Early Diagnosis Of Endometriosis Research Articles

Screening and identification of key biomarkers associated with endometriosis using bioinformatics and next-generation sequencing data analysis

BackgroundEndometriosis is a common cause of endometrial-type mucosa outside the uterine cavity with symptoms such as painful periods, chronic pelvic pain, pain with intercourse and infertility. However, the early diagnosis of endometriosis is still restricted. The purpose of this investigation is to identify and validate the key biomarkers of endometriosis.MethodsNext-generation sequencing dataset GSE243039 was obtained from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) between endometriosis and normal control samples were identified. After screening of DEGs, gene ontology (GO) and REACTOME pathway enrichment analyses were performed. Furthermore, a protein–protein interaction (PPI) network was constructed and modules were analyzed using the Human Integrated Protein–Protein Interaction rEference database and Cytoscape software, and hub genes were identified. Subsequently, a network between miRNAs and hub genes, and network between TFs and hub genes were constructed using the miRNet and NetworkAnalyst tool, and possible key miRNAs and TFs were predicted. Finally, receiver operating characteristic curve analysis was used to validate the hub genes.ResultsA total of 958 DEGs, including 479 upregulated genes and 479 downregulated genes, were screened between endometriosis and normal control samples. GO and REACTOME pathway enrichment analyses of the 958 DEGs showed that they were mainly involved in multicellular organismal process, developmental process, signaling by GPCR and muscle contraction. Further analysis of the PPI network and modules identified 10 hub genes, including vcam1, snca, prkcb, adrb2, foxq1, mdfi, actbl2, prkd1, dapk1 and actc1. Possible target miRNAs, including hsa-mir-3143 and hsa-mir-2110, and target TFs, including tcf3 (transcription factor 3) and clock (clock circadian regulator), were predicted by constructing a miRNA-hub gene regulatory network and TF-hub gene regulatory network.ConclusionsThis investigation used bioinformatics techniques to explore the potential and novel biomarkers. These biomarkers might provide new ideas and methods for the early diagnosis, treatment and monitoring of endometriosis.

A MODERN NONINVASIVE METHODS OF DIAGNOSIS GENITAL ENDOMETRIOSIS ASSOCIATED WITH INFERTILITY

Endometriosis is a disease characterized by an overgrowth of morphologically and functionally endometrium-like tissue outside the uterine cavity. Early diagnosis of endometriosis is very di ffi cult. The gold standard for diagnosis is the surgical method – laparoscopy, performed for infertility, pelvic pain or the presence of pelvic masses. However, this approach is currently being reconsidered, and the search for endometriosis markers for earlier diagnosis of this disease is relevant. The purpose of the literature review was to summarize the current data on promising noninvasive markers of endometriosis determined in various biological media. Materials and methods – summarized a modern data abot perspective noninvasive markes of genital endometriosis associated with infertility, determined diff erence biological fl uid. Results We evaluated more than 30 biomarkers in peritoneal fl uid, serum, urine, and saliva, as well as their combinations in publications that met the selection criteria. Studies have evaluated the diagnostic value and e ffi cacy of endometriosis biomarkers, but the results of these studies have sometimes been inconsistent. We were unable to identify a single biomarker or combination of biomarkers that was unequivocally clinically useful. The most signifi cant changes in biochemical composition were observed in peritoneal fl uid, but it requires invasive intervention to obtain it. Discussion. Saliva and urine studies have shown promising results in terms of diagnostic accuracy, but the evidence was of low quality for introduction into clinical guidelines. A number of serum biomarkers may be useful either for detecting endometriosis at early stages or for diff erentiating ovarian endometrioma from other benign ovarian masses, but the evidence for meaningful conclusions is insu fficient. Conclusion. None of the biomarkers have shown suffi cient accuracy for clinical use outside of the research environment, yet research in this area remains promising.

