Article

World Endometriosis Society consensus on the classification of endometriosis

Authors:
  • World Endometriosis Research Foundation (WERF)
  • Stanford University School of Medicine
  • Endometriosis Centre Villach Dres. Keckstein
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Abstract

Study question: What is the global consensus on the classification of endometriosis that considers the views of women with endometriosis? Summary answer: We have produced an international consensus statement on the classification of endometriosis through systematic appraisal of evidence and a consensus process that included representatives of national and international, medical and non-medical societies, patient organizations, and companies with an interest in endometriosis. What is known already: Classification systems of endometriosis, developed by several professional organizations, traditionally have been based on lesion appearance, pelvic adhesions, and anatomic location of disease. One system predicts fertility outcome and none predicts pelvic pain, response to medications, disease recurrence, risks for associated disorders, quality of life measures, and other endpoints important to women and health care providers for guiding appropriate therapeutic options and prognosis. Study design, size, duration: A consensus meeting, in conjunction with pre- and post-meeting processes, was undertaken. Participants/materials, setting, methods: A consensus meeting was held on 30 April 2014 in conjunction with the World Endometriosis Society's 12th World Congress on Endometriosis. Rigorous pre- and post-meeting processes, involving 55 representatives of 29 national and international, medical and non-medical organizations from a range of disciplines, led to this consensus statement. Main results and the role of chance: A total of 28 consensus statements were made. Of all, 10 statements had unanimous consensus, however none of the statements was made without expression of a caveat about the strength of the statement or the statement itself. Two statements did not achieve majority consensus. The statements covered women's priorities, aspects of classification, impact of low resources, as well as all the major classification systems for endometriosis. Until better classification systems are developed, we propose a classification toolbox (that includes the revised American Society for Reproductive Medicine and, where appropriate, the Enzian and Endometriosis Fertility Index staging systems), that may be used by all surgeons in each case of surgery undertaken for women with endometriosis. We also propose wider use of the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project surgical and clinical data collection tools for research to improve classification of endometriosis in the future, of particular relevance when surgery is not undertaken. Limitations, reasons for caution: This consensus process differed from that of formal guideline development, although based on the same available evidence. A different group of international experts from those participating in this process may have yielded subtly different consensus statements. Wider implications of the findings: This is the first time that a large, global, consortium-representing 29 major stake-holding organizations, from 19 countries - has convened to systematically evaluate the best available evidence on the classification of endometriosis and reach consensus. In addition to 21 international medical organizations and companies, representatives from eight national endometriosis organizations were involved, including lay support groups, thus generating and including input from women who suffer from endometriosis in an endeavour to keep uppermost the goal of optimizing quality of life for women with endometriosis. Study funding/competing interests: The World Endometriosis Society convened and hosted the consensus meeting. Financial support for participants to attend the meeting was provided by the organizations that they represented. There was no other specific funding for this consensus process. Mauricio Abrao is an advisor to Bayer Pharma, and a consultant to AbbVie and AstraZeneca; G David Adamson is the Owner of Advanced Reproductive Care Inc and Ziva and a consultant to Bayer Pharma, Ferring, and AbbVie; Deborah Bush has received travel grants from Fisher & Paykel Healthcare and Bayer Pharmaceuticals; Linda Giudice is a consultant to AbbVie, Juniper Pharmaceutical, and NextGen Jane, holds research grant from the NIH, is site PI on a clinical trial sponsored by Bayer, and is a shareholder in Merck and Pfizer; Lone Hummelshoj is an unpaid consultant to AbbVie; Neil Johnson has received conference expenses from Bayer Pharma, Merck-Serono, and MSD, research funding from AbbVie, and is a consultant to Vifor Pharma and Guerbet; Jörg Keckstein has received a travel grant from AbbVie; Ludwig Kiesel is a consultant to Bayer Pharma, AbbVie, AstraZeneca, Gedeon Richter, and Shionogi, and holds a research grant from Bayer Pharma; Luk Rombauts is an advisor to MSD, Merck Serono, and Ferring, and a shareholder in Monash IVF. The following have declared that they have nothing to disclose: Kathy Sharpe Timms; Rulla Tamimi; Hugh Taylor. Trial registration number: N/A.

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... Laparoscopy provides the only reliable way to definitively diagnose endometriosis; however, it is not routinely performed because it involves surgery [11]. Several endometriosis classification systems have been developed, such as the American Society for Reproductive Medicine classification, the Enzian classification, the American Association of Gynecological Laparoscopists classification, and the classification based on the Endometriosis Fertility Index [12]; however, most were developed for use by health professionals [12,13]. A tool is needed to help patients perceive their symptoms as pathological and to make them feel suspicious of their condition. ...
... Laparoscopy provides the only reliable way to definitively diagnose endometriosis; however, it is not routinely performed because it involves surgery [11]. Several endometriosis classification systems have been developed, such as the American Society for Reproductive Medicine classification, the Enzian classification, the American Association of Gynecological Laparoscopists classification, and the classification based on the Endometriosis Fertility Index [12]; however, most were developed for use by health professionals [12,13]. A tool is needed to help patients perceive their symptoms as pathological and to make them feel suspicious of their condition. ...
Article
Objective: This study aimed to develop and verify an endometriosis self-assessment tool (ESAT). Methods: A non-experimental, descriptive, correlational study design was used. Candidate items were developed based on a conceptual framework constructed using the results of in-depth interviews and an integrative literature review. The construct validity of the developed tool was also examined. One-hundred and forty-two participants (117 patients with endometriosis and 25 patients without endometriosis) were included in the validity and reliability tests. The data were collected between August and December 2018. Nomological validity was verified based on significant correlations between the ESAT and the quality-of-life scores. Results: A 21-item ESAT was developed, and its construct validity was supported. Exploratory factor analysis indicated that the tool consisted of four components (gastrointestinal symptoms, dysmenorrhea, usual symptoms, and the amount and characteristics of menstrual bleeding) with a variance of 61.6%. The variance in quality-of-life scores, as explained by the ESAT scores, was relatively high. Receiver operator characteristics (ROC) curve analysis indicated that ESAT scores significantly differentiated endometriosis from non-endometriosis with fair discriminatory power at a cut-off score of 50 (sensitivity 0.76, specificity 0.72, area under the curve [AUC]>0.75 [P<0.001]). This means that patients with ESAT scores >50 points were more likely to have endometriosis. Thus, the reliability of the ESAT was confirmed. Conclusion: The devised tool appears valid and reliable. This tool may allow women to determine their risk of endometriosis by distinguishing between normal and pathological menstruation-related symptoms.
... Endometriosis is defined as the presence of endometrial-like tissue outside of the uterine cavity, commonly proliferating onto the peritoneum and abdominal organs. This causes chronic inflammation with the formation of adhesions and is associated with pelvic pain and infertility (1,2). Ovarian endometriosis (endometrioma, OEM), as one subtype of endometriosis, is formed by an intraovarian hematoma surrounded by ovarian cortex caused by recurrent ectopic endometrial hemorrhages and is present in up to 17%-44% of patients with endometriosis (3)(4)(5). ...
... For these patients, the main reason of infertility was diagnosed low sperm quantity and quality, abnormal chromosome, or sexual dysfunction of their husband. Simultaneously, patients from the OEM group underwent previous laparoscopic surgery for unilateral or bilateral ovarian endometriomas, with clear pathological diagnosis, and were classified as stage II-IV according to the World Endometriosis Society consensus on the classification of endometriosis (2). The detailed information about the distribution (bilaterally or unilaterally), location, and size of lesions of all OEM patients included in this study is listed in Supplementary Table S6. ...
Article
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The outcomes of in vitro fertilization (IVF) for endometriotic women are significantly worse than for patients without ovarian endometriosis (OEM), as shown by fewer retrieved oocytes. However, the exact pathophysiological mechanism is still unknown. Thus, we conducted a prospective study that analyzed mRNA and lncRNA transcriptome between granulosa cells (GCs) from patients with fewer retrieved oocytes due to OEM and GCs from controls with male factor (MF) infertility using an RNA sequencing approach. We found a group of significantly differentially expressed genes (DEGs), including NR5A2 , MAP3K5 , PGRMC2 , PRKAR2A , DEPTOR , ITGAV , KPNB1 , GPC6 , EIF3A , and SMC5 , which were validated to be upregulated and negatively correlated with retrieved oocyte numbers in GCs of patients with OEM, while DUSP1 demonstrated the opposite. The molecular functions of these DEGs were mainly enriched in pathways involving mitogen-activated protein kinase (MAPK) signaling, Wnt signaling, steroid hormone response, apoptosis, and cell junction. Furthermore, we performed lncRNA analysis and identified a group of differentially expressed known/novel lncRNAs that were co-expressed with the validated DEGs and correlated with retrieved oocyte numbers. Co-expression networks were constructed between the DEGs and known/novel lncRNAs. These distinctive molecular signatures uncovered in this study are involved in the pathological regulation of ovarian reserve dysfunction in OEM patients.
... The EFI has gained worldwide acceptance amongst reproductive surgeons and clinicians working with medically assisted reproduction. The World Endometriosis Society (WES) has supported its use to predict fertility after endometriosis surgery (Johnson et al., 2017) and the Consensus on Recording Deep Endometriosis Surgery (CORDES) statement suggests that EFI can be used to predict the probability of spontaneous conception after surgery for endometriosis (Vanhie et al., 2016). ...
... Furhermore, an Enzian C3 finding increased the risk of complications greater than Clavien-Dindo grade I 56.3 times (p < 0.001). Based on the above information, several guidelines suggest the use of the Enzian classification for desciption of endometriosis (Johnson et al., 2017;Ulrich et al., 2014;Ulrich et al., 2013;Vanhie et al., 2016). ...
Article
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Background: Endometriosis is a common benign gynaecological disease that affects pelvic structures and causes adhesions. Endometriosis outside the pelvis exists but is rarer. Deep endometriosis may affect organs such as the urinary bladder, ureters, bowel and sacral roots. Adenomyosis (growth of endometrium in the myometrium, sometimes explained by disruption of the uterine junctional zone) frequently co-exists with deep endometriosis. Over the past decades, multiple attempts have been made to describe the anatomical extent of endometriosis. Out of approximately 20 classification systems suggested and published so far, three have gained widespread acceptance. These are the rASRM (American Society of Reproductive Medicine) classification, the Endometriosis Fertility Index (EFI) and the Enzian classification. Ideally, a classification system should be useful both for describing disease extent based on surgical findings and results of imaging methods (ultrasound, magnetic resonance imaging). Objectives: To highlight the advantages and disadvantages of the three classification systems. Methods: This is a narrative review based on selected publications and experience of the authors. We discuss the current literature on the use of the rASRM, EFI and Enzian classification systems for describing disease extent with imaging methods and for prediction of fertility, surgical complexity, and risk of surgical complications. We underline the need for one universally acceptable terminology to describe the extent of endometriosis. Conclusions: A useful classification system for endometriosis should describe the sites and extent of the disease, be related to surgical complexity and to disease-associated symptoms, including subfertility and should satisfy needs of both, imaging specialists for pre-operative classification and surgeons. The need for such a system is obvious and is provided by the #Enzian classification. Future research is necessary to test its validity.
... To be able to facilitate these relations, a standardized MRI reporting system is crucial. Classi cation of endometriosis is complicated, and in 2014, the World Endometriosis Society proposed a classi cation toolbox that includes the rASRM classi cation, the ENZIAN classi cation, and the Endometriosis Fertility Index (EFI) [7]. However, using multiple classi cations in daily practice is not practical and may not be used effectively. ...
... In contrast to the rectosigmoid region, compartment C does not involve the sigmoid colon. A meta-analysis evaluating both rectum and sigmoid colon lesions reported 83% sensitivity and 88% speci city [7]. Two other studies evaluated MRI accuracy of DIE lesions using the revised ENZIAN score, and both reported 86% sensitivity in compartment C. Speci cities of the compartment C in these studies were reported as 98% [12] and 89% [10]. ...
