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Endometriosis is a chronic oestrogen-dependent gynaecological disorder characterized by non-menstrual pelvic pain, infertility and the extrauterine growth of endometrial-like glands and stroma. It has been noted that the eutopic endometrium of women with endometriosis is functionally distinct from that of women without endometriosis. Moreover, ectopic endometrial implants are functionally different from the eutopic endometrium of women with endometriosis. However, the mechanisms directing these differences are ill-defined. It is proposed here that small membrane-bound extracellular vesicles called exosomes are important vehicles in the protection and transport of signalling molecules central to the dysregulation of endometrial function in women with endometriosis. Therefore, a critical review of the literature linking exosomes and their cargo to the pathobiology of endometriosis was conducted. Circulating peritoneal fluid and endometrial cell exosomes contained long non-coding RNA, miRNA and proteins involved in histone modification, angiogenesis and immune modulation that differed significantly in women with endometriosis compared with controls. Moreover, experimental evidence supports a role for exosomes and their cargo in angiogenesis, neurogenesis, immune modulation and endometrial stromal cell invasion. It is therefore suggested that exosomes play an important role in the pathophysiology of endometriosis., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Study Objective: To assess the feasibility of a noncontact radio sensor as an objective measurement tool to study postoperative recovery from endometriosis surgery., Design: Prospective cohort pilot study., Setting: Center for minimally invasive gynecologic surgery at an academically affiliated community hospital in conjunction with in-home monitoring., Patients: Patients aged above 18 years who sleep independently and were scheduled to have laparoscopy for the diagnosis and treatment of suspected endometriosis., Interventions: A wireless, noncontact sensor, Emerald, was installed in the subjects' home and used to capture physiologic signals without body contact. The device captured objective data about the patients' movement and sleep in their home for 5 weeks before surgery and approximately 5 weeks postoperatively. The subjects were concurrently asked to complete a daily pain assessment using a numeric rating scale and a free text survey about their daily symptoms., Measurements and Main Results: Three women aged 23 years to 39 years and with mild to moderate endometriosis participated in the study. Emerald-derived sleep and wake times were contextualized and corroborated by select participant comments from retrospective surveys. In addition, self-reported pain levels and 1 sleep variable, sleep onset to deep sleep time, showed a significant (p <.01), positive correlation with next-day-pain scores in all 3 subjects: r = 0.45, 0.50, and 0.55. In other words, the longer it took the subject to go from sleep onset to deep sleep, the higher their pain score the following day., Conclusion: A patient's experience with pain is challenging to meaningfully quantify. This study highlights Emerald's unique ability to capture objective data in both preoperative functioning and postoperative recovery in an endometriosis population. The utility of this uniquely objective data for the clinician-patient relationship is just beginning to be explored., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Aim: To systematically compare sexual function between non-treated women with and without endometriosis., Methods: A systematic review was performed on PubMed/Medline, Scopus, EMBASE, Web of Science and Cochrane Library databases searching studies that analyzed sexual function (assessed with the 19-item Female Sexual Function Index [FSFI]), and dyspareunia, chronic pelvic pain and dysmenorrhea (assessed with a visual analogue scale [VAS]) in women with and with endometriosis., Results: In 4 studies, non-treated women with endometriosis presented a higher risk of female sexual dysfunction (mean total FSFI score ≤ 26.55; OR = 2.38; 95% confidence interval [CI] = 1.12, 5.04). Although mean total FSFI scores were not significantly different between women with and without endometriosis (mean difference [MD] = -2.15; 95% CI -4.96, 0.67); all FSFI domain scores were significantly lower in women with endometriosis ( n  = 4 studies): desire (MD = -0.43; 95% CI -0.57, -0.19); arousal (MD = -0.66; 95% CI -1.15, -0.17); lubrication (MD = -0.41; 95% CI -0.79, -0.02); orgasm (MD = -0.40; 95% CI -0.73, -0.06); satisfaction (MD = -0.45; 95% CI -0.72, -0.18); and pain (MD = -1.03; 95% CI -1.34, -0.72). Women with endometriosis displayed differences (more severity) in terms of VAS scores (2 studies) for dyspareunia (MD = 1.88; 95% CI 0.38, 3.37) and chronic pelvic pain (MD = 2.92; 95% CI 1.26, 4.58); but not for dysmenorrhea., Conclusion: Non-treated women with endometriosis displayed altered sexual function as evidenced by lower scores in all FSFI domains, and severity of dyspareunia and chronic pelvic pain.