Development of Artificial Intelligence Utilizing Neural Network-Based Language Prediction Models in Early Diagnosis of Endometriosis

Development of Artificial Intelligence Utilizing Neural Network-Based Language Prediction Models in Early Diagnosis of Endometriosis

Modern non-invasive diagnosis of endometriosis

Introduction. Endometriosis is a disease characterized by an overgrowth of morphologically and functionally endometrium-like tissue outside the uterine cavity. Early diagnosis of endometriosis is very difficult. The gold standard for diagnosis is the surgical method − laparoscopy, performed for infertility, pelvic pain or the presence of pelvic masses. However, this approach is currently being reconsidered, and the search for endometriosis markers for earlier diagnosis of this disease is relevant.The purpose of the literature review was to summarize the current data on promising noninvasive markers of endometriosis determined in various biological media.Materials and methods. Scientific literature was searched in PubMed, ResearchGate, and Elibrary databases for 2017−2022 using a combination of Russian and English keywords: endometriosis, endometrioma, endometriosis pathogenesis, peritoneal fluid, biomarkers, serum markers.Results. We evaluated more than 30 putative biomarkers in peritoneal fluid, serum, urine, and saliva, as well as their combinations in publications that met the selection criteria. Studies have evaluated the diagnostic value and efficacy of endometriosis biomarkers, but the results of these studies have sometimes been inconsistent. We were unable to identify a single biomarker or combination of biomarkers that was unequivocally clinically useful. The most significant changes in biochemical composition were observed in peritoneal fluid, but it requires invasive intervention to obtain it.Discussion. Saliva and urine studies have shown promising results in terms of diagnostic accuracy, but the evidence was of low quality for introduction into clinical guidelines. A number of serum biomarkers may be useful either for detecting endometriosis at early stages or for differentiating ovarian endometrioma from other benign ovarian masses, but the evidence for meaningful conclusions is insufficient. Conclusion None of the biomarkers have shown sufficient accuracy for clinical use outside of the research environment, yet research in this area remains promising.

A comprehensive overview of exosome lncRNAs: emerging biomarkers and potential therapeutics in endometriosis.

Endometriosis is a gynecological condition that significantly impacting women's daily lives. In recent years, the incidence of endometriosis has been rising yearly and is now an essential contributor to female infertility. Exosomes are extracellular vesicles (EVs) that carry long noncoding RNA (lncRNA) and shield lncRNA from the outside environment thanks to their vesicle-like structure. The role of exosome-derived lncRNAs in endometriosis is also receiving more study as high-throughput sequencing technology develops. Several lncRNAs with variable expression may be crucial to the emergence and growth of endometriosis. The early diagnosis of endometriosis will be considerably improved by further high specificity and sensitivity Exosome lncRNA screening. Exosomes assist lncRNAs in carrying out their roles, offering a new target for creating endometriosis-specific medications. In order to serve as a reference for clinical research on the pathogenesis, diagnosis, and treatment options of endometriosis, this paper covers the role of exosome lncRNAs in endometriosis and related molecular mechanisms.

Endometriosis in Adolescents: Diagnostics, Clinical and Laparoscopic Features.

The early diagnosis of endometriosis in adolescents is not developed. We aim to conduct clinical, imaging, laparoscopic and histological analyses of peritoneal endometriosis (PE) in adolescents in order to improve early diagnosis. In total, 134 girls (from menarche to 17 years old) were included in a case-control study: 90 with laparoscopically (LS) confirmed PE, 44 healthy controls underwent full examination and LS was analyzed in the PE group. Patients with PE were characterized with heredity for endometriosis, persistent dysmenorrhea, decreased daily activity, gastrointestinal symptoms, higher LH, estradiol, prolactin and Ca-125 (<0.05 for each). Ultrasound detected PE in 3.3% and MRI in 78.9%. The most essential MRI signs are as follows: hypointense foci, the heterogeneity of the pelvic tissue (paraovarian, parametrial and rectouterine pouch) and sacro-uterine ligaments lesions (<0.05 for each). Adolescents with PE mostly exhibit initial rASRM stages. Red implants correlated with the rASRM score, and sheer implants correlated with pain (VAS score) (<0.05). In 32.2%, foci consisted of fibrous, adipose and muscle tissue; black lesions were more likely to be histologically verified (0.001). Adolescents exhibit mostly initial PE stages, which are associated with greater pain. Persistent dysmenorrhea and detected MRI parameters predict the laparoscopic confirmation of initial PE in adolescents in 84.3% (OR 15.4; <0.01), justifying the early surgical diagnostics and shortening the time delay and suffering of the young patients.

