Currently, several endometriosis classification systems are available in clinical practice; however, no single classification system can predict the severity of all pre-and post-operative symptoms of endometriosis, such as pain, infertility and fibrosis. The aim of the present review was to reconcile the concepts of endometriosis classification and the molecular aspects of endometriosis. Each keyword alone or in combination was used to search by applying the filters of the title and the publication years between January, 2000 and December, 2019. Several classifications systems have been proposed to categorize the severity of endometriosis. The cause of pain is not only related to anatomic abnormalities, but also to the imbalance between sensory and sympathetic innervation due to the abnormal secretion of a variety of cytokines. Endometriosis-related infertility is a group of diseases manifesting with various morphological and functional abnormalities that negatively affect fertility. Diagnostic imaging, which primarily provides morphological information, has limitations as disease progression is not associated with the prevalence and severity of infertility. Changes in the microenvironment caused by endometriosis-induced inflammation and oxidative stress can lead to impaired fertility. In particular, proinflammatory mediators (cytokines, interleukins and immune dysfunction), oxidative stress markers (hemoglobin, heme, free iron, ROS and antioxidants), hormonal imbalance, proteolytic enzymes and soluble adhesion molecules all may be potential markers for predicting infertility. The major cell types involved in the development of endometriosis-associated fibrosis are platelets, various inflammatory cells, such as macrophages, T lymphocytes, B lymphocytes and natural killer (NK) cells, ectopic endometrial cells, and sensory nerve fibers. A variety of symptoms, such as pain, infertility and fibrosis, involve interrelated signaling mechanisms. Beyond the structural and functional changes that characterize a variety of symptoms, there may be interrelated, common signaling pathways. The present review highlights the molecular mechanisms involved in endometriosis-associated symptoms such as pain, infertility and fibrosis. In order to create a disease severity scoring system that can predict each symptom of endometriosis, not only anatomical findings, but also biochemical parameters, such as oxidative stress are required.
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