Different Stages Of Endometriosis Research Articles

Preoperative predictive parameters for accurate detection of stage IV endometriosis

BackgroundSurgery is the main line of treatment of endometriosis. Patients with stage IV endometriosis have more extensive adhesions, which make the surgery difficult. There are no accurate non-invasive predictive preoperative parameters of stage IV endometriosis and no consensus has been reached.Therefore, the aim of the present study was to evaluate and detect preoperative non-invasive parameters for the detection of stage IV endometriosis.Patients and methodsIn the present study, we included 150 females admitted for surgical removal of endometriosis. We scored and classified endometriosis into four stages according to the revised ASRM classification. We compared between baseline characteristics of patients with different stages of endometriosis, and then we selected the best combination of diagnostic and predictive parameters of stage IV endometriosis.ResultsPredictors of stage IV endometriosis and indicators for safety surgery were as follows: VAS ≥ 4 (p < 0.001), fixed uterus (p = 0.005), fixed ovarian cysts (p < 0.001), tender uterosacral ligament nodule (p < 0.001), tender rectovaginal septum nodule (p = 0.003), bilateral endometriosis (p < 0.001), and sum of sizes of endometriotic nodules (p < 0.001).ConclusionFixed uterus, fixed ovarian cysts, tender uterosacral ligament nodule, tender rectovaginal septum nodule, bilateral endometriosis, and indications for surgery were significantly considered adequate predictive markers for stage IV endometriosis.

Comparison of Morphological and Digital-Assisted Analysis for BCL6 Endometrial Expression in Women with Endometriosis.

BCL6 (B-cell lymphoma 6) is a proto-oncogene and transcriptional repressor initially described as being involved in B-cell lymphoma. Recently, this factor has been identified as a promising tissue biomarker which could be used to diagnose women affected by endometriosis. Previous studies used HSCORE for BCL6 staining quantification in the endometrium. However, this semi-quantitative technique of analysis has some limitations, including a lack of objectivity, robustness, and reproducibility that may lead to intra- and inter-observer variability. Our main goal was to develop an original computer-assisted method to quantify BCL6 staining from whole-slide images reliably. In order to test the efficiency of our new digital method of quantification, we compared endometrial BCL6 expression between fertile and infertile women without or with different stages of endometriosis by using the widely used HSCORE analysis and our new automatic digital image analysis. We find a higher expression of BCL6 in the endometrium of infertile women with endometriosis and women with stage IV endometriosis. Furthermore, we demonstrate a significant correlation between the two types of independent measurements, indicating the robustness of results and also the reliability of our computer-assisted method for BCL6 quantification. In conclusion, our work, by using this original computer-assisted method, enables BCL6 quantification more objectively, reliably, robustly, and promptly compared to HSCORE analysis.

Robotic surgery in gynaecology: Scientific Impact Paper No. 71 (July 2022).

The use of robotic-assisted keyhole surgery in gynaecology has expanded in recent years owing to technical advances. These include 3D viewing leading to improved depth perception, limitation of tremor, potential for greater precision and discrimination of tissues, a shorter learning curve and improved comfort for surgeons compared with conventional keyhole and open abdominal surgery. Robotic-assisted keyhole surgery, compared with conventional keyhole surgery, improves surgical performance without increasing operating time, minimises blood loss and intra- or postoperative complications, while reducing the need to revert to abdominal surgery. Moreover, surgeons using a robot experience fewer skeletomuscular problems of their own in the short and long term than those operating without a robot as an additional tool. This Scientific Impact Paper looks at the use of a robot in different fields of gynaecological surgery. A robot could be considered safe and a more effective surgical tool than conventional keyhole surgery for women who have to undergo complex gynaecology surgery or have associated medical issues such as body-mass index (BMI) at 30 kg/m2 or above or lung problems. The introduction of the use of robots in keyhole surgery has resulted in a decrease in the number of traditional open surgeries and the risk of conversion to open surgery after traditional keyhole surgery; both of which should be considered when examining the cost-benefit of using a robot. Limitations of robotic-assisted surgery remain the associated higher costs. In womb cancer surgery there is good evidence that introducing robotics into the service improves outcomes for women and may reduce costs.

