**3. Classification**

The primary method of diagnosis is visualization of endometriotic lesions by laparoscopy, with or without histologic confirmation. Since the extent of endometriosis can vary widely between individuals, attempts have been made to develop a standardized classification to objectively assess the extent of endometriosis. Sampson, Acosta et al., and many other investigators developed staging systems that have all been criticized for multiple reasons,

associated with this disease, mainly with regard to the possible consequences on reproductive function and on the risk of developing gynecologic tumors, such as ovarian cancer (10-12). The prevalence in women without symptoms is 2-50%, depending on the diagnostic criteria used and the populations studied (9). The incidence of endometriosis is difficult to quantify, as women with the disease are often asymptomatic, and imaging modalities have low sensitivities for diagnosis. The primary method of diagnosis is laparoscopy, with or without biopsy for histologic diagnosis (13, 14). Using this standard, investigators have reported the annual incidence of surgically diagnosed endometriosis to be 1.6 cases per 1,000 women aged between 15 and 49 years. The incidence is 40-60% in women with dysmenorrhoea and 20-30% in women with subfertility. The severity of symptoms and the probability of diagnosis increase with age. The most common age of diagnosis is reported as around 40, although this figure came from a study in a cohort of

The clinical picture of endometriosis is widely heterogeneous. A correct diagnostic work-up of these patients can sometimes be very difficult, since there are a number of gynecological, intestinal and systemic diseases mimicking endometriosis, as well as other conditions that could be associated with or area consequence of this disorder. Therefore, multidisciplinary care should been courage to ensure correct evaluation and improve the management of

Although endometriosis was originally felt to be a disease only seen in women who had undergone a minimum of 5 years of ovulatory menstrual cycles, it is now well-documented that endometriosis can be seen as early as the premenarchal age group, in girls who have initiated thelarche (63). Prevalence is estimated to be 6–10% in the general female population and 35–50% of the patients experience pain and/or infertility. The prevalence in women without symptoms is 2-50%, depending on the diagnostic criteria used and the populations studied (9). The true incidence of endometriosis in adolescents is difficult to quantify and estimates vary among different studies. The incidence of endometriosis is difficult to quantify, as women with the disease are often asymptomatic, and imaging modalities have low sensitivities for diagnosis. Using this standard, investigators have reported the annual incidence of surgically diagnosed endometriosis to be 1.6 cases per 1,000 women aged between 15 and 49 years (64). The incidence is 40-60% in women with dysmenorrhoea and 20-30% in women with subfertility. According to the Endometriosis Association, 66% of adult women with endometriosis report the onset of pelvic symptoms before age 20, and those who seek care for symptoms as a teen see on average 4 or more physicians before

The primary method of diagnosis is visualization of endometriotic lesions by laparoscopy, with or without histologic confirmation. Since the extent of endometriosis can vary widely between individuals, attempts have been made to develop a standardized classification to objectively assess the extent of endometriosis. Sampson, Acosta et al., and many other investigators developed staging systems that have all been criticized for multiple reasons,

women attending a family planning clinic (15).

these patients (16).

**2. Prevalence** 

receiving a diagnosis (15).

**3. Classification** 

including their inability to predict clinical outcomes, especially pregnancy rates (PRs) in infertile patients. In 1979, the American Fertility Society (AFS) (now the American Society for Reproductive Medicine, or ASRM) first proposed a classification system. This was extensively evaluated, modified in 1985, and is still used today. Despite these revisions the currently used revised AFS system has serious limitations, including not effectively predicting the outcome of treatment.



The endometriosis fertility index (EFI) is a simple, robust, and validated clinical tool that predicts PRs for patients after surgical staging of endometriosis (see figure below). The EFI score ranges from 0–10, with 0 representing the poorest prognosis and 10 the best prognosis. Half of the points come from the historical factors and half from the surgical factors. Uterine abnormality was not included in the score. The EFI is very useful in developing treatment plans in infertile patients with endometriosis. The EFI is useful only for infertility patients who have had surgical staging of their disease. It is not intended to predict any aspect of endometriosis-associated pain. It is required that the male and female gametes are sufficiently functional to enable attempts at non-IVF conception. One factor found to predict pregnancy that is not included in the EFI is uterine abnormality. Sensitivity analysis showed that even with substantial variation in the assignment of functional scores the EFI varies very little (65).

Endometriosis 7

established. Two thirds of women with a diagnosis of endometriosis report having a family member with endometriosis. A large percentage of women with endometriosis have other co-morbidities such as fibromyalgia, chronic fatigue syndrome, hypothyroidism, allergies, asthma, and auto-immune disorders. The associated risk factors are directly related to low body mass index (BMI), and family history and are

The earliest and most widely accepted theory relates to retrograde menstruation through the fallopian tubes with subsequent dissemination of endometrial tissue within the peritoneal cavity. Sampson's theory of endometrial implantation, offered in the 1927, proposes that retrograde menstruation through the fallopian tubes was responsible for endometriotic lesions. Three prerequisites are necessary for Sampson's theory: (1) retrograde menstruation, (2) viability of menstrual endometrial cells, and (3) implantation of endometrial cells onto the peritoneal/ovarian surfaces (3). Since the introduction of his theory, retrograde menstruation has been confirmed at laparoscopy, and it appears to occur in the vast majority of women. Keettel and Stein in the 1950s demonstrated the viability of shed menstrual endometrial cells by invitro culture of menstrual endometrium (19). The viability of retrograde menstrual endometrium has been shown by Mungyer et al by culturing endometrial glands and stroma collected from peritoneal lavage (20). In addition to these invitro studies, Ridley and Edwards injected menstrual blood into the skin of women scheduled for a laparotomy in the next 3 to 6 months. On excision of this tissue, several women had endometriotic lesions at the injection site. Further circumstantial evidence supporting Sampson's theory is the increased risk of endometriosis in women with

Refluxed endometrial fragments adhere to and invade the peritoneal mesothelium and develop a blood supply, which leads to continued implant survival and growth. However, this theory fails to explain the presence of endometriosis in such remote areas outside the peritoneal cavity, as the lungs, skin, lymph nodes, and breasts. Moreover, the presence of the disease in early puberty and exceptionally also in newborns further contrasts the

The coelomic metaplasia theory claims that formation of endometriomas in the ovary or recto-vaginal endometriosis is caused by metaplasia of the coelomic epithelium, perhaps induced by environmental factors (23). Because the ovary and the progenitor of the endometrium, the müllerian ducts, are both derived from coelomic epithelium, metaplasia may explain the development of ovarian endometriosis. In addition, the theory has been extended to include the peritoneum because of the proliferative and differentiation potential

This theory would explain why most women have some degree of retrograde menstruation but only a little percentage has endometriosis and the presence of the disease in absence of menses. However, the absence of endometriosis in other tissues derived from coelomic

Mullerian anomalies and other outflow tract obstructions (21).

inversely related to exercise (18).

**5.2 Retrograde menstruation** 

validity of the theory (22).

**5.3 Coelomic metaplasia** 

of the peritoneal mesothelium.

epithelium argues against this theory (22).
