Field Of Endometriosis Research Articles

Unveiling the fibrotic puzzle of endometriosis: An overlooked concern calling for prompt action

Endometriosis is a benign, estrogen-dependent, persistent chronic inflammatory heterogeneous condition that features adhesions caused by estrogen-dependent periodic bleeding. It is characterised by a widely spread fibrotic interstitium that comprising of fibroblasts, myofibroblasts, collagen fibres, extracellular proteins, inflammatory cells, and active angiogenesis found outside the uterus. Thus, fibrosis is recognized as a critical component because of which current treatments, such as hormonal therapy and surgical excision of lesions are largely ineffective with severe side effects, high recurrence rates, and significant morbidity. The symptoms include dysmenorrhea (cyclic or non-cyclic), dyspareunia, abdominal discomfort, and infertility. The significant lack of knowledge regarding the underlying root cause, etiology, and complex pathogenesis of this debilitating condition, makes it challenging to diagnose early and to implement therapeutic approaches with minimal side effects presenting substantial hurdles in endometriosis management. Research on understanding the pathogenesis of endometriosis is still ongoing to find biomarkers and develop non-hormonal therapeutic approaches. Current clinical research indicates a close relationship between endometriosis and fibrosis, which is thought to be tightly linked to pain, a major factor for the decline in the patient’s quality of life but little is known about the underlying pathophysiological cellular and molecular signaling pathways that lead to endometriosis-related fibrosis. The available experimental disease models have tremendous challenges in reproducing the human characteristics of the disease to assess treatment effectiveness. Future translational research on the topic has been hindered by the lack of an adequate fibrotic model of endometriosis emphasizing the necessity of etiological exploration. This review article’s goal is to examine recent developments in the field and pinpoint knowledge gaps that exist with a focus on the development of novel fibrotic mouse models for the early diagnosis and treatment of endometriosis and how this knowledge aids in the development of novel anti-fibrotic treatments which opens fresh avenues for a thorough investigation and extended research in the field of endometriosis.

Unveiling the fibrotic puzzle of endometriosis: An overlooked concern calling for prompt action

Endometriosis is a benign, estrogen-dependent, persistent chronic inflammatory heterogeneous condition that features adhesions caused by estrogen-dependent periodic bleeding. It is characterised by a widely spread fibrotic interstitium that comprising of fibroblasts, myofibroblasts, collagen fibres, extracellular proteins, inflammatory cells, and active angiogenesis found outside the uterus. Thus, fibrosis is recognized as a critical component because of which current treatments, such as hormonal therapy and surgical excision of lesions are largely ineffective with severe side effects, high recurrence rates, and significant morbidity. The symptoms include dysmenorrhea (cyclic or non-cyclic), dyspareunia, abdominal discomfort, and infertility. The significant lack of knowledge regarding the underlying root cause, etiology, and complex pathogenesis of this debilitating condition, makes it challenging to diagnose early and to implement therapeutic approaches with minimal side effects presenting substantial hurdles in endometriosis management. Research on understanding the pathogenesis of endometriosis is still ongoing to find biomarkers and develop non-hormonal therapeutic approaches. Current clinical research indicates a close relationship between endometriosis and fibrosis, which is thought to be tightly linked to pain, a major factor for the decline in the patient’s quality of life but little is known about the underlying pathophysiological cellular and molecular signaling pathways that lead to endometriosis-related fibrosis. The available experimental disease models have tremendous challenges in reproducing the human characteristics of the disease to assess treatment effectiveness. Future translational research on the topic has been hindered by the lack of an adequate fibrotic model of endometriosis emphasizing the necessity of etiological exploration. This review article’s goal is to examine recent developments in the field and pinpoint knowledge gaps that exist with a focus on the development of novel fibrotic mouse models for the early diagnosis and treatment of endometriosis and how this knowledge aids in the development of novel anti-fibrotic treatments which opens fresh avenues for a thorough investigation and extended research in the field of endometriosis.

Artificial Intelligence in the Management of Women with Endometriosis and Adenomyosis: Can Machines Ever Be Worse Than Humans?

