{"paper_id":"3437fffa-39cb-40f5-af3a-0504d7cfb0a9","body_text":"1 Background\nEndometriosis is a chronic inflammatory condition involving endometrial-like glands at extrauterine sites that was first described by Rokitansky and Cullen in the late 19th century.1 It is associated with early menarche, late menopause, and Mullerian anomalies.2 It carries a hereditary component with a 6-fold increased risk in women with an affected first degree relative.3 A multiple hit hypothesis has been proposed to account for the etiology of endometriosis. It notes that the pathological manifestations of this disease are attributable to the culmination of repetitive genetic and epigenetic insults accumulated throughout a woman's lifetime.1 Cyclic retrograde menstruation has been proposed as the initiating spark that sets a cascade in motion. Further propagating factors involve a hostile environment that repetitively induce epigenetic changes that transforms a single cell into a clonal, collective group of ectopic endometrial glands.1 These clonal cells exhibit erratic, self-propagating hormonal behavior that includes increases in aromatase, estrogen production, and in progesterone resistance all of which sustain the growth of these lesions.4 Modern theories negate old paradigms as new research unravels the roles of uterine and bone marrow circulating adult stem cells, the immune system, and the microbiome's manipulation of the terroir necessary for endometriosis to thrive.5\nEndometriosis has a significant impact on women's health and health care costs. Endometriosis affects 6–10 % of reproductive aged women and greater than 175 million women worldwide.6,7 It was estimated in 2012 that the economic burden of endometriosis in the U.S alone was more than $49 billion.8 Early diagnosis is key and research suggests that a misdiagnosis with inflammatory bowel syndrome (IBS) and pelvic inflammatory disease (PID) is common.9 Clinical symptoms include severe dysmenorrhea, dyspareunia, sub-fertility, abdominopelvic pain, heavy menstrual bleeding, and postcoital bleeding.9 Most women with endometriosis suffer physically and emotionally in their day-to-day function as a result of these painful symptoms. These symptoms are oftentimes improved with surgery. Alarmingly, studies have reported a long delay in the diagnosis of endometriosis of up to 10 years.10\nDelayed diagnosis is not the only issue that complicates therapeutic management of this disease. A contentious topic within endometriosis studies continues to be establishing a reliable staging system. It has been suggested that superficial, ovarian, and deep infiltrative endometriosis lesions are different manifestations of the disease and data from Saavalainen et al. suggests that the distribution of occurrence is 51 %, 44 %, and 5 %, respectively.11 The revised American Society for Reproductive Medicine (rASRM) classification is frequently used in research to communicate standardized findings among researchers at the time of surgery. However, the rASRM classification does not correlate well with pain or fertility outcomes and does not consider deeply infiltrating endometriosis (DIE) in all locations.12,13 Recently, the #ENZIAN classification has been proposed to describe deep infiltrative endometriosis, ovarian, and superficial endometriosis and may be a more comprehensive, correlative, and practical tool to study the disease and the intraoperative findings.14 Regardless of the staging system used, both systems point to a need to correlate surgical findings with clinical manifestations of this disease. This is needed to foster novel approaches that. improve therapeutic management of infertility, pain, and endometriosis.","source_license":"CC0","license_restricted":false}