O-027 Small extracellular vesicle (sEV) protein cargo as potential biomarker for endometriosis

Abstract Study question Can an endometriosis-specific protein signature in small extracellular vesicles (sEV) from peritoneal fluid (PF) be utilised as a non-invasive biomarker of the condition? Summary answer Yes, potentially. We found differences in the concentrations and protein cargo of PF-derived sEV between controls and endometriosis samples, most notably in CD44 expression. What is known already Endometriosis, defined as endometrial-like tissue outside the uterus, causes pain and/or subfertility in 10% of reproductive age women. The cause is unknown, resulting in inadequate diagnostic methods and treatment options. There is no clinically relevant biomarker for endometriosis yet. Small extracellular vesicles (sEV), produced by virtually every cell, have been described in diseases such as cancer, diabetes, and pre-eclampsia, and could similarly be important in endometriosis. We previously identified sEV in PF of women with endometriosis, and here investigated the protein cargo of PF sEV as biomarker of the disease. Study design, size, duration PF samples were obtained from participants in the ENDOX study, Endometriosis CaRe Centre, Nuffield Department of Women’s and Reproductive Health, University of Oxford (REC ref. 09/H0604/58) according to WERF EPHect standards. Women between 18-49 years of age (n = 63) who had undergone diagnostic laparoscopy were classified according to cycle phase (proliferative/secretory/menstrual) and severity of endometriosis (ASRM stages I+II or stages III+IV). Exclusion criteria were hormonal treatment, malignancy, pregnancy, breastfeeding, and inability to understand the consent form. Participants/materials, setting, methods The participant groups were control proliferative, n = 7; control secretory, n = 9; control menstrual, n = 3; StI+II proliferative, n = 8; StI+II secretory, n = 10; St1+II menstrual, n = 7; StIII+IV proliferative, n = 5; StIII+IV secretory, n = 11; StIII+IV menstrual, n = 3. 1 mL PF was centrifuged to remove cells, debris, and microvesicles. sEV were isolated using size exclusion chromatography (SEC) and analysed by nanoparticle tracking analysis (NTA), immunoblotting, and mass spectrometry (LC-MS/MS). Main results and the role of chance We confirmed the presence of exosomes in PF from women at different stages of endometriosis and from disease-free patients at different menstrual cycle phases by NTA, immunoblotting and mass spectrometry. Enriched sEV were positive for ALIX, CD9, and syntenin. The mode size of PF particles from women with endometriosis was 115 ± 15.5 nm, whereas in non-endometriotic women it was 95 ± 17.3 nm (n.s.). sEV concentrations were higher in endometriosis compared to controls, and highest in stage III-IV endometriosis, followed by stage I-II endometriosis and controls, irrespective of menstrual cycle phase (P = 0.0210). sEV concentration in stage III-IV endometriosis decreased consistent with a transition from proliferative to secretory phase. Likewise, PF-derived sEV numbers within stage I-II endometriosis samples increased, as these samples transitioned from proliferative to secretory cycle phases. Proteomic analysis showed distinct distribution patterns of proteins within endometriosis PF-derived sEVs compared to controls. Consistent with earlier studies, we found CD44 as an sEV protein uniquely within the endometriosis population and contributing significantly to the separation of endometriosis and control samples by the highest variable importance projection (VIP) score in our data set. Limitations, reasons for caution The main limitation of this study is the small number of samples across the different groups, and the limited amount of PF per sample. Wider implications of the findings PF-derived sEV differ between endometriosis and control patients. Concentrations vary regardless of cycle phase and disease stage, and this difference appears to be reflected in the proteomics analysis. The presence of CD44 within sEV could help diagnose endometriosis. Trial registration number not applicable

Platelet-to-Lymphocyte Ratio and CA125 Level as a Combined Biomarker for Diagnosing Endometriosis and Predicting Pelvic Adhesion Severity.

