{"paper_id":"000a0138-f7b6-42c6-af02-f9bc0ae720a8","body_text":"J. Obstetrics Gynecology and Reproductive Sciences                                                                                                                                     Copy rights@ Vasilios Tanos et.al. \n \n \nAuctores Publishing LLC – Volume 6(2)-102 www.auctoresonline.org  \nISSN: 2578-8965   Page 1 of 9 \n \n \nCorrelation of Bladder Wall Endometriosis Histological Location, \nTo Infertility Patients’ Clinical Characteristics and Severity of \nPeritoneal Endometriosis \nSayed El-Akhras1, Mohamed Abo-elenen1, Christiana Demetriou2, Nafissa Mohamed Amin El Badawy3,4, Safinez Balami5, Vasilios Tanos6,1,* \n1Omam Hospital, Department of Gynecology and Obstetrics, 2 Elbatal Ahmed Abdelaziz St., 12611 Giza, Egypt  \n2Department of Primary Care and Population Health, University of Nicosia Medical School, 2408, Nicosia, Cyprus  \n3Ain Shams University, Faculty of Medicine, Department of Pathology, 38, Abbasia, Al Wailli, 11566 Cairo, Egypt  \n4President Scientific Council Egyptian Board of Pathology \n5St George’s, University of London MBBS Programme at the University of Nicosia Medical School, 2408, Nicosia, Cyprus \n6University of Nicosia - Medical School, and Aretaeio Hospital, 2024, Nicosia, Cyprus  \nCorresponding Author: Vasilios Tanos, University of Nicosia - Medical School, and Aretaeio Hospital, 2024, Nicosia, Cyprus  \nReceived date: October 25, 2021; Accepted date:  November 30, 2021; Published date: January 05, 2021 \nCitation: Sayed El-Akhras, Mohamed A. elenen, Christiana Demetriou  C., Nafissa M .A El Badawy, Balami S., Tanos V. (2022) Correlation of \nBladder Wall Endometriosis Histo logical Location, To Infertility Patients’ Clinical Characteristics and Severity of Peritoneal Endometriosis . J. \nObstetrics Gynecology and Reproductive Sciences; 6(2) DOI:10.31579/2578-8965/102 \nCopyright: © 2022, Vasilios Tanos, This is an open access art icle distributed under the Creative Commons Attribution License, which permits \nunrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. \nAbstract  \nStudy question:  What is the correlation of bladder wall e ndometriosis histological location, to the severity of peritoneal \nendometriosis in infertility patients?      \nSummary answer: Secondary infertility, back pain, micturition problems, history of ectopic pregnancy and number of abortions \ncan probably be considered as high-risk factors for bladder wall endometriosis for infertility patients.  \nWhat is known already: Bladder and/or ureter endometriosis occur in 70–85% among patients with deep infiltrating endometriosis. \nThe knowledge regarding the bladder wall in volvement with endometriosis in association to peritoneal endometriosis and infertility \npatients’ clinical characteristics is limited.   \nStudy design, size, duration: Retrospective, longitudinal cohort, Sixty-six, primary and secondary infertility patients, collection \nof surgical and clinical data between 2010 to 2018.  \nParticipants/materials, setting, and methods: An experienced histopathologist on endometriosis was asked to review all the \npatients’ histopathological results. The histopathological reported findings were reviewed prior to the study to reassure the bladder wall \ndepth of endometriosis involvement. \nThe operation and tissue macroscopic description reports before processing were also reviewed. Attention was paid for possibl e \ndiscrepancies or miss ed important data that could influence the histopathological results. In cases where results were equivocal, the \nparaffin blocks were available for additional sections for reassuring the diagnosis. An extra effort was made to meticulously  observe \nand identify the involvement of the bladder serosa, muscularis and mucosa with endometriotic cells and glands.   \nMain results and the role of chance: Primary infertility was the indication for the current laparoscopic surgeries in 32 out of 66 \n(48.5%) patients and secondary infertility for the rest of the group. The highest incidence of bladder endometriosis (BE) was detected \non the serosa of 12 patients and in the detrusor muscle (DM) of 11 cases. Bladder serosa endometriosis (BSE) was significantl y more \nprominent among patients with history of ectopic pregnancy (p=0.004) and among patients with secondary infertility (p=0.029). \nDestrusor muscle endometriosis (DME) was significantly more frequent (p=0.012) in patients with increasing number of abortion s. \nDME highest rates of 37.7% were observed among the severe spread of abdominal endometriosis as compared to 19% of the cases with \nbladder serosa endometriosis. No statistically significant difference found between serosa and detrusor muscle endometriosis \ninvolvement, when compared to severity and spread of endometriosis within the abdominal cavity. Back pain was most prominent with \n  Open Access  \n       Research Article \n   Journal of Obstetrics Gynecology and Reproductive Sciences \n                                                                                                                  Vasilios Tanos *                                                                                                                                                        \nAUCTORES \nGlobalize your   Research \n\nJ. Obstetrics Gynecology and Reproductive Sciences                                                                                                                                     Copy rights@ Vasilios Tanos et.al. \n \n \nAuctores Publishing LLC – Volume 6(2)-102 www.auctoresonline.org  \nISSN: 2578-8965   Page 2 of 9 \nstatistical significant difference (p=0.007) in 8 patients with BSE + DME as compared with other groups of patients (4 BSE, 3  DME \nand 3 BME+DME patients). Among 30 cases with an ovarian endometrioma detected by TVU, DME was diagnosed in 13 patients, in \nserosa of 10, and in serosa and DM of 6 patients. Statistical analysis was performed using Pearson chi -square, Fisher’s exact tests and \nthe Kruskal-Wallis test by STATA version 15 SE (StataCorp. 2017). \nLimitations, reasons for caution: This is a cohort retrospective study. There is a possibility that other areas with endometriosis \nwere also involved in the BW other than those diagnosed and treate d. The mixture of patients with primary and secondary infertility \ncould also affect the results, although statistical analysis did not show any significance in BWE, clinical symptoms and surgical findings. \nBE is rarely an isolated condition, and other forms of endometriosis are frequently concomitant  \nWider implications of the findings: Detrusor muscle endometriosis involvement was in 68% and bladder serosa in 32% of all \ncases with bladder endometriosis and infertility investigated. The severity of the peri toneal endometriosis can probably direct to \nmeticulous intraoperative investigation for bladder endometriosis.    \nStudy funding/competing interest(s): This study has been performed without any funding   \nKey words : bladder endometriosis; bladder wall endome triosis; peritoneal endometriosis; bladder endometriosis and patients’ \nclinical characteristics, histopathology and bladder endometriosis; \nRunning title: Bladder Endometriosis in infertility patients  \nIntroduction  \nUrinary tract endometriosis is evident in approximately 1% of women \nwith endometriosis (Leone Roberti Maggiore et al., 2017). Its prevalence \nincreases to 19–53% among patients with deep infiltrating endometriosis \n(DIE) (Gabriel et al., 2011; Knabben et al., 2015). DIE is a particular form \nof endometriosis that penetrates > 5 mm under the peritoneal surface \n(Koninckx and Martin, 1994). Bladder and/or ureter endometriosis occur \nin 70–85% of cases with severe endometriosis (Knabben et al., 2015).  \nThe anatomical proximity of the bladder to the ante rior cul-de-sac and \nuterus as well as the standing posture and the effects of gravity, have been \nsuspected to contribute in the development of endometriosis in the \nvesicovaginal septum (Vercellini et al., 2002).  The distance between the \nbladder and anterior uterine wall seems to be a crucial factor since no BE \nwas detected in cases with retroverted uterus (Vercellini et al ., 2002). \nSpontaneous growth of bladder peritoneum and interstitial endometriotic \nnodules is possible, induced by oestrogens during arti ficial reproductive \ntechniques and may cause obstetrical complications especially during \ncaesarean section (Somigliana et al., 2015a; Leone Roberti Maggiore et \nal., 2016). Trans-tubal regurgitation of menstrual endometrium facilitates \nimplantation on peritoneal surfaces. \nBE is  defined as the presence of  endometrial glands and stroma in the \ndetrusor muscle. The dome and the base are the most frequently affected \nsites. Primary  BE is extremely rare. It presents as a spontaneously \noccurring manifestation among a generalized pelvic endometriosis. So \nfar, the development of adenomyotic nodules found in the verumontanum, \ntrigone, ureterovesical junction and lateral wall of the bladder has been \nattributed to Mullerian duct remnant metaplasia (Vigano et al,. 2009). \nSecondary BE is considered a dissemination and progression of cells due \nto iatrogenic causes, occurring after pelvic surgery, such as caesarean \ndelivery or hysterectomy or secondary to other forms of pelvic \nendometriosis (Somigliana et al., 2007). BE is not  an independent form \nof the disease and at least one other site of the abdomen is involved Abrao \net al., 2009). According to ASRM staging system, the presence of BE is \nclassified as stage IV, as DIE.   \nWhen endometrial glands and stroma are present within the detrusor \nmuscle, it is defined as bladder adenomyosis. Ninety percent of patients \nwith BE, usually complain of urinary frequency, dysuria and less \nfrequently of bladder pain, urgency and haematuria Abrao et al., 2009). \nHence, dysuria, pelvic pain and m icturition problems in absence of \nurinary tract infection should raise suspicion and direct the mode of \nmanagement in these patients. \nBE as an isolated pathology does not seem to cause infertility. However, \nit is reported that surgical interventions in cas es with deep infiltrating \nendometriosis and BE lesions have been increasing the IVF pregnancy \nrates to 42–44% (Meuleman et al., 2009; . Soriano et al., 2011). In case \nof fertility treatment, it has been calculated that only 20 –25% of women \nmay really benefit from an isolated bladder nodule resection (Meuleman \net al., 2009). IVF appears to be more effective and less risky compared to \nbladder surgery in patients with moderate pelvic endometriosis and BE \n(Somigliana & Garcia-Velasco, 2015b). \nIn this cohort study, the impact of abdominal endometriosis on the bladder \nwall depth of endometriosis involvement has been investigated among \ninfertility patients. All patients were diagnosed with BE. The extent of the \nperitoneal endometriotic lesions diagnosed by laparoscopy was corelated \nto BE according to histopathological findings, including the bladder \nserosa, detrusor muscle and mucosa. Patients’ age, past health problems \nand operations, as well as present laparoscopic surgery results were \ninvestigated in relation to BE involvement. A potential association \nbetween patients’ parity, gravidity, infertility, pain status, and \nmenstruation characteristics with the bladder wall endometriosis \ninvolvement was also investigated.        \nStudy population \nSixty-six patients operated in Omam private Hospital in Cairo, diagnosed \nwith bladder endometriosis (BE) between 2010 and 2018 were included \nin this cohort study. Patients records, including age, gravidity, parity, \nobstetrical outcome, history of health problems and operations, cl inical \nsymptoms and examination results, current minimally invasive surgery \nindication and results, and histopathological reports were extracted, and \ncompiled into a database. Tables I, II and III demonstrate in detail \npatients’ clinical records and histop athological examination results in \nrelation to BE involvement.   \n \nClinical data  Patients No (%) Bladder Endometriosis P-value* \n \n  Serosa -21 \n \nDetrusor muscle \nInvolvement - 45 \n \n  n n  \n\nJ. Obstetrics Gynecology and Reproductive Sciences                                                                                                                                     Copy rights@ Vasilios Tanos et.al. \n \n \nAuctores Publishing LLC – Volume 6(2)-102 www.auctoresonline.org  \nISSN: 2578-8965   Page 3 of 9 \nAge: median (range) 33 (21-52) 31 (23-52) 33.0 (21-49) 0.820 \nGravidity (median range) 1.0 (0-9) 1.0 (0-9) 0.0 (0-8) 0.193 \nParity (median range) 0.0 (0-4) 0.0 (0-4) 0.0 (0-4) 0.547 \nAbortions (median range) 0.0 (0-7) 0.0 (0-4) 0.0 (0-7) 0.012 \nVaginal Deliveries (median range) 0.0 (0-4) 0.0 (0-4) 0.0 (0-3) 0.206 \nCaesarean Sections (median range) 0.0 (0-3) 0.0 (0-3) 0.0 (0-3) 0.968 \nEctopic Pregnancy (median range) 0.0 (0.0-0.0) 0.0 (0.0-4.0) 0.0 (0.0-0.0) 0.004 \n \n* P-value compares each variable between bladder endometriosis categories.  \nTable 1: Frequency of endometriosis on the bladder serosa and detrusor muscle associated with patients’ age and obstetrical history \nAs the numbers are no low, table 1 would benefit from showing n numbers \nand mean in addition to median and range.  Also ensuring that the \nabbreviation and terminology are consistent between the tables and the  \ntext in the paper.   \nWhy isn't the TVU data presented in the tables (polyps, fibroid)? \n \nClinical symptoms    All patients Bladder Endometriosis P-value* \n 66 Serosa Detrusor muscle \nInvolvement \n \n n (%) n (%) n (%)  \nMenstruation \nMenstrual Disturbances  19 (28.8) 8 (38.1) 11 (24.4) 0.254 \nAmenorrhea   5 (7.6) 3 (14.3) 2 (4.4) 0.159 \nAbnormal uterine Bleeding 1 (1.5) 1 (4.8) 0 (0) 0.140 \nPain Status \nAbdominal Pain  43 (65.1) 13 (61.9) 30 (66.7) 0.705 \nBack pain 19 (28.8) 4 (19) 15 (33.3) 0.233 \nDysmenorrhea   44 (66.7) 14 (66.7) 30 (66.7) 0.999 \nDyspareunia       28 (42.4) 11 (52.4) 17 (37.8) 0.264 \nDysuria   11 (16.7) 2 (9.5) 9 (20.0) 0.287 \nPast History of Health Problems \nInfertility (other type, male,etc) 32 (48.5) 12 (57.1) 20 (44.4) 0.336 \nInfertility I 20 (30.3) 5 (23.8) 15 (33.3) 0.433 \nInfertility II  12 (18.2) 7 (33.3) 5 (11.1) 0.029 \nUrinary tract infection  9 (13.8) 2 (9.5) 7 (15.6) 0.486 \nMicturition issues   5 (7.6) 1 (4.8) 4 (8.9) 0.555 \nVaginitis   8 (12.1) 4 (19) 4 (8.9) 0.239 \nPast History of Operations  \nAppendectomy 7 (10.6) 2 (9.5) 5 (11.1) 0.845 \nCesarean Section  13 (20) 4 (19) 9 (20.0) 0.894 \nCystectomy    10 (15.1) 3 (14.3) 7 (15.6) 0.893 \nLaparoscopy  11 (16.7) 4 (19.0) 7 (15.6) 0.723 \nLaparotomy   12 (18.2) 5 (23.8) 7 (15.6) 0.418 \nCurrent management  \nPre-Op US: Normal   7 (10.6) 4 (19) 3 (6.7) 0.128 \nPre-Op US: Ovarian endoma  30 (45.4) 10 (47.6) 20 (44.4) 0.809 \nLaparoscopy      58 (87.9) 19 (81) 41 (91.1) 0.933 \nHysteroscopy    56 (84.9) 19 (90.5) 37 (82.2) 0.384 \nCystoscopy   31 (47) 11 (52.4) 20 (44.4) 0.547 \nOvarian endoma excision 31 (47) 8 (38.1) 23 (51.1) 0.324 \nPelvic Endometriosis  31 (47) 10 (47.6) 26 (57.8) 0.440 \nPouch of Douglas occlusion 31 (47.0) 9 (42.9) 22 (48.9) 0.647 \nSeverity of endometriosis findings within the abdominal cavity, confirmed by biopsies                                                                                                                                 \nMild  20 (30.3) 8 (38.1) 12 (26.7) Pmild vs. moderate = 0.783 \nModerate  25 (37.9) 9 (42.9) 16 (35.6) Pmoderate vs. severe = 0.203 \nSevere  21 (31.8) 4 (19.0) 17 (37.7) Pmild vs. severe = 0.141 \n Poverall = 0.302 \n\nJ. Obstetrics Gynecology and Reproductive Sciences                                                                                                                                     Copy rights@ Vasilios Tanos et.al. \n \n \nAuctores Publishing LLC – Volume 6(2)-102 www.auctoresonline.org  \nISSN: 2578-8965   Page 4 of 9 \n   Endoma = endometrioma  \n* P-value compares each variable between bladder endometriosis categories \n* P-value from a Pearson chi-square test   \nFor categorical variables, the Pearson’s Chi-square test was used. For continuous non-normally distributed variables, the Kruskal-Wallis test \nwas used.  \n∞ Only among non-virgin participants (ntotal=60, nserosa=20, nDetrusor muscle Involvement within=37) \nTable 2. The frequency of bladder wall endometriosis involvement (serosa and detrusor muscle) associated to menstruation, pain status, past \nmedical and surgical history, management and endometriosis spread within the abdominal cavity \nClinical symptoms     Bladder Endometriosis Category P-value* \n Patients BSE DME  BSE & DME  BME & DME   \nNumber of patients  66 21 23 15 4  \n n (%) n (%) n (%) n (%) n (%)  \nMenstruation \nMenstrual disorders   19 (28.8) 8 (38.1) 7 (30.4) 2 (13.3) 1 (25) 0.440 \nAmenorrhea   5 (7.6) 3 (14.3) 2 (8.7) 0 (0) 0 (0) 0.538 \nAbnormal uterine Bleeding 1 (1.5) 1 (4.8) 0 (0) 0 (0) 0 (0) 0.635 \nPain Status \nAbdominal Pain  43 (65.1) 13 (61.9) 13 (56.5) 11 (73.3) 4 (100) 0.398 \nBack pain 19 (28.8) 4 (19) 3 (13) 8 (53.3) 3 (75) 0.007 \nDysmenorrhea   44 (66.7) 14 (66.7) 16 (69.6) 10 (66.7) 4 (100) 0.719 \nDyspareunia       28 (42.4) 11 (52.4) 7 (30.4) 6 (40) 2 (50) 0.505 \nDysuria   11 (16.7) 2 (9.5) 5 (21.7) 3 (20) 0 (0) 0.677 \nPast History of Health Problems \nPrimary Infertility I 20 (30.3) 5 (23.8) 9 (39.1) 5 (33.3) 0 (0) 0.448 \nSecondary Infertility II  12 (18.2) 7 (33.3) 2 (8.7) 3 (20) 0 (0) 0.179 \nUrinary tract infection  9 (13.8) 2 (9.5) 0 (0) 5 (33.3) 1 (25) 0.011 \nMicturition issues   5 (7.6) 1 (4.8) 1 (4.3) 1 (6.7) 1 (25) 0.456 \nVaginitis   8 (12.1) 4 (19) 1 (4.3) 3 (20) 0 (0) 0.340 \nPast History of Operations  \nAppendectomy 7 (10.6) 2 (9.5) 3 (13) 1 (6.7) 1 (25) 0.667 \nCesarean Section  13 (20) 4 (19) 4 (17.4) 2 (14.3) 1 (25) 1.000 \ns/p Ovarian Cystectomy    10 (15.1) 3 (14.3) 5 (21.7) 0 (0) 1 (25) 0.175 \ns/p Laparoscopy  11 (16.7) 4 (19.0) 4 (17.4) 3 (20) 0 (0) 1.000 \ns/p Laparotomy   12 (18.2) 5 (23.8) 5 (21.7) 0 (0) 2 (50) 0.059 \nCurrent management  \nInfertility 32 (48.5) 12 (57.1) 11 (47.8) 8 (53.3) 0 (0) 0.241 \nPre-Op Image: Normal   7 (10.6) 4 (19) 2 (8.7) 1 (6.7) 0 (0) 0.708 \nPre-Op Image: Ovarian \nendometrioma   \n30 (45.4) 10 (47.6) 13 (56.5) 6 (40) 0 (0) 0.223 \nLaparoscopy      58 (87.9) 17 (81) 21 (91.3) 15 (100) 3 (75) 0.172 \nHysteroscopy    56 (84.9) 19 (90.5) 17 (73.9) 14 (93.3) 4 (100) 0.352 \nCystoscopy                  31 (47) 11 (52.4) 10 (43.5) 7 (46.7) 2 (50 0.979 \nOvarian Cystectomy 31 (47) 10 (38.1) 13 (56.5) 7 (46.7) 2 (50) 0.689 \nPelvic Endometriosis  31 (47) 9 (42.9) 13 (56.5) 6 (40) 1 (25) 0.608 \nBSE = Bladder Serosa Endometriosis  \nDME = Detrusor Muscle Endometriosis  \nBME = Bladder Mucosa Endometriosis \nTable 3. The association of Bladder wall endometriosis histopathological diagnosis to menstruation and pain status, past health problems and \noperations and current management  \n \n\nJ. Obstetrics Gynecology and Reproductive Sciences                                                                                                                                     Copy rights@ Vasilios Tanos et.al. \n \n \nAuctores Publishing LLC – Volume 6(2)-102 www.auctoresonline.org  \nISSN: 2578-8965   Page 5 of 9 \nStudy design \nSurgical Management  \nAll patients underwent laparoscopy and were diagnosed with an \nendometriotic lesion on the bladder serosa mainly o n the anterior and \nfundal walls. Since the nodule develops from the outer layer of the bladder \nwall towards the detrusor muscle inner layer, local excision was \nperformed until free from endometriosis margins were visually \nconfirmed. In excisions that invol ved only the bladder serosa, a single \nlayer wound closure was performed, while for interstitial excisions, the \nwound was closed in 2 layers, using 2.0 and / or 3.0 PDS sutures. The \nbladder serosa integrity was then examined by infusing into the bladder \n300 ml of normal saline stained with methylene blue dye. The serosa part \nof the specimen was designated by placing a suture, assisting \nhistopathologist orientation. Cystoscopy was performed in 15 cases and \n11 cases underwent ureteric stenting.  \nHistopathology  \nThe histopathological reported findings were reviewed prior to the study \nto reassure the bladder wall depth of involvement. An experienced \nhistopathologist on endometriosis was asked to review all the patients’ \nhistopathological results. The operation an d tissue macroscopic \ndescription reports before processing were also reviewed. Attention was \npaid for possible discrepancies or missed important data that could \ninfluence the histopathological results. Light microscopy using x40 x100 \nmagnification was performed on all the patients’ sections slides. In cases \nwhere results were equivocal, the paraffin blocks were available for \nadditional sections for reassuring the diagnosis. An extra effort was made \nto meticulously observe and identify the involvement of the  bladder \nserosa, muscularis and mucosa with endometriotic cells and glands. \nStatistical analysis \nDemographic, reproductive and medical history variables were compared \nbetween women with different bladder wall endometriosis and \nadenomyosis involvement using  univariate tests. Bladder endometriosis \nwas investigated according to depth of BWE involvement and according \nto four histopathological localizations of endometriosis  \n(Serosa [BSE]  \nDetrusor muscle [DME])  \n(Serosa [BSE] vs. Detrusor muscle [DME]  \nMucosa [BME] & Detrusor muscle [DME]).  \nFor categorical variables, the Pearson chi -square or the Fisher’s exact \ntests were used, the latter being reserved for comparisons with small \nsample numbers. For continuous non -normally distributed variables, the \nKruskal-Wallis test was used. The statistical significance threshold was \nset at 0.05. Statistically significant associations with depth of BWE \ninvolvement were also tested with univariate logistic regression analysis. \nAll statistical analyses were performed using STA TA version 15 SE \n(StataCorp. 2017. Stata Statistical Software: Release 15. College Station, \nTX: StataCorp LLC). \nEthical approval:  The study was examined and approved by the \ninternal Bioethics committee of the OMAM Hospital, Cairo.   \nResults:  \nAmong 66 pati ents diagnosed with bladder biopsy confirmed \nendometriosis, in 21 cases, endometriosis was isolated on the bladder \nserosa (BSE) and in 45 cases endometriosis was found within the detrusor \nmuscle (DME) (Tables I&II). The frequency of bladder endometriosis \n(BE) involvement according to histological findings on bladder serosa \nand detrusor muscle, was investigated in association with age, gravidity, \nparity, number of abortions, ectopic pregnancies, normal deliveries and \ncaesarean sections, as demonstrated in Ta ble I. The frequencies of BSE \nand DME in association to menstruation, pain status, past medical and \nsurgical history, management and endometriosis spread within the \nabdominal cavity are presented in Table II.  \nThe average patients’ age recorded for BSE was  31 years and for DME \n33 years. No significance was found between the patients’ age in both \ngroups. No significance was found among the two groups for gravidity, \nparity, vaginal and caesarean section mode of delivery (Table I). BSE was \nsignificantly more p rominent among patients with history of ectopic \npregnancy (p=0.004) (Table I) and among patients with secondary \ninfertility (p=0.029) (Table II). DME was significantly more frequent \n(p=0.012) in patients with increasing number of abortions (Table I).  \nNo s ignificance was found between serosa and detrusor muscle \nendometriosis involvement, when compared to severity and spread of \nendometriosis within the abdominal cavity (Table II).   \nMicturition problems were reported by 5 (7.6%) patients, urinary tract \ninfection was diagnosed in 9 (13.8%) patients and vaginitis in 8 (12.1%) \nout of the 66 patients.  Looking at the four histopathological BWE \nlocalisation categories, among 5 patients with micturition problems, \nendometriosis was diagnosed in 1 patient in each 4 histological locations, \ni.e serosa, serosa + DM, DM + mucosa and mucosa. In 8 patients with \nvaginitis, BE was mostly detected in the bladder serosa and non in mucosa \nand DM (Table III).  \nSeven patients reported a past-operations history of appendicectomy and \n13 had caesarean sections, BE was mostly detected in BW and serosa. Ten \npatients had ovarian endometrioma surgery, 11 patients had laparoscopic \nsurgery and 12 patients had laparotomies for various health issues, and \nBE was mostly detected in bladder sero sa and DM. None of the past \nsurgeries reported were found to have any statistically significant \ncorrelation with the BWE subgroups diagnosis (Table II).    \nSince all patients with BE were stage IV according to ASRM \nendometriosis classification. In order to be able to fulfil the scope of our \nstudy, the severity of endometriosis within the abdominal cavity was \ndefined as mild when 20 cases presented only multiple foci of \nendometriosis in the pelvis, moderate when in 25 patients endometrioma \nwas present and se vere when 21 patients had deep infiltrating nodule/s. \nPearson x 2 test and Kruskal Wallis test used to compare each variable \nmild, moderate and severe endometriosis between BE histological \nlocations did not reach any significance (Table II). Although missin g of \nany significance, the statistical model showed a higher risk of DME when \nsevere endometriosis was reported in the abdominal cavity.     \nIn association with the four categories, the frequency of menstrual \nabnormalities and pain, including abdominal pai n dysmenorrhoea, \ndyspareunia and dysuria were associated with DME involvement, without \nany significance. However, back pain was most prominent and \nsignificance (p=0.007) in 8 patients with BSE + DME as compared to \nBSE found in the serosa of 4 patients; in DME of 3 patients and BME + \nDME of 3 patients. (Table III). An association between the BWE and \npatients’ past history of health problems and operations, as well as current \nmanagement findings and operative approach, did not show any \nsignificance among the endometriosis histological locations across the \nBW as defined above.   \nThe highest incidence of BE was detected in the DM in 9 patients with \nprimary (I) infertility and in the bladder serosa of 7 patients with \nsecondary (II) infertility (Table III). No significance was noted among the \nI and II infertility patients and the histological locations of endometriosis \non the serosa, DM and mucosa. Among patients with urinary tract \ninfection (UTI), endometriosis was mostly diagnosed with significance (p \n= 0.011), i n patients with endometriosis on the serosa and DM as \n\nJ. Obstetrics Gynecology and Reproductive Sciences                                                                                                                                     Copy rights@ Vasilios Tanos et.al. \n \n \nAuctores Publishing LLC – Volume 6(2)-102 www.auctoresonline.org  \nISSN: 2578-8965   Page 6 of 9 \ncompared to women with endometriosis throughout the BW (serosa, DM \nand mucosa). No UTI was reported among patients with DME alone \n(Table III).  \nPrimary infertility was the indication for the current lap aroscopic \nsurgeries in 32 out of 66 (48.5%) patients and secondary infertility for the \nrest of the group. The highest incidence of BE was detected on the serosa \nof 12 patients and in the DM of 11 cases. Preoperative uterine imaging by \nTVU revealed that in 7 cases with benign pathologies like fibroids and / \nor polyps, there was no correlation to any BE histological locations either. \nAmong 30 cases with an ovarian endometrioma detected by TVU, DME \nwas diagnosed in 13 patients, in serosa of 10, and in serosa a nd DM of 6 \npatients.          \nA group of 8 patients converted from laparoscopy to laparotomy. In 58 \npatients that underwent laparoscopic surgery DME was evident in 21 \ncases, in BSE in 17 women, BSE and DME in 15 women and BME and \nDME in 3 patients. However , no significance was found among the BE \nhistological locations and laparoscopic surgeries. Pelvic and abdominal \nendometriosis, stripping of endometrioma and cystoscopy were \ndiagnosed and performed in 31 (47%) patients and BSE and DME was \ndiagnosed in 38 – 56.5% of the cases without any significance. Among \n56 patients who underwent hysteroscopy, BSE was detected in 21 cases, \nin DME in 23 cases, in BSE+DME in 15 and BME+DME in 4 cases, \nhowever without reaching any significance (Table III).  \nUnivariate logist ic regression analysis of endometriosis on the bladder \nserosa and DM associated to menstruation, pain status, past medical and \nsurgical history, management and endometriosis spread within the \nabdominal cavity. No significance were found among patients’ age  and \nobstetrical history when univariate logistic regression analysis was \nperformed, comparing BSE and DME. BSE of 33.3% was significantly \nmore prevalent (p=0.036), among patients with secondary infertility as \ncompared to DME involvement 11.1%. No significance between BSE and \nDME were detected for the rest of the 27 parameters underwent regression \nanalysis.  \nDiscussion  \nIn this cohort study we tried to identify if histopathological locations of \nBWE were associated with patients’ age, obstetrical, medical an d \noperation history, clinical characteristics, management and spread of \nendometriosis within the abdominal cavity. Among the 66 patients with \nBE, histological sections diagnosed endometriosis in only 4 cases on the \nbladder mucosa 6%, in 21 cases on the serosa 32%, and in 45 cases within \nthe DM 64%. Many sections (19/66) 29% presented endometriosis in \nmore than one layer of the BW. The high incidence of 68.2% of DM \nendometriosis involvement, agrees with earlier studies which presented \nsimilar results (Leone Roberti Maggiore et al., 2017). The fact that no \nsignificance was found between BSE and DME involvement, when \ncompared to severity and spread of endometriosis within the abdominal \ncavity, complies with the current experience of symptoms variability and \nabdominal endometriosis severity (Table II). Although without any \nstatistical significance, the higher risk of DME when severe \nendometriosis was reported in the abdominal cavity draws the attention \nfor meticulous intraoperative BWE investigation. The statisti cally \nsignificant more frequent DME in patients with increasing number of \nabortions (p=0.012) seems to mimic the development of adenomyosis \nwithin the myometrium. The anatomical proximity of the bladder and \nuterus allows for the increased risk of trauma du ring the uterine \nintracavitary interventions and subsequently increased risk of developing \nDME, i.e. bladder wall adenomyosis. Circumstantial evidence suggests \nthat microtraumatizations allow for the activation of the ‘tissue injury and \nrepair’ mechanism w hich stimulates local estrogen production. \nConsequently, leading to permanent  hyperperistalsis and self -\nperpetuation of the disease process. (Leyendecker G. et.al., 2009) \nAbdominal and back pain  \nThere are higher rates of pain, infertility, micturition problems, past \noperations and severity of endometriosis findings within the abdominal \ncavity in patients with DME, as compared to those with BSE. Despite the \nfindings lacking significance, this supports previous literature findings \nand reassures the study’s results (Leone Roberti Maggiore et al., 2017).  \nIndeed, back pain was most prominent (p=0.007) in 8 patients with BSE \n+ DME as compared t o endometriosis in the other histopathological \nlocations of BWE; denoting the importance of BWE involvement within \nthe serosa and DM and might be considered as a significant pre-operative \nsymptom. This can be attributed to the neuroanatomy of the pelvis. D e \nSousa et al. demonstrated the spread of endometriosis from the uterine \ncavity along the autonomic nerves in the pelvis into the lumbosacral \nplexus [28]. Further spread of th e endometriotic lesions into the spinal \nnerves and even the dura of the spinal cord was proposed to be a possible \naetiology of DIE [1,28].  \nThe backpain symptom may direct patients to 3D ultrasound (US) and \nmagnetic resonance imaging (MRI) focusing on BWE diagnosis. It has \nbeen suggested that 3D US acquisition may improve endometriotic \nnodule localisation and evaluation of its size, volume, and infiltration of \nthe bladder wall in comparison to two -dimensional transvaginal \nultrasound (TVS) (Thonnon et al., 2015). TVS is the most accurate in \ndefining the size of the lesions, infiltration of the DM, and continuity with \nextravesical lesions (Fedele et al., 1997). Also reports  high accuracy, \nreproducibility and specificity but fair sensitivity in the diagnosis of BE \n(Tammaa  et al., 2015). BWE in TVS appears as a filling defect of the \nposterior wall with iso/hypoechoic protrusions into the lumen, usually not \nvascularised (Leone Roberti Maggiore et al., 2017).  \nLower urinary tract symptoms   \nThe higher rates of UTI (p=0.011) in patients with BSE+DME reflects the \nurinary bladder dysfunction due to BWE and to  chronic inflammation \ncaused by endometriosis. Dysuria has been reported in 21 –69% of \npatients with BWE. Bladder pain and frequency and less commonly \nhaematuria, urgency, and urinary incontinence are symptoms associated \nwith the presence of BWE (Villa et al., 2007;,Leone Roberti Maggiore  et \nal., 2015). Haematuria was reported in only 2 women out of the 66 \npatients. Patients experiencing urgency and/or urinary frequency, dysuria \nprovoked during bladder filling, raises the suspicion of a DME.  \nIn general, DIE is associated with lower urinary tract symptoms and the \nincidence ranges between 2% and 77% (Bonneau et al., 2013;,Ballester  \net al., 2014). Endometriosis and interstitial cystitis have been associated \nwith recurrent cystitis and overactive bladder and s ymptoms of chronic \nbladder and pelvic pain or discomfort, and may be accompanied with \npersistent urge to void or frequency in the absence of any identifiable \npathology or infection (van de Merwe et al., 2008;,Hanno  et al., 2010). \nUnivariate logistic regre ssion analysis did not show any significant \ncorrelation between DME and UTI micturition problems or vaginitis. A \nrecent study reported no difference in the rate of urgency, urinary \nfrequency, voiding symptoms and bladder pain between patient with \nposterior endometriosis plus BE compared with those with posterior \nendometriosis only (Panel et al ., 2016). Women of reproductive age \ncomplaining of lower urinary tract symptoms, particularly in combination \nwith dysmenorrhoea, back pain and/or anterior sensitivity during vaginal \nexamination, should be always considered as high risk for BWE. 2/3D \nTVS and MRI should follow although absence of endometriotic nodules \nin imaging cannot exclude BWE, hence, laparoscopy and eventually \ncystoscopy are necessary for final diagnosis and treatment.     \nCystoscopy  \nIn 15 out of 66 cases, cystoscopy was performed to rule out endometriotic \nlesions on the bladder mucosa. Four cases advancing from the bladder \n\nJ. Obstetrics Gynecology and Reproductive Sciences                                                                                                                                     Copy rights@ Vasilios Tanos et.al. \n \n \nAuctores Publishing LLC – Volume 6(2)-102 www.auctoresonline.org  \nISSN: 2578-8965   Page 7 of 9 \nserosa towards the DM and appearing on the mucosa were diagnosed. \nTypical red or bluish nodules have been observed but not any ulcerations, \nwhich comes into agreement with other studies (Thonnon et al ., \n2015;,Fedele et al., 1997). Cystoscopy has limited value for screening or \nroutine purposes in women with endometriosis and should be reserved for \nthose cases at high risk for BME. Identifying the endometriotic lesion \nposition, especially those close to the trigonum and ureteral ostia, \ninadvertent trauma can be avoided during surgery. Cystoscopy is \nmandatory in cases with suspicion of  malignancy, excluding bladder \ncarcinoma, varices, papillomas, angiomas, and detrusor mesenchymal \ntumours (Leone Roberti Maggiore et al., 2017).  \nInfertility \nThe highest incidence of BE involving only the serosa in 21 patients and \nonly the DM of 23 cases f ollows the results of other studies that BWE \npresents a severe form of endometriosis with bad prognosis for fertility \npotential [(Vercellini et al ., 2014a;,Vercellini et al ., 2014b)]. Logistic \nregression analysis as presented in the results, demonstrated t hat BSE \n33.3% was significantly more prevalent (p=0.036) among patients with \nsecondary infertility, as compared to DME involvement of 11.1%; this \nprobably reflects a partial protection by prior pregnancy, but not complete \nimmunity of the disease. Although current research suggests no evidence \non pregnancy reducing the size or number of endometriotic lesions, it \nmight be worth questioning the conclusions of these few studies of very \nlimited quality.  \nBrigitte Leeners, Fabia Damaso, Nicole Ochsenbein -Kölble, Cindy \nFarquhar, The effect of pregnancy on endometriosis —facts or \nfiction?, Human Reproduction Update, Volume 24, Issue 3, May -June \n2018, Pages 290–299, https://doi.org/10.1093/humupd/dmy004  \nWithin the context that adenomyosis may interfere with fertility, similarly \nwomen with BE may probably, at least partly, contribute to uterine \ndysfunction. However, in most series published, no adenomyotic nodules \nof the uterine wall were found in association with B E [Leone Roberti \nMaggiore U, et al. 2017]. Interestingly, 11 cases of male endometriosis \nreported in the literature, four developed endometriosis of the bladder \nconcomitant with high estrogen exposure, probably indicating a similar \nsusceptibility between t he detrusor muscle and myometrium [Leone \nRoberti Maggiore U, et al. 2017].   The fact that BSE was statistically \nsignificant among patients with secondary infertility and history of \nectopic pregnancy, reflects the consequences of endometriosis and \nformation of intrabdominal adhesions due to chronic inflammation.  \nAssociation with surgical procedures \nAlthough the big majority of the patients 53/66 (80.3%) had a history of \nabdominal operations, no significance was found of BWE and \nhistological subgroups, amon g these patients, neither of the 13 cases \nunderwent caesarean sections and the 10 cases after ovarian \nendometrioma surgery. In 46 out of 66 patients, 70% who had the bladder \nwall affected by endometriosis, underwent a gynaecological surgical \nprocedure prior to diagnosis of BE, raising the possibility of iatrogenic \ndissemination of endometriotic cells. However, a recent cross -sectional \nincidence of isolated BE, reported patients with and without a history of \nuterine surgery 37.5% and 41.7% respectively witho ut any significance \n(p = 0.6) (Leone Roberti Maggiore et al., 2017). Among BWE cases, the \nincidence observed was 58.6% (95% confidence interval [CI] 45.2–71.2) \nfor superficial peritoneal implants, 44.8% (95% CI 32.2–58.2) for ovarian \nendometriomas, 81.0% ( 95% CI 68.4 –89.6) for adhesions, and 27.6% \n(95% CI 16.7 -40.8). Hormonal treatments are effective for a temporal \ndisease suppression but not curing. Significant improvements in pain and \nurinary symptoms have been observed after excision of the whole bladder \nlesion, which also minimises the risk of recurrence [Soriano  et al., \n2016;,Seracchioli et al., 2010;,Chapron et al., 2010)].  \nSurgical Management  \nIn our study 45 cases underwent a full thickness bladder wall segmental \nexcision due to severity of the disease.  \nIn another 21 cases, BSE was diagnosed after wedge resection of the \nlesion and confirmation of clear margins from the disease. Several studies \nhave shown that segmental cystectomy is an effective technique with \nexcellent long -term results in terms of  symptom relief and recurrence \n[(Chapron et al., 2010;,Kjer et al., 2014)]. Excision of endometriotic \nnodules of the bladder may lead to inadvertent removal of healthy bladder \nmuscle, particularly in case of large endometriotic lesions. Postoperative \ncomplications and symptoms are mainly due to small bladder volume. An \neffort to spare most of the healthy bladder tissue is imperative. [(Fedele \net al., 2005;,Vercellini et al., 2009;,Antonelli  et al., 2006)]. Preventive \nureteric catheterisation was performed in 11 cases due to lesion proximity \nto trigonum. Ureters stenting can be of great help when surgery is \nperformed on the posterior bladder wall and endometriotic nodules are \nclose to the ureteral meatuses [(Vercellini et al., 1998)].  \nSurgery for BE usually  accompanies treatment for adhesions, \nendometriomas, superficial implants, and other deep localisations of the \ndisease (Somigliana et al ., 2007). Deep peritoneal endometriosis is \nassociated with adenomyosis and according to our study there is a higher \nrisk of DME in relation to severity of the peritoneal endometriosis; \nalthough there was no significance. [(Kunz et al., 2005;,Exacoustos et al., \n2013)]. Occasionally bladder lesions are buried under adhesions while \nchronic inflammation and extended fibrosis pr esent an operative \nchallenge. In a study by Kovoor et al 50% of infertile women with BWE \nconceived naturally after an intervention [(Wells et al ., 2014)]. The \nsurgery radicality of DIE and BWE for infertility treatment remains \ndebatable (Somigliana & Garcia-Velasco, 2015b).  \nStudy limitations  \nThis is a cohort retrospective study. There is a possibility that other areas \nwith endometriosis were also involved in the BW other than those \ndiagnosed and treated. The mixture of patients with any type of infertility, \nprimary and secondary infertility and history of past abdominal operations \ncould also affect the results, although statistical analysis did not show any \nsignificance in BWE, clinical symptoms and surgical findings. BE is \nrarely an isolated condition, an d other forms of endometriosis are \nfrequently concomitant (Vigano et al., 2009).   \nConclusions \nDME involvement presented 68% and BSE 32 of all cases with BE and \ninfertility investigated. S econdary infertility, back pains, micturition \nproblems and number of abortions can be considered as high-risk factors \nfor BE for women of reproductive age. The severity of the peritoneal \nendometriosis can probably direct to meticulous intraoperative \ninvestigation for BE.    \nAuthor’s roles \nDr Sayed El -Akhras: Performed all of the operations and collected the \nclinical and surgery data  \nMohamed Abo-elenen: Involved in patients’ data collection, review all \npatients’ files, collection of data and formation of the excel file  \nChristiana Demetriou: Statistical analysis, editing th e results, review the \narticle   \nNafissa Mohamed Amin El Badawy: Performed and review all patients’ \nhistopathology results, writing and review section of histopathology in \nmethods    \nSafinez Balami: review and editing of the article  \n\nJ. Obstetrics Gynecology and Reproductive Sciences                                                                                                                                     Copy rights@ Vasilios Tanos et.al. \n \n \nAuctores Publishing LLC – Volume 6(2)-102 www.auctoresonline.org  \nISSN: 2578-8965   Page 8 of 9 \nVasilios Tanos : Involve d in the operations, study concept and design, \nreview of patients’ data collection and preparation of the excel file, review \nof statistics and formation of tables, writing the manuscript and editing  \nFunding: No funding  \nConflict of interest: There is no conflict of interest for none of the \nauthors  \nReferences  \n1. Abrao MS, Dias Jr JA, Bellelis P, Podgaec S, Bautzer CR, \nGromatsky C. (2009) Endometriosis of the ureter and bladder \nare not associated diseases. Fertil Steril ; 91: 1662–7. \n2. Antonelli A, Simeone C, Zani D,  Sacconi T, Minini G, Canossi \nE, Cunico SC. (2006) Clinical aspects and surgical treatment of \nurinary tract endometriosis: our ex perience with 31 cases. Eur \nUrol; 49 :1093–7. \n3. Ballester M, Dubernard G, Wafo E, Bellon L, Amarenco G, \nBelghiti J, Daraï E. (2014) Evaluation of urinary dysfunction by \nurodynamic tests, electromyogra phy and quality of life \nquestionnaire before and after surgery for deep infiltrating \nendometriosis. Eur J Obstet Gynecol Reprod Biol; 179 \n4. Bonneau C, Zilberman S, Ballester M,  Thomin A, Thomassin-\nNaggara I, Bazot M, Daraï E. (2013) Incidence of pre - and \npostoperative urinary dysfunction associated with deep \ninfiltrating endometriosis: relevance of urodynamic tests and \ntherapeutic implications. Minerva Ginecol; 65: 385–405. \n5. Chapron C, Bourret A, Chopin N,  Dousset B, Leconte M, \nAmsellem-Ouazana D, de Ziegler D, Borghese B. (2010) \nSurgery for bladder endometriosis: long -term results and \nconcomitant management of associated posterior deep lesions.  \nHum Reprod; 25 :884–9. \n6. Exacoustos C, Luciano D, Corbett B,  De Felice G, Di \nFeliciantonio M, Luciano A, Zupi E. (2013) The uterine \njunctional zone: a 3 -dimensional ultrasound study of patients \nwith endometriosis. Am J Obstet Gynecol; 209 :248.e1-7. \n7. Fedele L, Bianchi S, Zanconato G, Bergamini V, Berlanda N, \nCarmignani L. (2005) Long -term follow-up after conservative \nsurgery for bladder endometriosis. Fertil Steril; 83 :1729–33. \n8. Fedele L, Bianchi S, Raffaelli R, Portuese A. (1997) Pre -\noperative assessment of bladder endometriosis. Hum Reprod; \n12 :2519–22. \n9. Gabriel B, Nassif J, Trompoukis P, Barata S, Wattiez A. \nPrevalence and management of urinary tract endometriosis: a \nclinical case series. Urology 2011; 78 :1269–74. \n10. Hanno P, Lin A, Nordling J,  Nyberg L, van Ophoven A, Ueda \nT, Wein A. (2010) Bladder Pain Syndrome Committee of the \nInternational Consultation on Incontinence. Neurourol Urodyn; \n29: 191–8. \n11. Kjer JJ, Kristensen J, Hartwell D, Jensen MA. (2014 ). Full-\nthickness endometriosis of the bladder: report of 31 cases. Eur \nJ Obstet Gynecol Reprod Biol  176 :31–3. \n12. Knabben L, Imboden S, Fellmann B, Nirgianakis K, Kuhn A, \nMueller MD. (2015 ). Urinary tract endometriosis in patients \nwith deep infiltrating endometriosis: prevalence, symptoms, \nmanagement, and proposal for a new clinical classification . \nFertil Steril 103 :147–52. \n13. Kunz G, Beil D, Huppert P, Noe M, Kissler S, Leyendecker G. \nAdenomyosis in endometriosis —prevalence and impact on \nfertility. Evidence from magnetic reso nance imaging. Hum \nReprod 2005; 20 :2309–16. \n14. Leone Roberti Maggiore U, Ferrero S, Candiani M, Somigliana \nE, Vigano P, Vercellini P. (2017 ). Bladder Endometriosis: A \nSystematic Review of Pathogenesis , Diagnosis, Treatment, \nImpact on Fertility, and Risk of Malignant Transformation. \nEuro Urol 2017; 71 :790 – 807. \n15. Leone Roberti Maggiore U, Ferrero S, Mangili G,  Bergamini \nA, Inversetti A, Giorgione V, Viganò P, Candiani M. (2016).A \nsystematic review on endometriosis during pregnancy: \ndiagnosis, misdiagnosis, complications and outcomes. \nHumReprod Update 22 :70–103. \n16. Leone Roberti Maggiore U, Ferrero S, Salvatore S. \n(2015).Urinary incontinence and bladder endometriosis: \nconservative management. Int Urogynecol . 26: 159–62. \n17. Meuleman C, Tomassetti C, D’Hoore A, V an Cleynenbreugel \nB, Penninckx F,  Vergote I,  D'Hooghe T.  (2011). Surgical \ntreatment of deeply infiltrating endometriosis with colorectal \ninvolvement. Hum Reprod Update . 17: 311–26. \n18. Panel P, Huchon C, Estrade -Huchon S, Le Tohic A, Fritel X, \nFauconnierA. (2016 ). Bladder symptoms and urodynamic \nobservations of patients with endometriosis confirmed by \nlaparoscopy. Int Urogynecol J 2016; 27: 445–51. \n19. Seracchioli R, Mabrouk M, Montanari G, Manuzzi L, Concetti \nS, Venturoli S. Conservative laparoscopic management of \nurinary tract endometriosis (UTE): surgical outcome and long-\nterm follow- up. Fertil Steril 2010; 94 :856–61. \n20. Somigliana E, Benaglia L, Paffoni A, Busnelli A, Vigano P, \nVercellini P. (2015 ). Risks of conservative mana gement in \nwomen with ovarian endometriomas undergoing IVF. Hum \nReprod Update  21: 486–99. \n21. Somigliana E, Garcia -Velasco JA. (2015 ). Treatment of \ninfertility associated with deep endometriosis: defini tion of \ntherapeutic balances. Fertil Steril; 104: 764–70. \n22. Somigliana E, Vercellini P, Gattei U, Chopin N, Chiodo I, \nChapron C. (2007 ). Bladder endometriosis: getting closer and \ncloser to the unifying metastatic hypothesis. Fertil Steril; 87: \n1287–90. \n23. Soriano D, Bouaziz J, Elizur S,  Zolti M, Orvieto R, Seidman \nD, Goldenberg M, Eisenberg VH. (2016). Reproductive \noutcome is fa vorable after laparoscopic resection of bladder \nendometriosis. J Minim Invasive Gynecol  23: 781–6. \n24. Tammaa A, Fritzer N, Lozano P,  Krell A, Salzer H, Salama M, \nHudelist G. (2015). Interobserver agr eement and accuracy of \nnon-invasive diagnosis of endometriosis by transvaginal \nsonography. Ultrasound Obstet Gynecol 2015; 46 :737–40. \n25. Thonnon C, Philip CA, Fassi -Fehri H, Bisch C, Coulon A, de \nSaint-Hilaire P, Dubernard G. (2015).Three -dimensional \nultrasound in the management of bladder endometriosis. J \nMinim Invasive Gynecol; 22 :403–9. \n26. van de Merwe JP, Nordling J, Bouchelouche P,  Bouchelouche \nK, Cervigni M,  Daha LK,  Elneil S,  Fall M,  Hohlbrugger \nG, Irwin P et al. (2008 ).Diagnostic criteria, classification, and \nnomenclature for painful bladder syndrome/ interstitial cystitis: \nan ESSIC proposal. Eur Urol 2008; 53 :60–7. \n27. Vercellini P, Consonni D, Barbara G, Buggio  L, Frattaruolo \nMP, Somigliana E. (2014 ). Adenomyosis and reproductive \nperformance after surgery for rectovaginal and colorectal \nendometriosis: a systematic review and meta -analysis. Reprod \nBiomed Online a; 28 :704–13. \n28. Vercellini P, Consonni D, Dridi D, Bracco B, Frattaruolo MP, \nSomigliana E. (2014 ). Uterine adenomyosis and in vitro \nfertilization outcome: a systematic review and meta -analysis. \nHum Reprod 2014b; 29 :964–77. \n29. Vercellini P, Somigliana E, Vigano P, Abbiati A, Barbara G, \nCrosignani PG. (2009 ). Surgery for endometriosis -associated \ninfertility: a pragmatic approach. Hum Reprod; 24 :254–69. \n\nJ. Obstetrics Gynecology and Reproductive Sciences                                                                                                                                     Copy rights@ Vasilios Tanos et.al. \n \n \nAuctores Publishing LLC – Volume 6(2)-102 www.auctoresonline.org  \nISSN: 2578-8965   Page 9 of 9 \n30. Vercellini P, Frontino G, Pisacreta A, De Giorgi O, Cattaneo \nM, Crosignani PG. (2002).The pathogenesis of bladder detrusor \nendometriosis. Am J Obstet Gynecol; 187 :538–42. \n31. Vercellini P, Pisacreta A, De Giorgi O, Yaylayan L, Zaina B, \nCrosignani PG. Management of advanced endometriosis. In: \nKempers RD, Cohen J, Haney AF, Younger JB, editors. (1998). \nFertility and reproductive medicine. Amsterdam: Elsevier \nScience; (city and country published  p. 369–86. \n32. Vigano` P, Somigliana E, Gentilini D, Benaglia L, Vercellini P. \nBack to the original question in endometriosis: implantation or \nmetaplasia? J Endometriosis 2009; 1: 1–8. \n33. Villa G, Mabrouk M, Guerrini M,  Mignemi G,  Montanari \nG, Fabbri E, Venturoli S, (2007).Relationship between site and \nsize of bladder endometriotic nodules and severity of dysuria. J \nMinim Invasive Gynecol  14: 628–32. \n34. Wells G, Shea B, O’Connell D,  Peterson J, Welch V, Losos M, \nTugwell P. (2014 ).The Newcastle -Ottawa Sca le (NOS) for \nassessing the quality of nonrandomised studies in meta -\nanalyses. Ottowa, ON: Ottowa Hospital Research Institute;  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n This work is licensed under Creative    \n   Commons Attribution 4.0 License \n \n \nTo Submit Your Article Click Here: Submit Manuscript \n \nDOI: 10.31579/2578-8965/102\n \nReady to submit your research? 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