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Purpose The aim of this study is to investigate the correlation between the magnetic resonance imaging (MRI) and intraoperative findings of deep infiltrating endometriosis using the #ENZIAN score. Methods This retrospective study included 64 patients who underwent surgery for deep infiltrating endometriosis between January 2017 and August 2020. Preoperative abdominopelvic MRI assessment was evaluated and scored using the #ENZIAN classification. Operative scores were considered the gold standard, and the sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of MRI for each category were calculated. Results MRI has higher sensitivity and specificity in showing the lesions of the compartments O (ovarian lesions), A (rectovaginal septum and posterior vaginal fornix), and B (uterosacral ligaments and parametrium) (100–100%, 100–100%, and 97–100%, respectively, p<0.001) compared to the other compartments. The lowest sensitivity, specificity, accuracy, and PPV of the MRI was found in compartment P (14%, 76%, 70%, and 7%, respectively). Conclusion We demonstrated that the #ENZIAN classification in MRI reports has significant sensitivity and specificity in compartments A, B (uterosacral ligaments and parametrium), and O. Furthermore, the determination of peritoneal lesions via MRI is inadequate.
... Endometriosis is a complex, inflammatory disease, characterized by lesions of endometrial tissue outside the uterus (1)(2)(3)(4). Endometriosis has an estimated prevalence of 6-15% of women in their reproductive age worldwide (5)(6)(7). The etiology of endometriosis is not fully understood (8). ...
... Current treatment approaches for pain and infertility (e.g., hormonal drugs or repeated surgical procedures) are not always effective and are often associated with unpleasant side effects (21,22). In addition, there is no direct association between histologic findings and disease symptoms, and disease progression is difficult to predict (3,23). ...
Article
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Background: Endometriosis is characterized by lesions of endometrial tissue outside the uterus. Chronic pain is considered as main symptom, but challenges can relate to various physical, mental, and social aspects of the women's lives. The aim of our study was to gain a holistic understanding of the everyday reality of women with endometriosis compared to healthy controls. Methods: The total sample comprised 12 hormone-free endometriosis patients (EP) and 11 age-matched healthy women (HC). A mixed-methods design was used comprising semi-structured interviews, standardized questionnaires and a comprehensive diary to assess pain ratings and various mental and physical symptoms over the course of a menstrual cycle. Interviews were recorded, transcribed, and evaluated according to phenomenological analysis using the MAXQDA software. Results: Interviews showed that living with endometriosis was associated with an impairment in everyday life. Physical strains, especially pain, high levels of psychological distress, and social limitations have been reported. Living with endometriosis affected the patients' personality and they “no longer felt like themselves.” Physical and psychological symptoms were reported to interfere with social interaction and participation. Evaluation of the standardized questionnaires revealed significant impairments in EP compared to HC in regard to anxiety and depression scores (both p < 0.001; Hospital Anxiety and Depression Scale), mental and physical quality of life (both p < 0.001; Short-Form Health Survey-12), stress ratings ( p < 0.001; Patient Health Questionnaire-15) and functional well-being ( p < 0.001; Functional Well-being-7). The highest levels of mean pelvic pain and dyschezia were observed in EP during menstruation, but mean pain ratings and dyschezia were increased in EPs compared to HP during the whole cycle. EP reported mental symptoms (e.g., depressed mood or anxiety) mainly during menstruation, while HC did not show any mental symptoms during the cycle. In addition, physical symptoms were elevated during the entire cycle in EPs (all p < 0.01). Discussion: The mixed-methods approach enabled to interpret the interviews, the standardized questionnaires, and the symptom diary in a broader context of everyday life. The symptoms do not appear to act independently, but rather influence each other. This leads to a complex interplay of physical, mental, and social impairments, with pain often being the starting point.
... To be able to facilitate these relations, a standardized MRI reporting system is crucial. Classification of endometriosis is complicated, and in 2014, the World Endometriosis Society proposed a classification toolbox that includes the rASRM classification, the ENZIAN classification, and the Endometriosis Fertility Index (EFI) [7]. However, using multiple classifications in daily practice is not practical and may not be used effectively. ...
... In contrast to the rectosigmoid region, compartment C does not involve the sigmoid colon. A meta-analysis evaluating both rectum and sigmoid colon lesions reported 83% sensitivity and 88% specificity [7]. Two other studies evaluated MRI accuracy of DIE lesions using the revised ENZIAN score, and both reported 86% sensitivity in compartment C. Specificities of the compartment C in these studies were reported as 98% [12] and 89% [10]. ...
Article
Full-text available
Purpose The aim of this study is to investigate the correlation between the magnetic resonance imaging (MRI) and intraoperative findings of deep infiltrating endometriosis using the #ENZIAN score. Methods This retrospective study included 64 patients who underwent surgery for deep infiltrating endometriosis between January 2017 and August 2020. Preoperative abdominopelvic MRI assessment was evaluated and scored using the #ENZIAN classification. Operative scores were considered the gold standard, and the sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of MRI for each category were calculated. Results MRI has higher sensitivity and specificity in showing the lesions of the compartments O (ovarian lesions), A (rectovaginal septum and posterior vaginal fornix), and B (uterosacral ligaments and parametrium) (100–100%, 100–100%, and 97–100%, respectively, p < 0.001) compared to the other compartments. The lowest sensitivity, specificity, accuracy, and PPV of the MRI was found in compartment P (14%, 76%, 70%, and 7%, respectively). Conclusion We demonstrated that the #ENZIAN classification in MRI reports has significant sensitivity and specificity in compartments A, B (uterosacral ligaments and parametrium), and O. Furthermore, the determination of peritoneal lesions via MRI is inadequate.
... Among them, rASRM classification is the most widely used. It is useful for physicians to report the severity of endometriosis (stages I-IV) in patients in simple terms [16,17]. This scoring system is based on the summation of values assigned to the following items: the size of the endometriosis lesions in the peritoneum and ovaries, adhesion on the ovaries and fallopian tubes, and partial or complete posterior cul-de-sac obliteration. ...
... The rASRM classification does not incorporate DIE infiltration into the retroperitoneal structures. As a supplement to the rASRM, the ENZIAN classification was developed to classify DIE [17]. Di Paola et al. [18] reported an excellent correlation between MRI-based ENZIAN scores and histopathological ENZIAN scores, particularly for rectovaginal septum, uterosacral ligament (USL), and rectosigmoid locations. ...
Article
Endometriosis, a common chronic inflammatory disease in female of reproductive age, is closely related to patient symptoms and fertility. Because of its high contrast resolution and objectivity, MRI can contribute to the early and accurate diagnosis of ovarian endometriotic cysts and deeply infiltrating endometriosis without the need for any invasive procedure or radiation exposure. The ovaries, which are the most frequent site of endometriosis, can be afflicted by multiple related conditions and diseases. For the diagnosis of deeply infiltrating endometriosis and secondary adhesions among pelvic organs, fibrosis around the ectopic endometrial gland is usually found as a T2 hypointense lesion. This review summarizes the MRI findings obtained for ovarian endometriotic cysts and their physiologically and pathologically related conditions. This article also includes the key imaging findings of deeply infiltrating endometriosis.
... Surgical visualization and sampling with histologic review are necessary to confirm the diagnosis of endometriosis, which makes diagnosis more difficult. In addition, clinical presentation, treatment response, or prognosis do not frequently correlate with classification and staging (7,8). ...
Article
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Endometriosis is a known estrogen-dependent inflammatory disease affecting reproductive-aged women. Common symptoms include pelvic pain, dysmenorrhea, dyspareunia, heavy menstrual bleeding, and infertility. The exact etiology of endometriosis is largely unknown, and, thus, the diagnosis and treatment of endometriosis are challenging. A complex interplay of many molecular mechanisms is thought to aid in the progression of endometriosis, most notably angiogenesis. This mini-review examines our current knowledge of the molecular etiology of endometriosis-associated angiogenesis and discusses anti-angiogenic therapy, in the blockade of endometriosis-associated angiogenesis, as potential non-hormonal therapy for the treatment of endometriosis.
... It is estimated that 176 million women worldwide suffer from endometriosis and 1.5 to 10% of them were in the reproductive age. 1,2 Endometriosis is associated with reduced quality of life due to chronic pelvic pain, dysmenorrhea, and dyspareunia as well as with infertility. It has been reported that 35 to 50% of women with endometriosis suffer from pain, infertility, or both. ...
Article
Full-text available
Background: Endometriosis is a condition associated with pelvic pain, infertility, and possibly with decreased quality of life as well as psychiatric disorder. The purpose of our study was to evaluate the association between pain characteristic, psychiatric disorder, and quality of life in women with endometriosis. Methods: A cross-sectional study was done involving 160 women with medical diagnosis of endometriosis. Pain intensity was evaluated using Visual Analog Scale (VAS), Quality of Life with Endometriosis Health Profile (EHP-30), and psychologic condition with Mini International Neuropsychiatric Interview International Classification of Diseases (Mini-ICD). Results: VAS and psychiatric disorder were associated with higher EHP-30 score (β = 9.3 (95% CI: 7.15-11.45; p < 0.001 and β = 28.51 (95% CI: 20.06-36.05; p < 0.001), respectively) and hence, lower quality of life. The strongest correlation between VAS and EHP-30 was in pain (r=0.586; p<0.001) and 'control and powerlessness' (r = 0.583; p < 0.001). VAS was also higher in subjects with depression (49.5 (25.4-77.8) vs 34.4 (6.1-74.6); p < 0.001). Conclusion: We conclude that severe endometriosis-related pain and the presence of psychiatric disorder were associated with lower quality of life. Comprehensive management of endometriosis is crucial to improve patients' quality of life.
... Endometriosis affects 10-15% of all women in reproductive age (Giudice & Kao, 2004). It is associated with chronic pelvic pain and infertility (Parasar et al., 2017), and it is subdivided into four categories: stage I (minimal), stage II (mild), stage III (moderate) and stage IV (severe) (Johnson et al., 2017). ...
Article
Conventional embryo assessment is performed by removing embryos from incubators at least once a day. However, it is static and limited to specific time points, reducing the amount of information that could potentially be obtained. Fortunately, the time-lapse system is a powerful technology that enables to observe embryo development progression by image acquisition at recurrent time intervals, without interfering in the culture conditions. There are numerous studies that used time-lapse incubators, focusing on embryo kinetics, patient characteristics and clinical outcomes. This review aims to find agreements in the literature concerning embryo kinetics and patient characteristics: age, body mass index, smoking habit, polycystic ovary syndrome and endometriosis; as well as culture conditions that involved culture media and oxygen concentration. Furthermore, they showed differences according to ploidy status, direct/reverse cleavage, gender and the potential association between embryo collapse and clinical outcomes.
... Moreover, the Mann-Whitney U-test for non-parametric variables was used to assess any possible significant difference between medians of the AFS score in patients, grouped according to the categories of the variable under exam (presence/absence of disease, or different levels of biomarkers) (27). All analyses were performed in vivo 36: 430-438 (2022) using Python 3.7.10 ...
Article
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Background/aim: Endometriosis is a gynecological estrogen-dependent inflammatory disease due to ectopic endometrial tissue and often associated with pelvic pain. Despite its high prevalence, there are still uncertainties about its pathogenesis, diagnosis, and therapy. Patients and methods: This study presents a retrospective study conducted on 4,401 endometriosis patients, 584 of which underwent laparoscopic procedures. The archived data about clinical signs, magnetic resonance imaging (MRI) results, topography of the endometriosis lesions (obtained via laparoscopy) associated diseases, sample analysis and histological findings were analyzed. Next, the statistical associations between the information for each case, provided by these diagnostic tools were determined. Results: MRI is the most sensitive and specific diagnostic system for ovarian lesions, but poor in sensitivity and specificity for deep endometriosis lesions and not indicated for peritoneal lesions which remain the exclusive prerogative of laparoscopy. Clinical signs are essential for diagnosing deep lesions. The Ca125 and Ca19.9 markers have a poor reliability and their negativity in symptomatic patients has no clinical value, while in positive cases it could probably be used as a monitoring parameter. Conclusion: The results generated will help provide an accurate picture of the topography and distribution of endometriotic lesions. Correlation analyses between the data generated by the clinical-instrumental examinations and those on the site of the disease identified by laparoscopy, allow to define the predictive value of the clinical-instrumental signs in the diagnosis and localization of endometriotic disease.
