Endometriotic Patients Research Articles

Role of thyroid dysimmunity and thyroid hormones in endometriosis

Endometriosis is characterized by the presence of ectopic endometrial cells outside the uterine cavity. Thyroid autoimmunity has been associated with endometriosis. This work investigated the potential pathophysiological link between endometriosis and thyroid disorders. Transcripts and proteins involved in thyroid metabolism are dysregulated in eutopic and ectopic endometrium of endometriotic patients, leading to resistance of ectopic endometrium to triiodothyronine (T3) action and local accumulation of thyroxine (T4). Thyroid-stimulating hormone (TSH) acts as a proliferative and prooxidative hormone on all endometria of endometriosis patients and controls, whereas T3 and T4 act to specifically increase ectopic endometrial cell proliferation and reactive oxygen species (ROS) production. Mouse studies confirmed the data gained in vitro since endometriotic implants were found to be bigger when thyroid hormones increased. A retrospective analysis of endometriosis patients with or without a thyroid disorder revealed an increased chronic pelvic pain and disease score in endometriotic patients with a thyroid disorder.

Effects of clarithromycin on inflammatory markers and clinical manifestations in postsurgical follow-up of patients with endometriosis: a double-blinded randomized placebo-controlled clinical trial

Studies showed anti-inflammatory and immunomodulatory effects of macrolide antibiotics such as clarithromycin in endometriosis. Therefore, the present study aims to investigate the therapeutic efficacy of clarithromycin in patients with endometriosis. This was a double-blinded randomized placebo-controlled trial conducted on endometriotic women during March 2016-2017 in Dena Hospital, Shiraz, Iran. Immediately after surgery, the patients were randomly divided into clarithromycin (real) (n = 120) and placebo group (n = 169). The real group received 500mg of clarithromycin everyday for 6months and the placebo group received the placebo. The serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), Erythrocyte sedimentation rate (ESR) and C-reactive protein as well as clinical symptoms at baseline and 3 and 6months of post-surgery were compared within and between groups. The scores of dysmenorrhea, dyschezia, dyspareunia, and non-menstrual pain significantly decreased in both real and placebo groups compared with the baseline values. However, the real group showed greater reductions compared with the placebo group (p < 0.001). Similarly, the serum levels of CRP, TNF-α, and IL-10 decreased in both groups compared with the baseline values, but the real group showed greater reductions. Interestingly, the reductions in the clinical symptoms and serum levels did not significantly differ between the real and placebo groups. Moreover, the reductions in the studied variables showed no dependence on the time. Clarithromycin may be an appropriate treatment in endometriotic patients. However, the non-significant differences between the real and placebo groups necessitate further studies on the therapeutic efficacy of clarithromycin.

Resveratrol reduces the expression of insulin-like growth factor-1 and hepatocyte growth factor in stromal cells of women with endometriosis compared with nonendometriotic women.

Resveratrol, a phytoalexin polyphenol, has antiproliferative, antiangiogenic, anti-inflammatory, and antioxidant properties. The present study has assessed the effect of resveratrol treatment on the expression of insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) in endometrial stromal cells (ESCs) from women with and without endometriosis. Endometrial tissues were obtained from 40 endometriotic patients and 15 nonendometriotic control women. After the enzymatic digestion, 13 eutopic ESCs (EuESCs), 8 ectopic ESCs (EESCs), and 11 control ESCs (CESCs) were treated with resveratrol (100μM) for 6, 24, and 48hr. The gene and protein expressions of IGF-1 and HGF were measured using real-time polymerase chain reaction and enzyme-linked immunosorbent assay methods, respectively. Results showed that resveratrol treatment decreased significantly the gene expression of IGF-1 and HGF in EuESCs, EESCs, and CESCs (p<0.05). The effect of resveratrol treatment on the reduction of IGF-1 gene expression was statistically more noticeable in EESCs compared with CESCs (p<0.05). Also, in the case of HGF gene expression, the reducing effect of resveratrol treatment was statistically more considerable in EESCs compared with EuESCs and CESCs (p<0.05 and p<0.01, respectively). The IGF-1 and HGF protein production decreased significantly in EuESCs and EESCs (p<0.05) but not in CESCs. These findings suggest that resveratrol treatment could reduce the expression of IGF-1 and HGF in ESCs especially in EESCs, which play a pivotal role in disease progression.

