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All about Endometriosis

What is Endometriosis ?
Endometriosis is characterized by growth of tissue which normally lines the uterine cavity (endometrium), outside of the uterus. Endometriosis can involve 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. Since endometriosis is essentially a normal tissue growing in an abnormal location, it will undergo the same changes as the tissue of the uterine lining throughout the menstrual cycle. Just like the normal endometrium, the endometriosis tissue will build up in response to ovarian estrogen hormone, then break down and shed. Unlike the normal endometrium lining the uterine cavity, the tissue and blood from endometriosis can not leave the body through the vagina, resulting in internal bleeding, inflammation and further spread of the endometriosis.

How common is endometriosis?
Endometriosis occurs in 5-10% of reproductive-age women and in 40% of infertile women. Endometriosis can lead to infertility by causing pelvic adhesions, abnormal ovulation, and interference with the ability of the fallopian tube to pick up the egg from the ovary. Endometriosis may also be associated with increased risk of a miscarriage.

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

» Retrograde (reflux) menstruation or backflow of menstrual tissue 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.

» 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 suggests that endometriosis cells actually originate in the bone marrow, explaining unusual cases of endometriosis ocurring in organs outside the abdominal cavity (lungs or brain).

» Immunologic deficiency has been proposed to explain why some women are more susceptible to endometriosis than others.

» Endometriosis tissue produces its own estrogen, and may support its own growth.

» Hereditary cause – if one identical twin has endometriosis, the other twin has high probability of suffering from the same condition.
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 symptoms of endometriosis?
» Pelvic pain is the most common symptom occurring just prior to or during menses.

» Painful intercourse.

» Infertility.

» Nausea, vomiting, mood swings, fatigue and diarrhea.

» Acute pain when an ovarian endometriosis cyst (chocolate cyst or endometrioma) ruptures. This can mimic symptoms similar to appendicitis.

Diagnosis of endometriosis
» The only definitive way to diagnose endometriosis is by laparoscopy. Any endometriosis implant seen at laparoscopy can be treated at the same time utilizing CO2 laser, coagulation (burning) or resection (cutting away the endometriosis tissue) techniques.

» Sometimes the physician can feel nodules in the patient's pelvic structures which may be painful to touch and suggestive of endometriosis.

» An ultrasound may demonstrate an ovarian endometriosis cyst. MRI and CT scans have also been reported to be helpful tools for detecting endometriosis.   

» A blood test for CA-125 is often elevated in patients with endometriosis and can be used to monitor the progression of the disease or evaluate how effective the treatment is.

Stages of endometriosis                                   
Laparoscopy is utilized to diagnose, stage, and treat endometriosis. 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 (they are termed chocolate because they contain a thick brownish fluid, mostly old menstrual blood).

» Endometriosis can be classified as:

» Mild stage I endometriosis ( photo on the left)

» Intermediate endometriosis is usually classified as stage II or stage III.

» Severe stage IV disease (chocolate cyst seen in photo on the right)

How does endometriosis cause infertility?
The exact mechanism for infertility in women with endometriosis is not clearly understood. The following theories for infertility-related endometriosis have been proposed:

» Pelvic adhesions (scarring) - interfere with the release of eggs from the ovary or with the ability of tube to pick up the egg after its release from the ovary (tubal function).

» Ovulatory dysfunction – endometriosis may interfere with the normal process of egg development.

» Disorders of fertilization or sperm penetration into the egg

» Immunologic factors - production of antibodies to the lining of the uterus (endometrium), and interfering with the implantation of the embryo

» Impaired embryo development and implantation – associated with reduced level of an adhesive like molecule (beta integrin).

» Environmental factors – Dioxin, microwave cooking with plastics, pesticides and hormones in food have been implicated by several investigators.

Endometriosis treatment – what are the options?
Treatment options for endometriosis depend on whether the goal is to restore fertility or improve pain symptoms.

» Medical treatment

» Surgical treatment

Medical treatment of endometriosis
Medical treatment of endometriosis is used most often when there is a recurrence of the disease or post operatively to treat residual endometriosis - when it was not possible to remove all of the endometriosis tissues. 
So, if you have endometriosis and pain and you are not planning to conceive right away, several medications are available to treat your symptoms:

» Non-steroidal anti-inflammatory drugs (NSAID)

» Progesterone - counteracts the action of estrogen and inhibits the growth of endometriosis, providing effective pain control. The most common progesterone medication prescribed is Norethindrone starting at a dose of 5 mg daily. Side effects include depression and weight gain.

» Progesterone-releasing intrauterine device (IUD) or vaginal progesterone suppositories have been shown to be helpful for women seeking pain management.

» Continuous oral contraceptives - eliminating menstrual flow, and reducing the menstrual pain associated with endometriosis.

» Danazol - steroid with some male hormone activity. It inhibits the growth of endometriosis but may cause hirsutism.

» Gonadotropin-releasing hormone agonists (GnRH agonist) - such as, Lupron or Synarel, cause profound pituitary suppression of ovarian function or "chemical menopause". They induce unpleasant menopausal symptoms, and over time may lead to osteoporosis. To avoid such side effects, progesterone, such as Norethindrone 5 mg daily, is often prescribed for patients who require treatment with GnRH for more than 6 months (progesterone add back).

