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      Endometriosis

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          Abstract

          Endometriosis is a common inflammatory disease characterized by the presence of tissue outside the uterus that resembles endometrium, mainly on pelvic organs and tissues. It affects ~5-10% of women in their reproductive years - translating to 176 million women worldwide - and is associated with pelvic pain and infertility. Diagnosis is reliably established only through surgical visualization with histological verification, although ovarian endometrioma and deep nodular forms of disease can be detected through ultrasonography and MRI. Retrograde menstruation is regarded as an important origin of the endometrial deposits, but other factors are involved, including a favourable endocrine and metabolic environment, epithelial-mesenchymal transition and altered immunity and inflammatory responses in genetically susceptible women. Current treatments are dictated by the primary indication (infertility or pelvic pain) and are limited to surgery and hormonal treatments and analgesics with many adverse effects that rarely provide long-term relief. Endometriosis substantially affects the quality of life of women and their families and imposes costs on society similar to those of other chronic conditions such as type 2 diabetes mellitus, Crohn's disease and rheumatoid arthritis. Future research must focus on understanding the pathogenesis, identifying disease subtypes, developing non-invasive diagnostic methods and targeting non-hormonal treatments that are acceptable to women who wish to conceive.

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          Most cited references 182

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          Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis.

          The identification of molecular differences in the endometrium of women with endometriosis is an important step toward understanding the pathogenesis of this condition and toward developing novel strategies for the treatment of associated infertility and pain. In this study, we conducted global gene expression analysis of endometrium from women with and without moderate/severe stage endometriosis and compared the gene expression signatures across various phases of the menstrual cycle. The transcriptome analysis revealed molecular dysregulation of the proliferative-to-secretory transition in endometrium of women with endometriosis. Paralleled gene expression analysis of endometrial specimens obtained during the early secretory phase demonstrated a signature of enhanced cellular survival and persistent expression of genes involved in DNA synthesis and cellular mitosis in the setting of endometriosis. Comparative gene expression analysis of progesterone-regulated genes in secretory phase endometrium confirmed the observation of attenuated progesterone response. Additionally, interesting candidate susceptibility genes were identified that may be associated with this disorder, including FOXO1A, MIG6, and CYP26A1. Collectively these findings provide a framework for further investigations on causality and mechanisms underlying attenuated progesterone response in endometrium of women with endometriosis.
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            Endometriosis and infertility: pathophysiology and management.

            Endometriosis and infertility are associated clinically. Medical and surgical treatments for endometriosis have different effects on a woman's chances of conception, either spontaneously or via assisted reproductive technologies (ART). Medical treatments for endometriosis are contraceptive. Data, mostly uncontrolled, indicate that surgery at any stage of endometriosis enhances the chances of natural conception. Criteria for non-removal of endometriomas are: bilateral cysts, history of past surgery, and altered ovarian reserve. Fears that surgery can alter ovarian function that is already compromised sparked a rule of no surgery before ART. Exceptions to this guidance are pain, hydrosalpinges, and very large endometriomas. Medical treatment-eg, 3-6 months of gonadotropin-releasing hormone analogues-improves the outcome of ART. When age, ovarian reserve, and male and tubal status permit, surgery should be considered immediately so that time is dedicated to attempts to conceive naturally. In other cases, the preference is for administration of gonadotropin-releasing hormone analogues before ART, and no surgery beforehand. The strategy of early surgery, however, seems counterintuitive because of beliefs that milder non-surgical options should be offered first and surgery last (only if initial treatment attempts fail). Weighing up the relative advantages of surgery, medical treatment and ART are the foundations for a global approach to infertility associated with endometriosis. Copyright 2010 Elsevier Ltd. All rights reserved.
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              High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis.

              Women with endometriosis may also have associated disorders related to autoimmune dysregulation or pain. This study examined whether the prevalence of autoimmune, chronic pain and fatigue and atopic disorders is higher in women with endometriosis than in the general female population. A cross-sectional survey was conducted in 1998 by the Endometriosis Association of 3680 USA members with surgically diagnosed endometriosis. Almost all responders had pain (99%), and many reported infertility (41%). Compared with published rates in the general USA female population, women with endometriosis had higher rates of hypothyroidism (9.6 versus 1.5%, P < 0.0001), fibromyalgia (5.9 versus 3.4%, P < 0.0001), chronic fatigue syndrome (4.6 versus 0.03%, P < 0.0001), rheumatoid arthritis (1.8 versus 1.2%, P = 0.001), systemic lupus erythematosus (0.8 versus 0.04%, P < 0.0001), Sjögren's syndrome (0.6 versus 0.03%, P < 0.0001) and multiple sclerosis (0.5 versus 0.07%, P < 0.0001), but not hyperthyroidism or diabetes. Allergies and asthma were more common among women with endometriosis alone (61%, P < 0.001 and 12%, P < 0.001 respectively) and highest in those with fibromyalgia or chronic fatigue syndrome (88%, P < 0.001 and 25%, P < 0.001 respectively) than in the USA female population (18%, P < 0.001 and 5%, P < 0.001 respectively). Hypothyroidism, fibromyalgia, chronic fatigue syndrome, autoimmune diseases, allergies and asthma are all significantly more common in women with endometriosis than in women in the general USA population.
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                Author and article information

                Journal
                Nature Reviews Disease Primers
                Nat Rev Dis Primers
                Springer Nature
                2056-676X
                December 2018
                July 19 2018
                December 2018
                : 4
                : 1
                Article
                10.1038/s41572-018-0008-5
                30026507
                © 2018

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