Endometriosis of the Appendix: When to Predict and How to Manage—A Multivariate Analysis of 1935 Endometriosis Cases

To evaluate appendiceal endometriosis (AE) prevalence and risk factors in endometriotic patients submitted to surgery. A retrospective cohort study. A tertiary level referral center, university hospital. One thousand nine hundred thirty-five consecutive patients who underwent surgical removal for symptomatic endometriosis. Electronic medical records of patients submitted to surgery over a 12-year period were reviewed. We assessed any correlation between demographic, clinical, and surgical variables and AE. In our center, appendectomy was performed using a selective approach. Appendix removal was performed in case of gross abnormalities of the organ, such as enlargement, dilation, tortuosity, or discoloration of the organ or the presence of suspected endometriotic implants. AE prevalence was 2.6% (50/1935), with only 1 false-positive case at gross intraoperative evaluation. In multivariate analysis using a stepwise logistic regression model, independent risk factors for AE were adenomyosis (adjusted odds ratio [aOR] = 2.48; 95% confidence interval [CI], 1.32-4.68), right endometrioma (aOR = 8.03; 95% CI, 4.08-15.80), right endometrioma ≥5 cm (aOR = 13.90; 95% CI, 6.63-29.15), bladder endometriosis (aOR = 2.05; 95% CI, 1.05-3.99), deep posterior pelvic endometriosis (aOR = 5.79; 95% CI, 2.82-11.90), left deep lateral pelvic endometriosis (aOR = 2.11; 95% CI, 1.10-4.02), and ileocecal involvement (aOR = 12.51; 95% CI, 2.07-75.75). Among patients with endometriosis submitted to surgery, AE was observed in 2.6%, and it was associated with adenomyosis, large right endometrioma, bladder endometriosis, deep posterior pelvic endometriosis, left deep lateral pelvic endometriosis, and ileocecal involvement.

Pelvic abscess after ovulation in a patient with recurrent ovarian endometriotic cysts: case report and literature review

Retrospective analysis of 1 case admitted to our hospital and 15 domestic and foreign literature reports of endometriotic cyst infertility patients with pelvic abscess clinical data after ovulation. One patient in our hospital was treated with recurrent EMS-assisted assisted pregnancy. The endometriotic cyst rupture with pelvic abscess improved after surgery. At home and abroad, 15 cases of infertility were caused by ovarian endometriosis cysts, and 3 of them were recurrent. All the 15 cases showed lower abdominal pain, repeated body temperature, elevated white blood cells and erythrocyte sedimentation rate, and pelvic mass under ultrasound. 7 cases were treated with surgery and 8 cases were treated conservatively. The prognosis was good. Key words: Endometriosis, ovary; Pelvic infection; Fertilization in vitro; Embryo transfer

The Role of Matrix Metalloproteinase2 (MMP2) in Serum and Peritoneal Fluid of Endometriotic Patients

Objective: To determine the role of matrix metalloproteinase-2(MMP-2) in serum and peritoneal fluid of endometrioticpatients.Methods: Research’s design using cross-sectional method in Dr.Wahidin Sudirohusodo hospital and several other hospitals inMakassar within May 2015 until May 2016. Subjects were chosenusing consecutive sampling technique. The examination usingthe ELISA method. The data were analysed using Fisher exact,t-independent, Mann-Whitney, and Spearman association.Results: A total of 50 subjects were recruited in this study. Mostlythe value of MMP-2 serum and peritoneal fluid in endometriosisgroup was higher compare to study control. There was significantdifferent between the total of MMP-2 serum and peritoneal fluid.There was also a significant association between the value ofMMP-2 serum and peritoneal fluid with endometriosis.Conclusion: The value of MMP-2 serum and peritoneal fluid werehigher in endometriotic patients compared to those withoutendometriosis. The higher the value of MMP-2 serum andperitoneal fluid, the higher the stage of endometriosis.[Indones J Obstet Gynecol 2018; 6-2: 104-109]Keywords: endometriosis, matrix metalloproteinase-2, MMP-2