... The screened results handled the classification of the individual subtypes of DIE very inconsistently. A separate inclusion criterion for the subtypes of DIE, for example according to ENZIAN [40], was therefore not formulated. Studies with patients without previous therapy for DIE and AM and those that included pre-treated patients were included. ...
Article
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Endometriosis (EM), especially deep infiltrating endometriosis (DIE) and adenomyosis (AM), are known to cause pain and sterility in young women. More recently, they have also been described as risk factors for obstetric complications. While the pathophysiology is not yet completely understood, they seem to share a common origin: archimetrosis. Methods: A systematic literature review was conducted to summarize the existing evidence on DIE and AM as risk factors for obstetric complications. Results: Preterm birth, caesarean section delivery (CS) and placental abnormalities are associated with the diagnosis of DIE and AM. Women with AM seem to experience more often hypertensive pregnancy disorders, premature rupture of membranes and their children are born with lower birth weights than in the control groups. However, many of the studies tried to evaluate AM, EM and DIE as separate risk factors. Moreover, often they did not adjust for important confounders such as multiple pregnancies, parity, mode of conception and maternal age. Therefore, prospective studies with larger numbers of cases and appropriate adjustment for confounders are needed to explore the pathophysiology and to prove causality.
... Furthermore, the classification system has limited value in scoring DIE [26]. The ENZIAN classification has been recommended to classify DIE by the European Society of Gynecological Endoscopy (ESGE), ESHRE and the World Endometriosis Society [27,28]. Additionally, the new #ENZIAN classification has been proposed and includes endometriosis of the peritoneum, endometriosis of the ovaries and the extent of adnexal adhesions, which makes up for the insufficiency of the ENZIAN classification [29]. ...
Article
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Background: This study aimed to summarize and analyze clinical characteristics and reproductive outcomes in postoperative deep infiltrating endometriosis (DIE). Methods: This retrospective cohort study included 55 reproductive-aged patients who were diagnosed with DIE, wished to conceive and underwent resection surgery at the Obstetrics and Gynecology Hospital, Fudan University, from January 2009-June 2017. Those with any plausible infertility factor or abnormalities in the partner's semen analysis were excluded. Patient characteristics, preoperative symptoms, infertility history, intraoperative findings and reproductive outcomes were followed up and recorded. Risk factors for reproductive outcomes were identified for women who became pregnant versus those who did not by univariate logistic regression. Additionally, pre- and postoperative endometriosis health profile questionnaire-30 (EHP-30), Knowles-Eccersley-Scott Symptom questionnaire (KESS), Cox Menstrual Symptom Scale (CMSS) and Female Sexual Function Index (FSFI) scores were used to evaluate the effect of DIE surgery on quality of life. Results: The average age was 30.22 ± 3.62 years, with no difference between the pregnancy and nonpregnancy groups. The average follow-up time was 26.57 ± 14.51 months. There were 34 pregnancies (61.82%): 24 (70.59%) conceived spontaneously and 10 (29.41%) by in vitro fertilization (IVF). Twenty-eight patients (82.35%) had term deliveries. The interval between operation and pregnancy was 10.33 ± 5.6 (1-26) months. Univariate analysis showed that a lower endometriosis fertility index (EFI) score (EFI < 8) was a risk factor for infertility (OR: 3.17 (1.15-10.14), p = .044). For patients with incomplete surgery, postoperative gonadotropin-releasing hormone agonist (GnRHa) administration improved the pregnancy rate (p < 0.05). Regarding quality of life, there was significant improvement (p < 0.05) in the postoperative EHP-30, KESS and CMSS scores compared with preoperative scores in both groups. Although there was no obvious difference in FSFI scores, significant improvement in dyspareunia was observed (p < 0.05). Conclusions: Overall, the postoperative pregnancy rate of DIE patients was 61.82%. Surgical management of DIE for patients with complaints of pain and with pregnancy intentions was feasible and effective. Long-term expectant treatment should not be advised for patients with lower EFI scores (EFI < 8), and postoperative IVF-ET may be a good choice. More cases should be enrolled for further study, and randomized studies are required.
... Women were asked whether they had physician diagnosed EM. Participants who responded "yes" indicated the year of diagnosis and whether it had been visually confirmed by laparoscopy, the clinical gold standard for endometriosis diagnosis [19]. For participants who answered "yes" but did not diagnose EM by laparoscopy can still be classified as EM only after being reported as EM by B-ultrasound. ...
Article
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Introduction To evaluate whether the incidence of hypertensive disorders of pregnancy (HDP) in pregnant women was related to endometriosis (EM), ovulation and embryo vitrification technology. Methods A retrospective cohort study was conducted on the clinical data of 3674 women who were treated with IVF / ICSI in the Reproductive Medicine Center of the First Affiliated Hospital of Sun Yat-sen University and maintained clinical pregnancy for more than 20 weeks. All pregnancies were followed up until the end of pregnancy. The follow-up consisted of recording the course of pregnancy, pregnancy complications, and basic situation of newborns. Results Compared with NC-FET without EM, HRT-FET without EM was found to have a higher incidence of HDP during pregnancy (2.7% V.S. 6.1%, P<0.001); however, no significant difference was found in the incidence of HDP between NC-FET and HRT-FET combined with EM (4.0% V.S. 5.7%, P>0.05). In total frozen-thawed embryo transfer (total-FET), the incidence of HDP in the HRT cycle without ovulation (HRT-FET) was observed to be higher than that in the NC cycle with ovulation (NC-FET) (2.8% V.S. 6.1%, P<0.001). In patients with EM, no significant difference was found in the incidence of HDP between fresh ET and NC-FET (1.2% V.S. 4.0%, P>0.05). Conclusion EM does not seem to have an effect on the occurrence of HDP in assisted reproductive technology. During the FET cycle, the formation of the corpus luteum may play a protective role in the occurrence and development of HDP. Potential damage to the embryo caused by cryopreservation seems to have no effect on the occurrence of HDP.
... Females suffer from pelvic pain, dysmenorrhea, and infertility (3), which constitutes a considerable economic burden of physical and psychological health. The revised American Society for Reproductive Medicine (rASRM) score (1997) is currently the most widely used classification system for staging endometriosis severity (4)(5)(6). As both are estrogen dependent disease, about 20-40% of women with endometriosis had concomitant adenomyosis (7). ...
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Background Emerging data suggest a significant association between migraine and endometriosis, however the relationship between migraine and endometriosis severity or adenomyosis is unclear. Our objectives were to explore the relationship between migraine and endometriosis, according to the endometriosis severity and co-exist with adenomyosis or not. Methods This case-control study of 167 endometriosis patients verified by surgery and 190 patients for other benign gynecological conditions (control subjects) was performed from September 2017 and January 2021. There is 49 adenomyosis detected by transvaginal ultrasound or histologic diagnosis among the endometriosis patients. Besides, we also included 41 adenomyosis but without endometriosis patients as a subgroup. All women completed a self-administered headache questionnaire and diagnosed as migraine according to the International Headache Society classification. The severity and stage of endometriosis was evaluated with revised American Society of Reproductive Medicine (rASRM) score. We used logistic regression to estimate the association between the presence of migraine and endometriosis severity while accounting for important confounders, including age, body mass index (BMI) and family history of migraine. We also estimate the risk of adenomyosis alone and adenomyosis with co-occurring endometriosis in migrainous women. Results Migraine was significantly more prevalent in endometriosis patients compared with controls (29.9% vs. 12.1%, p <0.05), but the prevalence was similar between isolated adenomyosis patients and controls (9.8% vs.12.1%, p >0.05). For all endometriosis and control participants, migraineurs were 4.6-times (OR=4.6; 95% CI 2.7-8.1) more likely to have severe endometriosis. However, the strength of the association decreased when the analysis examined in moderate stage (OR=3.6, 95% CI 2.1-6.2). The risk of mild and minimal endometriosis was not significant (OR=1.9, 95%CI 0.9-4.0; OR=1.6, 95% CI 0.8-3.4; respectively). When we divided the endometriosis patients according to whether co-occurring with adenomyosis. We found in migrainous women, the risk of endometriosis co-exist with adenomyosis increased, with nearly fivefold greater odds compared with control (OR=5.4;95% CI 3.0-9.5), and nearly two times higher than the risk of endometriosis without co-exist adenomyosis patients (OR=2.2; 95% CI 1.2-3.8). Conclusion Our study supports the strong association between migraine and endometriosis. We found migrainous women suffer more frequently from sever endometriosis, especially endometriosis with co-occurring adenomyosis. It is advisable to heighten suspicion for patients who presenting with either these conditions in order to optimize therapy.
... Endometriosis is a chronic inflammatory disease process characterized by the presence of endometriallike tissue outside the uterus. 1 It affects *10% of reproductive-age women worldwide. 2,3 Persistent pelvic pain, dysmenorrhea, dyspareunia, and dyschezia remain hallmarks of disease. ...
Article
Introduction: Endometriosis affects 1 in 10 women worldwide, with most experiencing difficulties achieving adequate symptom control. These difficulties have been compounded by the onset of the COVID-19 pandemic due to worldwide shifts in health care resource allocation. As cannabis is a relatively common form of self-management in endometriosis, this study aims to explore the impact of the COVID-19 pandemic on cannabis consumption in those with endometriosis. Methods: An anonymous, cross-sectional online international survey was developed and promoted by endometriosis advocacy/support organizations worldwide. Respondents needed to have a diagnosis of endometriosis and be aged between 18 and 55. Results: A total of 1634 responses were received from 46 different countries. The average age of respondents was 30, with a mean diagnosis age of 25. Eight hundred forty-six respondents (51%) reported consuming cannabis in the past 3 months, with 55% of these reporting use for symptom management only. One in five respondents (20%) reported having consumed cannabis previously, the most common reason for discontinuation (65%) was access difficulties during COVID. Those who had legal access were more likely to consume cannabis than those without (p<0.0001) and were more likely to disclose usage to health care professionals (p<0.0001). The most common reasons for consuming cannabis during COVID was increased stress/anxiety (59%) and lack of access to normal medical care (48%). Pre-pandemic, cannabis was mostly consumed at least once a day (61%) and in inhaled forms (51.6%). Consumption increased for most people (57%) during the pandemic. During the pandemic just under a quarter (23%) of respondents changed their mode of consumption, with a reduction in inhaled forms (39.5%) and an increase in consumption of edibles (40%) or oil (25.2%). Conclusions: Cannabis consumption, especially for symptom relief, was relatively common among those with endometriosis, with some people starting their consumption of cannabis due to health care restrictions that occurred due to the COVID-19 pandemic. Difficulties accessing cannabis and unpleasant/unwanted side effects were the most common reasons for lack of current cannabis consumption in those who had previously consumed it. Cannabis consumption may form an important part of endometriosis management especially when access to routine medical care is restricted.
... A prospective external validation of the recently published AAGL system should follow, including a headto-head comparison with existing and emerging endometriosis staging systems. Standardized surgical data collection would be advisable, as per the Consensus on Recording Deep Endometriosis Surgery statement (28). ...
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Objective To externally validate the "2021 AAGL Endometriosis Classification" staging system. Design Retrospective, diagnostic accuracy study Setting Multicentre Population or Sample Two hundred and seventy-two endometriosis patients (January 2016-October 2021) Methods Three independent observers analysed coded surgical data to assign an AAGL surgical stage (1 to 4) as the index test, and surgical complexity level (A to D) as the reference standard. Main Outcome Measures The diagnostic accuracy of each AAGL stage to predict corresponding AAGL surgical complexity level was determined. Receiver operating characteristic curves used to determine the accuracy of cut off points used in the AAGL staging system to discriminate between surgical complexity levels. Results 272 cases were analysed. Diagnostic accuracy (sensitivity, specificity, PPV and NPV) for three observers were: stage 1 to predict level A 97.9-98.7%, 60.2-64.2%, 75.0-76.9%, and 96.3-97.5%; stage 2 to predict level B 26.1-30.4%, 93.2-95.6%, 26.3-35.3%, and 92.9-93.6%; stage 3 to predict level C 7.5-10.0%, 93.8-94.8%, 33.3-42.1%, and 70.9-71.5%; stage 4 to predict level D 90.-95.0%, 90.1-91.7% &, 41.9-47.5%, and 99.1-99.6%. For three observers AUROC for A vs B/C/D (cut-point 9) 0.75-0.88, A/B vs C/D (cut-point 16) 0.81 and A/B/C vs D (cut-point 22) 0.95-0.96. Conclusions This external validation study demonstrates that the AAGL Endometriosis Classification performs poorly overall for the prediction of surgical complexity. The results from this external validation study suggest that the system in its current form is not generalizable to all endometriosis patients and should be reviewed before its universal implementation. Funding Nil Abstract Objective
... Endometriosis patients are typically staged by the visual appearance of lesions and adhesions according to the American Society for Reproductive Medicine's revised system. However, this staging does not correlate with patient symptoms or treatment outcomes (7). Looking beyond visual characteristics, clinical and experimental studies suggest that the growth and survival of lesions is enabled by a combination of immune dysfunction, hormone dysregulation, and aberrant blood vessel development (8)(9)(10). ...
