***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE To eluci date the potential mechanisms involved in the physiopathology of endometriosis . We analyzed the differential gene expression profiles of eutopic and ectopic tissues from women with endometriosis . DESIGN Prospect i ve laboratory study . SETTING University hospital . PATIENT(S ) Seventeen patients in whom endometriosis was diagnosed and 11 healthy fertile women . INTERVENTION(S ) Endometrial biopsy specimens from the endometrium of healthy women without endometriosis and from the eutopic and ectopic endometrium tissues of patients with endometriosis were obtained in the early proliferative phase of the menstrual cycle . MAIN OUTCOME MEASURE(S ) Six paired sample s of eutopic and ectopic tissue were analyzed by subtractive hybridization .  To evaluate the expression of genes found by rapid subtraction hybridization methods , we measured CTGF , SPARC , MYC , MMP , and IGFBP1 genes by real-time polymerase chain reaction in all sample s. RESULT ( S ) This study identified 291 deregulated genes in the endometriotic lesions . Significant expression differences were obtained for SPARC , MYC , and IGFBP1 in the peritoneal lesions and for MMP3 in the ovarian endometriomas . Additionally , significant differences were obtained for SPARC and IGFBP1 between the peritoneal and ovarian lesions . No significant differences were found for the studied genes between the control and the eutopic endometrium . CONCLUSION ( S ) This study identified 291 genes with differential expression in endometriotic lesions . The deregulation of the SPARC , MYC , MMP3 , and IGFBPI genes may be responsible for the loss of cellular homeostasis in endometriotic lesions BACKGROUND Little is known about the precise nature of the relationship between dysmenorrhoea ( DM ) and endometriosis . Our aim was to evaluate the relationship between the severity of DM in women with posterior deep infiltrating endometriosis ( DIE ) and indicators of the extent of their disease . METHODS Various indicators of the extent of DIE were recorded during surgery in 209 women . The severity of their DM was assessed with a  pain scale .  The scale was retrospective for 155 women and prospect i ve for 54 . Correlations were sought with an ordinal logistic regression model with cumulative odds . RESULTS On univariate analysis the following variables were related to the severity of DM : number of previous surgical procedures for endometriosis ; revised American Fertility society classification ; extensiveness of adnexal adhesion ; Douglas obliteration ; size of the posterior DIE implant ; extent of the sub-peritoneal infiltration by the posterior DIE ( rectal , vaginal or both versus sub-peritoneal only ) . Current infertility was associated with less severe DM . After multiple regression analysis , presence of a rectal or vaginal infiltration by the posterior DIE and extensiveness of adnexal adhesion were the only factors that remained related to DM severity . CONCLUSIONS The concept of ' very deep infiltrating endometriosis ' , defined as implants invading the wall of the pelvic organ , should be tested in future classification systems specifically addressed to the prediction of endometriosis-related pain OBJECTIVE To evaluate the expression of biomarkers of implantation , glycodelin A ( GdA ) , osteopontin  ( OPN ) , lysophosphatidic acid receptor 3 ( LPA3 ) , and HOXA10 , in eutopic endometrium of women with and without endometriosis . DESIGN Prospect i ve observational study . SETTING Clinical research center . PATIENT(S ) Twenty-four women with endometriosis and 23 healthy volunteers of similar age . INTERVENTION(S ) Secretory phase endometrial biopsy . MAIN OUTCOME MEASURE(S ) Expression of immunohistochemical staining intensity and localization of GdA , OPN , LPA3 , and HOXA10 in eutopic endometrium . RESULT ( S ) Endometrial GdA expression was significantly reduced in patients after cycle day 22 . The endometrium from women with endometriosis also showed decreased expression of OPN in the late secretory phase and LPA3 and HOXA10 expression in the midsecretory and late secretory phases . CONCLUSION ( S ) The decreased expression of these four biomarkers of implantation may indicate impaired endometrial receptivity in patients with endometriosis , providing one explanation for the subfertility observed even in women with few pelvic implants . Because many of these markers are P dependent , these findings suggest the possibility of reduced endometrial P action in this population To determine the value of  leukemia inhibitory factor ( LIF ) assessment for predicting the reproductive outcome Purpose To determine if endometrial gene expression is different in women with endometriosis-related infertility and fertile women . Methods Prospect i ve study of mid-follicular phase endometrium in 47 subjects in two phases : microarray study of 10 infertile women with endometriosis and five fertile controls , and a quantitative real-time PCR ( qRT-PCR ) study of 27 infertile women with endometriosis and 15 fertile controls .  