Artificial intelligence (AI) is experiencing advances and integration in all medical specializations, and this creates excitement but also concerns. This narrative review aims to critically assess the state of the art of AI in the field of endometriosis and adenomyosis. By enabling automation, AI may speed up some routine tasks, decreasing gynecologists' risk of burnout, as well as enabling them to spend more time interacting with their patients, increasing their efficiency and patients' perception of being taken care of. Surgery may also benefit from AI, especially through its integration with robotic surgery systems. This may improve the detection of anatomical structures and enhance surgical outcomes by combining intra-operative findings with pre-operative imaging. Not only that, but AI promises to improve the quality of care by facilitating clinical research. Through the introduction of decision-support tools, it can enhance diagnostic assessment; it can also predict treatment effectiveness and side effects, as well as reproductive prognosis and cancer risk. However, concerns exist regarding the fact that good quality data used in tool development and compliance with data sharing guidelines are crucial. Also, professionals are worried AI may render certain specialists obsolete. This said, AI is more likely to become a well-liked team member rather than a usurper.

Construction and evaluation of endometriosis diagnostic prediction model and immune infiltration based on efferocytosis-related genes.

Background: Endometriosis (EM) is a long-lasting inflammatory disease that is difficult to treat and prevent. Existing research indicates the significance of immune infiltration in the progression of EM. Efferocytosis has an important immunomodulatory function. However, research on the identification and clinical significance of efferocytosis-related genes (EFRGs) in EM is sparse. Methods: The EFRDEGs (differentially expressed efferocytosis-related genes) linked to datasets associated with endometriosis were thoroughly examined utilizing the Gene Expression Omnibus (GEO) and GeneCards databases. The construction of the protein-protein interaction (PPI) and transcription factor (TF) regulatory network of EFRDEGs ensued. Subsequently, machine learning techniques including Univariate logistic regression, LASSO, and SVM classification were applied to filter and pinpoint diagnostic biomarkers. To establish and assess the diagnostic model, ROC analysis, multivariate regression analysis, nomogram, and calibration curve were employed. The CIBERSORT algorithm and single-cell RNA sequencing (scRNA-seq) were employed to explore immune cell infiltration, while the Comparative Toxicogenomics Database (CTD) was utilized for the identification of potential therapeutic drugs for endometriosis. Finally, immunohistochemistry (IHC) and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were utilized to quantify the expression levels of biomarkers in clinical samples of endometriosis. Results: Our findings revealed 13 EFRDEGs associated with EM, and the LASSO and SVM regression model identified six hub genes (ARG2, GAS6, C3, PROS1, CLU, and FGL2). Among these, ARG2, GAS6, and C3 were confirmed as diagnostic biomarkers through multivariate logistic regression analysis. The ROC curve analysis of GSE37837 (AUC = 0.627) and GSE6374 (AUC = 0.635), along with calibration and DCA curve assessments, demonstrated that the nomogram built on these three biomarkers exhibited a commendable predictive capacity for the disease. Notably, the ratio of nine immune cell types exhibited significant differences between eutopic and ectopic endometrial samples, with scRNA-seq highlighting M0 Macrophages, Fibroblasts, and CD8 Tex cells as the cell populations undergoing the most substantial changes in the three biomarkers. Additionally, our study predicted seven potential medications for EM. Finally, the expression levels of the three biomarkers in clinical samples were validated through RT-qPCR and IHC, consistently aligning with the results obtained from the public database. Conclusion: we identified three biomarkers and constructed a diagnostic model for EM in this study, these findings provide valuable insights for subsequent mechanistic research and clinical applications in the field of endometriosis.

Novel Diagnostic Methods for Endometriosis

Endometriosis is a detrimental disease that affects millions of women globally often resulting in symptoms as serious as infertility. While this disease is so prevalent, limited research and funding in search of diagnostic methods exists to this day. Currently, the gold standard for diagnosing endometriosis is through an extremely invasive surgery called a laparoscopy. As many women do not want to go through with this surgery it leads to countless women around the world unaware of the fact that they possess this disease. This paper intends to evaluate the accuracy and effectiveness of emerging diagnostic techniques such as biomarkers, imaging modalities, and additional tests for the early detection and diagnosis of endometriosis. Through a comprehensive literature review and examining existing studies, this paper aims to highlight the positives and negatives of various diagnostic methods in order to replace the gold standard invasive laparoscopy surgery. By evaluating these various diagnostic techniques, the use of biomarkers and targeting miRNA cells proved to be more promising for future diagnosis of endometriosis. They were cost-effective, reliable, and non-invasive. The other diagnostic methods were somewhat favorable however they lacked enough research and reliability. Through these evaluations, it is able to be seen that there are additional methods for diagnosing endometriosis which are far less invasive. More money and research is required in the field of endometriosis and women’s health, in general, to acquire FDA funding for these methods and allow for fewer women globally to suffer from the painful side effects of this harmful disease.