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Endometriosis is a common but poorly understood disease. Symptoms can begin early in adolescence, with menarche, and can be debilitating. Despite this, people often suffer several years before being correctly diagnosed and adequately treated. Endometriosis involves the inappropriate growth of endometrial-like tissue (including epithelial cells, stromal fibroblasts, vascular cells, and immune cells) outside of the uterus. Computational models can aid in understanding the mechanisms by which immune, hormone, and vascular disruptions manifest in endometriosis and complicate treatment. In this review, we illustrate how three computational modeling approaches (regression, pharmacokinetics/pharmacodynamics, and quantitative systems pharmacology) have been used to improve the diagnosis and treatment of endometriosis. As we explore these approaches and their differing detail of biological mechanisms, we consider how each approach can answer different questions about endometriosis. We summarize the mathematics involved, and we use published examples of each approach to compare how researchers: (1) shape the scope of each model, (2) incorporate experimental and clinical data, and (3) generate clinically useful predictions and insight. Lastly, we discuss the benefits and limitations of each modeling approach and how we can combine these approaches to further understand, diagnose, and treat endometriosis.
... indicated the year of diagnosis and whether it had been visually con rmed by laparoscopy, the clinical gold standard for endometriosis diagnosis [17]. The remaining patients who were not diagnosed with EM by laparoscopy and those who were reported as EM by B-ultrasound during the treatment were also classi ed as EM. ...
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Introduction To evaluate whether the incidence of hypertensive disorders of pregnancy (HDP) in pregnant women was related to endometriosis (EM), ovulation and embryo vitrification technology. Methods A retrospective cohort study was conducted on the clinical data of 3674 women who were treated with IVF / ICSI in the Reproductive Medicine Center of the First Affiliated Hospital of Sun Yat-sen University and maintained clinical pregnancy for more than 20 weeks. All pregnancies were followed up until the end of pregnancy. The follow-up consisted of recording the course of pregnancy, pregnancy complications, and basic situation of newborns. Results Compared with NC-FET without EM, HRT-FET without EM was found to have a higher incidence of HDP during pregnancy (2.7% V.S. 6.1%, P<0.001); however, no significant difference was found in the incidence of HDP between NC-FET and HRT-FET combined with EM (4.0% V.S. 5.7%, P>0.05). In total frozen-thawed embryo transfer (total-FET), the incidence of HDP in the HRT cycle without ovulation (HRT-FET) was observed to be higher than that in the NC cycle with ovulation (NC-FET) (2.8% V.S. 6.1%, P<0.001). In patients with EM, no significant difference was found in the incidence of HDP between fresh ET and NC-FET (1.2% V.S. 4.0%, P>0.05). Conclusion EM does not seem to have an effect on the occurrence of HDP in assisted reproductive technology. During the FET cycle, the formation of the corpus luteum may play a protective role in the occurrence and development of HDP. Potential damage to the embryo caused by cryopreservation seems to have no effect on the occurrence of HDP.
... Endometriosis (EMS) is defined as the presence of ectopic endometrial glands and stroma outside of the uterine cavity and affects 6-10% of reproductive-aged women. Women with EMS can have symptoms of dyspareunia, dysmenorrhea, irregular uterine bleeding, and chronic pelvic pain [1][2][3]. Although medical therapies can relieve symptoms in up to 50-80% of cases, residual symptoms are still present in at least 20% of patients [4][5][6][7]. ...
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Objective To determine the potential diagnostic markers and extent of immune cell infiltration in endometriosis (EMS). Methods Two published profiles (GSE7305 and GSE25628 datasets) were downloaded, and the candidate biomarkers were identified by support vector machine recursive feature elimination analysis and a Lasso regression model. The diagnostic value and expression levels of biomarkers in EMS were verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting, then further validated in the GSE5108 dataset. CIBERSORT was used to estimate the composition pattern of immune cell components in EMS. Results One hundred and fifty-three differential expression genes (DEGs) were identified between EMS and endometrial with 83 upregulated and 51 downregulated genes. Gene sets related to arachidonic acid metabolism, cytokine–cytokine receptor interactions, complement and coagulation cascades, chemokine signaling pathways, and systemic lupus erythematosus were differentially activated in EMS compared with endometrial samples. Aquaporin 1 (AQP1) and ZW10 binding protein (ZWINT) were identified as diagnostic markers of EMS, which were verified using qRT-PCR and western blotting and validated in the GSE5108 dataset. Immune cell infiltrate analysis showed that AQP1 and ZWINT were correlated with M2 macrophages, NK cells, activated dendritic cells, T follicular helper cells, regulatory T cells, memory B cells, activated mast cells, and plasma cells. Conclusion AQP1 and ZWINT could be regarded as diagnostic markers of EMS and may provide a new direction for the study of EMS pathogenesis in the future.
... To establish clinical severity of endometriosis, we utilized the 1996 Revised Classification of Endometriosis from the American Society of Reproductive Medicine [33]. We classified our subjects into four stages as follows: stage 1 (minimal) with a score of 1 to 5, stage 2 (mild) with a score of 6 to 15, stage 3 (moderate) with a score of 16 to 40 and stage 4 (severe) with a score > 40 [34,35]. Endometriosis was minimal in 5 subjects, mild in 3 subjects, moderate in 4 subjects and severe in 8 subjects (Table 1). ...
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Endometriosis is an estrogen dependent gynecological disease associated with altered microbial phenotypes. The association among endogenous estrogen, estrogen metabolites, and microbial dynamics on disease pathogenesis has not been fully investigated. Here, we identified estrogen metabolites as well as microbial phenotypes in non-diseased patients ( n = 9) and those with pathologically confirmed endometriosis (P-EOSIS, n = 20), on day of surgery (DOS) and ~1–3 weeks post-surgical intervention (PSI). Then, we examined the effects of surgical intervention with or without hormonal therapy (OCPs) on estrogen and microbial profiles of both study groups. For estrogen metabolism analysis, liquid chromatography/tandem mass spectrometry was used to quantify urinary estrogens. The microbiome data assessment was performed with Next generation sequencing to V4 region of 16S rRNA. Surgical intervention and hormonal therapy altered gastrointestinal (GI), urogenital (UG) microbiomes, urinary estrogen and estrogen metabolite levels in P-EOSIS. At DOS, 17β-estradiol was enhanced in P-EOSIS treated with OCPs. At PSI, 16-keto-17β-estradiol was increased in P-EOSIS not receiving OCPs while 2-hydroxyestradiol and 2-hydroxyestrone were decreased in P-EOSIS receiving OCPs. GI bacterial α-diversity was greater for controls and P-EOSIS that did not receive OCPs. P-EOSIS not utilizing OCPs exhibited a decrease in UG bacterial α-diversity and differences in dominant taxa, while P-EOSIS utilizing OCPs had an increase in UG bacterial α-diversity. P-EOSIS had a strong positive correlation between the GI/UG bacteria species and the concentrations of urinary estrogen and its metabolites. These results indicate an association between microbial dysbiosis and altered urinary estrogens in P-EOSIS, which may impact disease progression.
... Up to 80% of women with endometriosis suffer from chronic pain, and up to 50% of women suffer from infertility. Endometriosis-related productivity loss and decreased quality of life lead to a heavy economic burden [1]. Endometriosis can be classified as superficial endometriosis (SUP), ovarian endometrioma (OMA), and deep endometriosis (DE) [2]. ...
Article
Background: Deep endometriosis (DE) is the most aggressive subtype of endometriosis. The diagnosis may be challenging, and no biomarkers that can discriminate women with DE from those without DE have been developed. Aim: To evaluate the role of blood hemostatic parameters and inflammatory indices in the prediction of DE. Methods: This case-control study was performed at the Women's Hospital, Zhejiang University School of Medicine between January 2015 and December 2016. Women with DE and women with benign gynecologic disease (control group) eligible for gynecological surgery were enrolled. Routine plasma hemostatic parameters and inflammatory indices were obtained before surgery. Univariate and multivariate analysis were performed. Receiver operating characteristic (ROC) curves were generated, and areas under the curve (AUC) were calculated to assess the predictive values of the selected parameters. Results: A total of 126 women were enrolled, including 31 with DE and 95 controls. Plasma fibrinogen (Fg, P < 0.01), international normalized ratio (P < 0.05), and C-reactive protein levels (P < 0.01) were significantly higher in women with DE compared with controls. Plasma hemoglobin (HB) levels (P < 0.05) and shortened thrombin time (P < 0.05) were significantly lower in women with DE than in controls. Plasma Fg levels [adjusted OR (aOR) 2.12, 95%confidence interval (CI): 1.31-3.75] and plasma HB levels (aOR 0.48, 95%CI: 0.29-0.78) were significantly associated with DE (both P < 0.05). ROC analysis showed that the diagnostic value of Fg or HB alone for DE was limited. The AUC of the combination of both markers as a dual marker index was 0.773 with improved sensitivity (67.7%) and specificity (78.9%) at cutoffs of 3.09 g/L and 126 g/L, respectively. Conclusion: The combination of Fg and HB was a reliable predictor of DE. A larger study is needed to confirm the findings.
... In 2017, a consensus statement of the World Endometriosis Society (WES) was the first global attempt to guide the usage of existing endometriosis classification systems. 1 The recommendation was that surgeons should use a uniform classification toolbox including the revised American Society for Reproductive Medicine (r-ASRM) classification 2 and, where appropriate, the Enzian classification 3 for deep endometriosis (DE) and the Endometriosis Fertility Index (EFI) 4 for fertility prediction. ...
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Objective: To assess the diagnostic performance of preoperative application of the Enzian classification (cEnzian) using surgical findings as reference standard DESIGN: A prospective international non-interventional study SETTING: 12 endometriosis centers in four European countries (Austria, Germany, Switzerland, and Czech Republic) POPULATION: 1062 women with endometriosis surgery METHODS: Extent of endometriosis was preoperatively classified using the cEnzian classification based on gynecological examination and/or transvaginal ultrasound (TVS) and/or magnetic resonance imaging (MRI). After subsequent surgery, the surgeon classified the intraoperative findings using the Enzian classification. Main outcome measures: Sensitivity, specificity, PPV, NPV, LR+, LR- and accuracy were calculated. Conditional frequencies of intraoperative Enzian codings and the corresponding 95 % confidence intervals were computed for each preoperative coding and visualised in plots. Results: Although overall consistency of cEnzian and Enzian was poor (35.14 %, 95%-CI 32.26-38.03), high specificities and negative predictive values (NPVs) of the cEnzian compartments could be demonstrated. Looking at the individual parts of the Enzian classification, the poorest diagnostic performance was detected for compartment B and the highest PPVs were found for category 3-lesions (> 3 cm), independently of the compartment. Conclusions: Using the Enzian classification in a non-invasive setting is a useful tool providing us with a 'at a glance' summary of the diagnostic workup regarding deep endometriosis with high specificities and NPVs. An attempt to merge the two new endometriosis classification systems (#Enzian and AAGL 2021) seems reasonable - with consideration of the respective advantages of each other.
