Endometriosis is a leading cause of infertility. It is a condition in which the uterine lining, the endometrium, grows outside the uterus on abdominal organs such as the ovaries, fallopian tubes, bowels and bladder. It is a progressive disease that tends to advance over time and can reoccur even after multiple treatments. The symptoms include pain during the menstrual period, pain during sexual intercourse and pain during bowel movements or urination.

The endometrial implants respond to hormonal stimulation throughout the menstrual cycle in the same fashion as the uterine lining. The lesions thicken during the menstrual cycle and shed like the normal lining inside the uterus causing bleeding within the abdomen. Consequently, since this cannot be discharged like the menstrual flow, it causes an immune reaction which eventually produces scar tissue. That scar tissue can modify the anatomical landmarks in the abdomen causing the fallopian tubes to be in an abnormal location, blocked or not in sync with the ovaries. The blood can also collect inside the ovary, causing an ovarian cyst, or “endometrioma” which can grow very large in size (4-5 inches or more). A byproduct of blood fills the endometrioma. It is brownish in appearance thus termed chocolate cyst fluid. Many times the ovarian cysts can interfere with ovulation or with the appropriate relationship with the tube.

The causes of endometriosis are unknown but there exists a few theories regarding its origin. One theory suggests that menstrual blood flows backward through the fallopian tubes. This retrograde travel provides access to the abdomen where the tissue implants and grows. Another theory proposes the transformation of normal tissue to endometriotic tissue.

DIAGNOSIS

Laparoscopic surgery is the definitive assessment for endometriosis. This procedure, performed on an outpatient basis, visually diagnoses endometriosis by inserting a small telescope inside the abdomen via a small incision underneath the umbilicus (belly button). With this procedure, the surgeon can quantitate the endometrial lesions and the amount of scar tissue (adhesions) and consequently can stage the patient. The presence of lesions on the bladder and the rectum can explain gastrointestinal or urinary symptoms. During this same procedure, the endometriosis can be removed by laser, heat or electro-coagulation. Even with the absence of macroscopic implants, biopsies have indicated the presence of microscopic endometriosis. Therefore, in some patients with severe unexplained chronic pelvic pain in which laparoscopy does not reveal a clear presence of endometriotic implants, random biopsies are taken from the abdomen and pelvis to diagnose the disease.

Laparoscopy has also been recommended for young women who have severe menstrual pain in the absence of other pathology and also in patients with chronic pelvic pain without any interest in fertility. Typically we perform laparoscopies during the first 10 days of the menstrual cycle to minimize the impact of vascular congestion in the pelvis. Additionally this will minimize the chance that the patient is inadvertently pregnant at time of surgery. We have seen patients who had prior laparoscopies without any diagnosis of endometriosis and after a thorough and very compulsive inspection of the pelvis and the abdomen the presence of endometriotic implants could be documented.

The serum marker CA 125 (cancer antigen 125) has been shown to be elevated in women with advanced stages of endometriosis. The levels vary between stages never reaching those usually detected in cases of ovarian cancer. However, multiple attempts to correlate the level of the abnormality of CA 125 to the stage of the disease have failed. Even moderate elevations of the cancer antigen have been seen in smokers, patients with ovarian cysts, and fibroids.

There are many forms in which endometriosis can present. Typical presentation is the presence of purple lesions that is indicative of old blood accumulation inside the tissue. Others include raspberry, pink and red lesions that can be found on multiple organs, vesicular, (clear lesions) and peritoneal defects, which are lapses in the integrity of the layer covering the abdomen (peritoneum).

Endometriosis can be classified based on the number of endometriotic implants and the number of pelvic adhesions. Based on the American Society for Reproductive Medicine there are four stages. Stage I (minimal), stage II (mild), stage III (moderate) and stage IV (extensive).

Interestingly, endometriosis is not confined to women but also has been diagnosed in men who have been treated with estrogen for prostate cancer.