Endometrial Stromal and Epithelial Cells Exhibit Unique Aberrant Molecular Defects in Patients With Endometriosis

Endometriosis is a chronic inflammatory disease that causes pain and infertility in women of reproductive age. To investigate the pathologic pathways in endometrial stromal and epithelial cells that contribute to the manifestation of endometriosis. In vitro cellular and molecular analyses of isolated eutopic endometrial stromal and epithelial cells. Eutopic stromal and epithelial cells from endometriotic and normal patients were isolated by fluorescence-activated cell sorting for paired sibling RNA sequencing and microRNA microarray. Aberrant pathways were identified using ingenuity pathway analysis networks and confirmed with in vitro modulation of the affected pathways in stromal and epithelial cell cultures. Both stromal versus epithelial cell types and paired endometriotic versus normal samples exhibited distinct hierarchical clustering. Compared to normal samples, there were 151 and 215 differentially expressed genes in the endometriotic stromal and epithelial populations, respectively, and concomitantly 9 and 16 differentially expressed microRNAs. Overall, endometriotic stromal and epithelial cells revealed distinct defects. In endometriotic stromal cells, key decidualization genes Zinc finger E-box Binding protein 1 (ZEB1), Heart And Neural crest Derivatives expressed 2 (HAND2), WNT4, and Interleukin 15 (IL-15) were found to be downregulated and Periostin (POSTN) and Matrix Metallopeptidase 7 (MMP7) were upregulated. Specifically, ZEB1 was downregulated in stromal cells by aberrant elevation in miR-200b. In contrast, ZEB1 was found to be upregulated in endometriotic epithelial cells through associated upregulation of transforming growth factor β1 (TGFβ1), inducer of the TGFβ1-Bone Morphogenetic Protein 2 (BMP2)-MMP2-Prostaglandin-endoperoxide Synthase 2 (COX2)-ZEB1 pathway, which activates epithelial-mesenchymal transition. Manifestation of endometriosis involves dysregulation of unique molecular pathways within the diseased endometrial stromal and epithelial cells in the endometrium. Targeting the cell type-specific defects may offer a novel approach to treating endometriosis.

Treatment of pelvic cavity pain caused by endometriosis with excision of invaded sacrospinous ligament.

Objective:To evaluate the clinical therapeutic effects of excision of invaded sacrospinous ligament on pelvic cavity pain caused by endometriosis.Methods:Eighty endometriotic patients treated in our hospital from January 2013 to December 2014 were chosen, and divided into a control group and an observation group. Regular operation (i.e. excision of endometriotic nidus and separation of pelvic cavity adhesion) was performed for the control group, while regular operation and sacrospinous ligament excision were conducted for the observation group. Intraoperative and postoperative conditions as well as postoperative pain remission of both groups were compared.Results:For the amount of bleeding during operation, the control group was (120±5.2) ml, while the observation group was (160±4.0) ml. For the duration of operation, the control group was (65±3.4) minutes, while the observation group was (92±2.6) min (p<0.05), with a significant difference. For the independent urination time after operation, the control group was (32±8.8) hour, while the observation group was (33±6.4) hour. For the evacuation time after operation, the control group was (38±2.6) hour, while the observation group was (39±3.0) hour (p>0.05), with a significant difference. The postoperative VAS scores of the two groups were significantly lower than those before operation, and the VAS score of the observation group was significantly lower than that of the control group, p<0.05.Conclusions:Sacrospinous ligament excision relieved pain caused by endometriosis, so it may be applicable to the endometriosis patients with sacrospinous ligament infiltration or severe pain.

