Moderate-severe Endometriosis Research Articles

Surgeon reported measures of stress and anxiety prior to and after elective gynecological surgery.

Performing surgical procedures is a recognized source of stress for surgeons. Vocational stress is an important contributor to performance, patient care, and burnout with dispositional and environmental factors contributing. Accurately assessing surgeon stress is critical to measuring effectiveness of stress reduction programs. The primary aim was to identify differences between surgeons' self-reported anticipated stress and anxiety prior to gynecological surgery, compared with their recollection of experienced stress and anxiety during surgery. Secondary aims assessed any differences by level of training, surgical type, and surgeon role. Attending and resident gynecologists performing routine elective surgeries completed a visual analog scale (VAS) assessing perceived stress and the State-Trait Anxiety Inventory (STAI) prior to and immediately after completing 161 elective surgeries including total laparoscopic hysterectomy, laparoscopic excision of moderate-severe endometriosis, or hysteroscopic myomectomy. Eight attending gynecologists and nine residents participated. Residents commenced as primary surgeon in 62/90 (69%) procedures. Stress experienced during surgery was greater than anticipated in 92/161 (57%) surgery episodes (mean VAS increase: 3.9; 95% CI: 1.1-6.8, p = 0.009). State anxiety was greater than anticipated in 99/161 (62%) episodes (mean state anxiety increase: 4.4; 95% CI: 3.0-5.8, p < 0.001). Greater preprocedural anticipatory stress and anxiety was observed in residents vs. attending gynecologists (VAS 51.9 vs. 22.8, p < 0.001; state anxiety 38.3 vs. 28.1, p < 0.001) and in primary vs. assistant surgeons (VAS 47.2 vs. 29.9, p < 0.001; state anxiety 36.9 vs. 28.3, p < 0.001). Intraoperative stress and anxiety were greater in primary surgeons (VAS 50.4 vs. 30.5, p < 0.001; anxiety 41.3 vs. 32.5, p < 0.001) and residents (VAS 43.4 vs. 31.7, p < 0.001; anxiety 53.5 vs. 33.7, p < 0.001) compared with assistants and attending gynecologists. Perceived stress and anxiety were positively correlated at both timepoints (r = 0.68, p < 0.001; r = 0.82, p < 0.001). When asked to reflect on stress experienced during surgery, our data show that stress during surgery is greater than anticipated for many surgical episodes. Self-reported stress symptoms commence prior to surgery and are more commonly reported by surgeons operating as primary surgeon and by those in training. Future research should focus on determinants of presurgical stress and examine when stressors become inhibitory to performance.

#138 : Effect of Endometriosis on Human ICSI, and Endometriosis Follicle Fluid on Mouse Oocyte Maturation and Mitochondria

Background and Aims: Endometriosis is the common cause of infertility. Assisted Reproductive Technology has become a promising choice for women with endometriosis, however, there is no consensus concerning the impact of endometriosis on the success rate. Our study was aimed to assess the impact of endometriosis on ICSI and to investigate the effect of endometriosis follicle fluid (FF) on mouse oocytes maturation and mitochondrial activity. Methods: Hormonal stimulation, embryo quality and success rate from moderate-severe and minimal-mild endometriosis were compared with tubal infertility patients as controls. Then animal experiments were carried out involving the co-culturing of mouse oocytes with FF from moderate-severe endometriosis patients to assess mitochondrial dye, oocyte maturation, and protein levels of cytochrome C and cyclin B1 using ELISA. Results: The number of follicles, mature oocytes, and fertilization rates were significantly lower in moderate-severe endometriosis group compared to control and minimal-mild endometriosis groups. This led to significantly decreased pregnancy rates in moderate-severe endometriosis group compared to minimal-mild endometriosis and control groups [26/72 (36.1%); 27/47 (57.4%); 85/152 (55.9%), p&lt;0.05, respectively]. Implantation rates in moderate-severe endometriosis group decreased significantly compared to control group [31/166 (18.7%) vs 113/392 (28.8%), OR 1.76; 95% CI 1.14 to 2.79; p&lt;0.05). Mitochondrial dye was significantly lower in mouse oocytes cultured with endometriosis FF compared to control and oocytes cultured with tubal factor FF. Cyclin B1 protein level was lower in oocytes cultured with endometriosis FF compared to control and oocytes cultured with tubal factor FF. There was no difference in cytochrome C protein level among groups. Conclusions: Our results showed that moderate-severe endometriosis is associated with reduced quality of oocyte and embryo and leads to lower success rates of ICSI. This research also showed FF could impair mouse oocytes nuclear maturation which may be related to reduced cyclin B1 level and decrease activity of mitochondria.