The most common places for endometriosis in the abdomen include the fallopian tubes and the ovaries. The impact on the tubes can be distortion of the normal anatomy and severe restriction of the mobility of the tube to capture the oocyte when released.

PAIN AND SYMPTOMS:

Levels of Pain

Endometriosis has been described in patients who are asymptomatic. We have found an inverse relationship between the stage of the disease and the symptoms of the patients. Patients with advanced stage endometriosis (stage III and IV) were less symptomatic than patients with stages I and II. An explanation for these findings includes the reactivity of the immune system to the endometrial implants and the differences in the immediate response between patients.

Why some women will develop some significant amount of pain with little disease and others will have almost no pain with extensive disease has been the subject of many researchers. Immune system activity and the presence of many pain relay factors are currently under investigation.

What is the relationship between spontaneous miscarriage and endometriosis? The literature is fraught with controversies regarding this issue. There are some studies that suggest an association between repeated miscarriage and endometriosis. Some authors contribute miscarriage to the abnormal hormonal profile and hormonal environment in the pelvis and around the uterus at the time of implantation. Others suggest the presence of cytotoxic factors in the pelvic fluid, which are detrimental for maintenance of pregnancy, or the inadequate release of hormones (progesterone) by the ovary after ovulation.

ENDOMETRIOSIS AND INFERTILITY:

The presence of pelvic adhesions between the tube and the ovaries many times indicate endometriosis despite the fact that lesions cannot be found. If the ovary contains a large endometrioma (cyst containing endometriotic implants) then

Additionally the implants may produce factors that can interfere with local environmental conditions necessary for implantation and pregnancy.

This issue has been the subject of many controversies in the literature. Some researchers advocate a significant reduction in fertility in advanced stages such as stage III and IV endometriosis while others indicate the presence of subfertility (the need for intervention to achieve pregnancy) in early stages such as stage I and II.

The outcome of IVF in patients with endometriosis is also controversial. Some researchers (mainly from Australia) suggest a reduced pregnancy rate following IVF in patient’s with advanced stages, while others (in the US mainly) have not found an association between the two.

In our practice we believe that Endometriosis plays a significant role in infertility. Since some reports have indicated that prior treatment of advanced stages of endometriosis can improve the pregnancy rate after IVF, we adopted this philosophy. We treat stage III and IV endometriosis with a course of Depo Lupron before undergoing IVF and embryo transfer.

TREATMENT:

Medical

The medical treatment for endometriosis includes GnRH agonist (Lupron), Danazol and continous oral contraceptive. Depo Lupron is a chemical that binds to GnRH receptors in the pituitary gland in the brain and stops the induction of the menstrual cycle by the central nervous system. The patient will be in a postmenopausal state as long as treatment continues. She will not have a period and she will have symptoms similar to patients during menopause. This includes the presence of hot flashes, mood swings, insomnia, difficulty to sleep, urinary and gastrointestinal symptoms, forgetfulness, memory problems, lack of energy and if used over a long period of time, weakening of the bones.

The GnRH agonist causes the endometrial implants to be thin and atrophic (inactive) however this outcome is only temporary and once the normal menstrual cycles resume, “feeding “of the endometriotic implants by the natural hormones responsible for the menstrual cycle can cause resumption of endometriotic growth and activity and over time to recurrent symptoms. As expected such treatment with GnRH is successful only on a temporary basis, usually no more than 6 months. In some occasions we give a small amount of estrogen to counteract the impact of postmenopausal symptoms and which subsequnetly counteracts the effect of GnRH agonist in women treated for a longer period of time.

It has been shown that about 2/3 of the patients will have almost the same amount of endometriosis symptoms and implants 18 months after cessation of treatment.

Danazol is a weak androgen (male hormone) has the similar effects in stopping the menstrual cycle and causes atrophy of the endometriotic implants. Unfortunately the drug has many side effects that include excess hair growth, deepening of the voice, and excessive weight gain as expected from the use of male hormone like substance.

