tolerable for most individuals. If a small enough dose of estrogen is used, often the side effects can be eliminated without significantly compromising the effectiveness of the treatment.

Suppressing Estrogen Production

Letrozole (Femara) is one of a relatively new class of medications known as aromatase inhibitors. Aromatse is the enzyme that converts male hormones to female hormones. If this enzyme is inhibited, estrogen production is inhibited. Letrozole is apporved only for use in the treatment of postmenopausal women with breast cancer. It is approved for these women because it so effectively lowers estrogen production. In women with endometriosis, letrozole does the same thing - it inhibits estrogen production and without estrogen endometriosis can not progress. Letrozole has proven a very effective treatment for endometriosis, particularly when taken in conjunction with a low dose oral contraceptive.

Precautions in Using Suppressive Therapies

While on suppressive therapies, particularly those that induce pseudomenopause, it is important to take a good multivitamin as well as some calcium supplementation. The lack of estrogen does result in the potential for development of at least a small amount of osteoporosis, or thinning of the bones, while on this therapy. The calcium and vitamins help to minimize this potential sideeffect. However, because of the potential development of osteoporosis and other menopause-related side effects, the length of time that these therapies may be used is limited. Although circumstances may dictate special considerations for some individuals, six months of therapy is usually considered maximal.

All forms of suppressive therapy must be viewed as exactly that - a means of suppressing the endometriosis. The endometriosis will not, in the vast majority of cases, progress while on this therapy. In most cases it actually improves. Suppressive therapies do not, however, cure the endometriosis. Upon their discontinuation, normal menstrual function resumes and the endometrial implants, which had been suppressed, also begin to function and respond to the cyclic hormone changes. Often within a relatively brief period of time, the endometriosis is right back where it was before the treatment was begun. Suppressive therapies should be viewed only as ways of buying time. If you know you have endometriosis and want to get pregnant, but for one reason or another must postpone your attempts to do so for another six months, then suppressive therapy may be a great idea. Suppressive therapy does not improve one's chances of getting pregnant. There is no data to suggest that medical therapy results in improved chances of conceiving. This is also true regarding its use after surgery for endometriosis. Suppressive therapy after surgery for endometriosis does little if anything to improve one's chances of getting pregnant. It is a good way to buy some time during which the endometriosis will not get worse; it is not a good way to improve your chances of getting pregnant.

Surgical Treatments

The obvious goal of surgical therapy is the elimination of all the endometrial implants. There are many different techniques for surgically treating endometriosis, but there are two important principles that need to be stressed right from the beginning and that will be explained in more detail later: 1) rarely is a major surgical procedure indicated to treat endometriosis for purposes of increasing your chances of getting pregnant, and 2) if there is no alteration of normal anatomy as a result of scarring from endometriosis, surgery to eliminate the endometriosis may or may not significantly improve one's chances of getting pregnant.

For Treatment of Scarring and Associated Pain

Surgical therapy for endometriosis must be considered from the standpoint of the two major symptoms of endometriosis; that is, pain and infertility. Let's first deal with pain. As noted above, endometrial implants are small collections of blood surrounded by scarring. The progressive nature of these implants causes more blood to accumulate while the scarring around it increases, often causing severe pain. The surgical eradication of these implants is an excellent means of improving if not eliminating endometriosis-associated pain. Again, even a small single implant can cause severe pain and there is little correlation between the amount of endometriosis present and the amount of pain. Therefore, if the history and physical exam are suggestive enough, laparoscopy and destruction of any endometriosis encountered should be considered for the potential relief of pain.

Laparoscopy

Laparoscopy is a minor surgical procedure done under general anesthesia and usually performed on an outpatient basis. A small incision less than an inch long is made under the belly button and a telescopelike instrument is inserted. A small amount of carbon dioxide is placed in the abdominal cavity to allow the surgeon to see the abdominal and pelvic organs. One to three additional incisions less than a quarter inch may also be used to introduce additional instruments. Through the laparoscope, the surgeon should be able to treat all but the most severe cases of endometriosis. Full recovery usually takes only a few days. Major surgery is typically required only if there is significant involvement of the bowel with endometriosis.