Adhesion is a significant biological characteristic of endometriosis, and accurate evaluation of the pelvic adhesion is necessary for surgical treatment. Serum CA125 is yet the most common used biomarker in the diagnosis and follow-up of patients with endometriosis despite of its high false-positive rate and low specificity. Herein, we aimed to examine the diagnostic value of the combination of the platelet-to-lymphocyte ratio (PLR) and CA125 for patients with different stages of endometriosis and their correlations with pelvic adhesion. We retrospectively analyzed the clinical data and blood count parameters of patients with both endometriosis and other benign ovarian tumors. The mean level of CA125, the PLR and the combined marker (the CA125 level multiplied by the PLR) in the EMs group were significantly higher than those in the Cyst group (P < 0.05). ROC curve analysis was used to compare the diagnostic values of serum PLR, CA125, and the combined marker in ovarian endometriosis. The cut-off value of the PLR was 176.835, with 28.3% sensitivity and 96.9% specificity. The cut-off value of CA125 was 31.67 U/mL, with 84.1% sensitivity and 87.4% specificity. The cut-off value of the combined marker was 3894.97, with 83.4% sensitivity and 95.8% specificity. It was found that the severity of adhesion in endometriosis was positively correlated with the PLR (r = 0.286, P < 0.01), CA125 (r = 0.276, P < 0.01), and combined marker (r = 0.369, P < 0.01). The combined marker showed the highest AUC value (0.751, 95% CI: 0.666–0.837), with a sensitivity of 56.0% and a specificity of 89.6%, and the cut-off value was 9056.94. Besides, the levels of CA125, PLR, and their combination were significantly elevated in patients with endometriosis. The combined marker was not only positively correlated with pelvic adhesion but also showed a greater diagnostic value and specificity than CA125 alone. These findings indicate that the combined marker may be a potential inflammatory biomarker playing an important role in the diagnosis and assessment of adhesion in endometriosis.

BDNF and TrKB expression levels in patients with endometriosis and their associations with dysmenorrhoea

BackgroundBrain-derived neurotrophic factor (BDNF) is a known regulator of the development and maintenance of chronic pain in various chronic disorders. Together with its high-affinity tyrosine kinase type B (TrKB) receptor, BDNF is extensively expressed in the mammalian female reproductive system. However, BDNF and TrKB expression in different stages of endometriosis and the relationship between the expression of each in ectopic lesions and endometriosis pain remain unclear.MethodsSixty-two women who underwent laparoscopic surgery were enrolled in this study: forty-six diagnosed with ovarian endometrioma (study group) and sixteen diagnosed with ovarian benign tumours (control group). Samples from eutopic endometrium and ovarian endometriotic lesions were obtained at laparoscopic surgery. BDNF and TrKB messenger RNA (mRNA) and proteins levels in the eutopic and ectopic endometrium of both groups were measured by real-time PCR and immunohistochemical staining, respectively. Before the surgery the visual analogue scale (VAS) was used to measure dysmenorrhoea.ResultsBDNF and TrKB expression levels were higher in ovarian endometriotic lesions than in eutopic endometrium and normal endometrium (P < 0.05), and there was no cyclical change. Furthermore, their expression levels were higher in eutopic endometrium than in normal endometrium (P < 0.05), and BDNF and TrKB levels were higher in stage IV ovarian endometriotic lesions than in stage II and III lesions (P < 0.05), with their expression being non-significantly higher in stage III than in stage II (P > 0.05). Additionally, correlation coefficients for the association analysis between the mRNA expression of BDNF or TrKB in eutopic endometrium and the dysmenorrhoea VAS score were r = 0.52 and r = 0.56 for BDNF and TrKB, respectively (P < 0.05). The correlation coefficients for the associations between BDNF and TrKB in both the eutopic and ectopic endometrium were r = 0.82 and r = 0.66, respectively (P < 0.05).ConclusionsBDNF and TrKB are closely related to dysmenorrhoea caused by endometriosis and may be important in the pathobiology or pathophysiology of endometriosis.

IVF Outcome in Patients with Different Stages of Endometriosis: Can AMH Be a Predictor?