Aberrant expression of epithelial leucine-rich repeat containing G protein–coupled receptor 5–positive cells in the eutopic endometrium in endometriosis and implications in deep-infiltrating endometriosis

To characterize leucine-rich repeat containing G protein-coupled receptor 5-positive (LGR5+) cells from the endometrium of women with endometriosis. Prospective experimental study. University hospital/fertility clinic. Twenty-seven women with endometriosis who underwent surgery and 12 healthy egg donors, together comprising 39 endometrial samples. Obtaining of uterine aspirates by using a Cornier Pipelle. Immunofluorescence in formalin-fixed paraffin-embedded tissue from mice and healthy and pathologic human endometrium using antibodies against LGR5, E-cadherin, and cytokeratin, and epithelial and stromal LGR5+ cells isolated from healthy and pathologic human eutopic endometrium by fluorescence-activated cell sorting and transcriptomic characterization by RNA high sequencing. Immunofluorescence showed that LGR5+ cells colocalized with epithelial markers in the stroma of the endometrium only in endometriotic patients. The results from RNA high sequencing of LGR5+ cells from epithelium and stroma did not show any statistically significant differences between them. The LGR5+ versus LGR5- cells in pathologic endometrium showed 394 differentially expressed genes. The LGR5+ cells in deep-infiltrating endometriosis expressed inflammatory markers not present in the other types of the disease. Our results revealed the presence of aberrantly located LGR5+ cells coexpressing epithelial markers in the stromal compartment of women with endometriosis. These cells have a statistically significantly different expression profile in deep-infiltrating endometriosis in comparison with other types of endometriosis, independent of the menstrual cycle phase. Further studies are needed to elucidate their role and influence in reproductive outcomes.

Dapsone hydroxylamine-mediated alterations in human red blood cells from endometriotic patients

Endometriosis, an estrogen-dependent chronic gynecological disease in women of reproductive age, is characterized by a systemic inflammation status involving also red blood cells (RBCs). In this study, we evaluated how the protein oxidative status could be involved in the worsening of RBC conditions due to dapsone intake in endometriotic women in potential treatment for skin or infection diseases. Blood samples from two groups of volunteers, control group (CG) and endometriosis patient group (PG), were analyzed for their content of band 3 tyrosine phosphorylation (Tyr-P) and high molecular weight aggregate (HMWA) in membranes, and glutathione (GSH) content and carbonic anhydrase (CA) activity in cytosol. In endometriotic patients, RBC showed the highest level of oxidative-related alterations both in membrane and cytosol. More interestingly, the addition of dapsone hydroxylamine (DDS-NHOH) could induce further increase of both membranes and cytosol markers, with an enhancement of CA activity reaching about 66% of the total cell enzyme amount. In conclusion, in PG the systemic inflammatory status leads to the inability of counteracting adjunctive oxidative stress, with a potential involvement of CA-related pathologies, such as glaucoma. Hence, the importance of the evaluation of therapeutic approaches worsening oxidative imbalance present in PG RBC is underlined.

Relationship between the magnetic resonance imaging appearance of adenomyosis and endometriosis phenotypes.