Endometriosis and its relationship with female infertility: an integrative review

This article presents an integrative literature review aimed at reviewing the relationship between endometriosis and female infertility between the years 2016-2022. In this type of study, the integrative review helps to obtain, identify and analyze a specific topic in the literature. Thus, the objective of this work is to extract information from the updated literature through articles selected between the years 2016-2022 in empirical categories called: “Relationship of endometriosis with female infertility”; “Early diagnosis of endometriosis and the influence on female infertility”; "Treatment of endometriosis and the impact on women's health", in order to relate endometriosis to female infertility in an integrative review. The conclusion is, therefore, that health professionals, who manage the treatment of endometriosis, should be attentive to early diagnosis, whether in the form of a questionnaire or laboratory tests, treatment and, consequently, the quality of women's life.

Newborn vaginal bleeding - Why to record?

Introduction: Neonatal menstruation is considered the most neglected uterine bleeding, but it was concluded to be a marker of fetal stress. It is more common in preeclampsia, fetal growth restriction, and isoimmunization.¹ It has a prevalence of 5% in healthy newborns, which is lower in preterm newborns and higher in low birth weight newborns.² Case description: A 6-days-old female born with 41 weeks of gestation presented a 2-day history of vaginal bleeding without other symptoms or history of trauma. Physical examination evidenced vaginal bleeding, without external lesions (fig.1). Complementary diagnostic tests were not performed. Following vigilance, vaginal bleeding was present for 6 days and stopped on the 10th day of life. Discussion: Vaginal bleeding in the neonatal period results from desquamation of the endometrium, triggered by the decline in circulating steroid hormones. It often begins 3 to 5 days after birth and typically lasts up to 10 days³ - a chronology similar to the case presented. Some newborns with neonatal menstruation experience retrograde menstruation, which causes implantation of endometrial cells in the abdominal cavity, which may lead to an increased risk of early endometriosis. Newborns who have this complication should be evaluated so that an early diagnosis of endometriosis can be made in the future in children who begin with pelvic pain or severe menstrual pain.

Patient Preferences for Early Diagnosis of Endometriosis and Associated Determinants in the United States: A Discrete Choice Experiment

Background: Endometriosis is a chronic and incurable gynecological disease that mainly affects women of reproductive age worldwide. It imposes clinical and economic burdens on patients, families, and society. A better understanding of the determinants of preferences towards early diagnosis of endometriosis may help develop programs and interventions to reduce the risk of more severe illness. We quantified patient preferences for early endometriosis diagnosis and explored whether preferences vary on the patient characteristics and pre-established social determinants of health. Methods: A discrete choice experiment (DCE) was designed to elicit women's preferences and willingness to pay for early diagnosis of endometriosis. Women ages 18 and older were eligible to participate in the study. The attributes (and levels) considered to describe hypothetical scenarios included diagnosis (immediate/postponed), the chance of advanced endometriosis and more severe illness (low/ high), time away from living, and professional activities (8 days, 15 days, 22 days and 30 days), and possible out-of pocket costs ($0, $15, $60 and $210). The effects of participants' characteristics and social determinants of health on the preference for early diagnosis were modeled using a Tobit model. Results: A total of 66 women with (2) or at-risk (64) of endometriosis completed the experiment. The respondents' age and insurance statuses significantly influenced their preference or choice for early diagnosis. On average, respondents were willing to give up $61.55 out-of-pocket cost to have a low risk of advanced endometriosis and more severe disease. The Tobit model indicates only age and insurance variables significantly affected early diagnosis preference. The results suggest that older ages and not having insurance increase the likelihood of respondents choosing early diagnosis than the younger age group and having insurance. Conclusions: This study indicates the importance of considering the patient characteristics and social determinants of health when designing and implementing health programs and interventions for endometriosis.