Background and Objectives: The role of Anti Mullerian Hormone (AMH) in determining the outcome of in vitro fertilization (IVF) in endometriosis has been controversial. This study was conducted to assess whether AMH can predict poor response in endometriosis patients undergoing IVF and to compare the IVF outcomes among the different stages of endometriosis. Methodology: A retrospective study was conducted among 90 endometriosis patients undergoing IVF using the flexible antagonist protocol from January 2016 to December 2018 at DY Patil Medical College, Navi Mumbai. Serum AMH levels were obtained from different patients, primary outcome being clinical pregnancy rate (CPR) while the secondary outcome included the number of oocytes retrieved, number of mature oocytes obtained, fertilization rates (FR), and number of good quality embryos formed. Data was analyzed with SPSS 16.0. Mann-Whitney U and chi-square tests were used to compare the outcomes of IVF with AMH level in different stages of endometriosis. Receiver Operator Characteristic (ROC) curves were plotted to know the predictive ability of AMH by determining the area under the curve (AUC), P value &lt; 0.05 was considered significant for all statistical tests. Results: AUC was found to be significant for AMH in detecting poor response among those with late staged endometriosis but with poor accuracy (AUC = 0.65, P = 0.02∗). Considering a median AMH level of 1.24 ng/mL with sensitivity and specificity of &gt; 60%, the primary and secondary outcomes were significantly higher among those with median AMH levels of more than 1.24 ng/mL compared to those with the median ≤ 1.24 ng/mL. The significance, however, was mainly found in the late stages of endometriosis (P &lt; 0.05). Fertilization rates, good quality embryos, and CPR did not vary with AMH levels among those with early stages of endometriosis (P &gt; 0.05). The outcomes of IVF did not vary significantly across the different stages of endometriosis except for good quality embryos which were formed in patients with early staged endometriosis (P &lt; 0.05). Conclusion: AMH levels may be a predictor of nonconception with poor accuracy in late stages of endometriosis (III/IV), while good quality embryos were obtained in patients with early stages of endometriosis.

Serum Diethyl Phthalate Levels in Infertile Females with Endometriosis

Background: Endometriosis has a complex multifactorial pathophysiology and is a leading cause of female infertility. Emerging evidence suggests the role of endocrine disrupting chemicals and environmental factors such as Diethyl phthalate (DEP) in the pathophysiology of the disease. Aim: To investigate the serum DEP levels in females with infertility having endometriosis and normal healthy counter parts. Methods: Married females (n=50) age 20-40 years, diagnosed with endometriosis and having history of &gt;1 year of infertility, were selected as cases. Age matched women (n=50) with proven fertility and screened negative for endometriosis were included as controls. Females on any medicine, having co morbid conditions were also excluded from the study. DEP concentration in serum was determined by using High performance liquid chromatography (HPLC). Results: Significantly higher levels (p=0.003) of DEP were seen in endometriosis females (3.76± 1.28 ng/ml) as compared to controls (2.61± 1.72 ng/ml). The comparison of DEP levels between different stages of endometriosis revealed an increasing, but no significant trend with advancement of the disease. Conclusion: High serum DEP levels in patients substantiate their role in disease pathophysiology. Therefore, it may be advisable to pay attention while using such compounds. There is an increased need to regulate the levels of such industrial compounds manufactured for daily use of human beings by efficient and judicious quality assurance plastics and by using the standards set by WHO and/or FDA. Keywords: Phthalate, Endometriosis, Diethyl phthalate, plasticizers, Infertility

The Role of Selected Chemokines in the Peritoneal Fluid of Women with Endometriosis—Participation in the Pathogenesis of the Disease

Endometriosis is a disorder characterized by the presence of endometrial tissue outside the uterine cavity, primarily into the peritoneal cavity. It is known as a complex, chronic inflammatory disease and it is strongly associated with immune dysregulation. Various soluble mediators of the immune and inflammatory responses, including chemokines, play an important role in these processes. The aim of the study was to understand the role of the chemokines MCP-1, MCP-2, MCP-3, MCP-4, MIP-1 α, MIP-1β, eotaxin 2, eotaxin 3, ENA-78, and fractalkine in the development of endometriosis through their assessment in the peritoneal fluid of women with endometriosis. The study group included 58 women with endometriosis who were diagnosed during laparoscopy and then confirmed by histopathology. In 15 women from the reference group, laparoscopic examination demonstrated a normal status of the pelvic organs without any evidence of endometriosis nor inflammation in the peritoneal cavity. The peritoneal fluid of women with endometriosis and of women from the reference group were examined. To determine the concentration of the studied chemokines, enzyme immunoassays for Luminex® platforms were used. In the peritoneal fluid of women with endometriosis, a statistically significant increase in the concentration of MIP-1β, eotaxin 2, eotaxin 3, ENA-78, and fractalkine and a decrease in the concentration of MCP-1, MCP-2, MCP-3, MCP-4, and MIP-1α were observed compared to the reference group. The concentration of these cytokines depended on the severity of the disease. Changes in the concentration of the studied chemokines in the peritoneal fluid of women with endometriosis suggest their participation in the pathogenesis of the disease. The differences in chemokines concentration observed in different stages of endometriosis may be associated with the presence of inflammation in the peritoneal cavity at each step of disease development.