What is the relationship between endometriosis phenotypes superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA), deep infiltrating endometriosis (DIE) and the adenomyosis appearance by magnetic resonance imaging (MRI)? Focal adenomyosis located in the outer myometrium (FAOM) was observed more frequently in women with endometriosis, and was significantly associated with the DIE phenotype. An association between endometriosis and adenomyosis has been reported previously, although data regarding the association between MRI appearance of adenomyosis and the endometriosis phenotype are currently still lacking. This was an observational, cross-sectional study using data prospectively collected from non-pregnant patients who were between 18 and 42 years of age, and who underwent surgery for symptomatic benign gynecological conditions between January 2011 and December 2014. For each patient, a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding the surgery. Only women with preoperative standardized uterine MRIs were retained for this study. Surgery was performed on 292 patients with signed consent and available preoperative MRIs. After a thorough surgical examination of the abdomino-pelvic cavity, 237 women with histologically proven endometriosis were allocated to the endometriosis group and 55 symptomatic women without evidence of endometriosis to the endometriosis free group. The existence of diffuse or FAOM was studied in both groups and according to surgical endometriosis phenotypes (SUP, OMA and DIE). Adenomyosis was observed in 59.9% (n = 175) of the total sample population (n = 292). Based on MRI, the distribution of adenomyosis was as follows: isolated diffuse adenomyosis (53 patients; 18.2%), isolated FAOM (74 patients; 25.3%), associated diffuse and FAOM (48 patients; 16.4%). Diffuse adenomyosis (isolated and associated to FAOM) was observed in one-third of the patients regardless of whether they were endometriotic patients or endometriosis free women taken as controls (34.2% (81 cases) versus 36.4% (20 cases)); P = 0.764. Among endometriotic women, diffuse adenomyosis (isolated and associated to FAOM) failed to reach significant correlation with the endometriosis phenotypes (SUP, 20.0% (8 cases); OMA, 45.2% (14 cases) and DIE, 35.5% (59 cases); P = 0.068). In striking contrast, there was a significant increase in the frequency of FAOM in endometriosis-affected women than in controls (119 cases (50.2%) versus 5.4% (3 cases); P < 0.001). FAOM correlated with the endometriosis phenotypes, significantly with DIE (SUP, 7.5% (3 cases); OMA, 19.3% (6 cases) and DIE, 66.3% (110 cases); P < 0.001). There was a possible selection bias due to the specificity of the study design, as it only included surgical patients in a referral center that specializes in endometriosis surgery. Therefore, women referred to our center may have suffered from particularly severe forms of endometriosis. This could explain the high number of women with DIE (166/237-70%) in our study group. This referral bias for women with severe lesions may have amplified the difference in association of FAOM with the endometriosis-affected patients compared to women without endometriosis. Furthermore, according to inclusion criteria, women in the endometriosis free group were symptomatic women. This may introduce some bias as symptomatic women may be more prone to have associated adenomyosis that in turn could have been overrepresented in the endometriosis free group. Whether this selection could have introduced a bias in the relationship between endometriosis and adenomyosis remains unknown. This study opens the door to future epidemiological, clinical and mechanistic studies aimed at better characterizing diffuse and focal adenomyosis. Further studies are necessary to adequately determine if diffuse and focal adenomyosis are two separate entities that differ in terms of pathogenesis. No funding supported this study. The authors have no conflict of interest to declare.

Ureterovesical reimplantation for ureteral deep infiltrating endometriosis: A retrospective study

Introduction and hypothesisSymptoms of endometriosis of the urinary tract consist of nonspecific signs that are often trivialized. However, late diagnosis may be responsible for an upstream impact. The aim of this study is to describe a population of patients who received ureterovesical reimplantation for deep infiltrating endometriosis. We evaluate the preoperative clinical and radiological symptoms and long-term surgical outcomes. MethodsAll the endometriotic patients who underwent ureterovesical reimplantation at Lille university hospital between 2003 and 2013 were included retrospectively. ResultsSeventeen patients were included. Urological symptoms of endometriosis were present in 53% of patients and 29% had a history of urological surgery. Delay between diagnosis and ureteral reimplantation was 64±65 months on average. Forty-seven percent of patients had urinary functional symptoms consisting mainly of lower back pain. The ureteral lesion was known preoperatively and associated with hydroureteronephrosis in 82% of cases. Thirty-five percent of patients had renal atrophy and renal function was impaired in 23% of cases. Mean follow-up was 45±27 months. Forty-one percent of patients presented at least one immediate postoperative complication–fistula, postoperative infection or nerve compression. Also, urinary functional symptoms, dyspareunia and dysmenorrhea were maintained in 47%. ConclusionUreterovesical reimplantation in a context of endometriosis is major surgery with frequent complications. It requires close collaboration between gynecologists, radiologists and urologists. Prior comprehensive patient information is essential. Diagnosis and early treatment of ureteral endometriosis lesions should help reduce the morbidity of this disease.

Micronized palmitoylethanolamide/trans-polydatin treatment of endometriosis-related pain: a meta-analysis.