Background: A large body of research highlights the importance of early-life environmental impact on the health outcome in adulthood. However, whether early-life adversity (ELA) has any impact on the development of endometriosis is completely unclear. In this study, we tested the hypothesis that ELA, as manifested by neonatal separation, can accelerate the progression of endometriosis in mouse through activation of the adrenergic receptor β2 (ADRB2) signaling pathway, leading to increased angiogenesis and progression of endometriotic lesions., Methods: Eight female Balb/C mice, in late pregnancy, were used used for this study, which later gave birth to 22 female newborn pubs. Eleven additional female Balb/C mice were also used as donors of uterine tissues. The 22 newborn pubs were randomly divided into 2 equal-sized groups, maternal separation (MS) and no separation (NS). Pubs in the MS group were separated from their dams for 3 h/day from postnatal day (PND) 1 to 21, while those in the NS control remained in the home cage with their dams. In adulthood (8-week old), 3 mice in each group were randomly selected to undergo a battery of behavior tests. The remaining 8 mice in each group were induced with endometriosis by intraperitoneal injection of uterine fragments from donor mice. Four weeks after the induction, all mice were sacrificed and their endometriotic lesions were excised for quantification and then prepared for immunohistochemistry analysis., Results: We confirmed that MS during infancy resulted in anxiety and depression-like behaviors as previously reported. We also found that in MS mice the lesion weight was increased by over 2 folds and generalized hyperalgesia was also significantly increased as compared with NS mice. Immunostaining analysis demonstrated that MS accelerated the development of endometriosis likely through decreased dopamine receptor D2 (DRD2) expression and activation of the ADRB2/cAMP-response element binding protein (CREB) signaling pathway, leading to increased angiogenesis and progression of endometriotic lesions., Conclusions: Exposure of female mouse pups to ELA such as MS during their infancy period accelerates the progression of endometriosis, possibly through altered neuronal wiring and hyperactivity of the hypothalamic-pituitary-adrenal axis.

Fibrotic tissue may contribute to the origin of some endometriosis-related symptoms, such as chronic pelvic pain and infertility. Alterations in the H19/miR-216a-5p/ACTA2 pathway may mediate the regulation of eutopic endometrial stromal cell (euESC) invasion and migration and may represent a potential mechanism underlying fibrous tissue formation or fibrosis in women with endometriosis. In this study, we aimed to determine the expression of H19 and ACTA2 in endometrial tissues of women with endometriosis. Two groups of 23 infertile women with endometriosis and 23 matched infertile women without endometriosis were investigated. Primary cultured cells of endometrial tissues were analyzed using RT-PCR and western blotting (WB) to determine expression of H19 and ACTA2. 5-Ethyl-2'-deoxyuridine, CCK8 and Transwell assays were used to study the functions of H19 and ACTA2. Human embryonic kidney 293 cells were used for luciferase assays to study miR-216a-5p binding sites with H19 and ACTA2. We found that H19 and ACTA2 levels were significantly higher in endometriosis euESCs than in control euESCs (P < 0.05) and were positively correlated in endometriosis euESCs. Luciferase assays indicated that H19 regulates ACTA2 expression via competition for inhibitory miR-216a-5p binding sites. Our results indicate that alterations in the estrogen/H19/miR-216a-5p/ACTA2 pathway regulated endometriosis euESC invasion and migration. Downregulation of H19 or ACTA2 inhibited endometriosis euESC invasion and migration; however, estrogen promoted endometriosis euESC invasion and migration via H19. The main limitation of our study was that experiments were conducted in vitro and further in vivo studies are required in the future. However, our study showed that primary cultured cells represented endometriosis cells more clearly than cell lines., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Purpose: Superficial peritoneal endometriotic (pEM) lesions are composed of endometrial glands and stroma, in addition to a third component-myofibroblasts and smooth muscles (SM)-like cells. The latter develops secondary to a metaplasia. In this study, we characterised the third component cells in pEM according to differentiation markers in different micro-compartments. Furthermore, a possible effect of TGFβ1 on myofibroblastic metaplasia in endometriotic epithelial cells was studied., Methods: Seventy-six premenopausal patients were included. Peritoneal biopsies were excised from EM patients (n = 23), unaffected peritoneum (peritoneum from EM patients but without EM components, n = 5/23) and non-EM patients (n = 10). All peritoneal biopsies were immunolabeled for ASMA, calponin, collagen I, desmin, TGFß receptor 1 (R1), R2 and R3 in addition to ultrastructure examination by transmission electron microscopy (TEM) (n = 1). TGFß1 level was measured in peritoneal fluid (PF) (EM, n = 19 and non-EM, n = 13) collected during laparoscopy. Furthermore, TGFß1 effect on myofibroblastic metaplasia was studied in vitro., Results: At the centre of pEM lesions, calponin immunolabeling outweighs the collagen I while in the periphery the reverse occurs. SM-like cells expressing desmin predominate at the periphery, while ASMA immunolabeling was detectable in all micro-compartments. Both indicate an abundance of myofibroblasts at the centre of pEM lesions and SM-like cells in the periphery. Although activated TGFß1 in PF did not differ between EM and non-EM, it inhibited the cell proliferation of the endometriotic epithelial cells and induced an upregulation in ASMA and collagen IA2 expression as well., Conclusion: The abundance of the myofibroblasts and SM-like cells points to a myofibroblastic metaplasia in pEM. Both cells are differentially arranged in the different micro-compartments of pEM lesions, with increasing cell maturity towards the periphery of the lesion. Furthermore, TGFß1 may play a role in the myofibroblastic metaplasia of the endometriotic epithelial cells. These findings provide a better insight in the micro-milieu in EM lesions, where most of the disease dynamics occur.

