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Endometriosis: advances and controversies in classification, pathogenesis, diagnosis, and treatment.F1000Research 2019Endometriosis is an enigmatic disease that could start at birth. Its pathogenesis is supported by different theories. Accumulating facts relate it to a multigenic... (Review)
Review
Endometriosis is an enigmatic disease that could start at birth. Its pathogenesis is supported by different theories. Accumulating facts relate it to a multigenic disorder. In this review of recent publications, the principal symptoms of the disease, pain and infertility, as well as its pathogenesis, diagnosis, and classification will be addressed. Endometriosis presents three main variants: superficial peritoneal disease, deep infiltrating endometriosis, and ovarian endometriomas. The management of the disease, surgery, and medical and alternative therapies will be discussed. Special reference will be made to the quality of surgery and how to understand patients with endometriosis and endometriosis.
Topics: Dysmenorrhea; Endometriosis; Female; Humans; Infertility, Female; Laparoscopy
PubMed: 31069056
DOI: 10.12688/f1000research.14817.1 -
Nature Genetics Feb 2023Endometriosis is a common condition in women that causes chronic pain and infertility and is associated with an elevated risk of ovarian cancer. We profiled...
Endometriosis is a common condition in women that causes chronic pain and infertility and is associated with an elevated risk of ovarian cancer. We profiled transcriptomes of >370,000 individual cells from endometriomas (n = 8), endometriosis (n = 28), eutopic endometrium (n = 10), unaffected ovary (n = 4) and endometriosis-free peritoneum (n = 4), generating a cellular atlas of endometrial-type epithelial cells, stromal cells and microenvironmental cell populations across tissue sites. Cellular and molecular signatures of endometrial-type epithelium and stroma differed across tissue types, suggesting a role for cellular restructuring and transcriptional reprogramming in the disease. Epithelium, stroma and proximal mesothelial cells of endometriomas showed dysregulation of pro-inflammatory pathways and upregulation of complement proteins. Somatic ARID1A mutation in epithelial cells was associated with upregulation of pro-angiogenic and pro-lymphangiogenic factors and remodeling of the endothelial cell compartment, with enrichment of lymphatic endothelial cells. Finally, signatures of ciliated epithelial cells were enriched in ovarian cancers, reinforcing epidemiologic associations between these two diseases.
Topics: Humans; Female; Transcriptome; Endometriosis; Endothelial Cells; Epithelial Cells; Epithelium
PubMed: 36624343
DOI: 10.1038/s41588-022-01254-1 -
Best Practice & Research. Clinical... Aug 2018Available medical treatments for symptomatic endometriosis act by inhibiting ovulation, reducing serum oestradiol levels, and suppressing uterine blood flows. For this,... (Review)
Review
Available medical treatments for symptomatic endometriosis act by inhibiting ovulation, reducing serum oestradiol levels, and suppressing uterine blood flows. For this, several drugs can be used with a similar magnitude of effect, in terms of pain relief, independently of the mechanism of action. Conversely, safety, tolerability, and cost differ. Medications for endometriosis can be categorized into low-cost drugs including oral contraceptives (OCs) and most progestogens, and high-cost drugs including dienogest and GnRH agonists. As the individual response to different drugs is variable, a stepwise approach is suggested, starting with OCs or low-cost progestogens, and stepping up to high-cost drugs only in case of inefficacy or intolerance. OCs may be used in women with dysmenorrhea as their main complaint, and when only superficial peritoneal implants or ovarian endometriomas <5 cm are present, while progestogens should be preferred in women with severe deep dyspareunia and when infiltrating lesions are identified.
