Prevalence and Origin

Endometriosis is a chronic condition that is characterized by the growth of functional endometrial glands and stroma outside of the uterine cavity. It is found in up to 10% of women of reproductive age and in as many as 25%-50% of women with infertility. The most widely held view to explain the underlying cause of endometriosis is Sampson’s theory which proposes that the retrograde flow of Endometrium through the Fallopian tubes leads to the deposition and growth of endometrial implants within the pelvis. However, up to 90% of women have been found via Laparoscopy to have retrograde menstrual flow, but not all develop endometriosis. This theory also fails to account for endometriosis in locations remote from the pelvis. Other potential origins of endometriosis include metaplasia of coelomic epithelial cells that line the peritoneal cavity, induction of the growth of endometrial cells from undifferentiated cells as a result of biochemical or immunologic factors, transformation of embryonic mullerian rest cells into endometrium caused by different endogenous stimuli, and hematogenous and lymphatic spread of endometrial tissue. Various lines of evidence lend support to each of these theories. Although no theory can account for all cases of endometriosis, the survival andImplantation of ectopic endometrial tissue appears to be dependent on alterations in the immune system, the presence of abnormal peritoneal proteins, as well as genetic and environmental influences. 4-8% of first degree relatives of women with endometriosis are also found to have the disorder.

Presentation

Women with endometriosis classically present with complaints of progressive dysmenorrhea, dyspareunia, irregular bleeding and cyclic pelvic pain, which may become chronic as the disease progresses. Occasionally, pain with urination or bowel movements may occur if the disease involves the bladder or bowel. Infertility is often found in women with endometriosis and may be the only symptom in some individuals.

Exactly how endometriosis impacts fertility is the subject of considerable debate and ongoing research. In moderate and severe (Stage III and IV) cases of endometriosis, distortion of the pelvic anatomy leading to mechanical barriers to fertility is likely to be an important mechanism. However, it is clear that even in Stage I and II (minimal and mild) disease when there is little, if any, distortion in the anatomy, fertility is still compromised. Using the current ASRM classification of endometriosis (ASRM 1996), the stage of disease does not correlate well with one’s chance of becoming pregnant following therapy.

Various studies have suggested that women with endometriosis have alterations in folliculogenesis, which may lead to poor Oocyte and Embryo quality. In addition, an increase in inflammatory cells and their products are elevated in women with endometriosis and might have a negative impact on the egg, the sperm or the embryo. Some studies have suggested that implantation may be reduced in women with endometriosis due to a lack of beta-3 integrin production. Beta-3 integrin is a cellular adhesion molecule that appears in the endometrium during the window of implantation and may be reduced, or deficient, in women with endometriosis. However, studies using embryos derived from donor oocytes, which are then transferred into women with endometriosis, fail to demonstrate a decrease in implantation rates. This suggests that it is the pelvic environment, possibly through its adverse impact on the gametes that has the predominant effect on fertility, and not uterine receptivity.

Diagnosis

The diagnosis of endometriosis is based on clinical suspicion, which can be confirmed only by surgical inspection and biopsy. In one study, a history of severe dysmenorrhea had a 78% positive predictive value, which increased to over 90%, when nodularity of the cul-de-sac on pelvic exam, was documented. Ultrasound may assist in the diagnosis of advanced disease, demonstrating the presence of endometriomas, which have a characteristic “ground-glass” appearance. MRI has been shown in some studies to have predictive values close to surgical intervention, especially when deep disease and endometriomas are present. Various serum markers including CA-125 and more recently, interleukin-6, have been found to be elevated in women with endometriosis, but their specificity and sensitivity to establish a diagnosis limit their clinical utility.

Treatment

Appropriate treatment of endometriosis depends on the severity of symptoms, the extent of disease, the woman’s age and her desire for pregnancy. Medical intervention with oral contraceptive pills, progestins, or GnRH agonists help to suppress Hormone levels and endometrial proliferation and may be effective in reducing symptoms associated with endometriosis. More recently, aromatase inhibitors and SERMS (selective estrogen receptor modulators) have been shown to reduce pain associated with endometriosis. However, these treatments do not appear to improve pregnancy rates following their use. In Stage I and II disease, laparoscopic removal or destruction of endometriosis is associated with a small, but significant increase in live birth rates. The data for Stage III and IV disease is less clear, but several studies suggest that surgery does increase the probability of pregnancy. Based on current data, the combination of medical therapy with surgery has not been shown to improve pregnancy rates.

The pregnancy rate per month (Cycle fecundity) appears to be reduced in women with untreated endometriosis. A 2 to 3-fold increase in cycle fecundity may be achieved using ovarian Stimulation (superovulation), with or without, insemination. Many studies have demonstrated that IVF success rates are not reduced in women with endometriosis vs. those undergoing treatment for other reasons. Because IVF success rates have continued to increase over the past decade, this approach will often maximize pregnancy rates in the shortest period of time and therefore, IVF may be the treatment of choice in women with infertility associated with endometriosis, especially in the later reproductive years. Removal of endometriomas does not appear to improve success with IVF and may damage the ovary, which ultimately, could compromise response to stimulation and lead to fewer recovered oocytes.

In summary, endometriosis is a common condition among women of reproductive age. Contrary to widespread belief, it is not always associated with symptoms of pain and may underlie seemingly “unexplained” infertility. While surgical treatment may improve live birth rates when compared to expectant management, other forms of fertility therapy are highly effective in achieving pregnancy. The best approach will vary based on the clinical situation, but the majority of couples will successfully conceive with treatment.