Endometriosis and Impaired Placentation: A Prospective Cohort Study Comparing Uterine Arteries Doppler Pulsatility Index in Pregnancies of Patients with and without Moderate-Severe Disease.

The aim of this study was to evaluate if moderate-severe endometriosis impairs uterine arteries pulsatility index (UtA-PI) during pregnancy when compared to unaffected controls. In this prospective cohort study, pregnant women with stage III–IV endometriosis according to the revised American Fertility Society (r-AFS) classification were matched for body mass index and parity in a 1:2 ratio with unaffected controls. UtA-PIs were assessed at 11–14, 19–22 and 26–34 weeks of gestation following major reference guidelines. A General Linear Model (GLM) was implemented to evaluate the association between endometriosis and UtA-PI Z-scores. Significantly higher third trimester UtA-PI Z-scores were observed in patients with r-AFS stage III–IV endometriosis when compared to controls (p = 0.024). In the GLM, endometriosis (p = 0.026) and maternal age (p = 0.007) were associated with increased third trimester UtA-PI Z-scores, whereas conception by in-vitro fertilization with frozen-thawed embryo transfer significantly decreased UtA-PI measures (p = 0.011). According to these results, r-AFS stage III–IV endometriosis is associated with a clinically measurable impaired late placental perfusion. Closer follow-up may be recommended in pregnant patients affected by moderate-severe endometriosis in order to attempt prediction and prevention of adverse pregnancy and perinatal outcomes due to a defective late placental perfusion.

Non-invasive diagnosis of endometriosis and moderate-severe endometriosis with serum CA125, endocan, YKL-40, and copeptin quadruple panel

Considering the complex pathogenesis of endometriosis, which is associated with many cellular or molecular processes, such as proliferation, angiogenesis, inflammation, we evaluated the diagnostic value of a quadruple panel of serum markers CA125, endocan, YKL-40 and copeptin, for the prediction of endometriosis and moderate – severe endometriosis. Seventy women with endometriosis and 70 women without endometriosis were evaluated. Serum CA125, endocan, copeptin and YKL-40 levels were significantly increased in women with endometriosis compared to the women without endometriosis and in the minimal – mild endometriosis group compared to the no-endometriosis group. YKL-40, endocan and copeptin levels were significantly increased in the moderate – severe endometriosis group compared to the mild –moderate endometriosis group but the difference in CA125 levels remained non-significant. The quadruple panel score had an AUC of 0.954, a sensitivity of 96.5% and specificity of 84.6% for prediction of moderate – severe endometriosis. Zero or one positive marker had a sensitivity of 91.4% and specificity of 88.57% to rule out endometriosis. In conclusion, a quadruple panel of serum markers-CA125, endocan, YKL-40, and copeptin may be beneficial for the diagnosis of endometriosis and especially moderate – severe endometriosis. Further studies are needed to prove the efficacy of this panel. Impact statement What is already known on this subject? Many serum markers including CA125 have been investigated so far and suggested to be associated with endometriosis. However, none of these markers is sensitive and specific enough to diagnose endometriosis. What do the results of this study add? A quadruple panel score (CA125, endocan, YKL-4 and copeptin) had an AUC of 0.954, a sensitivity of 96.5% and specificity of 84.6% for prediction of moderate – severe endometriosis. What are the implications of these findings for clinical practice and/or further research? A high score may be beneficial to warn the surgeon about the risk of moderate to severe endometriosis if the patient will be operated anyway. A negative test of the quadruple panel may show high odds that there is no endometriosis which may prevent unnecessary surgery.