Topics: Chronic Pain; Contraceptives, Oral; Dysmenorrhea; Dyspareunia; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Progestins; Quality of Life; Randomized Controlled Trials as Topic; Severity of Illness Index
PubMed: 29530425
DOI: 10.1016/j.bpobgyn.2018.01.015 -
JBRA Assisted Reproduction Aug 2019Endometriosis is a highly prevalent disease among women of reproductive age and is frequently associated to infertility. However, the mechanisms underlying... (Review)
Review
Endometriosis is a highly prevalent disease among women of reproductive age and is frequently associated to infertility. However, the mechanisms underlying endometriosis-related infertility are still not completely known. Several studies have been conducted in order to elucidate this question. Besides anatomical changes that may impair gametes and embryo transport along the tubes; a smaller ovarian reserve due to advanced endometriosis and endometriomas; and a dysregulated hypothalamic-pituitary-ovarian axis, there are pieces of evidence suggesting that the peritoneal ectopic endometrial foci may induce a local inflammatory response, with the recruitment of macrophages, cytokine release, and reactive oxygen species generation, leading to a pro-oxidant peritoneal microenvironment. These alterations may be systemically reflected and also affect the follicular microenvironment. A harmful follicular fluid may disrupt cumulus cells functions and, consequently, compromise oocyte competence. There is also evidence suggesting that the peritoneal fluid of women with endometriosis may alter sperm function. Reduced endometrial receptivity is also pointed as a possible mechanism involved in endometriosis-related infertility, which needs further investigation.
Topics: Endometriosis; Female; Fertilization in Vitro; Humans; Infertility, Female; Molecular Diagnostic Techniques; Peritoneal Diseases; Transcriptome
PubMed: 31091056
DOI: 10.5935/1518-0557.20190029 -
Ultrasound in Obstetrics & Gynecology :... Sep 2016The IDEA (International Deep Endometriosis Analysis group) statement is a consensus opinion on terms, definitions and measurements that may be used to describe the...
Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group.
The IDEA (International Deep Endometriosis Analysis group) statement is a consensus opinion on terms, definitions and measurements that may be used to describe the sonographic features of the different phenotypes of endometriosis. Currently, it is difficult to compare results between published studies because authors use different terms when describing the same structures and anatomical locations. We hope that the terms and definitions suggested herein will be adopted in centers around the world. This would result in consistent use of nomenclature when describing the ultrasound location and extent of endometriosis. We believe that the standardization of terminology will allow meaningful comparisons between future studies in women with an ultrasound diagnosis of endometriosis and should facilitate multicenter research. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Consensus; Endometriosis; Female; Humans; Pelvis; Peritoneal Diseases; Practice Guidelines as Topic; Ultrasonography
PubMed: 27349699
DOI: 10.1002/uog.15955 -
Journal of Minimally Invasive Gynecology Nov 2021Different classification systems have been developed for endometriosis, using different definitions for the disease, the different subtypes, symptoms and treatments. In... (Review)
Review
OBJECTIVE
Different classification systems have been developed for endometriosis, using different definitions for the disease, the different subtypes, symptoms and treatments. In addition, an International Glossary on Infertility and Fertility Care has been published in 2017 by the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) in collaboration with other organisations. An international working group convened over the development of a classification or descriptive system for endometriosis. As a basis for such system, a terminology for endometriosis was considered a condition sine qua non. The aim of the current study was to develop a set of terms and definitions be prepared on endometriosis that would be the basis for standardization in disease description, classification and research.
DATA SOURCES
The working group listed a number of terms relevant to be included in the terminology, documented currently used and published definitions, and discussed and adapted them until consensus was reached within the working group. Following stakeholder review, further terms were added, and definitions further clarified. Although definitions were collected through published literature, the final set of terms and definitions is to be considered consensus-based. After finalization of the first draft, the members of the international societies and other stakeholders were consulted for feedback and comments, which lead to further adaptations.
METHODS OF STUDY SELECTION
na TABULATION, INTEGRATION, AND RESULTS: A list of 49 terms and definitions in the field of endometriosis is presented, including a definition for endometriosis and its subtypes, different locations, interventions, symptoms and outcomes. Endometriosis is defined as a disease characterized by the presence of endometrium-like epithelium and/or stroma outside the endometrium and myometrium, usually with an associated inflammatory process.
CONCLUSION
The current paper outlines a list of 49 terms and definitions in the field of endometriosis. The application of the defined terms aims to facilitate harmonization in endometriosis research and clinical practice. Future research may require further refinement of the presented definitions.