... The lack of correlation between laparoscopic staging, the severity of symptoms, and response to treatment, has attributed little value to this classification system in clinical practice [38e40]. A consensus around the optimal classification for endometriosis is very much needed and the World Endometriosis Society has recently endeavored to attain this [41]. ...
Chapter
Diagnosing endometriosis has been a challenging and controversial concept for years. When considering a patient with pelvic pain, endometriosis may be suspected based on the clinical history and physical examination. While a presumptive clinical diagnosis can be provided, more accurate and tangible diagnostic tests may be sought by patients and clinicians. Historically, surgery was thought to be the only way to accurately diagnose endometriosis. While surgery remains a useful and accurate tool, there are many disadvantages including but not limited to risk, cost, and accessibility. Novel diagnostic strategies in the noninvasive category have been researched and implemented into clinical practice, while others remain experimental. In this chapter, we discuss the current gold standard surgical diagnosis as well as the novel strategies including imaging (ultrasound and magnetic resonance imaging) and biomarkers, a body specimen that can be tested in a laboratory for signs of endometriosis. Ultimately, we envision that a combination of noninvasive diagnostic tools, in addition to clinical history and physical examination, will achieve a diagnostic accuracy similar to or better than surgery.
... Demographics regarding age at the time of surgery, complaints, serum CA125 (cancer antigen 125), localizations of nodules on the digestive tract, nodule size and number, stage of endometriosis according to the revised American Society for Reproductive Medicine (rASRM) score and Enzian classification (11,12), other associated gynecologic diseases, surgical route, surgical procedures performed, operative time and bleeding, infection after surgery, and the postoperative complications related to each technique were all carefully recorded. ...
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Objective This study aims to evaluate the factors associated with complications and long-term results in the surgical treatment of intestinal deep endometriosis and to figure out the optimized treatment measures for bowel endometriosis.MethodsA retrospective study was performed in a single center in China. Medical charts were reviewed from 61 women undergoing surgical treatment for bowel endometriosis between January 2013 and August 2019 in the Department of General Gynecology, Women’s Hospital School of Medicine Zhejiang University. Multivariate regression analysis was utilized to investigate the impact of the stages of endometriosis and surgical steps (independent risk factors) on complications (and postoperative bowel dysfunction). The clinical characters, surgical procedures, postoperative treatment, complications, and recurrence rate were summarized and analyzed by using Lasso regression.ResultsSurgery type was the most important independent risk factor related to postoperative abnormal defecation in intestinal deep endometriosis patients (P < 0.05, OR = 34.133). Infection is the most important independent risk factor related to both postoperative complications (OR = 96.931) and recurrences after conservative surgery (OR = 4.667). Surgery type and age were significantly related to recurrences after conservative surgery.Conclusions We recommended conservative operation especially full-thickness disc excision to improve the quality of life of intestinal deep endometriosis patients. In addition, prevention of infection is very important to reduce the postoperative complications rate and the recurrence rate.
Article
Background: Endometriosis is a condition characterised by the presence of ectopic deposits of endometrial-like tissue outside the uterus, usually in the pelvis. The impact of laparoscopic treatment on overall pain is uncertain and a significant proportion of women will require further surgery. Therefore, adjuvant medical therapies following surgery, such as the levonorgestrel-releasing intrauterine device (LNG-IUD), have been considered to reduce recurrence of symptoms. OBJECTIVES: To determine the effectiveness and safety of post-operative LNG-IUD in women with symptomatic endometriosis. Search methods: We searched the following databases from inception to January 2021: The Specialised Register of the Cochrane Gynaecology and Fertility Group, CENTRAL (which now includes records from two trial registries), MEDLINE, Embase, PsycINFO, LILACS and Epistemonikos. We handsearched citation lists of relevant publications, review articles, abstracts of scientific meetings and included studies. We contacted experts in the field for information about any additional studies. Selection criteria: We included randomised controlled trials (RCTs) comparing women undergoing surgical treatment of endometriosis with uterine preservation who were assigned to LNG-IUD insertion, versus control conditions including expectant management, post-operative insertion of placebo (inert intrauterine device), or other medical treatment such as gonadotrophin-releasing hormone agonist (GnRH-a) drugs. Data collection and analysis: Two review authors independently selected studies for inclusion, and extracted data to allow for an intention-to-treat analysis. For dichotomous data, we calculated the risk ratio (RR) and 95% confidence interval (CI) using the Mantel-Haenszel fixed-effect method. For continuous data, we calculated the mean difference (MD) and 95% CI using the inverse variance fixed-effect method. Main results: Four RCTs were included, with a total of 157 women. Two studies are ongoing. The GRADE certainty of evidence was very low to low. The certainty of evidence was graded down primarily for serious risk of bias and imprecision. LNG-IUD versus expectant management Overall pain: No studies reported on the primary outcome of overall pain. Dysmenorrhoea: We are uncertain whether LNG-IUD improves dysmenorrhoea at 12 months. Data on this outcome were reported on by two RCTs; meta-analysis was not possible (RCT 1: delta of median visual analogue scale (VAS) 81 versus 50, P = 0.006, n = 55; RCT 2: fall in VAS by 50 (35 to 65) versus 30 (25 to 40), P = 0.021, n = 40; low-certainty evidence). Quality of life: We are uncertain whether LNG-IUD improves quality of life at 12 months. One trial demonstrated a change in total quality of life score with postoperative LNG-IUD from baseline (mean 61.2 (standard deviation (SD) 14.8) to 12 months (mean 70.3 (SD 16.2) compared to expectant management (baseline 55.1 (SD 17.0) to 57.0 (SD 33.2) at 12 months) (n = 55, P = 0.014, very low-certainty evidence). Patient satisfaction: Two studies found higher rates of satisfaction with LNG-IUD compared to expectant management; however, combining the studies in meta-analysis was not possible (n = 95, very low-certainty evidence). One study found 75% (15/20) of those given post-operative LNG-IUD were "satisfied" or "very satisfied", compared to 50% (10/20) of those in the expectant management group (RR 1.5, 95% CI 0.90-2.49, 1 RCT, n=40, very low-certainty evidence). The second study found that fewer were "very satisfied" in the expectant management group when compared to LNG, but there were no data to include in a meta-analysis. Adverse events: One study found a significantly higher proportion of women reporting melasma (n = 55, P = 0.015, very low-certainty evidence) and bloating (n = 55, P = 0.021, very low-certainty evidence) following post-operative LNG-IUD. There were no differences in other reported adverse events, such as weight gain, acne, and headaches. LNG-IUD versus GnRH-a Overall pain: No studies reported on the primary outcome of overall pain. Chronic pelvic pain: We are uncertain whether LNG-IUD improves chronic pelvic pain at 12 months when compared to GnRH-a (VAS pain scale) (MD -2.0, 95% CI -20.2 to 16.2, 1 RCT, n = 40, very low-certainty evidence). Dysmenorrhoea: We are uncertain whether LNG-IUD improves dysmenorrhoea at six months when compared to GnRH-a (measured as a reduction in VAS pain score) (MD 1.70, 95%.CI -0.14 to 3.54, 1 RCT, n = 18, very low-certainty evidence). Adverse events: One study suggested that vasomotor symptoms were the most common adverse events reported with patients receiving GnRH-a, and irregular bleeding in those receiving LNG-IUD (n = 40, very low-certainty evidence) AUTHORS' CONCLUSIONS: Post-operative LNG-IUD is widely used to reduce endometriosis-related pain and to improve operative outcomes. This review demonstrates that there is no high-quality evidence to support this practice. This review highlights the need for further studies with large sample sizes to assess the effectiveness of post-operative adjuvant hormonal IUD on the core endometriosis outcomes (overall pain, most troublesome symptom, and quality of life).
Article
Even if laparoscopy is awarded the status of a gold standard in the diagnosis of involuntary childlessness, assisted reproductive techniques (ART) have initiated a paradigm shift and many steps in the fertilization process are technically assisted. The question arises as to what evidence exists for the use of laparoscopy for the various causes of sterility. It is laparoscopy that keeps the proportion of so-called unexplained sterility low and that can be immediately expanded to include a surgical intervention. In the case of tubal pathology, laparoscopic salpingo-ovariolysis with preserved tubal patency leads to results that are superior to ART. Among the Fédération internationale de gynécologie et dʼobstétrique (FIGO) myoma types 0, 1, 2, 2–5, 3, 4, 5, 6, the myomas adjacent to the cavity of the uterus develop the highest fertility-blocking effects, which must also be assumed for the myoma types 3, 4, 5, 6, although the cavity is not distorted. Myoma types 0, 1, 2 are a domain of hysteroscopic surgical techniques, all others myomas can successfully be operated on laparoscopically as long as there is a sufficiently high plane between the optical trocar and the object for the insertion of the working trocars. For the various phenotypes of endometriosis, priority is given to laparoscopic intervention in cases of treatment-resistant pain. In particular, stenosing processes in the urinary tract and the intestines are indications for laparoscopy. In cases of hydrosalpinx, a benefit is ensured by laparoscopic salpingectomy before in vitro fertilization (IVF). There are subgroups of endometriosis that benefit from the principle of surgery first before ART.
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STUDY QUESTION What are the similarities and differences in endometrial B cells in the normal human endometrium and benign reproductive pathologies? SUMMARY ANSWER Endometrial B cells typically constitute less than 5% of total endometrial CD45+ lymphocytes, and no more than 2% of total cells in the normal endometrium, and while their relative abundance and phenotypes vary in benign gynaecological conditions current evidence is inconsistent. WHAT IS KNOWN ALREADY B cells are vitally important in the mucosal immune environment and have been extensively characterised in secondary lymphoid organs and tertiary lymphoid structures (TLSs), with the associated microenvironment germinal centre. However, in the endometrium, B cells are largely overlooked, despite the crucial link between autoimmunity and reproductive pathologies and the fact that B cells are present in normal endometrium and in benign female reproductive pathologies, scattered or in the form of lymphoid aggregates (LAs). A comprehensive summary of current data investigating B cells will facilitate our understanding of endometrial B cells in the endometrial mucosal immune environment. STUDY DESIGN, SIZE, DURATION This systematic review retrieved relevant studies from four databases (MEDLINE, EMBASE, Web of Science Core Collection, CINAHL) from database inception until November 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS The search strategy combined the use of subject headings and relevant text words related to ‘endometrium’, ‘B cells’ and B cell derivatives such as ‘antibody’ and ‘immunoglobulin’. Non-benign diseases were excluded using cancer related free-text terms, and searches were limited to English language and human subjects. Only peer-reviewed research papers were included. Each paper was graded as ‘Good’, ‘Fair’, or ‘Poor’ quality based on the NEWCASTLE-OTTAWA quality assessment scale. Only ‘Good’ quality papers were included. MAIN RESULTS AND THE ROLE OF CHANCE Twenty-seven studies met the selection criteria and were included in this review: 10 cross-sectional studies investigated B cells in the normal endometrium; and 17 case-control studies compared the characteristics of endometrial B cells in control and benign female reproductive pathologies including endometritis, endometriosis, infertility, abnormal uterine bleeding, endometrial polyps and uterine fibroids. In all studies, B cells were present in the endometrium, scattered or in the form of LAs. CD20+ B cells were more abundant in patients with endometritis, but the data were inconsistent as to whether B cell numbers were increased in endometriosis and patients with reproductive pathologies. LIMITATIONS, REASONS FOR CAUTION Although only “good” quality papers were included in this systematic review, there are variations in patients’ age, diagnostic criteria for different diseases and sample collection time among included studies. Additionally, a large number of the included studies only used immunohistochemistry as the identification method for endometrial B cells, which may fail to provide an accurate representation of the numbers of endometrial B cells. WIDER IMPLICATIONS OF THE FINDINGS Histological studies found that endometrial B cells are either scattered or surrounded by T cells in LAs: the latter structure seems to be under hormonal control throughout the menstrual cycle and resembles TLSs that have been observed in other tissues. Further characterisation of endometrial B cells and LAs could offer insights to endometrial B cell function, particularly in the context of autoimmune-associated pathologies such as endometriosis. Additionally, clinicians should be aware of the limited value of diagnosing plasma cell infiltration using only CD138. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by Finox Biotech. The authors have no conflicts of interests to declare. PROSPERO REGISTRATION NUMBER This systematic review was registered in PROSPERO in January 2020 (PROSPERO ID: CRD42020152915).