RNA-sequencing identifies differentially expressed genes in T helper 17 cells in peritoneal fluid of patients with endometriosis

Innate and adaptive immune factors play significant roles in the pathophysiology of endometriosis. T helper 17 (Th17) cells, a pro-inflammatory T cell subset, were considered to contribute to the progression of endometriosis lesions. However, the regulatory mechanisms of Th17 cells in endometriosis remain unidentified, partially due to the difficulty in recovering live Th17 cells from endometriosis patients. In this study, by flow cytometry analysis of a set of chemokine receptors including CXCR3, CCR4, CCR10, and CCR6, live RORγt-and-IL-17A-expressing Th17 cells were enriched from peritoneal fluid (PF) of patients with different stages of endometriosis for the first time, RNA-sequencing (RNA-Seq) of these PF Th17 cells revealed significantly up-regulated genes and down-regulated genes in stage I-II and stage III-IV endometriosis, compared with their counterparts in normal PF. In conclusion, this study provides a novel method to isolate live Th17 cells from endometriosis patients, unveils an array of differentially expressed genes in endometriosis Th17 cells, and offers valuable gene expression profile information for endometriosis clinical research.

EVALUATION OF OOOCYTE QUALITY IN PATIENTS WITH ENDOMETRIOSIS UNDERGOING INTRACYTOPLASMIC SPERM INJECTION

Endometriosis is a multifactorial disease and its effect on oocyte quality still unclear, several factors has effect on etiology, from other hand the studies of oocyte developmental are limited by ethical constraints on use of human oocytes and embryos for biomedical research also difficult to monitor the embryos transferred to uterus and the factors affected on embryo development and implantation.(96) Also, there are number of studies evaluated the negative impact of endometriosis on oocyte quality by several mechanism such as clinical and biological data in related to different stages of endometriosis: The aim of this study is to Evaluate the quality of oocytes in patients with endometriosis Undergoing ICSI. This was a retrospective cohort analysis of oocytes quality in which 100 infertile ladies with endometriosis compared with 200 infertile ladies without endometriosis were recruited from the infertility clinic of El-Shatby maternity University Hospital and a repro-Fertility Center. All the patients accepted and consented to the intra-cytoplasmic sperm injection program.

Role of Epithelial-to-Mesenchymal Transition Markers in Different Stages of Endometriosis: Expression of the Snail, Slug, ZEB1, and Twist Genes.

Among various epithelial-to-mesenchymal transition (EMT)-related transcription factors (TFs), altered expression levels of Snail-1, Snail-2/Slug, Twist, and ZEB1 have shown a significant association in different cancers having a higher risk of metastasis. However, their role in the circulation of endometriosis patients is not well understood. Hence, the present study was designed to evaluate the crucial role of these TFs in defining the molecular pathogenesis for endometriosis progression and differentiation from control subjects. The qualitative and quantitative expression analysis of Snail-1, Snail-2/Slug, Twist, and ZEB1 were analyzed in peripheral blood samples of 75 different stages of endometriosis patients and compared with 50 control subjects. Total RNA was extracted and converted into complementary DNA (cDNA) for relative quantification of each gene transcript using SYBRGreen-based reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). The Livak method of relative quantification was used for calculating the fold change in each TF compared with endogenous control. All four selected TFs showed significantly upregulated expression levels in endometriosis patients compared with control subjects. A three-fold increase was observed for Snail-1 (p = 0.0001), and a two-fold increase was observed for Snail-2 (p = 0.01), Twist (p = 0.0002), and ZEB1 (p = 0.001) in stage III and IV compared with stage I and II of endometriosis patients. The present study revealed that EMT-related TFs play a crucial role in the pathogenesis and differentiating different stages of endometriosis patients through expression analysis of specific molecular cascades using non-invasive tools.