Gut Microbiota Exceeds Cervical Microbiota for Early Diagnosis of Endometriosis.

The diagnosis of endometriosis is typically delayed by years for the unexclusive symptom and the traumatic diagnostic method. Several studies have demonstrated that gut microbiota and cervical mucus potentially can be used as auxiliary diagnostic biomarkers. However, none of the previous studies has compared the robustness of endometriosis classifiers based on microbiota of different body sites or demonstrated the correlation among microbiota of gut, cervical mucus, and peritoneal fluid of endometriosis, searching for alternative diagnostic approaches. Herein, we enrolled 41 women (control, n = 20; endometriosis, n = 21) and collected 122 well-matched samples, derived from feces, cervical mucus, and peritoneal fluid, to explore the nature of microbiome of endometriosis patients. Our results indicated that microbial composition is remarkably distinguished between three body sites, with 19 overlapped taxa. Moreover, endometriosis patients harbor distinct microbial communities versus control group especially in feces and peritoneal fluid, with increased abundance of pathogens in peritoneal fluid and depletion of protective microbes in feces. Particularly, genera of Ruminococcus and Pseudomonas were identified as potential biomarkers in gut and peritoneal fluid, respectively. Furthermore, novel endometriosis classifiers were constructed based on taxa selected by a robust machine learning method. These results demonstrated that gut microbiota exceeds cervical microbiota in diagnosing endometriosis. Collectively, this study reveals important insights into the microbial profiling in different body sites of endometriosis, which warrant future exploration into the role of microbiota in endometriosis and highlighted values on gut microbiota in early diagnosis of endometriosis.

O-057 The impact of diagnosis endometriosis as part of the fertility workup

Abstract Abstract text The impact of diagnosis endometriosis as part of the Fertility workup Endometriosis is a multifaceted disease that may go from completely asymptomatic to a debilitating condition with severe pelvic pain complicated infertility. In the last few years, how we approach fertility in women with endometriosis has clearly changed, postponing definitive/radical surgery till the patient has completed her family. As a clear association exists with endometriosis and infertility, during the fertility workup it is one of the diseases to investigate, as it may have been missed in previous annual gynecologic checkups. Here we may face two problems: a) the stigma of diagnosis a young women with the label “endometriosis”, as she may be under the pressure of a progressive disease that may or may not affect her quality of life, and b) if the diagnosis of endometriosis is positive, how this may affect the decision making process during the fertility journey. In this lecture we will discuss the difficulties of early diagnosis of endometriosis, why most of the previous test have failed, and the new opportunity that miRNAs seem to offer. Once endometriosis is diagnosed –early or late stages- how this may affect spontaneous chances of pregnancy, ovarian reserve, oocyte and embryo quality, endometrial receptivity, and last but not least, time to pregnancy. Obviously, the prognosis changes over time, and women’s age will be conditioning most of our decisions. We will try to identify whom to treat, to increase the absolute pregnancy rate, and when to treat, to reduce the time to pregnancy. Finally, we will discuss the opportunity of fertility preservation in this particular subgroup of women. Being aware of the potential damage that endometriosis by itself, or the associated ovarian surgery, may inflict on ovarian reserve make these women more proactive for fertility preservation.

Bioinformatics Analysis Identifies Molecular Markers Regulating Development and Progression of Endometriosis and Potential Therapeutic Drugs.