Topics: Consensus; Endometriosis; Female; Fertility Preservation; Humans; Infertility; Reproductive Techniques, Assisted
PubMed: 34690084
DOI: 10.1016/j.jmig.2021.08.032 -
International Journal of Environmental... May 2022Laparoscopic surgery was originally considered the gold standard in the treatment of endometriosis-related infertility. Assisted reproductive technology (ART) was... (Review)
Review
Laparoscopic surgery was originally considered the gold standard in the treatment of endometriosis-related infertility. Assisted reproductive technology (ART) was indicated as second-line treatment or in the case of male factor. The combined approach of surgery followed by ART proved to offer higher chances of pregnancy in infertile women with endometriosis. However, it was highlighted how pelvic surgery for endometriosis, especially in cases of ovarian endometriomas, could cause iatrogenic damage due to ovarian reserve loss, adhesion formation (scarring), and ischemic damage. Furthermore, in the last few years, the trend to delay the first childbirth, recent technological advances in ultrasound diagnosis, and technological progress in clinical and laboratory aspects of ART have certainly influenced the approach to infertility and endometriosis with, ART assuming a more relevant role. Management of endometriosis should take into account that the disease is chronic and involves the reproductive system. Consequently, treatment and counselling should aim to preserve the chances of pregnancy for the patient, even if it is not associated with infertility. This review will analyse the evolution of the management of infertility associated with endometriosis and propose an algorithm for treatment decision-making based on the most recent acquisitions.
Topics: Endometriosis; Female; Humans; Infertility, Female; Male; Ovarian Reserve; Pregnancy; Reproduction; Reproductive Techniques, Assisted
PubMed: 35627698
DOI: 10.3390/ijerph19106162 -
JBRA Assisted Reproduction Jan 2022This study aimed to assess the effect of endometrioma surgery on ovarian reserve by measuring anti-Müllerian hormone (AMH) levels. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to assess the effect of endometrioma surgery on ovarian reserve by measuring anti-Müllerian hormone (AMH) levels.
METHODS
This systematic review and meta-analysis included observational studies and randomized clinical trials published in English referenced in MEDLINE, SCOPUS and Cochrane (1982-2019). We included studies that reported AMH levels in the pre and post-operative period of patients undergoing laparoscopic surgery for endometrioma. Preoperative AMH was defined as the baseline AMH; short term AMH was measured no later than a month after surgery; medium term AMH was measured between one and six months after surgery; and long-term AMH was measured six or more months after surgery.
RESULTS
Thirty-six studies met the inclusion criteria. A significant decrease was observed in short, medium and long-term post-operative AMH levels when compared with baseline AMH. However, there were no differences between short and long-term post-operative AMH levels, suggesting a non-significant recovery after one year of follow-up. A significant decrease in post-operative AMH was observed in bilateral endometriomas compared with unilateral cases. In addition, patients with endometriomas presented a significant decline in post-operative AMH compared with patients with other benign ovarian conditions. The decrease in post-operative AMH was significantly greater in bilateral cystectomy when compared with vaporization with bipolar energy or laser. We also observed a greater decrease in post-operative AMH with bipolar energy hemostasis compared with suture and hemostatic agents. These results should be taken with caution due to the high heterogeneity of the studies analyzed.
CONCLUSIONS
Endometrioma surgery has a deleterious effect on short, medium, and long-term post-operative AMH levels. Bilateral endometriomas and endometriomas greater than 7 cm have been associated with greater decreases in AMH. The mechanical resection of healthy tissue and the inflammatory damage on the ovarian cortex might explain the diminishing of ovarian reserve.
Topics: Anti-Mullerian Hormone; Endometriosis; Female; Humans; Laparoscopy; Observational Studies as Topic; Ovarian Diseases; Ovarian Reserve
PubMed: 34755503
DOI: 10.5935/1518-0557.20210060 -
The Cochrane Database of Systematic... Feb 2016About 10% of women of reproductive age suffer from endometriosis. Endometriosis is a costly chronic disease that causes pelvic pain and subfertility. Laparoscopy, the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
About 10% of women of reproductive age suffer from endometriosis. Endometriosis is a costly chronic disease that causes pelvic pain and subfertility. Laparoscopy, the gold standard diagnostic test for endometriosis, is expensive and carries surgical risks. Currently, no non-invasive tests that can be used to accurately diagnose endometriosis are available in clinical practice. This is the first review of diagnostic test accuracy of imaging tests for endometriosis that uses Cochrane methods to provide an update on the rapidly expanding literature in this field.