Endometriosis classification systems: an international survey to map current knowledge and uptake.

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. 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? 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. Uptake, feedback and future intentions. 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. 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. 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.

Peroxisome Proliferator-Activated Receptor Alpha (PPAR-α) as a Regulator of the Angiogenic Profile of Endometriotic Lesions.

Endometriosis is a disease that affects a significant proportion of women and its infiltrative pattern is entirely dependent on the vascular supply of lesions. Several factors seem to trigger the process of angiogenesis in endometriotic lesions. During the last years, peroxisome proliferator-activated receptors (PPARs), a group of nuclear proteins that regulate gene transcription and that seem to regulate energy consumption and expenditure, have been also implicated in the pathophysiology of angiogenesis. Their ability to regulate the course of cancer and improve the survival rates of patients has been extensively studied and seems to be partially dependent on alteration of the vascular supply of malignant lesions. Research in the field of endometriosis is scarce in the international literature and mainly focused on PPAR-gamma. However, indirect evidence suggests that PPAR-alpha (PPAR-α) may also regulate the vascular supply of endometriotic lesions as well. Specifically, PPAR-α agonists seem to downregulate angiogenesis by increasing the expression of several anti-angiogenic molecules, including thrombospondin-1 (TSP-1) and gypenoside 140 (gp140), as well as factors that are involved in the mitogen-activated protein kinase cascade. In the present article, we summarize existing indirect and direct evidence that indicates the existence of an association between the expression of PPAR-α and endometriosis to help future research in this field.

An International Terminology for Endometriosis, 2021.

Different classification systems have been developed for endometriosis, using different definitions for the disease, the different subtypes, symptoms and treatments. In addition, an International Glossary on Infertility and Fertility Care was published in 2017 by the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) in collaboration with other organisations. An international working group convened over the development of a classification or descriptive system for endometriosis. As a basis for such system, a terminology for endometriosis was considered a condition sine qua non. The aim of the current paper is to develop a set of terms and definitions on endometriosis that would be the basis for standardisation in disease description, classification and research. The working group listed a number of terms relevant to be included in the terminology, documented currently used and published definitions, and discussed and adapted them until consensus was reached within the working group. Following stakeholder review, further terms were added, and definitions further clarified. Although definitions were collected through published literature, the final set of terms and definitions is to be considered consensus-based. After finalisation of the first draft, the members of the international societies and other stakeholders were consulted for feedback and comments, which led to further adaptations. A list of 49 terms and definitions in the field of endometriosis is presented, including a definition for endometriosis and its subtypes, different locations, interventions, symptoms and outcomes. Endometriosis is defined as a disease characterised by the presence of endometrium-like epithelium and/or stroma outside the endometrium and myometrium, usually with an associated inflammatory process. The current paper outlines a list of 49 terms and definitions in the field of endometriosis. The application of the defined terms aims to facilitate harmonisation in endometriosis research and clinical practice. Future research may require further refinement of the presented definitions. A consensus based international terminology for endometriosis for clinical and research use.

Endometriosis classification, staging and reporting systems: a review on the road to a universally accepted endometriosis classification.

In the field of endometriosis, several classification, staging and reporting systems have been developed. However, endometriosis classification, staging and reporting systems that have been published and validated for use in clinical practice have not been systematically reviewed up to now. The aim of the current review is to provide a historical overview of these different systems based on an assessment of published studies. A systematic Pubmed literature search was performed. Data were extracted and summarised. Twenty-two endometriosis classification, staging and reporting systems have been published between 1973 and 2021, each developed for specific and different purposes. There is still no international agreement on how to describe the disease. Studies evaluating different systems are summarised showing a discrepancy between the intended and the evaluated purpose, and a general lack of validation data confirming a correlation with pain symptoms or quality of life for any of the current systems. A few studies confirm the value of the Enzian system for surgical description of deep endometriosis. With regards to infertility, the endometriosis fertility index has been confirmed valid for its intended purpose. Of the 22 endometriosis classification, staging and reporting systems identified in this historical overview, only a few have been evaluated, in 46 studies, for the purpose for which they were developed. It can be concluded that there is no international agreement on how to describe endometriosis or how to classify it, and that most classification/staging systems show no or very little correlation with patient outcomes. This overview of existing systems is a first step in working towards a universally accepted endometriosis classification.