Endometriosis, a common disease that presents as polymorphism, invasiveness, and extensiveness, with clinical manifestations including dysmenorrhea, infertility, and menstrual abnormalities, seriously affects quality of life in women. To date, its underlying etiological mechanism of action and the associated regulatory genes remain unclear. This study aimed to identify molecular markers and elucidate mechanisms underlying the development and progression of endometriosis. Specifically, we downloaded five microarray expression datasets, namely, GSE11691, GSE23339, GSE25628, GSE7305, and GSE105764, from the Gene Expression Omnibus (GEO) database. These datasets, obtained from endometriosis tissues, alongside normal controls, were subjected to in-depth bioinformatics analysis for identification of differentially expressed genes (DEGs), followed by analysis of their function and pathways via gene ontology (GO) and KEGG pathway enrichment analyses. Moreover, we constructed a protein–protein interaction (PPI) network to explore the hub genes and modules, and then applied machine learning algorithms support vector machine-recursive feature elimination and least absolute shrinkage and selection operator (LASSO) analysis to identify key genes. Furthermore, we adopted the CIBERSORTx algorithm to estimate levels of immune cell infiltration while the connective map (CMAP) database was used to identify potential therapeutic drugs in endometriosis. As a result, a total of 423 DEGs, namely, 233 and 190 upregulated and downregulated, were identified. On the other hand, a total of 1,733 PPIs were obtained from the PPI network. The DEGs were mainly enriched in immune-related mechanisms. Furthermore, machine learning and LASSO algorithms identified three key genes, namely, apelin receptor (APLNR), C–C motif chemokine ligand 21 (CCL21), and Fc fragment of IgG receptor IIa (FCGR2A). Furthermore, 16 small molecular compounds associated with endometriosis treatment were identified, and their mechanism of action was also revealed. Taken together, the findings of this study provide new insights into the molecular factors regulating occurrence and progression of endometriosis and its underlying mechanism of action. The identified therapeutic drugs and molecular markers may have clinical significance in early diagnosis of endometriosis.

Medical management of endometriosis.

Endometriosis is a benign gynecologic disorder that is defined as functional endometrial tissue outside of the uterine cavity. It is an estrogen-dependent, inflammatory disease that leads to symptoms of pelvic pain, dysmenorrhea, dyspareunia, and infertility, occurring in 6-10% of reproductive aged women. The severity of the disease ranges from asymptomatic to debilitating symptoms that have a major impact on women's lives. It is a chronic, recurrent disease, frequently requiring long term management until menopause and beyond. It is considered a chronic disorder that is managed with surgery, medical treatment, and oftentimes, both. Current medical therapy for endometriosis is considered suppressive of the disease, rather than curative. Fortunately, many patients do experience improvement and control of their symptoms with medical therapy. However, long-term efficacy of the medical treatments is often limited by side effects and the cost of therapy, and symptoms do tend to recur after discontinuation of these medications. This review summarizes our understanding of the pathogenesis of endometriosis and provides more in-depth discussion of specific medical management options used to treat endometriosis, including mechanism of action and side effects. It also provides recommendations on strategy with a forward look to novel endometriosis treatments in the future. The authors emphasized that endometriosis is a chronic disorder requiring long term medical therapy. Early diagnosis of endometriosis is key in preventing severe, debilitating symptoms and progression of disease. By utilizing our current knowledge of the pathophysiology of endometriosis and by correctly implementing currently available medical and surgical therapies we can significantly reduce the physical, psychosocial and financial burden of this chronic, recurrent and indolent disease. Current available medications are suppressive therapies, but the authors are looking forward to future therapies that can effectively cure or at least control endometriosis with minimal side effects. Future research should continue to look for the genetic trigger for endometriosis which can lead us to its underlying pathogenesis and eventually a cure or prevention.

Endometriose, dificuldades no diagnóstico precoce e a infertilidade feminina: Uma Revisão

A endometriose é uma patologia que afeta milhares de mulheres no mundo, isso se deve à presença de tecido endometrial extrauterino, que responde à estimulação hormonal e pode causar uma reação inflamatória resultando em sintomas como dor pélvica crônica severa e infertilidade. No Brasil, cerca de 7 milhões de mulheres sofrem com a doença, cujo diagnóstico, prontuário e pesquisas são altamente deficientes, o que dificulta a recuperação das pacientes. Desse modo, este estudo teve como objetivo investigar as dificuldades no diagnóstico precoce da endometriose e sua relação com a infertilidade feminina por meio de uma revisão narrativa. Foram realizadas buscas bibliográficas nas seguintes bases de dados: SciELO, PubMed/MEDLINE e BVS, por se tratarem de bases de dados que concentram publicações de excelência voltadas para a área da saúde. A seleção dos estudos publicados nas bases de dados foi compreendida entre os anos de 2001 a 2021, utilizando os descritores reconhecidos pelos DECs: “Endometriosis”, “Early Diagnosis”, “Infertility Female” e “Treatmet Alternatives”. Assim, obtivemos resultados de estudos que abordam aspectos envolvidos na dificuldade de se obter o diagnóstico precoce da endometriose, além dos tratamentos disponíveis. Evidenciamos que a endometriose ainda é uma doença de etiopatogenia incerta, e que essa incerteza contribui para a dificuldade de diagnóstico da doença, na qual a falta de informações se destaca como um dos principais fatores que dificultam o diagnóstico precoce da endometriose.