Article
Introduction: Endometriosis is characterised by the presence of endometrium-like tissue outside the uterus, and is often associated with chronic pelvic pain, infertility, and compromised quality of life. Development of reliable methods of early diagnosis, staging, and classification of endometriosis would allow for restriction of disease progression by its early detection and strategising towards its early treatment and management. Diagnostic options: Typically, diagnosis and staging of endometriosis include a history and physical examination followed by clinical, imaging, and laparoscopic findings. Surgical inspection of lesions at laparoscopy with histological confirmation remains the most reliable procedure towards the detection of endometriosis and its classification. Although there are many putative peripheral biomarkers having potential diagnostic values for endometriosis, further studies are necessary for their validation. Classification systems: Based on anatomical, clinical, imaging, and several pathophysiological findings, various classifications and staging systems of endometriosis, e.g., revised American Society for Reproductive Medicine (rASRM), ENZIAN, Endometriosis Fertility Index (EFI) and Foci–Ovarian endometrioma–Adhesion–Tubal endometriosis–Inflammation (FOATI) scoring systems, have so far been postulated. However, there is no fool-proof diagnostic and classification approach available for the disease due to the general failure of current systems to reflect reproducible correlation with the major symptoms of endometriosis. Conclusion: A ‘toolbox approach’, using all the available diagnostic and classification systems maximising the information available to healthcare providers and females, is a recent recommendation. Development of collaborative research networks for the harmonisation of patient information, biological sample collection, and its storage, and that of methodological and analytical tools in a wider patient base is necessary to discover reliable leads for future diagnostic options and a classification system for endometriosis.
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Chronic pelvic pain (CPP) causes important negative effects on quality of life. Endometriosis is the most common cause of CPP in females, and diagnostic delay is over six years internationally. Data remain scarce for CPP impact or diagnostic delay in Aotearoa New Zealand. This study used an online survey to explore the impact of CPP on various life domains for those aged over 18. Additionally, for those with an endometriosis diagnosis, diagnostic delay and factors affecting this over time were explored. There were 800 respondent (620 with self-reported endometriosis). CPP symptoms, irrespective of final diagnosis, started prior to age 20 and negatively impacted multiple life domains including employment, education, and relationships. Mean diagnostic delay for those with endometriosis was 8.7 years, including 2.9 years between symptom onset and first presentation and 5.8 years between first presentation and diagnosis. Five doctors on average were seen prior to diagnosis. However, there was a reduction in the interval between first presentation and diagnosis over time, from 8.4 years for those presenting before 2005, to two years for those presenting after 2012. While diagnostic delay is decreasing, CPP, irrespective of aetiology, continues to have a significant negative impact on the lives of those affected.
Article
Endometriosis is a gynecological condition characterized by the growth of endometrium-like tissues inside and outside the pelvic cavity. The evolution of the disease can lead to infertility in addition to high treatment costs. Currently, available medications are only effective in treating endometriosis-related pain; however, it is not a targeted treatment. The objective of this work is to review the characteristics of the disease, the diagnostic means and treatments available, as well as to discuss new therapeutic options.
Article
Objective In the field of endometriosis, several classification, staging and reporting systems have been developed, but do clinicians routinely use these classification systems, which system do they use and what are the clinicians’ motivations? Data sources A cross-sectional study was performed to gather data on the current use of endometriosis classification systems, problems encountered and interest in a new simple surgical descriptive system for endometriosis. Of particular focus were three systems most commonly used: the Revised American Society for Reproductive Medicine (rASRM) classification, the Endometriosis Fertility Index (EFI), and the ENZIAN classification. Data were analysed by SPSS. A survey was designed using the online SurveyMonkey tool consisting of 11 questions concerning three domains—participants background, existing classification systems and intentions with regards to a new classification system for endometriosis. Replies were collected between 15 May and 1 July 2020. Methods of study selection na Tabulation, integration and results The final dataset included the replies of 1178 clinicians, including surgeons, gynecologists, reproductive endocrinologists, fertility specialists and sonographers, all managing women with endometriosis in their clinical practice. Overall, 75.5% of the professionals indicate that they currently use a classification system for endometriosis. The rASRM classification system was the best known and used system, the EFI system and ENZIAN system were known by a majority of the professionals but used by only a minority. The lack of clinical relevance was most often selected as a problem with using any system. The findings of the survey suggest that clinicians worldwide are open to using a new classification system for endometriosis that can achieve standardized reporting, and is clinically relevant and simple. The findings therefore support future initiatives for the development of a new descriptive system for endometriosis and provide information on user expectations and conditions for universal uptake of such a system. Conclusion Even with a high uptake of the existing endometriosis classification systems (rASRM, ENZIAN and EFI), most clinicians managing endometriosis would like a new simple surgical descriptive system for endometriosis.
Article
Endometriosis is a chronic gynecological disease affecting one in ten reproductive-age women. It is defined as the presence of endometrium-like tissue outside the uterus. Beyond this placid anatomical definition, endometriosis is a complex, hormonal, inflammatory, and systemic condition that poses significant familial, psychological, and economic burden. The interaction between the cardiovascular system and endometriosis has become a field of interest as the underlying mutual mechanisms become better understood. On the basis of accumulating fundamental and clinical evidence, it is likely that there exists a close relationship between endometriosis and the cardiovascular system. Therefore, investigating the endometriosis– cardiovascular interaction is highly clinically significant. In this Review, we highlight our current understanding of the pathophysiology of endometriosis with systemic hormonal, proinflammatory, pro-angiogenic, immunologic, and genetic processes beyond the peritoneal microenvironment. Additionally, we provide current clinical evidence about how endometriosis interact with cardiovascular risk factors and cardiovascular disease. To date, only small associations between endometriosis and cardiovascular disease have been reported in observational studies, inherently limited by the potential influence of unmeasured confounding. Cardiovascular disease in women with endometriosis remains understudied, under-recognized and underdiagnosed. More detailed study of the cardiovascular-endometriosis interaction is needed to fully understand its clinical relevance, underlying pathophysiology, possible means of early diagnosis and prevention.
Article
Background: Women with endometriosis may have an increased risk of adverse pregnancy outcomes. Research has focused on infertility clinic populations limiting generalisability. Few studies report differences by endometriosis severity. Objectives: We investigated the relationships between endometriosis diagnosis, staging and typology and pregnancy outcomes among an operative and population-based sample of women. Methods: Menstruating women ages 18-44 years enrolled in the ENDO Study (2007-2009), including the operative cohort: 316 gravid women undergoing laparoscopy/laparotomy at surgical centres in Utah and California; and the population cohort: 76 gravid women from the surgical centres' geographic catchment areas. Pregnancy outcomes were ascertained by questionnaire and included all pregnancies prior to study enrolment. Endometriosis was diagnosed via surgical visualisation in the operative cohort and pelvic magnetic resonance imaging in the population cohort. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) were estimated using generalised linear mixed models for pregnancy outcomes, adjusting for women's age at study enrolment and at pregnancy, surgical site, body mass index and lifestyle factors. Results: Women in the operative cohort with visualised endometriosis (n = 109, 34%) had a lower prevalence of live births, aPR 0.94 (95% CI 0.85, 1.03) and a higher prevalence of miscarriages, aPR 1.48 (95% CI 1.23, 1.77) compared with women without endometriosis. The direction and magnitude of estimates were similar in the population cohort. Women with deep endometriosis were 2.98-fold more likely (95% CI 1.12, 7.95) to report a miscarriage compared with women without endometriosis after adjusting for women's age at study enrolment and at pregnancy, surgical site and body mass index. No differences were seen between endometriosis staging and pregnancy outcomes. Conclusions: While there was no difference in number of pregnancies among women with and without endometriosis in a population-based sample, pregnancy loss was more common among women with endometriosis, notably among those with deep endometriosis.
Article
Objective: To evaluate the effect of hormonal suppression on fertility when administered to infertile patients or patient wishing to conceive after surgery for endometriosis. Data sources: A systematic search of MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov was performed by two independent reviewers from the databases' inception until December 2020. Methods of study selection: We included randomized controlled trials comparing any suppressive hormonal therapy to an inactive control (placebo or absence of treatment) after conservative surgery for endometriosis. Studies that did not report fertility outcomes after surgery were excluded. Tabulation, integration and results: This systematic review and meta-analysis was registered in PROSPERO. Two reviewers extracted data and assessed the risk of bias as well as the strength of evidence using GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines were followed. Relative risks (RRs) were pooled by quantitative random effect meta-analysis. From 3,138 citations, 19 trials (2,028 patients) were included. Overall, no difference was observed between the treatment and the control group for pregnancy (RR 1.15; 95% CI 1.00-1.32) and live births (RR 1.05; 95% CI 0.84-1.32). When pooling all hormonal therapies, the duration of administration of postoperative therapy was identified as a substantial source of heterogeneity between studies (I2 difference=74%) with increased chances of pregnancy compared with control when administered for at least 3 months (RR 1.22; 95% CI 1.04-1.43). Gonadotropin-releasing hormone (GnRH) agonists (14 trials, 1,721 patients) were associated with increased chances of pregnancy compared with placebo or no treatment (RR 1.20; 95% CI 1.03-1.41; I2=25%). Data were limited for other hormonal treatments with no significant difference between groups. Subgroup analyses taking into account the use of fertility treatments (insemination or in vitro fertilization), stages of the disease and risk of bias of included trials did not modify the results. Conclusion: Postoperative hormonal suppression should be considered on a case-by-case basis to enhance fertility while balancing this benefit with the risks of delaying conception. If chosen, GnRH agonists would be the treatment of choice, and a duration of at least 3 months should be favored. Systematic review registration: PROSPERO, CRD42021224424.
Article
There is no licensed treatment for refractory chronic cough; off-label therapies have limited efficacy and can produce adverse effects. Excessive adenosine triphosphate signaling via P2X3 receptors is implicated in refractory chronic cough, and selective P2X3 receptor antagonists such as eliapixant (BAY 1817080) are under investigation. The objective of the study was to investigate the safety and tolerability of ascending repeated oral doses of eliapixant in healthy volunteers. We conducted a repeated-dose, double-blind, randomized, placebo-controlled study in 47 healthy male individuals. Subjects received repeated twice-daily ascending oral doses of eliapixant (10, 50, 200, and 750 mg) or placebo for 2 weeks. The primary outcome was frequency and severity of adverse events. Other outcomes included pharmacokinetics and evaluation of taste disturbances, which have occurred with the less selective P2X3 receptor antagonist gefapixant. Peak plasma concentrations of eliapixant were reached 3–4 h after administration of the first and subsequent doses. With multiple dosing, steady-state plasma concentrations were reached after ~ 6 days, and plasma concentrations predicted to achieve ≥ 80% P2X3 receptor occupancy (the level required for efficacy) were reached at 200 and 750 mg. Increases in plasma concentrations with increasing doses were less than dose proportional. After multiple dosing, mean plasma concentrations of eliapixant showed low peak–trough fluctuations and were similar for 200- and 750-mg doses. Eliapixant was well tolerated with a low incidence of taste-related adverse events. Eliapixant (200 and 750 mg) produced plasma concentrations that cover the predicted therapeutic threshold over 24 h, with good safety and tolerability. These results enabled eliapixant to progress to clinical trials in patients with refractory chronic cough. Clinicaltrials.gov: NCT03310645 (initial registration: 16 October, 2017). There are few effective treatments for patients with a long-term (chronic) cough. It is thought that chronic cough is caused by nerves becoming oversensitive, wrongly causing a cough when there is no need. We tested a new drug called eliapixant in 47 healthy men. Eliapixant reduces the excessive nerve signaling responsible for chronic cough. We looked for side effects of eliapixant and measured how it behaves in the body. In particular we looked for side effects relating to the sense of taste because gefapixant, a similar drug to eliapixant, can affect taste. Participants took one of four eliapixant doses or a placebo twice daily for 2 weeks. The highest levels of eliapixant in the blood were seen 3–4 h after taking the drug, and stable concentrations were seen after about 6 days. At the two highest doses, eliapixant reached concentrations in the body that should be high enough to work in patients with chronic cough. Side effects were generally similar between eliapixant and placebo. Taste-related side effects were mild and went away without needing treatment. The positive results of this study meant that eliapixant could be tested in patients with chronic cough.