Objective: To assess the impact of endometriosis of the posterior cul-de-sac on quality of sleep, average daytime sleepiness and insomnia., Study Design: This age-matched case-control study was conducted in a tertiary referral centre for the diagnosis and treatment of endometriosis between May 2012 and December 2013. It included 145 women with endometriosis of the posterior cul-de-sac (cases; group E) and 145 patients referred to our Institution because of routine gynaecologic consultations (controls; group C). This study investigated whether sleep is impaired in patients with endometriosis of the posterior cul-de-sac. Sleep quality, daytime sleepiness and insomnia were assessed using the following self-administered questionnaires: the Pittsburgh Sleep Quality Index, the Epworth sleepiness scale and the Insomnia Severity Index, respectively. The primary objective of the study was to evaluate sleep quality in the two study groups. Secondary outcomes of the study were to assess average daytime sleepiness and insomnia in the two study groups., Results: The prevalence of poor sleep quality was significantly higher in group E (64.8%) than in group C (15.1%; p<0.001). The prevalence of excessive daytime sleepiness was significantly higher in group E (23.4%) than in group C (12.9%; p=0.033). Patients of group E experienced subthreshold insomnia (29.0%) and moderate clinical insomnia (16.6%) significantly more frequently than patients in group C (24.4% and 5.0%; p=0.002)., Conclusion: A substantial proportion of women with endometriosis of the posterior cul-de-sac experiences poor sleep quality, excessive daytime sleepiness and insomnia., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: The aim of the current study was to evaluate the effect of surgical removal of endometriosis on dyspareunia, sexual function, quality of sex life and interpersonal relationships., Study Design: A questionnaire-based multicentre prospective study was conducted in six tertiary referral centres in Austria and Germany. Ninety-six patients with histologically proven endometriosis and dyspareunia were included. Before surgery and averagely 10 months postoperatively (range 9-12 months), the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS) were used to screen women's sexuality. Additionally, we evaluated psychological parameters and pain intensity during/after sexual intercourse via a self-administered questionnaire., Results: Pain scores measured via NAS during/after intercourse decreased significantly after surgery. Frequencies of interrupted sexual intercourse, feelings of guilt towards the partner, being afraid of pain before/during sexual intercourse and feelings of being a burden for the relationship also decreased significantly in patients with peritoneal endometriosis and deep infiltrating endometriosis. Interestingly, sexually related personal distress did not improve in women with peritoneal endometriosis/vaginal resection, but improved in cases of deep infiltrating endometriosis (DIE)., Conclusion: Radical laparoscopic excision of endometriosis offers an effective treatment option and offers a significant improvement in dyspareunia and quality of sex life., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The aim of this study is to evaluate prospectively the presence of endometriosis in the peritoneum of the ovarian fossa of patients affected by endometriomas and its correlation with the adhesion between this peritoneum and endometrioma., Methods: Patients presenting ovarian endometriomas and candidate to laparoscopy were considered for inclusion in the study. Patients underwent laparoscopic excision of endometriomas. The presence of adherence of the ovarian fossa to endometrioma was investigated. In all patients, the removal of a peritoneum fragment from the ovarian fossa of the affected ovary was carried out., Results: 68 patients were enrolled in the study. 48 patients presented adhesions to the ovarian fossa. Histopathologic examination of the peritoneum of the ovarian fossa revealed the presence of endometriosis in 87 % of patients presenting adhesions of the endometriomas with ovarian fossa; surprisingly it was present only in 15 % of patients not presenting this condition (p < 0.0001). Pain symptoms were more frequent in patients with endometriomas adhesion to the ovarian fossa. CA125 levels were not statistically significantly different between groups. At 12-month follow-up, four patients presented endometrioma recurrence. All of them presented adhesion of the ovarian fossa to the endometrioma in the first operation., Conclusions: There is a strong association between adhesion of the endometriomas to the ovarian fossa and the presence of endometriosis on the peritoneal surface of the fossa. This condition significantly correlates with pain symptoms and may predict endometrioma recurrence. The removal of this peritoneum in case of adherent endometrioma may potentially reduce the incidence of recurrence.

Endometriosis affects fertility in many women and may partly be due to decreased endometrial receptivity. Several mechanisms have been suggested, notably, progesterone resistance for which a number of candidate biomarkers have been suggested. Here we demonstrate aberrant levels of steroid hormone receptors and the small heat shock protein αB-crystallin in eutopic endometrial epithelium from 38 women with peritoneal endometriosis diagnosed during investigation for secondary infertility. Spontaneous pregnancies within 1 year after medical and surgical treatment for endometriosis were recorded and semi-quantitative immunohistochemistry data compared between women with endometriosis who did or did not become pregnant and healthy controls. Stronger immunostaining for ER-α was detected in luminal and glandular endometrial epithelium from women with endometriosis who did not become pregnant during the post-treatment observation period versus endometriosis patients who became pregnant and controls. Staining levels of PR and PR-B were lower in patients without subsequent pregnancies than in the two other groups. Endometrial levels of αB-crystallin in endometriosis patients similar to those in controls were strongly correlated with the chance of becoming pregnant, whereas higher or lower levels were not.