The use of continuous oral contraceptive (pseudopregnancy) or the presence of pregnancy is well known to be associated with concomitant high levels of both estrogen and progesterone. This in turn induces atrophy of the endometriotic implants. Unfortunately this treatment may cause many side effects such as increase in weight gain, bloating, breast tenderness and mood swings. Some patients will abandon oral contraceptive use because they prefer the symptoms of endometriosis rather than the outcome of the treatment.

In Europe, treatment for endometriosis includes, Gestrinone which is a synthetic form of natural progesterone which causes the same effect as Danazol and the GnRH agonist. Because of significant side effects this treatment has never been approved in the US.

As mentioned in the diagnosis, laparoscopy with either laser or electro-coagulation has been found to be very successful in women with endometriosis. The treatment not only decreases the number of implants and reduces the presence of scar tissue but also is successful especially in cases where endometriomas (cyst in the ovary composed of a breakdown of blood product) are present. This procedure can restore the normal anatomy of the pelvis and consequently result in pregnancy. Interestingly, many pregnancies occur immediately during the first 3-6 months after surgery. Drainage of ovarian cyst or simple lasering of the superficial aspect of endometriotic implants is insufficient. The eradication of the endometriotic implants itself in different locations such as the tubes, ovaries or the bladder is more important.

Many researchers have described various treatments of endometriosis on the bowel including removing loops of bowel that are affected by endometriosis beyond the superficial layer. Some patients respond extremely well to this treatment modality, however many patients had recurrence of endometriosis in other places in their abdomen underscoring the importance that many factors are responsible for the induction of endometriosis.

About 5% of women have been described to redevelop endometriosis after the removal of the tubes, ovaries and uterus. As retrograde transport of endometrial tissue would not be the source of the new implants, the theory that normal tissue transforms to endometriotic tissue would appear credible.

ADENOMYOSIS

Adenomyosis is endometriosis inside the muscle of the uterus itself (adeno means gland and myosis means muscle). The presence of the endometrial lining inside the wall of the uterus (internal endometriosis) can have a major impact on the size of the uterus, the ability to get pregnant and to maintain the pregnancy, and on abnormal menstrual bleeding and chronic pelvic pain. Many patients complain about irregular menstrual bleeding, chronic pelvic pain, repeated miscarriages and an enlargement of the uterus, which can mimic the presence of fibroids. The presence of adenomyosis is diagnosed today via MRI where the thickness of the muscle is measured in different locations of the uterus and compared to the normal uterine wall. The treatment for this condition is controversial. Temporary relief via hormonal treatment with Depo Lupron is an option, but unfortunately, no surgical treatment is available.

In our practice when we diagnose with adenomyosis and the patient has a history of repeated miscarriage, we treat her with 3-6 months of Depo Lupron to reduce the amount of implants inside the wall of the uterus. We then proceed with infertility therapy, either via IVF or some other measures. This method has seen successful to assist many of our patients in conceiving and maintaining their pregnancies.

Endometriosis is a familial and common disease in women of reproductive age who are seeking fertility and in women who have chronic pelvic pain. The precise diagnosis of endometriosis can be done only via a surgical procedure called laparoscopy. During the time of diagnosis, treatment of the endometriotic implants can be accomplished, excision of scar tissue and reconstructive surgery of the pelvis can be performed and the resumption of the normal pelvic environment can be established. A combination of surgical and medical treatment is important in the long-term eradication of advanced endometriosis.

The medical treatment following surgical therapy is complimentary in many patients and it results in significant long-term disease-free status. The impact of endometriosis on fertility, repeated pregnancy losses and abnormal ovulation has been very well known. It is controversial whether early stages of endometriosis affect infertility or subfertility and whether the treatment of severe endometriosis before procedures such as IVF is warranted in order to increase the chances for fertility outcome. It is our belief that endometriosis is a treatable disease. Many patients are happy to know that their symptoms are derived from a real condition and not an imaginary disease.