MiR-532-3p: a possible altered miRNA in cumulus cells of infertile women with advanced endometriosis

Research questionIs the profile of microRNA (miRNA) altered in cumulus cells of infertile women with early (EI/II) and advanced (EIII/IV) endometriosis? DesignIn this prospective case–control study, a miRNA profile including 754 targets was evaluated in samples of cumulus cells from infertile women with endometriosis (5 EI/II, 5 EIII/IV) and infertile controls (5, male and/or tubal factor) undergoing ovarian stimulation for intracytoplasmic sperm injection, using TaqMan® Array Human MicroRNA Cards A and B. The groups were compared with Kruskal–Wallis test, followed by Benjamini–Hochberg correction and Dunn's post hoc test. An in silico enrichment analysis was performed to list the possibly altered pathways in which the altered miRNA target genes are involved. ResultsOnly the miRNA miR-532-3p showed significant differences among the analysed groups, being down-regulated in the EIII/IV group compared with the infertile control group, as well as compared with the EI/II group. The enrichment analysis showed that some genes regulated by this miRNA are involved in important pathways for the acquisition of oocyte competence, such as the oxytocin, calcium, Wnt, FoxO, ErbB and Ras signalling pathways, as well as the oocyte meiosis pathway. ConclusionThe present findings bring new perspectives to understanding the follicular microenvironment of infertile women with different stages of endometriosis. It is suggested that the dysregulation of miR-532-3p may be a potential mechanism involved in the aetiopathogenesis of endometriosis-related infertility. Further studies are needed to evaluate these pathways in cumulus cells of infertile women with the disease, as well as their impact on the acquisition of oocyte competence.

The Use of Indocyanine Green to Identify Endometriosis Intraoperatively [34B

INTRODUCTION: The gold standard for diagnosis of endometriosis is a tissue biopsy. Endometriosis can be a debilitating cause of pelvic pain. Since symptoms can be nonspecific, presumptive diagnosis without tissue biopsy may be difficult. Recently, indocyanine green (ICG), a fluorescent dye that identifies vascular areas, has been used to help identify the vascular lesions of endometriosis, specifically the “clear” lesions that can easily be missed during surgery. METHODS: A retrospective chart review and data analysis was performed on patients upon whom ICG was used from July 2014 to January 2019. Preoperative symptoms, including abnormal uterine bleeding, pelvic pain, dyspareunia, and fibroids were analyzed using Fisher exact test. identification of “clear” lesions with ICG was analyzed using Fisher exact test. RESULTS: Of 56 patients who underwent laparoscopic excision of endometriosis with ICG, 46 with positive fluorescence had pathology-confirmed endometriosis; 10 had negative pathology with no ICG fluorescence and 10 had fluorescence but no endometriosis. This indicates a positive predictive value of 82% and a sensitivity of 100%. There was no statistically significant difference with preoperative symptoms. Clear lesions were identified using ICG in 100% of patients with endometriosis; however, there was no statistically significant difference when compared to patients without endometriosis. CONCLUSION: ICG dye utilization offered a diagnosis of endometriosis in 46 of 56 patients. ICG is safe, inexpensive, and may help physicians diagnose endometriosis. Additional patients should be recruited to add power to the data. A future research study could analyze the possible differences in uptake of ICG in different stages of endometriosis.

Alterations of CD4+T Cell Subsets in Blood and Peritoneal Fluid in Different Stages of Endometriosis.