An international terminology for endometriosis, 2021.

STUDY QUESTIONCan a set of terms and definitions be prepared on endometriosis that would be the basis for standardization in disease description, classification and research?SUMMARY ANSWERThe current paper outlines a list of 49 terms and definitions in the field of endometriosis.WHAT IS KNOWN ALREADYDifferent classification systems have been developed for endometriosis, using different definitions for the disease, the different subtypes, symptoms and treatments. In addition, an International Glossary on Infertility and Fertility Care was published in 2017 by the International Committee for Monitoring Assisted Reproductive Technologies (ICMART) in collaboration with other organisations.STUDY DESIGN, SIZE, DURATIONAn international working group convened over the development of a classification or descriptive system for endometriosis. As a basis for such a system, a terminology for endometriosis was considered a condition sine qua non. The working group listed a number of terms relevant to be included in the terminology, documented currently used and published definitions, and discussed and adapted them until consensus was reached within the working group. Following stakeholder review, further terms were added, and definitions further clarified.PARTICIPANTS/MATERIALS, SETTING, METHODSAlthough definitions were collected through published literature, the final set of terms and definitions is to be considered consensus-based. After finalization of the first draft, the members of the international societies and other stakeholders were consulted for feedback and comments, which led to further adaptations.MAIN RESULTS AND THE ROLE OF CHANCEA list of 49 terms and definitions in the field of endometriosis is presented, including a definition for endometriosis and its subtypes, different locations, interventions, symptoms and outcomes. Endometriosis is defined as a disease characterized by the presence of endometrium-like epithelium and/or stroma outside the endometrium and myometrium, usually with an associated inflammatory process.LIMITATIONS, REASONS FOR CAUTIONFuture research may require further refinement of the presented definitions.WIDER IMPLICATIONS OF THE FINDINGSThe application of the defined terms aims to facilitate harmonization in endometriosis research and clinical practice.STUDY FUNDING/COMPETING INTEREST(S)The meetings and activities of the working group were funded by the American Association of Gynecologic Laparoscopists, European Society for Gynecological Endoscopy, European Society of Human Reproduction and Embryology and World Endometriosis Society. A.W.H. reports grant funding from the MRC, NIHR, CSO, Wellbeing of Women, Roche Diagnostics, Astra Zeneca, Ferring, Charles Wolfson Charitable Trust, Standard Life, 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. 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 and personal fees from AbbVie, and personal fees from Roche outside the submitted work. C.T. reports grants, non-financial support and other from Merck SA, non-financial support and other from Gedeon Richter, 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, Roche Diagnostics Inc, Volition Rx, outside the submitted work; she is also a Board member (Secretary) of the World Endometriosis Society and World Endometriosis Research Foundation, Research Advisory Board member of Wellbeing of Women, UK (research charity), and Chair, Research Directions Working Group, World Endometriosis Society. 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.TRIAL REGISTRATION NUMBERN/A.

P–509 Patients’ Uses and Experiences of Medically-Assisted Reproduction in France in 2020