Aim: The aim of this study was to determine whether an optimized 3.0-Tesla magnetic resonance imaging (MRI) protocol is sensitive and specific enough to detect patients with endometriosis., Material and Methods: This was a prospective cohort study with consecutive patients. Forty consecutive patients with clinical suspicion of endometriosis underwent 3.0-Tesla MRI, including a T2-weighted high-resolution fast spin echo sequence (spatial resolution=0.75 ×1.2 ×1.5 mm³) and a 3D T1-weighted high-resolution gradient echo sequence (spatial resolution=0.75 ×1.2 × 2.0 mm³). Two radiologists reviewed the dataset with consensus reading. During laparoscopy, which was used as reference standard, all lesions were characterized according to the revised criteria of the American Fertility Society. Patient-level and region-level sensitivities and specificities and lesion-level sensitivities were calculated., Results: Patient-level sensitivity was 42% for stage I (5/12) and 100% for stages II, III and IV (25/25). Patient-level specificity for all stages was 100% (3/3). The region-level sensitivity and specificity was 63% and 97%, respectively. The sensitivity per lesion was 61% (90% for deep lesions, 48% for superficial lesions and 100% for endometriomata). The detection rate of obliteration of the cul-the-sac was 100% (10/10) with no false positive findings. The interreader agreement was substantial to perfect (kappa=1 per patient, 0.65 per lesion and 0.71 for obliteration of the cul-the-sac)., Conclusions: An optimized 3.0-Tesla MRI protocol is accurate in detecting stage II to stage IV endometriosis., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

Endometriosis is a complex gynecological disease, characterized by the presence and growth of endometrial tissue outside the uterus, resulting in pelvic pain and infertility. It occurs in 10% of women in their reproductive age. The viable endometrial cells enter the peritoneal cavity by retrograde menstruation, implant, and cause lesions ectopically; depending on their ability to survive, attach, grow, and invade. These "normal" endometrial cells turn "endometriotic" apparently because of inherent abnormalities present in them. Information on these molecular abnormalities is now being sought through proteomic approaches. Recent proteome-based comparisons between the eutopic endometrium from normal women and patients with endometriosis have revealed several proteins (many of which are shown to have a role in several cancers), of which a few have been validated as potential players in the etiology of endometriosis. After an initial in-flow of information from these proteome studies of eutopic endometrium, focus now needs to be expanded to the changes in the various protein PTMs and their upstream effectors present in these tissues. Early diagnosis of endometriosis through noninvasive means is the need of the hour as well-which would require the use of the presently existing immunoassays, along with the advancing MS-based proteomics. In this review, we aim to discuss these future thrust areas of human endometriosis proteomics and also present the proteomic advances made so far in understanding the molecular basis of endometriosis., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Analysis of published series reveals that no more than a fourth of subfertile patients undergoing surgery for peritoneal endometriotic implants, rectovaginal endometriotic lesions, or recurrent endometriomas achieved conception spontaneously. First-line surgery for ovarian endometriotic cysts appears associated with a better reproductive performance, that is, a mean postoperative pregnancy rate of ∼50%. At the same time, excision of endometriomas paradoxically seems to induce gonadal damage. With the exception of peritoneal disease, no randomized trials are available to assess the effect of surgery in subfertile women with endometriosis. Therefore, it is not possible to define the absolute benefit increase of the treatment of ovarian and rectovaginal lesions. The decision to undergo surgery for endometriosis-associated subfertility must be shared with the woman after detailed information and taking into account several additional conditions, such as presence of pain, large or complex adnexal masses, bowel or ureteral stenosis, and coexisting infertility factors. When considering surgery, a therapeutic equipoise should be reached that includes demonstrated benefits, potential morbidity, and costs of treatment alternatives. Particularly in case of recurrent endometriosis, in vitro fertilization should generally be preferred to surgery. The role of surgery in endometriosis-associated subfertility includes temporary pain relief in symptomatic women desiring a spontaneous conception., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Study Question: Is the occurrence of pelvic pain in women with ovarian endometrioma associated with coexisting peritoneal lesions (PLs)?, Summary Answer: Pelvic pain in women with ovarian endometrioma is usually associated with coexisting PLs. An increased tissue inflammatory reaction with elevated prostaglandin (PG) production may be responsible for the generation of pain., What Is Known Already: Severe pelvic pain in women with ovarian endometrioma is reported to be associated with deeply infiltrating endometriosis. However, information on pelvic pain in women with ovarian endometriosis with and without coexistent peritoneal superficial lesions is limited., Study Design, Size and Duration: Retrospective clinical study with case-controlled biological research using prospectively collected tissue samples derived from women with and without endometriosis and their retrospective evaluation., Participants/materials, Setting, Methods: We performed a retrospective cohort study conducted in 2988 cases who had laparoscopic surgery for indications of ectopic pregnancy, tubal infertility and other benign gynecologic diseases. We analyzed the occurrence of pelvic pain in the cases with ovarian endometrioma according to the distribution of coexisting PLs and pattern of intrapelvic adhesions. Inflammatory reaction of eutopic and ectopic endometria was measured by immunoreaction to macrophage marker, CD68. The tissue expression of cyclooxygenase (COX) 2 was examined by immunohistochemistry and tissue concentrations of PG F2α were measured by ELISA., Main Results and the Role of Chance: Among the 2988 surgical cases, 350 (11.7%) were found to have ovarian endometrioma at laparoscopy. Coexisting PLs were present in 269 of these women and in this group 85.4% of cases experienced pelvic pain and 14.6% had no pain. In contrast, among the 81 women with ovarian endometrioma only, 38.3% cases experienced pelvic pain and 61.7% cases had no pain and the difference between the groups was statistically significant (P < 0.01). The infiltration of CD68-immunoreactive macrophages was significantly higher in the eutopic and ectopic endometria of women with peritoneal endometriosis than in ovarian endometrioma. The tissue expression of COX2 and levels of PGF2α were significantly higher in both the eutopic and ectopic endometria derived from women with peritoneal endometriosis than in similar tissues derived from women with ovarian endometrioma., Limitations, Reasons for Cautions: Lack of evaluation in the detection of general or disseminated deeply infiltrating endometriosis in the pelvic cavity could be a bias or limitation in this study. Further multicenter prospective studies are needed to strengthen our current findings., Wider Implications of the Findings: Our findings may provide some new insights to understand the physiopathology of pelvic pain in women with ovarian cystic endometriosis and may hint at proper surgical manipulation to prevent the recurrence of pelvic pain in these women., Study Funding/competing Interest(s): This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Sports, Culture, Science and Technology of Japan. There is no conflict of interest related to this study., Trial Registration Number: Not applicable.