Endometrioma ethanol sclerotherapy could increase IVF live birth rate in women with moderate-severe endometriosis.

To examine the impact of ethanol sclerotherapy (EST) for endometrioma on in vitro fertilization (IVF) cumulative live birth rates (CLBR) in women with moderate-severe endometriosis. This retrospective cohort study included women with moderate-severe endometriosis (revised American Fertility Society stage III-IV) and endometrioma who underwent IVF with the ultra-long agonist protocol. We compared two groups: women undergoing EST for endometrioma before IVF (EST group), and women whose endometrioma was left in situ during IVF (No-EST group). The primary outcome was the CLBR per IVF cycle, including fresh and frozen embryo transfers. The secondary endpoints included the complication rate, number of mature oocytes retrieved, clinical pregnancy rate and pregnancy loss rate. Seventy-four women were included in the study, with 37 in the EST group and 37 in the No-EST group, representing 67 and 69 IVF cycles, respectively. The population and cycle characteristics were comparable between the two groups, especially the ovarian response to stimulation. The CLBR was significantly increased in the EST group compared to the No-EST group (31.3% vs. 14.5%, p = 0.03). The clinical and biochemical pregnancy rates were significantly increased in the EST group (37.3% vs. 15.9%, p = 0.01 and 43.3% vs. 23.2%, p = 0.01, respectively). Multivariate analysis revealed a significantly increased chance of live birth in women exposed to EST before IVF with an adjusted OR of 2.68 (95% confidence interval, CI: 1.13-6.36, p = 0.02). In the EST group, we reported one major complication Clavien and Dindo classification grade III, complication involving an ovarian abscess that required a laparoscopic drainage. EST is an interesting technique to improve IVF success rates in women with moderate-severe endometriosis. EST could be discussed before IVF in infertile women.

PI3K/AKT pathway is altered in the endometriosis patient’s endometrium and presents differences according to severity stage

Based on the inflammatory nature and hormone-dependency of endometriosis, PI3K/AKT signaling appears to influence its progression. Could the endometriosis stages be linked to differential changes in PI3K/AKT pathway regulation? The objective is to evaluate the expression of PI3K, PTEN, AKT and p-AKT in endometrial human biopsies, according to the presence or absence of the disease, and to assess the underlying differences regarding the endometriosis stages. Biopsy specimens of the ectopic and eutopic endometrium were obtained from twenty women with untreated peritoneal endometriosis as well as endometrium biopsies from nine controls. Our study revealed an increased expression of PI3K in eutopic and ectopic endometrium from patients with endometriosis, and a reduced expression of PTEN and increased levels of AKT phosphorylation, compared to control endometrium. Both eutopic and ectopic endometrium from patients with minimal-mild endometriosis expressed a significant reduced PTEN level compared to the respective endometrium from patients with moderate-severe endometriosis. The ratio p-AKT/total AKT showed higher levels of AKT phosphorylation in endometriotic tissue from patients with minimal-mild endometriosis. This study has firmly confirmed the alteration in PI3K/AKT pathway regulation and demonstrated clear differences between the stages of endometriosis, emphasizing the importance of this pathway in the first stage of the disease.

