*2.4. Clinical Presentation and Diagnostic Tools*

Endometriosis is difficult to diagnose for many reasons: lack of clear understanding of etiologic factors, diversity of hypotheses for pathogenesis, different clinical presentation of the disease, and existence of asymptomatic cases [62]. Careful patient interview including family history, detailed examination, and additional imaging work-up are required for diagnosis [63,64].

Most women diagnosed with endometriosis present with multiple diverse symptoms [25]. Commonly reported complaints include chronic pelvic pain, dysmenorrhea, dyspareunia, dyschezia, and infertility/subfertility [25,33,39].

Chronic pelvic pain accounts for 10% of outpatient gynecologic visits, while local pain or tenderness on pelvic examination is associated with pelvic disease in 97% of patients and with endometriosis in 66% of patients [65]. Dysmenorrhea and general pelvic pain are common symptoms of endometriosis, regardless of age at diagnosis [66]. Pelvic pain due to endometriosis is usually chronic (lasting ≥6 months) and is associated with dysmenorrhea (in 50 to 90% of cases), dyspareunia, deep pelvic pain, and lower abdominal pain with or without back and loin pain [65]. Most women experience pain of different severity: from mild or moderate pain (pain usually requiring medication) to severe pain (pain requiring medications and bed rest) during menses over the lifetime [66]. Pain in endometriosis has a complex mechanism. Increased systemic and local proinflammatory cytokines and growth factors due to the chronic inflammation in endometriosis contribute to the mechanism of chronic pain development through persistent noxious stimulation, chronic inflammation, and nerve injury, which will alter pain processing and result in central sensitization [25,62]. Surgical treatment in many cases increases central sensitization, and patients often report worsening of symptoms after surgery [25,67]. The severity of pain is often associated with the depth of endometriotic infiltration rather than the size of the lesion or cyst [25,62,68]. Dyspareunia is another common symptom that is closely related to pain and nerve sensitization [25].

Some patients may experience gastrointestinal (nausea and vomiting, more frequent bowel movements accompanying pelvic pain) and urinary (frequent urination when experiencing menstrual pain) symptoms [65,66].

Infertility and subfertility are other important issues related to endometriosis. In cases of severe and deep infiltrating endometriosis [22,33,69], the mechanism of infertility is the alteration of normal anatomy of the reproductive organs [25]. However, in cases of a small ectopic endometrial implants/lesions, the mechanism of infertility is not clear yet. The authors suggested an endometrial defect as the explanation of implantation impairment in endometriosis. This hypothesis is supported by numerous studies showing decreased expression of several biomarkers of implantation [25,69].

Following the key steps during the initial clinical examination in the diagnosis of women with endometriosis, imaging investigations should be done in order to confirm the condition. Some biological tests invented currently have little or no merit in the diagnosis of endometriosis, and no biomarker tests have been identified to be conclusive [26,62,70,71]. In contrast, imaging techniques led to substantial improvements in the diagnosis of endometriosis [25,62,72]. The most helpful tools are transvaginal ultrasound (TVUS) [73,74] and MRI [62,72]. In addition, sigmoid, ileocecal, and urological lesions can be detected with supplementary radiological techniques such as transrectal sonography (TRS), rectal endoscopic sonography (RES) [75,76], multidetector CT scan with retrograde colonic opacification and late urography, and/or uro-MRI [62,77]. However, a recent Cochrane meta-analysis reported inconclusive data from TRS and RES studies [77]. If using these methods, it is important to remember that TRS (5 MHz frequency) enables a limited analysis of the rectosigmoid colon, whereas RES (7.5–12 MHz) provides an overview of the whole sigmoid and rectosigmoid colon with higher spatial resolution [72].