Background: Xanthohumol is a prenylated flavonoid isolated from hops, which is known to act as a pleiotropic cancer chemopreventive agent owing to its anti-proliferative, anti-inflammatory and anti-angiogenic properties. In the present study, we analyzed, for the first time, whether this dietary compound may also be used for the treatment of endometriosis., Methods: Peritoneal and mesenteric endometriotic lesions were surgically induced in BALB/c mice by uterine tissue transplantation into the abdominal cavity. The animals were treated daily with 100 µM xanthohumol (n= 8) or vehicle (control, n= 8) via the drinking water, starting 3 days before tissue transplantations. Lesion growth, cyst formation and vascularization were subsequently analyzed by means of high-resolution ultrasound imaging (at Day 0 and then once per week for 28 days), caliper measurements, western blotting, histology and immunohistochemistry over 4 weeks., Results: In the treatment and control groups, uterine grafts developed typical endometriotic lesions with cyst-like dilated glands surrounded by a vascularized endometrial stroma. However, xanthohumol efficiently decreased the size of these lesions at Day 28, independent of their localization within the peritoneal cavity, compared with control (peritoneal: P =0.041; mesenteric: P =0.038). This was associated with a reduced level of phosphoinositide 3-kinase protein. Moreover, vascularization of xanthohumol-treated lesions was suppressed, as indicated by a significantly lower microvessel density at Day 28 when compared with vehicle-treated controls (peritoneal: P =0.026; mesenteric: P =0.004). Additional analyses revealed that treatment with xanthohumol did not affect the histomorphology, proliferation and vascularization of the uterine horns and ovaries., Conclusions: Taken together, these experimental findings suggest that xanthohumol inhibits the development of endometriotic lesions in mice without inducing serious side effects in the reproductive organs. Thus, xanthohumol represents a promising dietary phytochemical that, after further testing, may be considered for the use in the selective treatment of endometriotic lesions.

We found an increased expression of the TAGLN gene in endometriotic lesions compared with the eutopic endometrium of the same patients by real-time polymerase chain reaction. It is possible that this deregulation contributes to the development and maintenance of endometriosis by being involved in the pathways of organization of cytoskeletal architecture., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

There was no difference in the density of nerve fibers across the menstrual cycle in peritoneal endometriotic lesions. These findings may explain why patients with peritoneal endometriosis often have painful symptoms throughout the menstrual cycle., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The Dutch version of the Endometriosis Health Profile-30 (EHP-30) showed a high return rate and data completeness, low floor and ceiling effects, as well as good internal consistency, test-retest reliability and construct validity. The questionnaire is a reliable and valid instrument for the measurement of health-related quality of life in women with endometriosis., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Endometriosis is considered to be an inflammatory disease, and macrophages are the most numerous immune cells in endometriotic lesions. However, the mechanisms underlying the elevation of macrophages and their role in the pathogenesis and manifestations of endometriosis still remain unclear., Methods: The number of macrophages stained for CD68 in endometriotic lesions (n = 24) and in peritoneum distant from the lesions (n = 14) from women with endometriosis was compared with the number of macrophages in normal peritoneum from women without endometriosis (n = 18). Peritoneal lesions were also double-stained for CD68 and protein gene product 9.5 to study the relationship between macrophages and nerve fibres., Results: The densities of macrophages in peritoneal endometriotic lesions and unaffected peritoneum from women with endometriosis were both significantly higher than that in normal peritoneum from women without endometriosis (P < 0.001). More nerve fibres were also found in the areas where increased numbers of macrophages were identified., Conclusions: There was a significant elevation of macrophages in both normal peritoneum and peritoneal lesions from women with endometriosis compared with normal peritoneum from women without endometriosis. These cells may well play roles in the growth and development of endometriotic lesions and in the generation of pain through interaction with nerve fibres.