The association between experiences with patient-centred care and health-related quality of life in women with endometriosis

In this cross-sectional study, we investigated whether patient-centred endometriosis care (PCEC) is associated with health-related quality of life (HRQOL). Dutch-speaking women with endometriosis, treated by laparoscopy in a university clinic between 2009 and 2010, were eligible (n = 194). Endometriosis Health Profile-30 and ENDOCARE questionnaire were used to assess HRQOL and PCEC, respectively. Overall and subscale scores were converted to a scale from 0 (best score) to 100 (worst score). Linear regression analyses were conducted while controlling for confounders. Participants (n = 109) had a mean age of 35.4 years; 79.6% had moderate–severe endometriosis. Mean scores for overall HRQOL and PCEC were 29.3/100 and 38.0/100, respectively. The PCEC-subscale ‘continuity’ was significantly associated with overall HRQOL (P = 0.029). A significant association was found between overall PCEC and the HRQOL-subscale ‘social support’ (P = 0.026). The PCEC-subscales ‘information’ and ‘continuity’ were significantly associated with the HRQOL-subscales ‘emotional wellbeing’ and ‘social support’ (P < 0.05). The PCEC-subscale ‘respect’ was significantly associated with the HRQOL-subscale ‘emotional wellbeing’ (P = 0.023). Multivariable regression analyses produced no significant associations, including all subscales of PCEC. Providing PCEC could lead to better HRQOL, especially if paying attention to ‘continuity’, ‘respect’ and ‘information’. Large-scale longitudinal research is needed.

Endometrium or embryo quality in minimal or mild endometriosis - related infertility

Background : There is controversy related to pathogenesis and mechanism by which minimal or mild endometriosis affects fertility in women. It is accepted that moderate-severe endometriosis disrupt the anatomical relationships between fallopian tube and ovary. Some researchers found impaired implantation in patients with endometriosis, but such defects in implantation may be caused by either embryos or altered endometrium. Further investigations on follicular fluids have also found differences between women with endometriosis and women without the disease. In addition, recent advances on implantation research, show features in the eutopic endometrium of women with endometriosis that are not found in endometrium of women without the disease, although it is controversial. The review aims at describing the available information from the eutopic endometrium or embryo standpoint infertility related to endometriosis. Objective : To explore the interrelation of the eutopic endometrium or embryo in women with infertility and the endometriosis. Methods : Retrospective review of literature using all the available English databases, Cochrane register and articles which addressed the question “Whether the endometrium or embryo quality is different in women with endometriosis associated infertility?“ Conclusion : Although contradictory results have been reported, different clinical studies have demonstrated worse success rates for pregnancy in women with endometriosis compared with healthy women or with tubal factor among those that found lower pregnancy rates in women with endometriosis compared with controls without the disease, some found alterations in implantation rates in women with endometriosis when they were compared with controls. The debate continues, and other approaches should be developed before we can determine the authentic origin of the defects that make conception more difficult in these patients. These new studies must include an adequate design and controls, in order to avoid misleading data that can complicate the interpretation of the pathophysiology of this enigmatic disease.

Ovarian Reserve In Infertile Women with and without Endometriosis Measured with Anti Müllerian Hormone

Objective: To compare serum Anti Müllerian Hormone (AMH) levels&#x0D; in infertile women with and without endometriosis, and to determine&#x0D; the mean levels of serum AMH in every stage of endometriosis.&#x0D; Method: We performed a cross-sectional study. Sixty-eight subjects&#x0D; who have undergone laparoscopy and fulfilled both inclusion and&#x0D; exclusion criteria are recruited consecutively. They are divided into&#x0D; two groups, namely group with endometriosis and without endometriosis.&#x0D; Blood samples are taken from each subject before laparoscopy,&#x0D; where serum AMH levels are then measured. The difference&#x0D; in mean levels of each group are tested with Mann-Whitney&#x0D; test.&#x0D; Result: The mean levels of serum AMH were significantly lower in&#x0D; the endometriosis group than those in the group without endometriosis (2.30 1.8 ng/ml vs 3.75 2.13 ng/ml; p=0.005). Using&#x0D; Kruskal-Wallis test, it was found that there was a statistically significant difference among endometriosis groups based on the severity of endometriosis. There was no significant difference in the mean serum AMH levels between the minimal-mild endometriosis group and without endometriosis group (p=0.34), but the mean levels of serum AMH were significantly lower in the moderate-severe endometriosis compare to the group without endometriosis (p

Impact of endometriosis on surgical outcomes and complications of total laparoscopic hysterectomy.