» Aromatase inhibitors (AI) – Aromatase Inhibitors block the production of estrogen and can cause regression of endometriosis in patients who did not respond to surgery. The advantage of this treatment is that it is simpler, cheaper and associated with fewer side effects (such as bone loss and hot flushes) as compared with Lupron. A promising medical therapy utilizing Aromatase Inhibitors such as Letrozole or Anastrozole in combination with Norethindrone Acetate or oral contraceptives is under evaluation.

» Another promising treatment involves taking progesterone antagonists such as Mifepristone 50 mg daily, which has been shown to decrease the growth of endometriosis and pain symptoms.

Surgical treatment of endometriosis - Laparoscopy
The goals of surgery are:
» Maintain or restore normal reproductive function – fertility preservation.
» Remove as much of the endometriosis tissue as possible without damaging normal tissue.
» Decrease or eliminate pain.
» Increase the likelihood of a successful pregnancy in infertile patients.
» Prevent progression of the disease.

Keep in mind that:
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 child birth 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.

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.
» If you have a chocolate cyst (endometrioma) which is causing severe pain. Although removal of chocolate cysts (cystectomy) improves pain symptoms, researchers are not sure yet whether the surgery also improves fertility. In fact, it is difficult to avoid removing healthy ovarian tissue during endometriosis surgery, and there is some concern that this may reduce the ovarian reserve   and affect future fertility.
» If there are contraindications to taking medications (side effect, allergies, blood clots, hypertension).
» If you have recurrent endometriosis and you are not trying to get pregnant soon, medical treatment of endometriosis is preferable to surgery.
Recent advances in computer assisted robotic laparoscopic technique   for the treatment of uterine fibroids may ultimately replace conventional laparoscopy for many other gynecologic conditions including endometriosis.

I have endometriosis and I want to conceive, what can I do?
If you have endometriosis and you are hoping to conceive soon, medical or surgical treatment may not be your best choice. You should be considering ovulation induction therapy   and IVF.
Gonadotropin and IUI treatment

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 normal day 3 FSH and estradiol levels.
» Your husband’s sperm count is normal.
» Your tubes are open.
» In Vitro Fertilization (IVF)
» IVF treatment has the highest success rates for patients with endometriosis-related infertility. Depending on your age, success rates range between 30-50%. Endometriosis has little effect on IVF success rates and surgical treatment of endometriosis before undergoing IVF is unnecessary.

You should consider IVF if:
» 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 day 3 FSH, estrogen or Clomiphene Challenge tests are abnormal, indicative of diminished ovarian reserve .
» You have severe endometriosis; conventional treatment is less likely to succeed.
» You have mild or moderate endometriosis and failed to conceive with conventional fertility treatment. 

Endometriosis and Infertility

Endometriosis, a cause of female infertility, is a condition in which endometrial tissue, the tissue that lines the inside of the uterus, grows outside the uterus and attaches to other organs in the abdominal cavity such as the ovaries and fallopian tubes. Endometriosis is a progressive disease that tends to get worse over time and can reoccur after treatment. Symptoms include painful menstrual periods, abnormal menstrual bleeding and pain during or after sexual intercourse.

Endometriosis infertility typically develops in women of reproductive age. Endometriosis is a common medical condition where the tissue lining the uterus (the endometrium, from endo, "inside", and metra, "womb") is found outside of the uterus, typically affecting other organs in the pelvis. The condition of endometriosis can lead to serious health problems, primarily pain and infertility. Endometriosis can affect any woman of reproductive age, from menarche to menopause, regardless of race, ethnicity, whether or not she has children, or socio-economic status. Most women with endometriosis are in their 20s and 30s. Endometriosis infertility can be treated successfully by female fertility specialists.

• Endometriosis causes pain in some women and can also cause infertility.
• 5-10% of all women have endometriosis. Most of these women are not infertile.
• 30-40% of infertile women have endometriosis.

Cause of Endometriosis

The cause of endometriosis is unknown though there are a few theories that suggest possible causes. One theory suggests that during menstruation, some of the menstrual tissue backs up through the fallopian tubes into the abdomen where it implants and grows. Another theory indicates that it is a genetic birth abnormality in which endometrial cells develop outside the uterus during fetal development.

Diagnosis of Endometriosis

A laparoscopy, an outpatient surgical procedure, is necessary to confirm a diagnosis of endometriosis after a medical history review and pelvic exam. After the initial diagnosis, your physician will classify your condition as stage 1 (minimal), stage 2 (mild), stage 3 (moderate) or stage 4 (extensive) based on the amount of scarring and diseased tissue found. Based on the stage of endometriosis, your physician will determine the best treatment plan for you which may include medication or surgery, or a combination of both.

Mild Endometriosis

Women with any stage of endometriosis (mild, moderate, or severe) can have severe lower abdominal and pelvic pain - or they might have no pain or symptoms whatsoever.
Although mild endometriosis is associated with infertility in some women, many fertile women also have mild endometriosis. A cause and effect relationship between mild endometriosis and infertility has not been established. It might be that infertility and delayed pregnancy predisposes women to developing endometriosis, rather than the endometriosis causing the infertility.

Severe Endometriosis

Severe endometriosis causes pelvic scarring and distortion of pelvic anatomy. The tubes can become damaged or blocked and the ovaries often contain cysts of endometriosis (endometriomas) and may become adherent to the uterus, bowel or pelvic side wall. Any of these anatomic distortions can result in infertility.

Treatment of endometriosis

Treatment for endometriosis associated with infertility needs to be individualized for each woman. There are no easy answers, and treatment decisions depend on factors such as the severity of the disease and its location in the pelvis, the age of the woman, length of infertility, and the presence of pain or other symptoms.