Endometriosis

What is endometriosis?

Endometriosis was first described over 300 years ago. It is a chronic and progressive inflammatory disease that is highly estrogen-dependent. Endometriosis is often associated with debilitating pelvic pain and infertility. It causes pelvic inflammation, tubal or ovarian scarring, abnormal ovulation, and interference with the ability of the fallopian tube to pick up the egg from the ovary. Endometriosis affects 5-10% of reproductive-age women and 40% of infertile women. 

The word endometriosis derives from the word “endometrium” which refers to the lining of the uterus. Endometriosis is characterized by growth of normal endometrium (uterine lining), in an abnormal location outside of the uterus, such as the ovaries, fallopian tubes, bladder, bowel, vagina and skin surgical incision scars. On rare occasions, the tissue can even implant in more distant organs such as the lung.

Just like the normal endometrium, the endometriosis tissue is also stimulated by ovarian estrogen hormone. During menstruation, the endometriosis tissue within the pelvic cavity also breaks down and bleeds. Menstruation from endometriosis lesions within the pelvic cavity has no outlet, and cannot leave the body through the vagina, resulting in internal bleeding, inflammation and further spread of the endometriosis.

Endometriosis is most common in reproductive age women and improves with menopause when the ovary stops producing ovarian estrogen.

Interestingly, endometriosis tissue has been shown to produce its own estrogen, and may support its own growth. This may explain reports of endometriosis in postmenopausal women without increased estrogen levels.

What are the risks of endometriosis?

• In addition to pain and infertility, patients with endometriosis have 2-3 times the risk of ovarian cancer compared with patients with no history of endometriosis.
• Endometriosis may also be associated with pregnancy complications such as increased risk of a miscarriage, gestational hypertension, intrauterine growth retardation (IUGR) and Placenta Previa (placenta covering the cervix).

What is the cause of endometriosis?

The exact cause of endometriosis is unknown, but several theories have been proposed to explain the origin of endometriosis:

• Retrograde (reflux) menstruation: Sampson in 1927 was the first to propose that endometriosis is caused by backflow of menstrual fluid, containing live cells, from the uterus, through the fallopian tubes, into the abdominal cavity. The backflow of menstrual tissue may be caused by narrowing of the cervix which forces the tissue to flow in the opposite direction during menses.
• Genetic and hereditary cause: Hereditary factors are estimated to account for 50% of endometriosis. The risk of developing endometriosis is 10% higher in first-degree relatives of women with endometriosis. If one identical twin has endometriosis, the other twin has high probability of suffering from the same condition.
• Coelomic metaplasia: This theory holds that certain primitive cells within the abdominal cavity change (differentiate) into cells that are normally found lining the uterine cavity (endometrial cells).
• Stem Cell theory of endometriosis: This theory suggests that endometriosis cells actually originate in the bone marrow, explaining unusual cases of endometriosis occurring in organs outside the abdominal cavity (lungs or brain).
• Alterations to the immune system: Inflammation caused by endometriosis results in defective immune response that normally eliminates the menstrual debris from the pelvic cavity and promotes the implantation and growth of endometrial tissue inside the abdomen. Immunologic deficiency has been proposed to explain why some women are more susceptible to endometriosis than others.
• Genetic/epigenetic theory: Lifestyle factors such as nutrition, behavior, stress, physical activity, working habits, smoking and alcohol consumption can modify gene expression responsible for endometriosis.
• Oxidative stress and environmental factors: Other factors may increase risk of endometriosis. Most experts believe that a combination of some or all of the above mechanisms may explain why endometriosis occurs in some women while sparing others.

What are the most common symptoms of endometriosis?

The most common symptoms of endometriosis are pain, infertility and systemic symptoms. Endometriosis pain is often cyclical and is characterized as sharp, shooting or knifelike stabbing. It usually occurs in the lower abdomen before and during menstruation. Endometriosis may also be associated with painful sexual intercourse, painful bowel movements and painful urination.

Endometriosis is far more than just a lesion in the pelvis. Endometriosis stem cells travel throughout the body and may contribute to the distant effects of the disease. 

Systemic manifestations of endometriosis include:

• Fatigue is reported in 50% of women diagnosed with endometriosis
• Hypersensitivity to pain: The brain is altered leading to increased pain perception and migraines (Central sensitization)
• Depression and anxiety
• Altered metabolism: Endometriosis may cause metabolic changes that can decrease body mass index and lower average body weight.

Why is endometriosis so painful?

There are 3 main theories for pain in patients with endometriosis:

• Cytokines are proteins produced by specialized cells called macrophages in patients with endometriosis. The cytokinins regulate the inflammatory reactions which cause the pain in endometriosis patients.
• Bleeding from endometriosis implants in the abdominal cavity cause irritation and pain
• Irritation or direct invasion of pelvic nerves by endometriotic implants

Diagnosis of Endometriosis

Precise diagnosis of endometriosis is quite challenging since cyclical pain does not always indicate endometriosis. Pelvic pain, which is the most common symptom of endometriosis, can also result from other gynecologic conditions, such as pelvic infection, pelvic scar tissue, fibroids or ovarian cysts.

Pelvic pain mimicking endometriosis pain can also occur with non-gynecological conditions such Irritable Bowel Syndrome, bladder inflammation and Fibromyalgia.

Another important point is that the intensity and character of the pain associated with endometriosis rarely correlate with the severity of disease.