OBJECTIVES
• To provide estimates of the diagnostic accuracy of imaging modalities for the diagnosis of pelvic endometriosis, ovarian endometriosis and deeply infiltrating endometriosis (DIE) versus surgical diagnosis as a reference standard.• To describe performance of imaging tests for mapping of deep endometriotic lesions in the pelvis at specific anatomical sites.Imaging tests were evaluated as replacement tests for diagnostic surgery and as triage tests that would assist decision making regarding diagnostic surgery for endometriosis.
SEARCH METHODS
We searched the following databases to 20 April 2015: MEDLINE, CENTRAL, EMBASE, CINAHL, PsycINFO, Web of Science, LILACS, OAIster, TRIP, ClinicalTrials.gov, MEDION, DARE, and PubMed. Searches were not restricted to a particular study design or language nor to specific publication dates. The search strategy incorporated words in the title, abstracts, text words across the record and medical subject headings (MeSH).
SELECTION CRITERIA
We considered published peer-reviewed cross-sectional studies and randomised controlled trials of any size that included prospectively recruited women of reproductive age suspected of having one or more of the following target conditions: endometrioma, pelvic endometriosis, DIE or endometriotic lesions at specific intrapelvic anatomical locations. We included studies that compared the diagnostic test accuracy of one or more imaging modalities versus findings of surgical visualisation of endometriotic lesions.
DATA COLLECTION AND ANALYSIS
Two review authors independently collected and performed a quality assessment of data from each study. For each imaging test, data were classified as positive or negative for surgical detection of endometriosis, and sensitivity and specificity estimates were calculated. If two or more tests were evaluated in the same cohort, each was considered as a separate data set. We used the bivariate model to obtain pooled estimates of sensitivity and specificity when sufficient data sets were available. Predetermined criteria for a clinically useful imaging test to replace diagnostic surgery included sensitivity ≥ 94% and specificity ≥ 79%. Criteria for triage tests were set at sensitivity ≥ 95% and specificity ≥ 50%, ruling out the diagnosis with a negative result (SnNout test - if sensitivity is high, a negative test rules out pathology) or at sensitivity ≥ 50% with specificity ≥ 95%, ruling in the diagnosis with a positive result (SpPin test - if specificity is high, a positive test rules in pathology).
MAIN RESULTS
We included 49 studies involving 4807 women: 13 studies evaluated pelvic endometriosis, 10 endometriomas and 15 DIE, and 33 studies addressed endometriosis at specific anatomical sites. Most studies were of poor methodological quality. The most studied modalities were transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI), with outcome measures commonly demonstrating diversity in diagnostic estimates; however, sources of heterogeneity could not be reliably determined. No imaging test met the criteria for a replacement or triage test for detecting pelvic endometriosis, albeit TVUS approached the criteria for a SpPin triage test. For endometrioma, TVUS (eight studies, 765 participants; sensitivity 0.93 (95% confidence interval (CI) 0.87, 0.99), specificity 0.96 (95% CI 0.92, 0.99)) qualified as a SpPin triage test and approached the criteria for a replacement and SnNout triage test, whereas MRI (three studies, 179 participants; sensitivity 0.95 (95% CI 0.90, 1.00), specificity 0.91 (95% CI 0.86, 0.97)) met the criteria for a replacement and SnNout triage test and approached the criteria for a SpPin test. For DIE, TVUS (nine studies, 12 data sets, 934 participants; sensitivity 0.79 (95% CI 0.69, 0.89) and specificity 0.94 (95% CI 0.88, 1.00)) approached the criteria for a SpPin triage test, and MRI (six studies, seven data sets, 266 participants; sensitivity 0.94 (95% CI 0.90, 0.97), specificity 0.77 (95% CI 0.44, 1.00)) approached the criteria for a replacement and SnNout triage test. Other imaging tests assessed in small individual studies could not be statistically evaluated.TVUS met the criteria for a SpPin triage test in mapping DIE to uterosacral ligaments, rectovaginal septum, vaginal wall, pouch of Douglas (POD) and rectosigmoid. MRI met the criteria for a SpPin triage test for POD and vaginal and rectosigmoid endometriosis. Transrectal ultrasonography (TRUS) might qualify as a SpPin triage test for rectosigmoid involvement but could not be adequately assessed for other anatomical sites because heterogeneous data were scant. Multi-detector computerised tomography enema (MDCT-e) displayed the highest diagnostic performance for rectosigmoid and other bowel endometriosis and met the criteria for both SpPin and SnNout triage tests, but studies were too few to provide meaningful results.Diagnostic accuracies were higher for TVUS with bowel preparation (TVUS-BP) and rectal water contrast (RWC-TVS) and for 3.0TMRI than for conventional methods, although the paucity of studies precluded statistical evaluation.