Chapter
Classification of the disease has been used primarily for the postoperative staging of the disease. Unfortunately, the most commonly used rASRM classification does not correlate with symptoms or other important parameters, and cannot be used for non-invasive diagnostics. Moreover, it does not take into account deep infiltrating endometriosis but also extra pelvic endometriosis. The EFI is for calculating the probability of pregnancy but does not contain differential information on the location and extent of lesions. The ENZIAN classification is predominantly used to describe DE. The applicability of the Enzian classification with MRI and TVS is possible and allows to assess the difficulty of the surgical procedure and the risk of surgery. The recently released updated version, called the #ENZIAN classification, represents a comprehensive description of peritoneal and ovarian endometriosis as well as adnexal adhesions in addition to deep endometriosis. This system is anatomically logical, easy to use, and more reproducible, providing the physician with a clear picture of the disease. The good correlation between the non-invasive and surgical description of the extent of the disease based on the #Enzian scheme provides a consistent and clear classification of endometriosis, especially DE, but also secondary adhesions.
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Purpose This article presents a novel concept of the evolution and, thus, the pathogenesis of uterine adenomyosis as well as peritoneal and peripheral endometriosis. Presently, no unifying denomination of this nosological entity exists. Methods An extensive search of the literature on primate evolution was performed. This included comparative functional morphology with special focus on the evolution of the birthing process that fundamentally differs between the haplorrhine primates and most of the other eutherian mammals. The data were correlated with the results of own research on the pathophysiology of human archimetrosis and with the extant presentation of the disease. Results The term Archimetrosis is suggested as a denomination of the nosological entity. Archimetrosis occurs in human females and also in subhuman primates. There are common features in the reproductive process of haplorrhine primates such as spontaneous ovulation and corpus luteum formation, spontaneous decidualization and menstruation. These have fused Müllerian ducts resulting in a uterus simplex. Following a usually singleton pregnancy, the fetus is delivered in the skull position. Some of these features are shared by other mammals, but not in that simultaneous fashion. In haplorrhine primates, with the stratum vasculare, a new myometrial layer has evolved during the time of the Cretaceous–Terrestrial Revolution (KTR) that subserves expulsion of the conceptus and externalization of menstrual debris in non-conceptive cycles. Hypercontractility of this layer has evolved as an advantage with respect to the survival of the mother and the birth of a living child during delivery and may be experienced as primary dysmenorrhea during menstruation. It may result in tissue injury by the sheer power of the contractions and possibly by the associated uterine ischemia. Moreover, the lesions at extra-uterine sites appear to be maintained by biomechanical stress. Conclusions Since the pathogenesis of archimetrosis is connected with the evolution of the stratum vasculare, tissue injury and repair (TIAR) turns out to be the most parsimonious explanation for the development of the disease based on clinical, experimental and evolutionary evidence. Furthermore, a careful analysis of the published clinical data suggests that, in the risk population with uterine hypercontractility, the disease develops with a yet to be defined latency phase after the onset of the biomechanical injury. This opens a new avenue of prevention of the disease in potentially affected women that we consider to be primarily highly fertile.
Article
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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.
Article
Objective: To evaluate the effect of a sex education program on sexual function and sexual quality of life in women with endometriosis. Methods: In a quasi-experimental study, women with endometriosis who had undergone laparoscopic surgery were assigned to an intervention group (n = 36) or a control group (n = 36). The intervention group received a sex education program consisting of two sessions a week (90 minutes each) for two consecutive weeks; the control group received none. Both groups were followed for 12 weeks. Sexual function and sexual quality of life were assessed on the Female Sexual Function Index (FSFI) and the Sexual Quality of life-Female (SQOL-F) questionnaire before the intervention, as well as 8 and 12 weeks after the intervention. Outcomes were analyzed using Student's t-test, the Chi-square test (χ2), Fisher's exact test, and repeated measures analysis of variance (rANOVA). Results: The mean age of the study participants was 36.9 ± 5.7 years. The two groups did not differ significantly in terms of demographics and pre-intervention clinical characteristics. At the end of the study, sex education reduced Female Sexual Dysfunction (FSD) by 58.1% in the intervention group. The mean FSFI score increased significantly in the intervention group from pre-intervention to 8 and 12 weeks post-intervention compared to the scores in the control group (p < 0.001). Conclusions: Sex education appears to be a promising intervention for reducing sexual dysfunction and improving sexual function and sexual quality of life in women with endometriosis. Future studies should encompass longer periods of follow-up in order to obtain further data on the efficacy of sex education in this setting.
Article
Introduction When using Chinese Herbal Medicine (CHM) to treat endometriosis, the effects of CHM on the ovarian functions have received little attention. This systematic review and meta-analysis aimed to evaluate the effects and safety of CHM on the ovarian functions in patients with endometriosis. Methods Eight electronic databases were searched from their inception to March 2, 2021. We compared the CHM group to the control group, all of which included were randomized controlled trials (RCTs). Statistical analysis was performed through standard mean difference of hormonal levels: Estradiol(E2), Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH). Subgroup analysis and sensitivity analysis were conducted. Results A total of 844 patients from 11 RCTs were included. In E2 levels, the analysis revealed a significant effect in favour of CHM group comparing to the control group (SMD=3.05, 95%CI=0.29 to 1.32, P=0.002).Through the subgroup analyses, there were still significant effects in both nonoperative subgroup (SMD=2.04, 95%CI=0.04 to 1.88, P=0.04) and postoperative subgroup (SMD=2.19, 95%CI=0.08 to 1.42, P=0.03). There were no significant differences between the two subgroups in both FSH levels (P > 0.05) and LH levels (P > 0.05), and the subgroup analyses got similar results. No adverse events were reported. Conclusions CHM may improve ovarian functions in patients with endometriosis through increasing E2 levels whether surgery or not, which may provide a referable and safe treatment of endometriosis. Due to the weak evidence, high-quality clinical trials are needed to support this conclusion. (PROSPERO ID is CRD42021240162)
Article
Full-text available
Chronic pelvic pain (CPP) causes important negative effects on quality of life. Endometriosis is the most common cause of CPP in females, and diagnostic delay is over six years internationally. Data remain scarce for CPP impact or diagnostic delay in Aotearoa New Zealand. This study used an online survey to explore the impact of CPP on various life domains for those aged over 18. Additionally, for those with an endometriosis diagnosis, diagnostic delay and factors affecting this over time were explored. There were 800 respondent (620 with self-reported endometriosis). CPP symptoms, irrespective of final diagnosis, started prior to age 20 and negatively impacted multiple life domains including employment, education, and relationships. Mean diagnostic delay for those with endometriosis was 8.7 years, including 2.9 years between symptom onset and first presentation and 5.8 years between first presentation and diagnosis. Five doctors on average were seen prior to diagnosis. However, there was a reduction in the interval between first presentation and diagnosis over time, from 8.4 years for those presenting before 2005, to two years for those presenting after 2012. While diagnostic delay is decreasing, CPP, irrespective of aetiology, continues to have a significant negative impact on the lives of those affected.
Article
Objectives To assess whether hysterectomy in patients with endometriosis is associated with higher proportion of complications compared with patients without, and whether route of hysterectomy affects this outcome. Study design This is a population-based retrospective cohort study. Data were prospectively obtained from three National Swedish Registers. Patients undergoing a benign hysterectomy between 2015 and 2017 in Sweden were included in the study and were grouped according to a histology-proven diagnosis of endometriosis. Different hysterectomy modes were compared in patients with endometriosis. Perioperative data and postoperative complications up to 1 year after surgery were collected and measured. Results In all, 8,747 patients underwent a benign hysterectomy, and 1,166 patients with endometriosis was compared with 7,581 patients without. Patients with endometriosis had higher proportion of complications (adjusted Odds ratio aOR 1.2, 95% CI 1.0-1.4), were more often converted to abdominal hysterectomy (aOR 1.7, 95% CI 1.1-2.6), had higher estimated blood loss (EBL) (200-500 ml; aOR 1.8, 95% CI 1.4-2.3, >500 ml; aOR 3.1, 95% CI 2.2-4.4) and a longer operative time (1-2 hours; aOR 2.1, 95% CI 1.4-3.2, >2 hours; aOR 4.3, 95% CI 2.7-6.6) than endometriosis-free patients. The conversion rate was 13.8 times higher in total laparoscopic hysterectomy (TLH) compared with robotic-assisted laparoscopic hysterectomy (RATLH) (aOR 13.8, 95% CI 3.6-52.4). Conclusion Higher conversion rate, higher EBL and higher frequency of complications were seen in patients with endometriosis. RATLH was associated with lower conversion rate compared to TLH.
Article
Study question: Which classification system for endometriosis do clinicians use most frequently, and why? Summary answer: Even with a high uptake of the three existing endometriosis classification systems, most clinicians managing endometriosis would like a new simple surgical descriptive system for endometriosis. What is known already: In the field of endometriosis, several classifications, staging and reporting systems have been developed and published, but there are no data on the uptake of these systems in clinical practice. Study design size duration: A survey was designed using the online SurveyMonkey tool consisting of 11 questions concerning three domains-participants background, existing classification systems and intentions with regards to a new classification system for endometriosis. Replies were collected between 15 May and 1 July 2020. Participants/materials setting methods: A cross-sectional study was performed to gather data on the current use of endometriosis classification systems, problems encountered and interest in a new simple surgical descriptive system for endometriosis. The particular focus was on the three systems most commonly used: the Revised American Society for Reproductive Medicine (rASRM) classification, the endometriosis fertility index (EFI), and the ENZIAN classification. Data were analysed to detect statistically significant differences among user groups. Main results and the role of chance: The final dataset included the replies of 1178 clinicians, including surgeons, gynaecologists, reproductive endocrinologists, fertility specialists and sonographers, all managing women with endometriosis in their clinical practice. Overall, 75.5% of the professionals indicate that they currently use a classification system for endometriosis. The rASRM classification system was the best known and used system, while the EFI system and ENZIAN system were known by a majority of the professionals but used by only a minority. The lack of clinical relevance was most often selected as a problem with using any system. The vast majority of respondents replied positively to the question on whether they would use a simple surgical descriptive system available for endometriosis, if available. Limitations reasons for caution: While the total number of respondents was acceptable, some regions/professions were not sufficiently represented to draw conclusions. Wider implications of the findings: The findings of the survey suggest that clinicians worldwide are open to using a new classification system for endometriosis that can achieve standardized reporting and is clinically relevant and simple. The findings therefore support future initiatives for the development of a new descriptive system for endometriosis and provide information on user expectations and conditions for universal uptake of such a system. Study funding/competing interests: The meetings and activities of the working group were funded by the American Association of Gynecologic Laparoscopists, European Society for Gynecological Endoscopy, ESHRE and World Endometriosis Society. A.W.H. reports grant funding from the MRC, NIHR, CSO, Roche Diagnostics, Astra Zeneca, Ferring, Charles Wolfson Charitable Trust, Standard Life, and consultancy fees from Roche Diagnostics, AbbVie, Nordic Pharma and Ferring, outside the submitted work. In addition, A.W.H. has a patent Serum biomarker for endometriosis pending. He is Chair of TSC for STOP-OHSS and CERM trials and Chair of RCOG Academic Board 2018-2021. M.A. reports being member of the executive board and vice president of AAGL. N.P.J. reports personal fees from Abbott, Guerbet, Myovant Sciences, Vifor Pharma, Roche Diagnostics outside the submitted work; he is also President of the World Endometriosis Society and chair of the trust board. S.M. reports grants from AbbVie, DoD, NIH and Marriot Family Foundation, honoraria from University British Columbia and WERF, support for speaking at conferences (ESHRE, CanSAGE, Endometriosis UK, UEARS, IFFS, IASP, National Endometriosis Network UK) participation on Advisory Boards from AbbVie and Roche, outside the submitted work. She also discloses having a leadership or fiduciary role in SWHR, WERF, WES, ASRM and ESHRE. C.T. reports grants, consulting and speakers' fees non-financial support and other from Merck SA, non-financial support and other consulting fees from Gedeon Richter and Nordic Pharma, and support for meeting attendance non-financial support from Ferring Pharmaceuticals, outside the submitted work and without private revenue. K.T.Z. reports grants from Bayer Healthcare, MDNA Life Sciences, Volition Rx, and Evotec (Lab282-Partnership programme with Oxford University), non-financial support from AbbVie Ltd, all outside the submitted work; and is a Board member (Secretary) of the World Endometriosis Society and World Endometriosis Research Foundation. J.P. reports personal fees from Hologic, Inc., outside the submitted work; he is also a member of the executive boards of ASRM and SRS. The other authors had nothing to disclose.