Abstract Study question What are the uses and real-life experiences of patients currently treated in France in medically-assisted reproduction (MAR) centers? Summary answer One in four patients is in a situation of significant pain in relation to MAR; half are not optimistic about the outcome of their treatment. What is known already Internationally, work on the quality of life and impact of treatments has been completed in the field of endometriosis (Culley et al. 2017). In the field of MAR in France, one study underlines an important level of general well-being, with nearly 4 people out of 5 who say they are rather content (Coudrière et al. 2020). A better understanding of this result is however still lacking, especially in respect to whether patients actually believe in the success of their treatments, or how dependent satisfaction is on variables, like age, secondary infertility or the number of years engaged in fertility treatments. Study design, size, duration We conducted an online self-administered questionnaire by means of a two-step process: a first survey dedicated to patients’ uses was carried out from January 15, 2020 to February 26, 2000; the following and complementary survey about real-life experience was conducted from March 3, 2020 to April 10, 2020. The initial sample included 1503 people before selecting relevant participants. Participants/materials, setting, methods The final sample of 967 patients targets patients that were enrolled in a French procreative medical center at the time of the study. Were excluded from the sample: ex-patients, patients who have not started treatment or are not followed in France, solo and homosexual care patient trajectories. The questionnaire was composed of 178 questions. In the questionnaire dealing with MAR uses, six fields were examined; in the case of real-life experience, eight themes were questioned. Main results and the role of chance The study shows that one in four patients suffers significantly in relation to MAR care; nearly half are pessimistic about treatment outcome and 65% claim that MAR prevents full enjoyment of everyday life. Further findings include: MAR is globally satisfying regarding the quality of care provided by practitioners and staff (80%), general administration of patients (77 to 87%), first encounters with staff and center (78 to 91%), quality of dialogue (81%), physical state of the premises (82 to 97%), continuum with professional activity (73%). Where centers/practitioners need to pay attention: one out of two patients wanted more means of communication; time management was an issue; 41% state that infertility prevents entrepreneurial outreach and general success; treatments strongly disrupt work for 83% and reduce performances for 79%; work rights, while known, were not respected in ¼ cases. Discoveries made: young women are not very positive, men are not well-identified in such medical trajectories, women’s body image is completely transformed for 95%, 85.5% of women are depressed by seeing a pregnant woman, and 15% do not think about wanting a child daily. Limitations, reasons for caution This research, carried out online, was distributed mainly through a grassroot organization, potentially biasing representativeness. Also, the study finished at the start of the first French confinement. Previous studies show that the general context does not impact results, but this limitation cannot be ignored (Fisher, Bayhem, 2019). Wider implications of the findings: These findings underline the need for a comprehensive conception of MAR, including more than medical support. It highlights anew the need to better take men into account in future research as well as people in their twenties as knowledge of these categories of people is still lacking. Trial registration number Not applicable

Bioluminescent imaging in induced mouse models of endometriosis reveals differences in four model variations.

ABSTRACTOur understanding of the aetiology and pathophysiology of endometriosis remains limited. Disease modelling in the field is problematic as many versions of induced mouse models of endometriosis exist. We integrated bioluminescent imaging of ‘lesions’ generated using luciferase-expressing donor mice. We compared longitudinal bioluminescence and histology of lesions, sensory behaviour of mice with induced endometriosis and the impact of the gonadotropin-releasing hormone antagonist Cetrorelix on lesion regression and sensory behaviour. Four models of endometriosis were tested. We found that the nature of the donor uterine material was a key determinant of how chronic the lesions were, as well as their cellular composition. The severity of pain-like behaviour also varied across models. Although Cetrorelix significantly reduced lesion bioluminescence in all models, it had varying impacts on pain-like behaviour. Collectively, our results demonstrate key differences in the progression of the ‘disease’ across different mouse models of endometriosis. We propose that validation and testing in multiple models, each of which may be representative of the different subtypes/heterogeneity observed in women, should become a standard approach to discovery science in the field of endometriosis.

The relation between endometrioma and ovarian cancer.

The relationship between endometrioma and ovarian cancer is a topic of discussion in the field of endometriosis and to date it is still debated whether ovarian endometriosis may represent a risk factor for ovarian cancers. A literature search was carried out using Cochrane Library, EMBASE, Medline and Google Scholar up to October 2020. Primary outcome of interest was ovarian cancer incidence in patients with endometriosis. Secondary outcome was ovarian cancer prognosis in patients with endometriosis compared to patient without endometriosis. Patients with ovarian endometriosis has a slight increase risk of developing ovarian cancer (merely 1.8%), being the general population risk for ovarian cancer 1.31%. In patient at postmenopausal age, long-lasting endometriosis, early-age diagnosis, infertility and/or infertility treatment the risk of developing ovarian cancer is higher. Endometriosis-related ovarian cancers are generally clear cell and endometrioid and are diagnosed at early stage compared to non-endometriosis related ovarian cancer. The lifetime risk for ovarian cancer is low in endometriosis patients in general and higher in subgroups of patients allowing a tailored management based on patient characteristics. Endometriosis is a chronic disease negatively affecting the quality of life, nonetheless, concerns on ovarian cancer should be avoided in order to reduce the burden of the disease on women's health.