Total laparoscopic hysterectomy (TLH) in the case of endometriosis may be extremely challenging. Our aim has been to analyze perioperative details and complications of TLH in women with vs. women without endometriosis. Consecutive women who underwent TLH for endometriosis (endometriosis group) were compared with consecutive patients who had TLH for other conditions (controls) in terms of perioperative outcomes. Patients in the endometriosis group were analyzed, according to the severity of the disease. One-hundred and twelve women in the endometriosis group, 29 (25.9%) with minimal-mild, and 83 (74.1%) with moderate-severe stage disease (rAFS score), respectively, were compared with 572 controls. Conversion rate was 0.8 vs. 0.5% (P=0.51), and median operative time was 75 vs. 55min (pxxx=x) in the endometriosis group vs. Intraoperative complications were similar between groups (P=0.56). Postoperative complications occurred in 10 (12.3%) women in the endometriosis group vs. 12 (3.3%) among the controls (P=0.002). The severity of complications according to Clavien-Dindo classification system was higher in the endometriosis group (Clavien-Dindo >2: 7.5 vs. 1.9%). The risk of organ lesions, urinary lesions, postoperative complications, and severe adverse events was significantly higher in women with moderate-severe endometriosis vs. No differences between patients with minimal-mild endometriosis and controls were found. TLH in the case of endometriosis is associated with longer operative time and an almost fourfold increase in the risk and severity of complications compared with controls. In particular, the adjunctive risk of adverse events is specific for moderate/severe-stage disease but not for minimal/mild endometriosis.

Clinical Outcome After Radical Excision of Moderate—Severe Endometriosis With or Without Bowel Resection and Reanastomosis

To assess the clinical outcome of women requiring laparoscopic excision of moderate-severe endometriosis in women with and without bowel resection and reanastomosis. Two hundred three patients with laparoscopically excised moderate (n = 67) or severe (n = 136) endometriosis (rAFS: revised endometriosis classification of the American Fertility Society) were prospectively followed during a median of 20 months (1-45 months) using a CONSORT-inspired checklist. Patients completed the EHP30 Quality-of-Life Questionnaire and visual analogue scales (VAS) for dysmenorrhea, chronic pelvic pain, and deep dyspareunia and answered questions about postoperative complications, reinterventions/recurrences, and fertility outcome 1 month before and 6, 12, 18, and 24 months after surgery. Clinical outcome was compared between women with deeply infiltrative endometriosis undergoing CO2 laser ablative surgery with bowel resection (study group, 76/203; 37%) and without bowel resection (control group, 127/203; 63%). Both groups were similar with respect to population characteristics and clinical outcome, except for mean rAFS score [higher in study group (73 ± 31) than in control group (48 ± 26)] and minor complication rate [higher in study group (11%) than in control group (1%)]. In both groups, mean VAS and EHP30 scores improved significantly and remained stable for 24 months after surgery, with a pregnancy rate of 51%. Within 1, 2, and 3 years follow-up, the cumulative reintervention rate was 1%, 7%, and 10%, respectively, and the cumulative endometriosis recurrence rate was 1%, 6%, and 8%, respectively. Clinical outcome after CO2 laser laparoscopic excision of moderate-severe endometriosis was comparable in women with or without bowel resection and reanastomosis, except for a higher minor complication rate occurring in women with bowel resection and reanastomosis (NCT00463398).