Validation of Five Gene Expression Signature for Diagnosis of Endometriosis

Study Objective To validate a complex gene expression biomarker for the diagnosis of endometriosis created based on differences between molecular signatures of endometrium from women with and without endometriosis. Design Prospective observational cohort study. II-1. Evidence obtained from a well-designed, controlled trial without randomization. Setting Department of Reproductive Medicine and Surgery at the A.I. Evdokimov Moscow State Medical and Dental University. Patients or Participants 50 women with endometriosis and 35 women without endometriosis (control group). Interventions Laparoscopic excision of endometriotic foci, hysteroscopy with endometrial sampling. RNA was isolated from all samples and stored in RNA Later. Following histologic analysis of all samples, RNA sequencing was performed using Illumina HiSeq 3000 equipment for single-end sequencing. Unique bioinformatics algorithms were validated using experimental gene expression datasets. Measurements and Main Results We performed gene expression analysis of dataset containing 100 samples (50 endometrial and 50 endometriotic) of patients with endometriosis and 35 endometrial samples from patients of control group. We created several different gene expression signatures and validated them on separated groups of samples. The final gene signature was constructed with the core genes commonly shared by all preliminary signatures. This endometrial genetic signature successfully differentiated samples of endometriotic lesions from endometrial samples of healthy women (area under the ROC curve (AUC) =0.982. The comparison of our dataset of 100 samples of endometrial and endometriotic tissue with preexisting dataset containing 120 samples of other tissues (cervix, ovary, stomach, lung) revealed high sensitivity (94%) and specificity (97%) in the ability of studied molecular signature to equally identify endometrium and endometriotic tissue of patients with endometriosis. Conclusion We obtained a complex genetic biomarker that could be potentially used as a basis for early diagnosis of endometriosis via utilization of endometrial biopsy.

Endometriose: causas, implicações e tratamento da infertilidade feminina através das técnicas de reprodução assistida

A endometriose é um distúrbio inflamatório estrogênio-dependente, caracterizada pelo crescimento exacerbado de tecido endometrial e células do estroma fora da cavidade uterina. A qualidade de vida é diminuída em mulheres com endometriose, principalmente com o agravamento dos sintomas. Tendo em vista a importância da endometriose para saúde pública, o presente artigo teve por objetivo explanar a fisiopatologia da endometriose, as formas de diagnóstico e tratamento, bem como as implicações da doença na fertilidade feminina e formas de tratamento através da reprodução assistida. Para tanto, foram selecionadas 50 referências de língua portuguesa e inglesa datadas entre os anos de 2014 a 2020, prioritariamente. A etiologia da endometriose é complexa, cercada por diversas teorias, e o diagnóstico precoce é crucial para a minimização dos danos à fertilidade, visto que 30 a 50% das mulheres com endometriose exibem quadro de infertilidade. São observadas diversas complicações em pacientes acometidas pela patologia que levam à infertilidade. A fim de manter a fertilidade feminina, técnicas de reprodução assistida têm sido utilizadas com sucesso. Diante do exposto, conclui-se que para a manutenção da qualidade de vida e fertilidade feminina, o diagnóstico precoce da endometriose é imprescindível. Além disso, as técnicas de reprodução assistida surgem como a linha de tratamento com maior sucesso terapêutico para mulheres acometidas por endometriose que desejam engravidar.