To demonstrate clinical effectiveness of micronized palmitoylethanolamide-trans-polydatin combination in reducing endometriotic chronic pelvic pain. Other endometriotic-pains were also assessed. Systematic reviews of PubMed, SCIELO, Scopus, and AJOL. Randomized trials and observational studies reporting a visual analogue scale for pain or similar in endometriotic patients were reviewed. A mean improvement of visual analogue scale (or visual analogue scale-like) scores at enrollment and at a three-month follow-up was assessed and interpreted clinically. Four studies of poor quality were available. In a heterogeneous sample of endometriotic patients with pain, the administration of micronized palmitoylethanolamide/trans-polydatin (400 mg/40 mg) twice a day for three months provided a clinically relevant improvement of chronic pelvic pain and dysmenorrhea while improving deep dyspareunia to a limited degree. No clinically relevant improvement was found for dyschezia. More studies are warranted for assessing the drugs-related efficacy.

New procedure for the endometriosis diagnosis

Previous studies revealed that when endometrial cells from GFP (Green Fluorescent Protein) mice were introduced into peritoneal cavity of RFP (Red Fluorescent Protein) mice to induce a murine model of endometriosis, GFP+ cells epithelial cells were aberrantly found in the stromal compartment of the eutopic endometrium of RFP mice two, three and four months after surgery. Arrays and immunofluorescence (IF) of these aberrant cells showed that GFP+ cells co-expressed cytokeratin (CK, epithelial marker) and Leucine-rich Repeat Containing G protein-Coupled Receptor 5 (LGR5, stem cell marker of the intestine). The aim of this study was to prove wether this process occurs in the human endometrium of patients affected with endometriosis and to characterize this type of cells in order to is to develop a non-invasive diagnostic test for this disease. Experimental case-control study. Uterine Aspirates from women with endometriosis (n=26) and healthy donors (n=11) were collected from women undergoing surgery for endometriosis or ovum pick-up for donation. Endometriotic patients were dividen in ovarian endometriosis (n=9), pelvic endometriosis (n=3), Deep Infiltrating Endometriosis (n=9) and Adenomyosis (n=4). Samples were aspirates was washed with 1x PBS and placed into 4% formaldehyde for fixation and paraffin embedding. Paraffin-embedded fixed samples were sectioned for hematoxylin and eosin (H&E) staining to determine the stage of the menstrual cycle and for immunofluorescence experiments. Dating of phases of the menstrual cycle was determined by two pathologists according to the criteria of Noyes.Subsequently Immunofluorescence (IF) staining was performed to co-localize LGR5 with E-Cadherine and LGR5 with Citokeratine in the epithelial and stromal compartment. Additionally LGR5+ cells were isolated through cell sorting and mRNA was sequenced. IF analysis on paraffin embedded tissue of mice confirmed that GFP+ cells co-localize with LGR5 and E-cadherin (ECAD, epithelial marker). LGR5+ cells in epithelium and stroma of human eutopic endometrium from patients and donors by FACS and IF. LGR5+ cells co-localize aberrantly with ECAD and CK in the stroma from 17 and 22 of 26 endometriotic patients respectively, whereas there is no colocalization in none of 11 donors. We also performed a pilot study using RNA-sequencing of the LGR5+/- cells from uterine biopsies from four patients of each type of endometriosis and healthy donors in order to identify a genetic signature of the disease and its subgroups. An aberrant expression of epithelial cells was found in the eutopic endometrium of women affected with endometriosis compared to healthy women. These aberrant cells were isolated and their experession was compared to healthy endometrium and each different subtype of endometriosis revealing that each type have a characteristic genetic signature that may led us to potentially establish an new and less invasive diagnostic tool for the diagnosis of endomteriosis.