Laparoscopic management of moderate: Severe endometriosis

OBJECTIVES:To assess the feasibility of laparoscopic surgery in cases of moderate-severe endometriosis.MATERIALS AND METHODS:A prospective study was carried out in a tertiary centre over a period of 2 years. Moderate to severe endometriosis was defined by revised American fertility society (rAFS) classification (41 patients). Various procedures were done to provide symptomatic relief. Feasibility of laparoscopic surgery and various patient parameters were analysed.RESULTS:Various procedures like adhesiolysis in POD, excision of endometriomas, resection of endometriotic nodules in the recto-vaginal septum, ureterolysis and total laparoscopic hysterectomy with/ without oophorectomy were done. Majority of patients underwent cystectomy for endometriomas (53.6%) or adhesiolysis with excision of endometriotic nodule (36.5%). Total laparoscopic hysterectomy with or without ooperectomy was done in 31.7% patients. Of the total 9 patients with primary infertility and moderate-severe endometriosis, 5 patients (55.5%) conceived after surgery.CONCLUSION:There is good evidence that in experienced hands laparoscopic surgery helps in long-term symptomatic relief, improves pregnancy rates and reduces recurrence of disease with largely avoiding complications.

Prevalence of endometriosis diagnosed by laparoscopy in adolescents with dysmenorrhea or chronic pelvic pain: a systematic review

BACKGROUND Endometriosis associated with pain symptoms in adolescents has been extensively reported, but the exact prevalence is unclear because pain symptoms may be atypical and endometriosis can only be diagnosed by laparoscopy. The aim of this paper is to provide a systematic review of the prevalence of endometriosis diagnosed by laparoscopy in adolescents. METHODS A systematic literature search was carried out for relevant articles published between 1980 and 2011 in the databases PUBMED and EMBASE, based on the keywords 'endometriosis', 'laparoscopy', 'adolescents' and 'chronic pelvic pain (CPP)'. In addition, the reference lists of the selected articles were examined. RESULTS Based on 15 selected studies, the overall prevalence of visually confirmed endometriosis was 62% (543/880; range 25-100%) in all adolescent girls undergoing laparoscopic investigation, 75% (237/314) in girls with CPP resistant to treatment, 70% (102/146) in girls with dysmenorrhea and 49% (204/420) in girls with CPP that is not necessarily resistant to treatment. Among the adolescent girls with endometriosis, the overall prevalence of American Society of Reproductive Medicine classified moderate-severe endometriosis was 32% (82/259) in all girls, 16% (17/108) in girls with CPP resistant to treatment, 29% (21/74) in girls with dysmenorrhea and 57% (44/77) in girls with CPP that is not necessarily resistant to treatment. Due to the quality of the included papers an overestimation of the prevalence and/or severity of endometriosis is possible. CONCLUSIONS About two-thirds of adolescent girls with CPP or dysmenorrhea have laparoscopic evidence of endometriosis. About one-third of these adolescents with endometriosis have moderate-severe disease. The value of early detection of endometriosis in symptomatic adolescents and the indications for laparoscopic investigation in adolescents require more research.

A high sensitivity assay is more accurate than a classical assay for the measurement of plasma CRP levels in endometriosis

BackgroundEndometriosis is associated with chronic subclinical inflammation. C-reactive protein (CRP), a marker of inflammation, could serve as a biomarker of endometriosis. We tested the hypothesis that a high sensitivity CRP assay (hsCRP) is more accurate than a classical CRP assay in the detection of subclinical inflammation in plasma of women with endometriosis.MethodsCRP levels were measured by hsCRP and classical CRP assays in plasma of 204 women with endometriosis and 91 women without endometriosis. Both assays were compared with respect to their value for the diagnosis of endometriosis.ResultsThe number of plasma samples with detectable CRP was significantly higher (100%) using the hsCRP assay when compared to the classical CRP assay (42.7%) (p < 0.0001). Significantly increased CRP plasma levels were found in women with endometriosis when compared with controls when the hsCRP assay was used in samples obtained during the luteal phase (p = 0.008). The highest discriminative ability for the diagnosis of endometriosis was also obtained using the hsCRP assay during the luteal phase, especially for moderate -severe endometriosis. At a cut-off level of hsCRP > 0.71 mg/L, moderate-severe stages were diagnosed with 80.7% sensitivity and 63.9% specificity during the luteal phase. Using a similar cut-off value for CRP analyzed by the classical method, moderate-severe endometriosis was diagnosed with lower sensitivity (67.7%, p = 0.06) and comparable specificity (63.9%).ConclusionsThe hsCRP assay was superior to the classical CRP assay for the detection of low CRP levels and for revealing subclinical inflammation in plasma of women with endometriosis.