Differential expression and functional analysis of micro RNAs in &lt;em&gt;Papio anubis&lt;/em&gt; induced with endometriosis for early detection of the disease

Endometriosis is a common gynecological disorder affecting approximately 10% of women of reproductive age who often experience chronic pelvic pain and infertility. Laparoscopy, which is invasive and expensive, is the gold standard for diagnosis of endometriosis. A simple minimally-invasive test for endometriosis-specific biomarkers which is yet to be realized would offer a timely and accurate diagnosis for the disease thereby allowing early treatment intervention. Although aberrant microRNA expression has been implicated in endometriosis in several studies, conflicting results have been reported. This study hypothesized that the use of an appropriate animal model will provide a unique entry point for the discovery of biomarkers for early diagnosis of endometriosis. The study aimed at identifying miRNAs that are differentially expressed in eutopic endometrium of induced endometriosis in Papio anubis for early detection of endometriosis. Female adult baboons (n = 3) were induced with endometriosis by intraperitoneal inoculation of autologous menstrual endometrium. We sequenced small RNA samples obtained from normal (control) and diseased eutopic endometrium. Quality reads from the sequences were subjected to differential expression analysis to identify dysregulated microRNAs and genes from other non-coding small RNA in the samples using a bioinformatics approach. Through in-silico analysis, gene targets of the dysregulated miRNA and their functions were determined. Our findings show significant high expression of seven microRNAs namely miR-199a-3p, miR-145-5p, miR-214-3p, miR-143-3p, miR-125b-5p, miR-199a-5p and miR-10b-5p. The study also reveals five microRNAs that were significantly down regulated and they include miR-29b-3p, miR-16-5p, miR-342-3p, miR-378a-3p and let-7g-5p. Seventeen genes from non-coding small RNAs were significantly dysregulated. The dysregulated microRNAs and genes play important roles in pathogenesis of endometriosis. Our findings indicate that specific miRNA signatures are associated with endometriosis, and the dysregulated miRNAs could constitute new and informative biomarkers for early diagnosis of endometriosis.

Gene Expression Signature in Diagnosis of Endometriosis

Study Objective To develop a prototype of a complex gene expression biomarker for the diagnosis of endometriosis based on differences between molecular signatures of endometrium from women with and without endometriosis. Design Prospective observational cohort study. II-1. Evidence obtained from a well-designed, controlled trial without randomization. Setting Department of Reproductive Medicine and Surgery at the A.I. Evdokimov Moscow State Medical and Dental University. Patients or Participants 30 women with endometriosis and 15 women without endometriosis (control group). Interventions Laparoscopic excision of endometriotic foci, hysteroscopy with endometrial sampling. RNA was isolated from all samples and stored in RNA Later. RNA sequencing was performed using Illumina HiSeq 3000 equipment for single-end sequencing. Unique bioinformatics algorithms were developed and validated using experimental and public gene expression datasets. Measurements and Main Results We performed gene expression analysis of dataset containing 83 samples (30 endometrial and 53 endometriotic) and 15 samples (endometrial) of patients with and without endometriosis respectively. We extracted a complex molecular signature of 38 genes and found that the expression of 26 genes in it was significantly increased while the expression of 12 genes was significantly repressed in the endometrium of patients with endometriosis. This endometrial genetic signature successfully differentiated 53 samples of endometriotic lesions from 15 endometrial samples of healthy women (area under the ROC curve (AUC) =1. The comparison of our dataset of 83 samples of endometrial and endometriotic tissue with preexisting dataset containing 134 samples of other tissues (cervix, ovary, stomach, lung) revealed high sensitivity (94%) and specificity (97%) in the ability of studied molecular signature to equally identify endometrium and endometriotic tissue of patients with endometriosis. Conclusion We obtained a complex molecular biomarker that could be used as a basis for early diagnosis of endometriosis via utilization of endometrial biopsy. Our findings indicate that easily accessible eutopic endometrium can be potentially used as a non-surgical marker for the presence of endometriosis.