Increased percentage of Th17 cells in peritoneal fluid is associated with severity of endometriosis

AimTh17 cells are a newly discovered T helper lymphocyte subpopulation, producing interleukin IL-17. Th17 cells are present in blood and peritoneal fluid (PF) at different stages of endometriosis. We aim to establish their potential importance in the pathogenesis and clinical features of the disease. MethodsThe percentage of Th17 cells among T helper lymphocytes was determined in the PF and peripheral blood (PB) of patients with endometriosis and in the control group by flow cytometry using monoclonal antibodies: anti-CD-4-FITC, anti-CD-3-PE/Cy5, and anti-IL-17A-PE. ResultsTh17 percentage is increased in PF in comparison with PB in both endometriotic patients and in the control group. In severe endometriosis, the percentage of Th17 cells in PF was higher than with early (I/II stage) endometriosis. A positive correlation between the percentage of Th17 cells in PF and the white blood cell count in PB was found in patients with endometriosis. ConclusionTargeting the activity of PF Th17 cells may have an influence on the proliferation of ectopic tissue and clinical manifestations of the disease.

Overexpression of chloride channel-3 is associated with the increased migration and invasion ability of ectopic endometrial cells from patients with endometriosis.

Is chloride channel-3 (ClC-3) involved in regulating the biological behavior of endometrial stromal cells (ESCs)? ClC-3 promotes endometriotic cell migration and invasion. ClC-3 plays a significant role in the migration and invasion of various kinds of cells. An ITALIC! in vitro investigation of the effect of ClC-3 on the migration and invasion of ectopic ESCs from patients with endometriosis. The ectopic and eutopic endometrial samples from 43 female patients with endometriosis and the endometrial samples from 39 non-endometriotic female patients were collected. Primary cells from these samples were isolated and cultured. Real-time RT-PCR, immunohistochemistry and western blot were used to detect the expression of ClC-3 and matrix metalloproteinase 9 (MMP-9). Small interfering RNA (siRNA) technology was employed to knock down ClC-3 expression. The migration and invasion ability of ESCs was measured by the transwell assay with uncoated or Matrigel-coated membranes. The expression of ClC-3 mRNA and proteins was significantly up-regulated in the ectopic tissues from endometriotic patients, while that in the eutopic endometrial tissues of the same patients did not significantly differ from that in non-endometriotic patients. The migration and invasion ability and MMP-9 expression was increased in the ESCs from ectopic endometrial tissues. The knockdown of ClC-3 expression by ClC-3 siRNA inhibited ESC migration and invasion and attenuated the expression of MMP-9. ClC-3 expression level was well-correlated to the clinical characteristics and symptoms of endometriosis patients, including infertility, dysmenorrhea, chronic pelvic pain, dyspareunia and diameter of endometriosis lesion. Further studies are needed to examine the regulatory mechanism of estrogen on ClC-3 expression of ESCs. ClC-3 is involved in the migration and invasion processes of ESCs and can regulate MMP-9 expression. Up-regulation of ClC-3 expression may contribute to endometriosis development by regulating MMP-9 expression. This work was supported by the National Natural Science Foundation of China (81173064, 81272223, 81273539), the Ministry of Education of China (20124401110009), the Natural Science Foundation of Guangdong Province (S2011010001589) and the Science and Technology Programs of Guangdong (2013B051000059), Guangzhou (2013J500015) and Dongguan (2011108102006). The authors have no conflict of interest.

Evaluation of oxidative stress markers and intra-extracellular antioxidant activities in patients with endometriosis

ObjectiveThe aim of the study is to evaluate alterations in intracellular and extracellular antioxidant enzymes activities and serum oxidative stress markers in patients with endometriosis. Study designThe current prospective study consisted of 31 female patients with endometriosis and 27 healthy controls. Serum total thiol, native thiol, disulphide, catalase, myeloperoxidase, and ceruloplasmin concentrations were measured. Laboratory and clinical data of all participants were recorded to compare the differences between the study and the control groups. ResultsSerum native thiol and total thiol levels in the study group were significantly lower than those in the control group [(p=0.009, p=0.03, respectively)]. Serum catalase levels are significantly higher in patients with endometriosis comparing to the control group (p=0.009). ConclusionsThe finding that significant differences in serum total thiol, native thiol, and catalase levels observed in endometriotic patients supports that oxidative stress carries weigh in the pathophysiological aspects of endometriosis. Also significantly low levels of extracellular antioxidants and significantly high levels of intracellular antioxidants in endometriotic patients may arise from differences of free radicals in endometriosis and the activity levels of endometriosis. These non-invasive serum markers might give us an opportunity to monitor the disease's progress during the treatment.