Evaluation of endometrial biomarkers for semi-invasive diagnosis of endometriosis

To test the hypothesis that specific proteins and peptides are expressed differentially in eutopic endometrium of women with and without endometriosis and at specific stages of the disease (minimal, mild, moderate, or severe) during the secretory phase. Patients with endometriosis were compared with controls. University hospital. A total of 29 patients during the secretory phase were selected for this study on the basis of cycle phase and presence or absence of endometriosis. Endometriosis was confirmed laparoscopically and histologically in 19 patients with endometriosis of revised American Society for Reproductive Medicine stages (9 minimal-mild and 10 moderate-severe), and the presence of a normal pelvis was documented by laparoscopy in 10 controls. Protein expression of endometrium was evaluated with use of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. The differential expression of protein mass peaks was analyzed with use of support vector machine algorithms and logistic regression models. Data preprocessing resulted in differential expression of 73, 30, and 131 mass peaks between controls and patients with endometriosis (all stages), with minimal-mild endometriosis, and with moderate-severe endometriosis, respectively. Endometriosis was diagnosed with high sensitivity (89.5%) and specificity (90%) with use of five down-regulated mass peaks (1.949 kDa, 5.183 kDa, 8.650 kDa, 8.659 kDa, and 13.910 kDa) obtained after support vector machine ranking and logistic regression classification. With use of a similar analysis, minimal-mild endometriosis was diagnosed with four mass peaks (two up-regulated: 35.956 kDa and 90.675 kDa and two down-regulated: 1.924 kDa and 2.504 kDa) with maximal sensitivity (100%) and specificity (100%). The 90.675-kDa and 35.956-kDa mass peaks were identified as T-plastin and annexin V, respectively. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry analysis of secretory phase endometrium combined with bioinformatics puts forward a prospective panel of potential biomarkers with sensitivity of 100% and specificity of 100% for the diagnosis of minimal to mild endometriosis.

Increased exposure to dioxin-like compounds is associated with endometriosis in a case–control study in women

Although endometriosis is thought to be an environmental disorder initiated by dioxin exposure, this association is controversial. This study was performed to test the hypothesis that endometriosis occurs more often in women exposed to higher concentrations of dioxin-like compounds (DLC) than in those women exposed to lower concentrations. Plasma samples collected prior to laparoscopic surgery from 96 women with endometriosis and 106 control patients with a normal pelvis were measured for DLC concentrations using the dioxin-responsive chemical-activated luciferase expression bioassay. The results showed that concentration (mean+/-SD) of DLC was marginally higher in patients with endometriosis (22.3+/-9.3pg CALUX-TEQ/g lipid) than in controls (20.5+/-10.8pg). After categorization of patients in a group with 'low' plasma concentrations (<25th centile) and a group with 'high' plasma concentrations (>75th centile) of DLC, the age-adjusted odds ratio to have endometriosis was 2.44 (95% CI 1.04-5.70; P=0.04) for women with high concentrations of DLC and it increased to 3.01 (95% CI 1.06-9.04; P=0.03) when only women with moderate severe endometriosis were considered. In conclusion, women exposed to higher plasma concentrations of DLC were at higher risk of having endometriosis than women exposed to lower concentrations of DLC within normal environmental concentrations.