Objective: To assess whether deep endometriosis has different risk factors compared with endometriosis at other sites. In epidemiological terms, this should be the case if deep endometriosis represents a different condition than ovarian and peritoneal endometriosis., Design: Case-control study., Setting: University hospitals., Patient(s): The first group of cases included 181 women with a diagnosis of deep endometriosis. The second group of cases included 162 women with endometriosis at other sites. The control group included women younger than 55 years of age who were admitted for acute non-gynecological, non-hormonal, non-neoplastic conditions., Intervention(s): Questionnaire., Main Outcome Measure(s): Odds ratios., Result(s): The age distribution of women with cases of deep and ovarian and pelvic endometriosis was not statistically significantly different. A higher body mass index decreased the risk of both deep as well as ovarian and pelvic endometriosis: the estimated ORs for women reporting a body mass index of > or =21 vs. those reporting a body mass index of <21 were 0.6 (95% confidence interval [CI], 0.3-0.8) for deep endometriosis and 0.6 (95% CI, 0.4-0.9) for pelvic and ovarian endometriosis. Parous women were at decreased risk: in comparison with nulliparae, the odds ratio for deep endometriosis was 0.1 (95% CI, 0.1-0.2) for women reporting one or more births. The corresponding value for pelvic and ovarian endometriosis was 0.1 (95% CI, 0.1-0.2)., Conclusion(s): This study suggests that deep as well as ovarian and pelvic endometriosis share similar risk factors.

Objective: To evaluate the phenotype, proliferative, and differentiation capacities in vitro of stromal cells derived from peritoneal, ovarian, and deeply infiltrating endometriosis., Design: Experimental study using phase contrast microscopy, immunocytochemistry, and functional bioassays., Setting: University-based laboratory., Patient(s): Women with and without endometriosis undergoing surgery for benign indications., Intervention(s): None., Main Outcome Measure(s): The stability in vitro of stromal cells derived from peritoneal (n = 18), ovarian (n = 29), and deeply infiltrating (n = 14) endometriotic lesions, as well as endometrium from women with (n = 5) and without endometriosis (n = 5) was evaluated by detection of endometrial markers. The proliferative and differentiation capacity of the cells was assessed by the use of cell doubling estimation and in vitro decidualization assays., Result(s): The expression of the progesterone receptor and CD10 in stromal cells derived from the three types of endometriotic lesions is retained in culture up to passage 10. The doubling time of stromal cells from deeply infiltrating lesions is lower than that of endometrial stromal cells. Levels of prolactin and insulin-like growth factor binding protein-1 (IGFBP-1) are reduced in supernatants from stromal cells derived from the three types of lesions and from the endometrium of women with endometriosis., Conclusion(s): The peritoneal, ovarian, and deeply infiltrating endometriotic stromal cell lines we describe retain in vivo tissue markers. Loss of differentiation capacity of the endometriotic cell lines and endometrial cells from women with endometriosis may influence the capacity for proliferation and survival of these cells in the ectopic environment.

Purpose of Review: To review the concept of typical, subtle and invisible endometriosis and analyze the evolution and progression of the disease, as well as some factors possibly involved in the pathogenesis., Recent Findings: Although rejected by Redwine, the concept of non-visible endometriosis has been proven to exist. Some new ideas on the implication of reactive oxygen species in the development of endometriosis and its early stages are described here., Summary: The increased diagnosis of endometriosis can be explained not only by the increased experience and ability of the surgeon to detect typical and non-typical endometriotic lesions, but also by a better understanding of the pathogenesis.

Objective: To evaluate the effect of antileukotriene therapy, we examined the morphologic alteration in experimental rat endometriosis both with and without leukotriene receptor antagonist treatment., Design: Light and electron microscopic analysis., Setting: Tochigi Institute of Clinical Pathology, Japan., Animal(s): Female Sprague-Dawley rats maintained on a schedule of 12 hours of light and 12 hours of dark for 2 weeks., Intervention(s): Uterine transplants were attached to rat peritoneum via the surgical autotransplantation technique. After autotransplantation, the rats were given daily administration of leukotriene receptor antagonist, and the lesions were examined at 4 and 7 days after autotransplantation., Main Outcome Measure(s): The morphologic comparison of rat endometriosis with and without antileukotriene therapy., Result(s): In the rats treated with leukotriene receptor antagonist, a significant decrease in stromal proliferation was observed when compared with nontreated rats. The treated rats showed not only the suppression of infiltration and activation of mast cells but also widespread apoptosis of proliferative fibroblasts in the lesions., Conclusion(s): Our results reveal that a leukotriene receptor antagonist has significant therapeutic value for the treatment of rat endometriosis. It is likely that antileukotriene therapy would be efficacious in the treatment and prevention of human endometriosis.