BackgroundEndometriosis is a chronic inflammatory disorder with known immune disturbances. The aim of this study was to compare the frequency of different CD4+ T cells [T helper (Th)1, Th2, Th17 and regulatory T cells (Tregs)] in peripheral blood (PB) and peritoneal fluid (PF) of patients that have early and advanced stages of endome- triosis with a control group.Materials and MethodsIn this case control study, PB and PF samples were collected from women aged 24-40 years who underwent laparoscopy procedures. The frequency of CD4+ T subsets were analysed by flow cytometry and com- pared between three study groups; early endometriosis (stage I, II), advanced endometriosis (stage III, IV) and control (no endometriosis). T cell numbers were compared between the PB and PF in each of the aforementioned groups.ResultsNo statistically significant difference was found between the study groups regarding the numbers of Th1, Th2 and Th17 cells in PB. The PF of patients with advanced endometriosis had increased numbers of Th17 cells compared to the control group (P=0.003), with P values of 0.059 and 0.045 in both menstrual phases. Increased numbers of Th2 cells in PF from early compared to advanced stages of endometriosis were detected exclusively in the luteal phase (P=0.035). The control group had increased numbers of Treg and Th2 cells in the PF compared to PB (both, P value=0.046). However, in the early stages of endometriosis there were more Th2, Th17 and Treg cells in the PF compared to PB (P values: 0.005, 0.047 and 0.013, respectively), while the number of Th17 cells was higher in the PF compared with PB in the advanced stages of endometriosis (P= 0.013).ConclusionThere were increased numbers of Th17 cells in the PF of patients with advanced stages of endometriosis, which could be related to the severity of this disease.

The levels of matrix metalloproteinase-9 and neutrophil gelatinase-associated lipocalin in different stages of endometriosis

This study was designed to explore matrix metalloproteinase-9 (MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) levels and MMP-9/NGAL ratio in women with and without endometriosis diagnosed surgically and/or histopathologically. The correlation between biomarkers and the severity of the disease is analysed. The revised American Fertility Society classification system was used to determine the severity of endometriosis. Serum MMP-9 and Ca125, urine NGAL levels were measured in all participants. Serum MMP-9 levels were significantly higher in the study group (n = 60) compared to controls (n = 31) (15.0 pg/mL (6.0–143.0) vs. 12.0 (4.0–18.0), respectively; p=.002). MMP-9 levels were significantly higher in severe endometriosis compared to mild endometriosis subgroups (p<.001). No significant difference was found between NGAL levels in study and control groups (p>.05). The diagnostic value of MMP-9 and NGAL is not superior than CA-125 for endometriosis. Nevertheless, MMP-9 might be a potential predictive marker for advanced stage of the disease.Impact StatementWhat is already known on this subject? The gold standard diagnostic test for diagnosis of endometriosis is laparoscopy combined with histopathological confirmation of eutopic endometrial glands and/or stroma. Both invasiveness and possible accompanying complications limit the preference regarding the surgical approach. Among non-invasive markers none has been accepted as gold standard neither for diagnosis nor for determining the severity of the disease. MMPs are extracellular endopeptidases, which have a significant role in degradation and remodelling of extracellular matrix for cellular migration and invasion. Among these, MMP-9 has been shown to be higher in eutopic/ectopic endometrial tissue in women with endometriosis and has been suggested to have a role in pathogenesis of endometriosis by promoting invasion of the endometriotic lesions. NGAL is an acute phase protein, which is involved in a variety of physiological and pathophysiological processes. The molecule has also been revealed to correlate with endometriosis pathophysiology through the epithelial–mesenchymal transition process which is the basis for the onset of endometriosis. But also, NGAL which composes a complex with MMP-9 (MMP-9 and NGAL complex), has been shown to protect MMP-9 from autodegradation in vitro which might be a contributing factor for endometriosis pathophysiology.What the results of this study add? MMP-9 cut-off level for prediction of severe endometriosis is a novel finding obtained from this study with acceptable sensitivity and specificity. On the other hand, NGAL seems to have no significant value either for diagnosis of for determining severity of the disease. After all, MMP-9 might be an easy use acceptable biomarker for endometriosis but further studies on larger populations are needed.What the implications are of these findings for clinical practice and/or further research? MMP might be a potential non-invasive predictive marker for advanced stage disease.