Closing the communication loop between gynecological surgeons, diagnostic imaging experts and pathologists in endometriosis: building bridges between specialties.

Closing the communication loop between gynecological surgeons, diagnostic imaging experts and pathologists in endometriosis: building bridges between specialties.

Endometriotic cell culture contamination and authenticity: a source of bias in in vitro research?

STUDY QUESTIONAre the primary cell cultures and cell lines used in endometriosis research of sufficient quality?SUMMARY ANSWERPrimary cells used in endometriosis research lack purity and phenotypic characterisation, and cell lines are not genotypically authenticated.WHAT IS KNOWN ALREADYThe poor reproducibility of in vitro research and the lack of authenticity of the cell lines used represent reasons of concern in the field of reproductive biology and endometriosis research.STUDY DESIGN, SIZE, DURATIONIn the present study, past in vitro research in the field of endometriosis was systematically reviewed to determine whether the appropriate quality controls were considered. In addition, we explored the performance of Paired Box 2 (Pax2) as an endometrium specific marker in endometrial and endometriotic primary cell cultures; we also characterised the most diffused endometriosis cell lines with respect to important markers including the short tandem repeat (STR) profile.PARTICIPANTS/MATERIALS, SETTING, METHODSLiterature review part: almost 300 published protocols describing the isolation and creation of primary cell cultures from endometriosis were reviewed. Wet-lab part: primary cells isolated from 13 endometriosis patients were analysed by immunohistochemistry, immunofluorescence and FACS for the expression of Pax2. Cell lines Z11 and Z12, the most diffused endometriosis cell lines, were characterised with respect to the expression of Pax2, steroid hormone receptors and STR profile.MAIN RESULTS AND THE ROLE OF CHANCEFrom the literature review work, we underscored the lack of sufficient cell purity and phenotypic characterisation of primary cell cultures, which present high risk of contaminations from surrounding non-endometriotic tissues. Past work based on the use of cell lines was reviewed as well, and it emerged that cell line authentication was never performed.In an effort to address these weaknesses for future research, we present data on the performance of Pax2, a suitable marker to exclude ovarian (and other non-endometrial) cell contaminations from primary cell cultures; STR profiles of cell lines Z11 and Z12 were analysed and indicated that the cells were authentic. These profiles are now available for authentication purposes to researchers wishing to perform experiments with these cells.A quality control pipeline to assure sufficient quality of in vitro research in the field of reproductive biology and endometriosis is proposed. We encourage scientists, research institutes, journal reviewers, editors and funding bodies to raise awareness of the problem and adopt appropriate policies to solve it in the future.LARGE-SCALE DATASTR profiles of cell lines Z11 and Z12 are deposited at the Cellosaurus database—web.expasy.org.LIMITATIONS, REASONS FOR CAUTIONThere may be additional markers suitable to assess cell quality.WIDER IMPLICATIONS OF THE FINDINGSFuture in vitro research in endometriosis and the reliability of outcomes can be improved by using the recommendations presented in this study.STUDY FUNDING/COMPETING INTEREST(S)The study was partly financed by the ‘Stichting Fertility Foundation’ (The Netherlands). The authors declare no existing conflict of interest.TRIAL REGISTRATION NUMBERNon-applicable.

Ignored Because It Is Benign - It Is Time to Treat Endometriosis as if It Were Cancer.

We are proposing a shift in mindset in the field of endometriosis, whereby care for patients with endometriosis mirrors that of patients with gynaecological cancer. To achieve this, we advocate for the recognition of complex benign gynaecology as a subspecialty. Since the establishment of gynaecological oncology as a subspecialty, outcomes for patients with ovarian cancer have improved, with their care managed by multidisciplinary teams in specialized units. Despite the marked difference in the primary treatment goal between these two conditions, they share common diagnostic and therapeutic challenges. We believe that care management by a multidisciplinary team of dedicated and specialized health care professionals will lead to improved outcomes, including improved quality of life, for people living with endometriosis.