This review summarizes the recent literature concerning new data on the pathogenesis of peritoneal endometriosis and its natural evolution. Indeed, the main concern in endometriosis is the choice of treatment in cases of infertility problems: medical or surgical. This concern could hypothetically be avoided if endometriosis were considered as a spontaneously regressive phenomenon. The present paper also discusses the risk of recurrence and the results of in-vitro fertilization and embryo transfer in cases of ovarian endometriosis. Whatever type of surgery is performed, the results of in-vitro fertilization and embryo transfer are not impaired, especially if damage to the ovarian cortex is avoided. Further studies are required to determine if oocytes from endometriosis patients are altered and could be responsible for the development of lower quality embryos.

Background: The relationship between frequency and severity of pain symptoms and site, stage and morphological characteristics of endometriotic lesions was analysed in a multicentre cross-sectional observational study., Methods: A total of 469 women (median age 31 years, range 18-45) who met the following criteria were consecutively observed in the participating centres during the study period: age 18-45 years, first laparoscopic or laparotomic diagnosis of endometriosis, pain symptoms lasting > or = 6 months, pain as the main or only complaint of the condition, absence of pelvic anomalies and no previous pelvic surgery. Dysmenorrhoea and non-menstrual pain were evaluated using a multidimensional verbal rating scale. The women were requested to grade the severity of dysmenorrhoea, non-menstrual pelvic pain and deep dyspareunia using a 10-point linear analogue scale., Results: Dysmenorrhoea was present in 77% of subjects with ovarian endometriosis, 88% of those with endometriosis of the peritoneum, 92% of subjects with endometriosis of both ovary and peritoneum and in all the subjects with endometriosis of rectovaginal septum. These differences were not statistically significant after Bonferroni's correction. No marked difference emerged between the severity of dysmenorrhoea and site of endometriosis, but women with ovarian endometriosis tended to have lower scores (not significant). No clear association emerged between frequency and severity of non-menstrual pain, dyspareunia and site of endometriosis and the presence and severity of dysmenorrhoea, non-menstrual pain and dyspareunia. Dyspareunia was more frequently reported in women with only atypical endometriosis (56.8%) versus 47.7% in women with typical endometriosis, but with borderline significance (P = 0.05). Dyspareunia occurred in 68.2% of patients with both typical and atypical lesions., Conclusions: The results of this study find no clear-cut association between stage, site or morphological characteristics of pelvic endometriosis and pain.

Natural history of endometriosis is unpredictable. Some recent data show that endometriosis is a progressive disease. Minimal lesions are transient and peritoneal implants are reorganized continuously. So, minimal endometriosis could be considered like a transient statement close to physiology. In favourable statement such as the decreased activation of NK cells, the variable secretions of cytokines, pelvic macrophages and growth factors, the peritoneal implants evoluted like a progressive disease until severe endometriosis. Endometriosis is a frequent cause of pelvic pain with dysmenorrhea, dyspareunia, chronic pelvic pain and infertility. The diagnosis can be suspected by a clinical examination preferentially during menstruation with fixed uterine retroversion peritoneal infiltration, retraction of the rectum and retrovaginal endometriosis, and adnexal cyst.

Endometriosis is characterised by the presence in abnormal situation of a tissue resembling the endometrium with glands and stroma. Several assumptions try to explain the development of this tissue. The oldest, the theory of the metaplasia, suggests that under various influences the coelomic tissues would be transformed into endometrium. Most often agreed, the theory known as the implantation theory, explains why the endometrial cells and fragment desquamated during menstrual period transported through the fallopian tubes into the peritoneal cavity (physiological phenomenon) could under certain conditions implant, proliferate and develop overcoming the local mechanisms of defence. The peritoneal cavity of the normal women have the capacity to prevent the evolution towards endometriosis. The reasons of an evolution towards the endometriosis and its symptoms (pain, sterility, adherences are probably numerous implying the immune system, the endometrium, the macrophages, the cells natural killer, the peritoneum the fallopian tubes. The failure to removes the peritoneal cavity of the fragments would induce an inflammatory local state with hyperactivation of the macrophages which secrete many molecules, of which some could lead the metaplasia of the peritoneum or the development of müllerian residues.

The hypothesis is advanced that endometriosis, an ovarian steroid hormone-dependent process, is physiologic unless recurrent bleeding in the ectopic implants causes progressive disease and symptoms. Diagnosis should take into account the detection of chronic bleeding, and efficient medical treatment can be achieved by amenorrhea without the induction of hypoestrogenism.