Gene expression was determined by DNA microarray , and qRT-PCR used for 12 “ promising ” genes based on the microarray analysis . Results Compared to fertile controls , women with stage I – II endometriosis had 23 , and women with stage III – IV had 35 genes that were significantly up- or down-regulated by microarray . However , using qRT-PCR , only chemokine lig and ( CXCL ) 13 was significantly down-regulated and somatostatin was significantly up-regulated with early endometriosis , and only CXCL 14 was significantly down-regulated with advanced endometriosis compared to fertile controls . Conclusions Our findings indicate that the pattern of gene expression in proliferative-phase endometrium is different when comparing tissue from patients with endometriosis versus fertile controls . Recognition of these endometrial alterations could be helpful to diagnose and stage endometriosis , and may provide insight to explain why conception rates are low in women with endometriosis OBJECTIVE To examine the expression of gremlin-1 ( GREM1 ) on the levels of messenger RNA ( mRNA ) and protein in eutopic endometrium and its serum level in patients with endometriosis . DESIGN Prospect i ve , experimental study using reverse-transcription polymerase chain reaction , Western blot , immunofluorescence , and ELISA . SETTING Gynecological oncology laboratory in a department of obstetrics and gynecology in a medical college in China . PATIENT(S ) Thirty-five patients with endometriosis and 23 healthy control women . INTERVENTION(S ) During surgery , the eutopic endometria and peripheral serum were obtained from the patients with endometriosis and the control women . MAIN OUTCOME MEASURE(S ) The cellular compartment location of GREM1 expression was examined by using immunofluorescent double staining . The expression levels of mRNA and protein for GREM1 were determined by reverse-transcription polymerase chain reaction and Western blot , respectively . The serum level of GREM1 was measured by indirect ELISA . RESULT ( S ) The expression of GREM1 was defined within endometrial blood vessel endothelium exclusively , with the concomitant expressions of GREM1 and CD146 . The expression of GREM1 on the levels of mRNA and protein was significantly higher in eutopic endometria of patients with endometriosis than in those from healthy control women . According to the ELISA established in our laboratory , the concentration of GREM1 in peripheral serum that was collected during the follicular menstrual phase of patients with endometriosis was significantly higher than that in serum from healthy control women . CONCLUSION ( S ) Gremlin-1 plays a role to some extent in the aberrant angiogenesis of eutopic endometrium in patients with endometriosis . It is possible that the peripheral serum level of GREM1 is a prospect i ve serum biomarker of endometriosis OBJECTIVE To analyze the expression of the glycodelin gene to better underst and the molecular environment of endometriotic lesions and to eluci date the potential mechanisms that underlie the complex physiopathology of endometriosis . DESIGN Prospect i ve laboratory study . SETTING University hospital . PATIENT(S ) Eleven healthy fertile women and 17 patients with endometriosis in the early proliferative phase of the menstrual cycle . INTERVENTION(S ) Endometrial biopsy specimens were obtained from the endometrium of healthy women without endometriosis ( controls ) and from eutopic and ectopic endometrium tissues ( pelvic and ovarian endometriotic implants ) of endometriosis patients . MAIN OUTCOME MEASURE(S ) The glycodelin relative expression level by real-time polymerase chain reaction ( PCR ) analysis . RESULT ( S ) The glycodelin down-regulation found in the endometriotic lesions was 332.26 and 123.17-fold lower , respectively , when compared with the eutopic tissue and the control endometrium . CONCLUSION ( S ) Glycodelin may be one of the molecules that contributes to the loss of cellular homeostasis in endometriotic lesions OBJECTIVE To develop a clinical tool that predicts pregnancy rates ( PRs ) in patients with surgically documented endometriosis who attempt non-IVF conception . DESIGN Prospect i ve data collection on 579 patients and comprehensive statistical analysis to