Relationship between Patient Age and Disease Features in a Prospective Cohort of 1560 Women Affected by Endometriosis

ObjectiveTo assess the relationship between age, location of the disease, and surgical procedures performed in patients undergoing surgical management of endometriosis. DesignRetrospective study using data prospectively recorded in the North-West Inter Regional Female Cohort for Patients with Endometriosis database. SettingUniversity tertiary referral center. PatientsWomen who underwent surgical management of symptomatic endometriosis between April 2009 and April 2014. InterventionsPatients were allocated to 6 groups according to their age at the time of surgery: ≤20, 21 to 25, 26 to 30, 31 to 35, 36 to 40 and >40 years. Patient characteristics, prior history, location of endometriotic lesions, stage of disease, intraoperative findings, and surgical procedures were retrieved from a prospectively recorded database. Measurements and Main ResultsPatient characteristics, symptoms, location of endometriosis, and type of surgery performed were compared between groups. In total, 1560 procedures were performed. Of these, more than one-half were carried out in women between the age of 26 to 35 years and the majority were performed in women aged between 26 and 30 years. Only 2% of procedures were performed in women under the age of 20 years. The mean stage of the disease at the time of surgical diagnosis was stage II for women younger than 20 years, stage III for those in the age group of 21 to 25 years, and stage IV for those older than 26 years. The rate of diagnosis of deep colorectal nodules increased progressively from 20 to 26 years and remained stable thereafter. ConclusionOur data confirm that endometriosis is a disease that probably progresses from adolescence until the adult period when symptoms (pain or infertility) become debilitating and require surgery. Our data suggest that policies relating to the prevention and early diagnosis of endometriosis should focus on women younger than 25 years.

DETERMINATION OF ANTIGEN LEVELS: T-PLASTIN, TRANSGELIN AND CA-125 IN BABOONS WITH INDUCED ENDOMETRIOSIS

Endometriosis is defined as the presence of endometrial-like tissue outside the uterine cavity and is associated with chronic intra-pelvic inflammation. Its symptoms, which are often severe, have a negative impact on a woman’s quality of life. They include chronic pelvic pain and infertility. It is estimated that about 10% women in their reproductive ages are affected by the disease globally. Currently, diagnostic methods are laparoscopy with histological confirmation and non-invasive such as ultrasound and the quantification of CA-125 biomarker in serum. CA-125 is known to be elevated in endometriosis, however it does not have sufficient diagnostic power as a single biomarker of endometriosis. Due to this, there is a need to determine other antigens that would act as potential biomarkers for endometriosis. It has been observed that Transgelin and T-Plastin are upregulated in endometriosis lesions and in secretory phase of endometrium respectively. There is insufficient data available showing the concentration of T-plastin in serum or plasma in the development of endometriosis. The main objective of this study was to identify whether T-plastin, Transgelin and CA-125 are potential biomarkers in early diagnosis of endometriosis using animal model for endometriosis. The baboon model represents clinically relevant research models for endometriosis. This study compared the levels of T-plastin, Transgelin and CA-125 in the peripheral blood and peritoneal fluid of baboons before and after induction of endometriosis. In this prospective, case-control study, ten female baboons ( Papio anubis , 9-15 kg each) of proven fertility that have had at least one menstruation during captivity, were induced by intra-pelvic injection of menstrual endometrium on day 1 or 2 of menstruation followed by staging laparoscopy. Serum and peritoneal fluid samples were collected prior to induction to serve as controls.T-Plastin, Transgelin and CA-125 were measured using commercially available ELISA Kits. Data was analyzed using non-parametric test and level of significance at p&lt;0.005. T-Plastin and Transgelin had insignificant p values in both peripheral blood and peritoneal fluid while CA-125 showed p=0.0003 in peripheral blood and p=0.0279 in peritoneal fluid. Diagnostic performance of individual biomarkers was determined by Receiver Operating Characteristic (ROC) with the Area under the curve (AUC) equal to 0.5 showing T-Plastin and Transgelin in both serum and peritoneal fluid unreliable for use as biomarkers in endometriosis. CA-125 levels in peritoneal fluid had an AUC of 0.7900 indicating it can be used as potential biomarkers for endometriosis. Key words: Endometriosis, biomarkers, T-Plastin, Transgelin, CA-125, ELISA, Olive Baboons. DOI : 10.7176/ALST/75-06 Publication date :August 31 st 2019