135. GENOME-WIDE ASSOCIATION STUDY IDENTIFIES A LOCUS AT 7p15.2 ASSOCIATED WITH THE DEVELOPMENT OF MODERATE - SEVERE ENDOMETRIOSIS

Endometriosis is a common gynaecological disease associated with severe pelvic pain and sub-fertility. There is considerable debate whether different endometriosis stages represent disease progression, or whether moderate-severe (rAFS III/IV) disease is pathological and minimal-mild (rAFS I/II) an epiphenomenon. We conducted a genome-wide association study using 540 082 SNPs in 3194 surgically confirmed endometriosis cases and 7060 controls from Australia and the UK. We used novel statistical methods to estimate the proportion of common variation explained by all markers and performed polygenic predictive modelling for disease stage, both showing significantly increased genetic loading among the 42% of cases with moderate-severe endometriosis. The strongest signals of association were also observed for moderate-severe disease. We subsequently genotyped 72 SNPs in an independent US dataset comprising 2392 endometriosis cases and 1646 controls. An association with rs7798431 on 7p15.2 for moderate-severe endometriosis (P = 6.0 × 10–8, OR = 1.34 (1.21–1.49)) was replicated, reaching combined genome-wide significance (P = 1.7 × 10–9; OR = 1.26 (1.17–1.35)). The implicated inter-genic region involves a 48 kb segment of high LD upstream of plausible candidate genes NFE2L3 and HOXA10. This locus is the first to be robustly implicated in the aetiology of endometriosis, with evidence of association limited to moderate-severe disease.

Non-invasive diagnosis of endometriosis based on a combined analysis of six plasma biomarkers

Lack of a non-invasive diagnostic test contributes to the long delay between onset of symptoms and diagnosis of endometriosis. The aim of this study was to evaluate the combined performance of six potential plasma biomarkers in the diagnosis of endometriosis. This case-control study was conducted in 294 infertile women, consisting of 93 women with a normal pelvis and 201 women with endometriosis. We measured plasma concentrations of interleukin (IL)-6, IL-8, tumour necrosis factor-alpha, high-sensitivity C-reactive protein (hsCRP), and cancer antigens CA-125 and CA-19-9. Analyses were done using the Kruskal-Wallis test, Mann-Whitney test, receiver operator characteristic, stepwise logistic regression and least squares support vector machines (LSSVM). Plasma levels of IL-6, IL-8 and CA-125 were increased in all women with endometriosis and in those with minimal-mild endometriosis, compared with controls. In women with moderate-severe endometriosis, plasma levels of IL-6, IL-8 and CA-125, but also of hsCRP, were significantly higher than in controls. Using stepwise logistic regression, moderate-severe endometriosis was diagnosed with a sensitivity of 100% (specificity 84%) and minimal-mild endometriosis was detected with a sensitivity of 87% (specificity 71%) during the secretory phase. Using LSSVM analysis, minimal-mild endometriosis was diagnosed with a sensitivity of 94% (specificity 61%) during the secretory phase and with a sensitivity of 92% (specificity 63%) during the menstrual phase. Advanced statistical analysis of a panel of six selected plasma biomarkers on samples obtained during the secretory phase or during menstruation allows the diagnosis of both minimal-mild and moderate-severe endometriosis with high sensitivity and clinically acceptable specificity.

Microrna expression profiling of eutopic endometrium from women with versus without moderate-severe endometriosis

OBJECTIVE: An innate or acquired abnormality of the endometrium may contribute to the pathophysiology of endometriosis. MicroRNAs (miRNA) are non-coding RNAs involved in post-transcriptional regulation of target gene expression, with increasing support for critical functions in health and disease. We previously reported evidence for progesterone resistance in the early secretory endometrial (ESE) gene expression signatures in women with moderate-severe endometriosis. Using the same RNA specimens, we performed microRNA expression profiling to allow an integrated transcriptome-miRNA analysis of ESE in the setting of endometriosis.

Utility of screening for other causes of infertility in women with “known” polycystic ovary syndrome

We investigated the prevalence of abnormal screening results (questionnaire and testing for other causes of oligo-ovulation, male or tubal factor infertility) in a group of 1,313 oligo-ovulatory women (included and excluded subjects) whose condition was screened for inclusion in the Pregnancy in Polycystic Ovary Syndrome trial, a multicenter clinical trial that was conducted at 13 sites in the United States. Other than failure to demonstrate laboratory evidence of hyperandrogenemia, the most common reasons for subject exclusion were persistent oligospermia and tubal factor infertility.