Lasers

The means by which the endometrial implants are destroyed seems to be inconsequential. There are several different types of lasers available, including carbon dioxide, argon, KTP and YAG. One can also use electro-cautery. It doesn = t matter! All that is important is that the cells of the implant are destroyed without causing significant damage to the surrounding tissue. Surgical therapy for pain associated with endometriosis is often a very effective procedure and can result in a tremendous decrease in the amount of pain an individual experiences.

For Treatment of Infertility

Surgical therapy for endometriosis-associated infertility is an entirely different matter. If there is no significant alteration of normal pelvic anatomy as a result of scarring associated with endometriosis, there is debate as to whether or not a laparoscopy and treatment of the endometriosis improves the chances of conception. If one has less than moderate endometriosis according the classification depicted above, there is no benefit to doing a laparoscopy and destroying the lesions. How does one know how much endometriosis there is unless one does a laparoscopy to find out? First of all, the physician has done a pelvic exam, which will provide reliable information about pelvic anatomy. Secondly, the initial pelvic ultrasound has revealed whether or not there is an endometrioma present in the ovaries. It is very uncommon to have moderate endometriosis without some ovarian involvement that will be visible on ultrasound, or significant findings on the pelvic exam. Therefore, a good initial evaluation will allow a reliable determination of the potential extent of disease.

If there is ovarian involvement or significant scarring (adhesions) present, laparoscopic surgical intervention is warranted. Any endo-metrioma(s) can be removed from the ovaries, any adhesions cut and removed and all visible lesions destroyed. This can and should all be done through the laparoscope rather than with major surgery. Aside from the fact that recovery is much easier and quicker for a laparoscopy than for major surgery, studies have shown that the results achieved from laparoscopic treatment are every bit as good if not better than those achieved with major surgery. The technology and instrumentation necessary to perform thorough treatment for all but the most severe cases of endometriosis through the laparoscope are available. If you are going to have a laparoscopy to evaluate for the presence of endometriosis, ask your surgeon how she or he intends to treat it. Do not have major surgery to treat endometriosis unless it is determined to be very severe.

For many years, the data did not support laparoscopy for treating mild endometriosis. In 1998 Dr. Jarrett wrote the following: "There is no rationale for doing a laparoscopy to treat minimal or mild disease when dealing with endometriosis-associated infertility. Many studies have been done. All but one of these studies demonstrate that surgical treatment of mild endometriosis is not associated with any improvement in the chances of getting pregnant. This makes sense! You will recall that there are many mechanisms by which endometriosis impairs fertility. None of these are really altered by eliminating the endometrial implants. For example, if the endometriosis has altered the motility or ability of the fallopian tube to pick up an egg from the ovary, it is difficult to imagine that treating the implants will restore this function. The same is true for most of the other proposed mechanisms of endometriosis-associated infertility. There is ample evidence showing that the chances of getting pregnant with mild endometriosis are the same whether one pursues A expectant management (simple continued attempts at conceiving without any intervention) or has a laparoscopy to destroy the endometriosis. Couples with infertility associated with endometriosis without anatomic alteration should be treated and approached like couples with unexplained infertility, and this does not include doing a laparoscopy."

However, at this time new evidence has accumulated that may suggest that treating even mild endometriosis is warranted. This date demonstrates that successful conception in women with endometriosis is more likely is those women are suppressed for a couple of months prior to the IVF attempt with Lupron (see above). This is postulated to be a result of the suppression of some of the factors that prevent implantation. This data is compelling, and one could anticipate much the same effect, for a short period of time, folloiwng laparoscopic treatment of endometriosis.

Overall, the chances of successfully conceiving with endometriosis are inversely proportional to the extent of the disease: The worse the endometriosis is, the harder it becomes to get pregnant. Fortunately, truly severe endometriosis is uncommon. Exact percentages obviously are very individual, but with proper management and treatment, the vast majority of women with endometriosis will successfully conceive.

In the presence of significant anatomic alteration, i.e. scarring and adhesions as a result of endometrioisis, one should consider proceeding directly to In Vitro Fertilization. The alteration of normal anatomic relationships as a result of the scarring makes normal conception much more difficult. Furthermore, any time one attempts conception, particularly with the use of ovulation induction hormones and medicaitons, the resulting hormonal changes probably accelerate the progression of endometriosis. In the presence of less significant disease, more conservative approaches are warranted.