Article
Objective To investigate the heterogeneity of somatic cancer-driver mutations within patients and across endometriosis types. Design A single-center cohort, retrospective study. Setting Tertiary specialist-care center at a university hospital. Patient(s) Patients with surgically and histologically confirmed endometriosis of at least 2 anatomically distinct types (ovarian, deep infiltrating, and superficial). Intervention(s) None. Main Outcome Measure(s) Specimens were analyzed for the presence or absence of somatic cancer-driver mutations using targeted panel sequencing with orthogonal validation using droplet digital polymerase chain reaction and mutation-surrogate immunohistochemistry. Result(s) It was found that 13 of 27 patients had informative somatic driver mutations in endometriosis lesions; of these 13 patients, 9 had identical mutations across distinct lesions. Endometriomas showed a higher mutational complexity, with functionally redundant driver mutations in the same gene and within the same lesions. Conclusion(s) Our data are consistent with clonality across endometriosis lesions, regardless of subtype. Further, the finding of redundancy in mutations within the same gene and lesions is consistent with endometriosis representing an oligoclonal disease with dissemination likely to consist of multiple epithelial clones traveling together. This suggests that the current anatomically defined classification of endometriosis does not fully recognize the etiology of the disease. A novel classification should consider genomic and other molecular features to promote personalized endometriosis diagnosis and care.
Article
Background: In the field of endometriosis, several classification, staging and reporting systems have been developed and published, but there are no data on the uptake of these systems in clinical practice. Objectives: The objective of the current study was to examine whether clinicians routinely use the existing endometriosis classification systems, which system do they use and what are the clinicians' motivations? Materials and methods: A cross-sectional study was performed to gather data on the current use of endometriosis classification systems, problems encountered and interest in a new simple surgical descriptive system for endometriosis. Of particular focus were three systems most commonly used: the Revised American Society for Reproductive Medicine (rASRM) classification, the Endometriosis Fertility Index (EFI), and the ENZIAN classification. Data were analysed by SPSS. A survey was designed using the online SurveyMonkey tool consisting of 11 questions concerning three domains- participants' background, existing classification systems and intentions with regards to a new classification system for endometriosis. Replies were collected between 15 May and 1 July 2020. Main outcome measures: Uptake, feedback and future intentions. Results: The final dataset included the replies of 1178 clinicians, including surgeons, gynaecologists, reproductive endocrinologists, fertility specialists and sonographers, all managing women with endometriosis in their clinical practice. Overall, 75.5% of the professionals indicate that they currently use a classification system for endometriosis. The rASRM classification system was the best known and used system, the EFI system and ENZIAN system were known by a majority of the professionals but used by only a minority. The lack of clinical relevance was most often selected as a problem with using any system. The findings of the survey suggest that clinicians worldwide are open to using a new classification system for endometriosis that can achieve standardised reporting, and is clinically relevant and simple. Conclusions: Even with a high uptake of the existing endometriosis classification systems (rASRM, ENZIAN and EFI), most clinicians managing endometriosis would like a new simple surgical descriptive system for endometriosis. What is new?: The findings therefore support future initiatives for the development of a new descriptive system for endometriosis and provide information on user expectations and conditions for universal uptake of such a system.
Article
Full-text available
Endometriosis affects an estimated 176 million women worldwide during the prime years of their lives. Yet many clinical questions remain unanswered, treatment failures are common, and there is little investment in investigating disease mechanisms. The World Endometriosis Research Foundation (WERF) has been created to provide a global platform where resources and intelligence are pooled to enable international collaboration in order to find answers so that treatments for endometriosis can be improved and prevention can become reality in future generations of women. WERF is now working with 30 centres in 19 countries conducting prospective studies investigating the impact of endometriosis, disease predictability, and personal and societal cost. (Journal of Endometriosis 2010; 2: 3-6).
Article
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Objective To harmonize standard operating procedures (SOPs) and standardize the recording of associated data for collection, processing, and storage of human tissues relevant to endometriosis. Design An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries on five continents. Setting In 2013, two workshops were conducted followed by global consultation, bringing together 54 leaders in endometriosis research and sample processing from around the world. Patient(s) None. Intervention(s) Consensus SOPs were based on: 1) systematic comparison of SOPs from 24 global centers collecting tissue samples from women with and without endometriosis on a medium or large scale (publication on >100 cases); 2) literature evidence where available, or consultation with laboratory experts otherwise; and 3) several global consultation rounds. Main Outcome Measure(s) Standard recommended and minimum required SOPs for tissue collection, processing, and storage in endometriosis research. Result(s) We developed “recommended standard” and “minimum required” SOPs for the collection, processing, and storage of ectopic and eutopic endometrium, peritoneum, and myometrium, and a biospecimen data collection form necessary for interpretation of sample-derived results. Conclusion(s) The EPHect SOPs allow endometriosis research centers to decrease variability in tissue-based results, facilitating between-center comparisons and collaborations. The procedures are also relevant to research into other gynecologic conditions involving endometrium, myometrium, and peritoneum. The consensus SOPs are based on the best available evidence; areas with limited evidence are identified as requiring further pilot studies. The SOPs will be reviewed based on investigator feedback and through systematic triannual follow-up. Updated versions will be made available at: http://endometriosisfoundation.org/ephect.
Article
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Objective To harmonize the collection of nonsurgical clinical and epidemiologic data relevant to endometriosis research, allowing large-scale collaboration. Design An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries on five continents. Setting In 2013, two workshops followed by global consultation, bringing together 54 leaders in endometriosis research. Patients None. Intervention(s) Development of a self-administered endometriosis patient questionnaire (EPQ), based on [1] systematic comparison of questionnaires from eight centers that collect data from endometriosis cases (and controls/comparison women) on a medium to large scale (publication on >100 cases); [2] literature evidence; and [3] several global consultation rounds. Main Outcome Measure(s) Standard recommended and minimum required questionnaires to capture detailed clinical and covariate data. Result(s) The standard recommended (EPHect EPQ-S) and minimum required (EPHect EPQ-M) questionnaires contain questions on pelvic pain, subfertility and menstrual/reproductive history, hormone/medication use, medical history, and personal information. Conclusion(s) The EPQ captures the basic set of patient characteristics and exposures considered by the WERF EPHect Working Group to be most critical for the advancement of endometriosis research, but is also relevant to other female conditions with similar risk factors and/or symptomatology. The instruments will be reviewed based on feedback from investigators, and—after a first review after 1 year—triannually through systematic follow-up surveys. Updated versions will be made available through http://endometriosisfoundation.org/ephect.
Article
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Objective: To standardize the recording of surgical phenotypic information on endometriosis and related sample collections obtained at laparoscopy, allowing large-scale collaborative research into the condition. Design: An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries. Setting: Two workshops were conducted in 2013, bringing together 54 clinical, academic, and industry leaders in endometriosis research and management worldwide. Patient(s): None. Intervention(s): A postsurgical scoring sheet containing general and gynecological patient and procedural information, extent of disease, the location and type of endometriotic lesion, and any other findings was developed during several rounds of review. Comments and any systematic surgical data collection tools used in the reviewers' centers were incorporated. Main Outcome Measure(s): The development of a standard recommended (SSF) and minimum required (MSF) form to collect data on the surgical phenotype of endometriosis. Result(s): SSF and MSF include detailed descriptions of lesions, modes of procedures and sample collection, comorbidities, and potential residual disease at the end of surgery, along with previously published instruments such as the revised American Society for Reproductive Medicine and Endometriosis Fertility Index classification tools for comparison and validation. Conclusion(s): This is the first multicenter, international collaboration between academic centers and industry addressing standardization of phenotypic data collection for a specific disease. The Endometriosis Phenome and Biobanking Harmonisation Project SSF and MSF are essential tools to increase our understanding of the pathogenesis of endometriosis by allowing large-scale collaborative research into the condition.
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Study question: Is there a global consensus on the management of endometriosis that considers the views of women with endometriosis? Summary answer: It was possible to produce an international consensus statement on the current management of endometriosis through engagement of representatives of national and international, medical and non-medical societies with an interest in endometriosis. What is known already: Management of endometriosis anywhere in the world has been based partially on evidence-based practices and partially on unsubstantiated therapies and approaches. Several guidelines have been developed by a number of national and international bodies, yet areas of controversy and uncertainty remain, not least due to a paucity of firm evidence. Study design, size, duration: A consensus meeting, in conjunction with a pre- and post-meeting process, was undertaken. Participants/materials, setting, methods: A consensus meeting was held on 8 September 2011, in conjunction with the 11th World Congress on Endometriosis in Montpellier, France. A rigorous pre- and post-meeting process, involving 56 representatives of 34 national and international, medical and non-medical organizations from a range of disciplines, led to this consensus statement. Main results and the role of chance: A total of 69 consensus statements were developed. Seven statements had unanimous consensus; however, none of the statements were made without expression of a caveat about the strength of the statement or the statement itself. Only two statements failed to achieve majority consensus. The statements covered global considerations, the role of endometriosis organizations, support groups, centres or networks of expertise, the impact of endometriosis throughout a woman's life course, and a full range of treatment options for pain, infertility and other symptoms related to endometriosis. Limitations, reasons for caution: This consensus process differed from that of formal guideline development. A different group of international experts from those participating in this process would likely have yielded subtly different consensus statements. Wider implications of the findings: This is the first time that a large, global, consortium, representing 34 major stake-holding organizations from five continents, has convened to systematically evaluate the best available current evidence on the management of endometriosis, and to reach consensus. In addition to 18 international medical organizations, representatives from 16 national endometriosis organizations were involved, including lay support groups, thus generating input from women who suffer from endometriosis.
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Several endometriosis classifications were proposed, based on the assumption that endometriosis is a progressive disease, and designed to score severity of visible lesions. In addition, several specific classifications, e.g., for deep endometriosis, were proposed. None of these classifications however, have been validated to be predictive for diagnosis, treatment prognosis, recurrence, progression or for the associated infertility or pain. The difficulties derive from the fact that pathophysiology and the natural history are still uncertain. A classification should avoid assumptions. It seems established beyond reasonable doubt that endometriosis presents as subtle, typical, cystic, and deep lesions and that severity of each lesion is related to size or volume. By pathology, these four lesions present as active, burnt-out, inactive, and active lesions, respectively. Besides this, there are many uncertainties. It is unclear whether endometriosis is one disease progressing ultimately into severe endometriosis or whether typical, cystic, and deep endometriosis represents three different diseases, each being an end stage. It is unclear whether endometriotic cells are different from endometrial cells or whether only the environment is different. It is unclear how adenomyosis, Müllerianosis, and peritoneal pockets should be considered. We therefore suggest a descriptive classification with the severity of Subtle, Typical, Cystic, Deep, Adenomyotic, and peritoneal pocket lesions, estimated by their area or volume. This classification should permit to evaluate the actual uncertainties in order to build subsequently a validated classification. The similarity of the classes for superficial and cystic lesions with the rAFS classification is considered an advantage. It is discussed why adhesions need not to be scored. In conclusion, a simple classification scoring separately severity of subtle, typical, cystic, deep, adenomyotic, and peritoneal pocket lesions is suggested. This will permit to confirm or reject statistically many of the actual uncertainties on endometriosis and to evaluate what the predictive power of the severity of each type of lesion is, both essential elements for a validated endometriosis classification. KeywordsClassification–Endometriosis–Adenomyosis–Peritoneal pockets–Müllerianosis
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