Evaluation for endometriosis include the following steps:

• Pelvic examination: It is notoriously inaccurate in estimating the severity of endometriosis. Sometimes the physician can feel nodules in the patient’s pelvic structures which may be painful to touch and suggestive of endometriosis.
• Ultrasound, and MRI imaging: Imaging may demonstrate ovarian endometriosis cyst but they do not improve the diagnostic accuracy of endometriosis.
• Blood tests: A CA-125 blood test may be elevated in patients with endometriosis and can be used to monitor the progression of the disease or evaluate how effective the treatment is.
• Ovarian reserve assessment: Surgical treatment of endometriosis often adversely affects the ovarian reserve especially when ovarian endometriosis cysts are removed. It is therefore important to obtain baseline Day 3 FSH, estrogen and AMH levels and an ultrasound to count the number of follicles in the ovaries (antral Follicle Count or AFC), before considering surgical or medical treatment of endometriosis.
• Laparoscopy: The only definitive way to diagnose and stage endometriosis is by laparoscopy. Endometriosis tissue may appear as dark blue, powder-burn black, red or white implants involving the pelvic organs, and intra-abdominal areas. Larger lesions may be seen within the ovaries as endometriomas or chocolate cysts containing thick brownish fluid, representing old menstrual blood. Surgical treatment of active endometriosis during laparoscopy often utilizes CO2 laser, coagulation (burning) or excision techniques.

How does endometriosis cause infertility?

The exact mechanism for infertility in women with endometriosis is not clearly understood, however infertility with endometriosis may be attributed to several factors:

• Endometriosis may interfere with the normal process of egg development and ovulation
• Pelvic inflammation may also cause poor egg quality or embryo development and interfere with embryo implantation
• Progressive reduction in egg number (diminished ovarian reserve), which may result in a poor reproductive outcome even with in vitro fertilization (IVF)
• Pelvic inflammation associated with endometriosis may result in pelvic scar tissue. Scar tissue may interfere with the release of eggs from the ovary or with the ability of the fallopian tube to pick up the egg after ovulation
• Endometriosis may adversely affect fertilization or sperm penetration into the egg.
• Endometriosis is associated with immunologic alterations such as antibodies to the lining of the uterus (endometrium), which may interfere with implantation of the embryo
• Impaired embryo development and implantation – associated with reduced level of an adhesive like molecule (beta integrin)

Treatment of Endometriosis

Treatment options for endometriosis largely depend on whether the goal is to restore or preserve fertility or simply to improve pain symptoms.

Treatment options for endometriosis include:

• Surgery
• Medical suppression of endometriosis
• In Vitro Fertilization (IVF)
• Fertility Preservation (egg or embryo freezing)

Surgical Treatment of Endometriosis

You are a candidate for laparoscopic surgery if:

• You are experiencing undiagnosed pelvic pain or infertility. Any endometriosis tissue seen during diagnostic laparoscopy can be treated at the same time with CO2 laser or coagulation.
• There are contraindications to taking medications (side effects, allergies, blood clots, hypertension).
• You have recurrent endometriosis and you are not trying to get pregnant soon, medical treatment of endometriosis is preferable to surgery.

The goals of surgical treatment of endometriosis include the following considerations:

• Fertility preservation– Maintain or restore normal reproductive function.
• Remove as much of the endometriosis tissue as possible without damaging normal tissue
• Decrease or eliminate pain

Key points to keep in mind:

• There is no cure for endometriosis
• Almost 50% of patients having laparoscopic removal of endometriosis will have recurrent pain symptoms within a year
• Surgery may result in more pelvic adhesions, increased pain and infertility
• Pregnancy and childbirth may slow the progression of endometriosis
• Hysterectomy and removal of the ovaries may be an option for women who have completed their family, but even then, there is no guarantee that endometriosis and pain will not recur.

Medical Suppression of Endometriosis

The goals of medical treatment are to reduce pain of endometriosis and protect your fertility. The most common medications utilized to treat endometriosis include:

• Oral Contraceptives: Combined oral contraceptives containing estrogen and progesterone, have historically been the first option. They prevent ovulation and reduce menstrual blood flow.
• Progesterone: For some patients, progesterone alone seems to work better than alternative endometriosis treatment options.
• Oral pituitary suppression: Oral GnRH antagonists, such as Elagolix, have emerged as a potential alternative to oral contraceptive therapy. The medication is taken orally once or twice daily and has been shown to be highly effective for treating endometriosis.

I have endometriosis and I want to conceive. What are my options?

Ovulation stimulation (Clomid or Letrozole) with Intrauterine Insemination (IUI)

The treatment may be appropriate for you If:

• You have minimal endometriosis and you are not ready yet for IVF. Pregnancy rates for patients with endometriosis average about 15% per cycle.
• You are under 40 and you have a normal ovarian reserve.
• Your husband’s sperm count is normal.
• Your fallopian tubes are open.

In Vitro Fertilization (IVF)

Even mild cases of endometriosis can negatively impact egg development and fertilization. It can lower embryo implantation and pregnancy rates and increase miscarriage rate. This may be due to a heightened inflammatory response or autoimmune factors with endometriosis.

You should consider IVF if:

• You have mild or moderate endometriosis and failed to conceive with conventional fertility treatment.
• You have severe endometriosis since conventional treatment is less likely to succeed.
• You have endometriosis and there is an additional infertility factor such as tubal or male factors.
• You are over 40. Regardless of the severity of endometriosis, time is of the essence; your eggs are deteriorating at a faster rate and you need an aggressive treatment to help you conceive without further delay.
• Your egg count or AFC and AMH level indicate diminished ovarian reserve.

Egg Freezing

When to consider egg freezing:

• In young patients with severe endometriosis, especially those with ovarian chocolate cysts, egg freezing is a valid treatment option to protect their fertility before undergoing extensive surgery. Such surgery may compromise the ovarian reserve by decreasing the quantity of eggs remaining in the ovary and increase risk of scar tissue and compromise future fertility.
• Women with male partners may consider embryo freezing if no immediate pregnancy is planned.