derive a new staging system -- the endometriosis fertility index (EFI)--from data rather than a priori assumptions , followed by testing the EFI prospect ively on 222 additional patients for correlation of predicted and actual outcomes . SETTING Private reproductive endocrinology practice . PATIENT(S ) A total of 801 consecutively diagnosed and treated infertile patients with endometriosis . INTERVENTION(S ) Surgical diagnosis and treatment followed by non-IVF fertility management . MAIN OUTCOME MEASURE(S ) The EFI and life table PRs . RESULT ( S ) A statistically significant variable used to create the EFI was the least function score ( i.e. , the sum of those scores determined intraoperatively after surgical intervention that describe the function of the tube , fimbria , and ovary on both sides ) . Sensitivity analysis showed that the EFI varies little , even with variation in the assignment of functional scores , and predicted PRs . CONCLUSION ( S ) The EFI is a simple , robust , and vali date d clinical tool that predicts PRs after endometriosis surgical staging . Its use provides reassurance to those patients with good prognoses and avoids wasted time and treatment for those with poor prognoses Background The role of estrogen receptor beta ( ERβ ) in pathogenesis of endometriosis remains to be eluci date d. In this study , we have examined the expression of the four main ERβ transcript isoforms in human endometrial tissue in women with or without endometriosis . Methods Total RNA was isolated from native endometrial tissue and transcript levels of ERα , β1 , β2 , β4 , β5 were analyzed by means of RT-PCR . We compared the results with regard to menstrual cycle phase as well as to presence or absence of endometriosis . We prospect ively harvested the endometrium of ten women without endometriosis ( five for each cycle phase ) and eight patients with endometriosis ( five in the proliferative phase , three in the secretory phase ) . Results ERα , β1 , β2 , and β5 transcripts were detected in both cycle phases . During the proliferative phase , healthy women had a significantly higher ERα/ERβ1-ratio than patients with endometriosis . Irrespective of the cycle phase , ERα-mRNA level was significantly higher than transcript levels of ERβ isoforms . Conclusions ERα , β1 , β2 , and β5 are expressed in human endometrium . The individual receptors differed in terms of expression strength but there was no relevant change during the cycle . The decreased ERα/ERβ1-ratio in proliferative endometrium of endometriosis patients suggest that ERβ1 might be involved in the pathogenesis of endometriosis . Further studies should be undertaken to substantiate the role of ERβ in endometrial pathology BACKGROUND The aim of our study was to test the hypothesis that multiple-sensory small-diameter nerve fibres are present in a higher density in endometrium from patients with endometriosis when compared with women with a normal pelvis , enabling the development of a semi-invasive diagnostic test for minimal-mild endometriosis . METHODS Secretory phase endometrium sample s ( n = 40 ) , obtained from women with laparoscopically/histologically confirmed minimal-mild endometriosis ( n = 20 ) and from women with a normal pelvis ( n = 20 ) were selected from the biobank at the Leuven University Fertility Centre . Immunohistochemistry was performed to localize neural markers for sensory C , Adelta , adrenergic and cholinergic nerve fibres in the functional layer of the endometrium . Sections were immunostained with anti-human protein gene product 9.5 ( PGP9.5 ) , anti-neurofilament protein , anti-substance P ( SP ) , anti-vasoactive intestinal peptide ( VIP ) , anti-neuropeptide Y and anti-calcitonine gene-related polypeptide . Statistical analysis was done using the Mann-Whitney U-test , receiver operator characteristic analysis , stepwise logistic regression and least-squares support vector machines . RESULTS The density of small nerve fibres was approximately 14 times higher in endometrium from patients with minimal-mild end 
    Output:
    
Although PGP 9.5 met the criteria for a replacement test , it demonstrated considerable inter study heterogeneity in diagnostic estimates , the source of which could not be determined .
Several endometrial biomarkers , such as endometrial proteome , 17βHSD2 , IL-1R2 , caldesmon and other neural markers ( VIP , CGRP , SP , NPY and combination of VIP , PGP 9.5 and SP ) showed promising evidence of diagnostic accuracy , but there was insufficient or poor quality evidence for any clinical recommendations .
We have also identified a number of biomarkers that demonstrated no diagnostic value for endometriosis .