Female sexual dysfunction in patients with endometriosis: Indian scenario.

BACKGROUND:Female sexual dysfunction (FSD) in Indian women is often overlooked due to cultural beliefs and considered as social taboos. Sexuality is an important and integral part of life. There are many causes of sexual dysfunction, but the prevalence of FSD in endometriotic patients is still underdiagnosed.MATERIALS AND METHODS:Study design - Cross-sectional observational study conducted at tertiary care center, from June 2015 to March 2016. Sample size - Fifty-one patients in reproductive age group (18–47 years) who were diagnosed with endometriosis on diagnostic laparoscopy were included. Methods - FSD was assessed with a detailed 19-item female sexual function index questionnaire. All six domains of sexual dysfunction, i.e., desire, arousal, lubrication, orgasm, satisfaction, and pain were studied. Exclusion - Patients with other gynecological, medical or surgical history were excluded.RESULTS:Out of 51 patients with endometriosis, 47.06% of patients had sexual dysfunction. With the increase in staging of endometriosis, sexual dysfunction prevalence is also rising. FSD was 100% in patients with severe endometriosis as compared to 33.33% in minimal endometriosis.CONCLUSION:Every individual deserves good sexual life. The sexual dysfunction associated with endometriosis should also be taken into consideration while managing these patients.

Therapeutic effects of mifepristone combined with Gestrinone on patients with endometriosis.

Objective:To evaluate the clinical therapeutic effects of mifepristone combined with gestrinone on patients with endometriosis.Methods:A total of 150 endometriotic patients treated in our hospital between January 2014 and December 2015 were randomly divided into a control group and a treatment group (n=75). The control group began to orally take gestrinone capsules on the second day after menstruation started (2.5 mg/time, twice/week). The treatment group orally took mifepristone tablets (12.5 mg/time, once/day), and the dosage and administration of gestrinone capsules were the same as those of the control group. After 24 weeks of consecutive treatment, the clinical therapeutic effects of the two groups were assessed, and the pelvic symptom score, clinical sign score, serum sex hormone levels and pregnancy outcomes were compared.Results:The total effective rates of control and treatment groups were 77.3% and 90.7% respectively, between which the difference was statistically significant (P<0.05). After treatment, the scores of pelvic symptoms (dysmenorrhea, dyspareunia, pelvic pain) and clinical signs (pelvic tenderness, induration) significantly reduced (P<0.05). Each score of the treatment group decreased more significantly than that of the control group did (P<0.05). The serum follicle hormone, luteinizing hormone, estrogen and progesterone levels were significantly lower than those before treatment (P<0.05). Each level of the treatment group dropped more significantly than that of the control group did (P<0.05). The pregnancy rates in the 6th and 12th months of follow-up were 28.0% and 13.3% in the control group respectively, and 42.7% and 29.3% in the treatment group respectively. Such rates of the two groups were significantly different at each follow-up time point (P<0.05).Conclusion:Mifepristone combined with gestrinone had satisfactory clinical therapeutic effects on endometriosis by reducing hormone levels and improving pregnancy outcomes. Therefore, this regimen is worthy of promotion and application in clinical practice.

Performance of Circulating Placental Growth Factor as A Screening Marker for Diagnosis of Ovarian Endometriosis: A Pilot Study.

The aim of this study is to compare the circulating placental growth factor (PlGF) concentration in women with and without endometrioma to verify the performance of this marker to diagnose the disease. In this case-control study, thirteen women with histological diagnosis of ovarian endometriosis were compared with women without endometriosis disease. PlGF plasma levels of endometriotic patients and controls were investigated using a fluorescence immunoassay technique. PlGF showed a direct correlation with body mass index (BMI) only in the control group (P=0.013). After adjustment for BMI values, PlGF median value in endometriosis group (14.7 pg/mL) resulted higher than in control group (13.8 pg/ mL, P=0.004). PlGF is a promising peripheral blood marker that can discriminate between patients with and without ovarian endometriosis.