The role of l-carnitine and omega-3 fatty acids in prevent meiotic damages to bovine oocytes matured in vitro with follicular fluid from womem with different stages of endometriosis

The role of l-carnitine and omega-3 fatty acids in prevent meiotic damages to bovine oocytes matured in vitro with follicular fluid from womem with different stages of endometriosis

Correlation of CA-125 with different stages of endometriosis

&lt;p class="Abstract"&gt;This study was conducted to evaluate the association of serum cancer antigen (CA-125) level with the severity of pelvic endometriosis. Seventy diagnosed cases of pelvic endometriosis were included in this study. The CA-125 level was estimated in all these patients, cutoff value of the serum CA-125 level was considered 35.0 U/mL. The correlations between serum CA-125 and different stages of endometriosis were evaluated by linear regression analysis. In Stage I of endometriosis, the mean serum CA-125 level was 21.8 ± 15.1 U/mL, in Stage II 26.0 ± 17.3 U/mL, in Stage III 83.2 ± 48.9 U/mL and in Stage IV 117.0 ± 41.6 U/mL. A significant positive correlation (r=0.729; p=0.001) was found between the serum CA-125 and different stages of endometriosis.&lt;/p&gt;

Expression of inflammatory cytokines in serum and peritoneal fluid from patients with different stages of endometriosis

Objective: To investigate the level of inflammatory cytokines in endometriosis patients, and explore the relationship between IL-37 concentration and endometriosis stages. Methods: Inflammatory cytokine concentrations from 27 patients with different stages of endometriosis and 52 controls without endometriosis were examined by ELISA. Then, the specificity and sensitivity of cytokines for distinguishing from controls and the different stages of endometriosis were analyzed using the ROC curve. Results: The difference in serum concentrations of IL-37, IL-17A, IL-10, and IL-2 between the endometriosis and control groups was statistically significant (p < .01). Compared with controls, significantly higher levels of serum IL-37 and IL-10, and significantly lower levels of serum IL-17A and IL-2 were detected in patients with endometriosis (p < .01). Furthermore, IL-2 concentration was significantly higher in peritoneal fluid (PF) in the endometriosis group (p = .0034), IL-10 concentrations in PF were significantly lower in the early-stages of endometriosis than in the more advanced groups (p = .0439), and IL-4 concentration in PF was significantly higher in more advanced endometriosis (p = .0228). The sensitivity and specificity of serum IL-37 for distinguishing endometriosis were 81.48% and 83.33%, respectively, and the cutoff concentration was 69.84 pg/ml. For IL-17A, the sensitivity and specificity were 96.30% and 100%, respectively, and the cutoff concentration was 57.54 pg/ml. For IL-10, the sensitivity and specificity was 92.59% and 100%, respectively, and the cutoff concentration was 3.301 pg/ml. For IL-2, the sensitivity and specificity were 74.07% and 93.75%, respectively, and the cutoff concentration was 1.813 pg/ml. For PF IL-2, the sensitivity and specificity were 29.73% and 100%, respectively, and the cutoff concentration was 1.06 pg/ml. Conclusions: IL-37, IL-17A, IL-10, and IL-2 may play a significant role in immune response in endometriosis. IL-37 levels may be used as a diagnostic marker for endometriosis.

Correlation between serum and peritoneal fluid glutathione S-transferases T1 concentration with different stages of endometriosis

Abstract Endometriosis is a gynecological disease defined by the histological presence of endometrial glands and stroma outside the uterine cavity. Ectopic endometrial cell proliferation and chronic inflammation in endometriosis were shown to be associated with oxidative stress (OS) induction. OS is a condition in which reactive oxygen species (ROS) overproduction and antioxidant deficiency cause a shift in oxidant/antioxidant balance. Glutathione S-transferases (GSTs) comprise a family of eukaryotic and prokaryotic phase II metabolic isozymes best known for their ability to catalyze the conjugation of the reduced form of glutathione (GSH) to xenobiotic substrates for the purpose of detoxification. The aim of this project was to study the concentrations of GSTT1 in the serum and peritoneal fluid (PF) of patients with different stages of endometriosis. Frothy two PF and serum from normal and 152 from different stages of patients with endometriosis (stage I: n = 30, stage II: n = 39, stage III: n = 43 and stage IV: n = 40) were included in this study. The level of GSTT1 in the serum was determined by enzyme linked immunosorbent assay (ELISA). The results showed the presence of GSTT1 in all serum and peritoneal fluid samples, while, starting from stages I to IV endometriosis, a significant decrease in GSTT1 concentration was seen as compared to controls. It is concluded that levels of GSTT1 is negatively correlated with advanced stages of endometriosis. It is also suggested that the detection of serum and/or peritoneal fluid GSTT1 concentration may be valuable in the classifying of endometriosis.