Endometriosis is classically defined as the growth of endometrial cells at sites outside the uterus. It is a common disease characterized by infertility, chronic pain and adhesion formation. Immune dysregulation, evidenced by decreased clearance of endometrial cells and aberrant production of cytokines by peritoneal fluid leukocytes, has been proposed as a mechanism which allows implantation and growth of ectopic endometrium. Cytokines are primary components of intercellular signaling between uterine epithelial and stromal cells, leukocytes, and the developing conceptus. Because their production is regulated by sex hormones, cytokines are well-placed to play a key role in the extensive tissue remodeling required to accommodate menstruation, implantation and pregnancy. Understanding this specialized hormonally-responsive mucosal immune system within the uterus will be critical to understanding the potential importance of the immune system in the pathogenesis of endometriosis. In this review, highlights of studies describing leukocyte populations, cytokines and cytokine receptors in uterine and ectopic endometrium and their proposed role in the regulation of immune processes and endometrial growth are presented, followed by a review of current data on immune aspects of endometriosis. Studies directed at investigating the hormonal regulation of cytokine secretion by uterine and peritoneal cell populations, and the effect of cytokines on endometrial proliferation, should provide a more complete understanding of their potential role in normal uterine growth and in the pathogenesis of endometriosis.

The contrasting findings obtained in the studies that have attempted to correlate the stage of endometriosis with severity of pain symptoms suggest that some specific characteristics of the lesions are more implicated in the genesis of pain than disease extension per se. Thus, fresh, metabolically active, intraperitoneal implants may cause functional pain symptoms such as dysmenorrhea, whereas infiltrating, nodular and fibrotic lesions are responsible for organic-type pain such as deep dyspareunia. Women with symptomatic endometriosis seem to have reduced peripheral beta-endorphin production in comparison with pain patients without the disease, although neuroendocrine modulation of pelvic nociceptive stimuli is far from clear. There is little evidence to support the notion that specific psychiatric features render some women more vulnerable to developing endometriosis, as results from investigations performed on women with asymptomatic lesions are very similar to normative data. Moreover, it appears that the psychological profile of symptomatic patients with the disease is no different from those with pain and a normal pelvis or other gynecological conditions. Consequently, the local biochemical and physical effects of lesions seem to be the most important factors in determining frequency and severity of symptoms.

Asymptomatic endometriosis is likely to be a physiological phenomenon of very limited relevance to both the physician and the patient. The evolution of our understanding of this phenomenon is a parable for modern medicine. It is likely that access to a new diagnostic technique, a powerful armoury of medical and surgical treatments and the necessity for doctors to feel they are doing something positive for the patient, have created an incorrect disease model for asymptomatic endometriosis. As responsible clinicians and medical scientists it behoves us to honestly re-examine our approach to this phenomenon.

The concept of endometriosis and strategies for its treatment are reviewed. Treatment is mainly endocrine-based, using progestogens, danazol and luteinizing hormone-releasing hormone (LHRH) agonists. Such treatment is complex, and therapy strategies have to be tailored to the individual; the choice of treatment, therefore, depends on the metabolic and side-effects of each compound.

The local environment of peritoneal fluid (PF) surrounding the endometriotic implant is immunologically dynamic and links the reproductive and immune systems. Peritoneal fluid contains a variety of free floating cells, including macrophages, mesothelial cells, lymphocytes, eosinophils and mast cells. Macrophages are attracted to the peritoneal environment more abundantly than any other cell type. These scavengers promote cellular growth and viability through secretion of growth factors and cytokines. It is now becoming evident that cytokines play an important role in reproduction at various levels, including gamete function, fertilization and embryo development, implantation and postimplantation survival of the conceptus. Peritoneal fluid has been shown to affect negatively ovum capture by the fimbria, sperm survival, spermatozoon-oocyte interaction and embryonic development. We have recently identified the presence of two pro-inflammatory chemoattractant cytokines for monocyte/macrophages (MCP-1) and for granulocytes (interleukin-8, IL-8) in the PF. Concentrations of both IL-8 and MCP-1 are not only elevated in PF of women with endometriosis compared to those without endometriosis, but they are related to the severity of the disease. Over the past 70 years, at least a dozen theories have been proposed to explain the histogenesis and aetiology of endometriosis. It appears that the aetiology is multifactorial, and today a composite theory of retrograde menstruation with implantation of endometrial fragments in conjunction with peritoneal factors to stimulate cell growth is the most widely accepted explanation for peritoneal endometriosis.

Peritoneal endometriotic implants and adjacent normal peritoneum from five patients were analyzed for prostaglandin (PG) release. Each tissue biopsy was incubated using medium 199 in triplicate at 37 degrees C for six hours, and PGF2 alpha and PGE2 concentrations were measured in the incubation medium every two hours. This study demonstrates that peritoneum involved with endometriosis releases significantly more PGF2 alpha and PGE2 (P less than .05) than adjacent normal peritoneum, and suggests that peritoneal endometriotic implants may be a source of the elevated peritoneal fluid PG levels previously reported in patients with endometriosis.