AUTHORS' CONCLUSIONS
None of the evaluated imaging modalities were able to detect overall pelvic endometriosis with enough accuracy that they would be suggested to replace surgery. Specifically for endometrioma, TVUS qualified as a SpPin triage test. MRI displayed sufficient accuracy to suggest utility as a replacement test, but the data were too scant to permit meaningful conclusions. TVUS could be used clinically to identify additional anatomical sites of DIE compared with MRI, thus facilitating preoperative planning. Rectosigmoid endometriosis was the only site that could be accurately mapped by using TVUS, TRUS, MRI or MDCT-e. Studies evaluating recent advances in imaging modalities such as TVUS-BP, RWC-TVS, 3.0TMRI and MDCT-e were observed to have high diagnostic accuracies but were too few to allow prudent evaluation of their diagnostic role. In view of the low quality of most of the included studies, the findings of this review should be interpreted with caution. Future well-designed diagnostic studies undertaken to compare imaging tests for diagnostic test accuracy and costs are recommended.
Topics: Chronic Disease; Cross-Sectional Studies; Diagnostic Imaging; Endometriosis; Female; Humans; Magnetic Resonance Imaging; Ovarian Diseases; Pelvis; Positron-Emission Tomography; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Ultrasonography
PubMed: 26919512
DOI: 10.1002/14651858.CD009591.pub2 -
Advances in Clinical and Experimental... Mar 2019An approach to ovarian endometrial cysts has changed considerably during recent years, especially in regard to treatment of recurrent endometriosis, fertility sparing... (Review)
Review
An approach to ovarian endometrial cysts has changed considerably during recent years, especially in regard to treatment of recurrent endometriosis, fertility sparing and infertility management. Surgical treatment is the primary therapeutic option. The most efficient types of treatment are radical procedures involving adhesiolysis, removal of the cyst along with its capsule and any remaining endometriotic foci. However, small asymptomatic cysts should not be treated surgically, especially in patients older than 35 years. Surgical treatment can be considered in infertile women and those who failed to get pregnant despite 1-1.5 years of trials, as well as in cases in which in vitro fertilization is not an option. Also large cysts, with more than 4 cm in diameter, should be treated surgically due to the risk of their rupture or torsion. The most efficient preventive measure for recurrent ovarian endometriosis is unilateral oophorectomy with sparing the contralateral ovary. Such a procedure should be considered in women who are no longer interested in childbearing or present with another endometriotic cyst in the same ovary. The role of pharmacotherapy is fairly limited; it should be considered in patients in whom diffuse endometriosis is associated with pain. Therapeutic agents from the following groups can be used: estrogen-progestin preparation, gestagens, including progesteronereleasing intrauterine systems and gonadotropin-releasing hormone agonists. Women with infertility should get pregnant as soon as possible, and in patients who failed to get pregnant and/or are older than 35 years, in vitro fertilization should be the treatment of choice.
Topics: Endometriosis; Endometrium; Female; Humans; Infertility, Female; Laparoscopy; Neoplasm Recurrence, Local; Ovarian Cysts; Ovariectomy; Pregnancy
PubMed: 30659784
DOI: 10.17219/acem/90767