A potential role of cyclin-dependent kinase inhibitor 1 (p21/WAF1) in the pathogenesis of endometriosis: Directions for future research

Endometriosis is a common gynecological disorder that affects approximately 6–10% of the female population impairing the quality of life of patients. Several pathophysiologic pathways have been proposed as potential regulators of its severity; however, to date, the processes that trigger the onset and that influence the severity of the disease are not fully understood; hence, leading to disease recurrence in approximately 10–67% of cases. Cyclin-dependent kinase inhibitor 1 (p21/WAF1) is a protein that is a major target of p53 and is related to cell cycle arrest (it regulates transition from the G1 to the S phase) when DNA damage is detected. Its activity has been also linked to the angiogenic potential of tumors as it promotes the expression of various kinases that are responsible for endothelial development and function. Although several articles have underlined the importance of this protein in cancer cell development and tumor growth, there are no relevant data in the field of endometriosis. Indirect evidence suggests, however, that it may be involved in the pathogenesis of endometriosis as it inhibits the activity of various kinases which have been correlated with the course and severity of the disease. The present article investigates the background theory that implies the potential role of cyclin-dependent kinase inhibitor 1 (p21/WAF1) in the pathogenesis of endometriosis. Implications for future research are also provided given that indirect evidence seem to associate downregulation of p21 with decreased growth and invasiveness of human endometrial stromal cells.

Urocortin Expression in Endometriosis: A Systematic Review.

Urocortin (UCN) is a neuropeptide that belongs to the corticotrophin-releasing hormone family and is expressed by eutopic and ectopic human endometria. The past years, this expression has been thoroughly investigated in the field of endometriosis. The objective of this systematic review is to accumulate current evidence related to the expression of UCN in tissue and blood samples of patients suffering from endometriosis. Literature search was designed accord- ing to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and primarily conducted using the Medline (1966-2018), Scopus (2004-2018), EMBASE (1947-2018) and Clinicaltrials.gov (2008- 2018) databases, along with the reference lists of electronically retrieved full-text papers. Overall, eight studies were retrieved. Current evidence suggests that the expression of UCN is increased in patients with ovarian endometriomas and that its levels may correlate with the severity of the disease. The diagnostic efficacy of UCN1 plasma levels was evaluated in three studies. Two of them suggested that the sensitivity and specificity of the method may reach, and even exceed, 80%. However, the wide variation in outcome reporting and outcome reporting measures in endome- triosis among the included studies precludes meta-analysis of available data. Therefore, although UCN seems to be a promising biomarker for the identification and follow-up of patients that suffer from endometriosis, more studies are needed to reach firm conclusions with respect to its predictive accuracy.

Mesenchymal stem cells: a promising tool for targeted gene therapy of endometriosis.

Endometriosis is a leading, benign gynecological disorder around the world. Last few years have witnessed tremendous growth in the field of endometriosis and endometrial stem-cell research. Despite advancements in the biology and pathology of endometriosis, disease recurrence is still an enigma. Gene therapy holds promise in treating many pathologic conditions including endometriosis. Mesenchymal stem cells (MSCs) serve as ideal candidates for regenerative medicine and cell-based therapies. Owing to their specificity to the endometrium, residing endometrial MSC populations could be utilized as ideal candidates for targeting endometrial disorders. Recently, we demonstrated their flexibility for gene transduction using adenoviral vectors. The review highlights the potential of endometrial MSCs in devising targeted gene therapies for endometriosis.

How to Develop an Electronic Clinical Endometriosis Research File Integrated in Clinical Practice.

Endometriosis is associated with a range of pelvic-abdominal pain symptoms and infertility. It is a chronic disease that can have a significant impact on various aspects of women's lives, including their social and sexual relationships, work, and study. Despite several international guidelines on the management of endometriosis, there is a wide variety of clinical practice in the management of endometriosis, resulting in many women receiving delayed or suboptimal care. In this paper we discuss the possibilities and benefits of using electronic health records for clinical research in the field of endometriosis. The development of a wide range of clinical software for electronic patient records has made the registration of large datasets feasible and the integration of research files and clinical files possible. Integration of global standards on registration of endometriosis care in electronic health records could improve reporting of research data and facilitate the execution of large, multicentre randomized trials on the management of endometriosis. These highly needed trials could bring us the evidence needed for the optimisation of management of women with endometriosis.