{"paper_id":"586be795-d4b6-4750-a5a2-d855f613d2f5","body_text":"Archives of Women Health and Care\nVolume 4 Issue 1\nResearch Open\nARCH Women Health Care, Volume 4(1): 1–5, 2021 \nIntroduction\nEM is one of the most common gynecological diseases and affects \napproximately 10% of women of a reproductive age [1,2]. It is defined \nas the presence of endometrial and/or stromal cells outside the uterine \ncavity and is most likely to be found disseminated on the peritoneum \nof the pelvic cavity like in the pouch of Douglas, on the sacrouterine \nligaments, in the ovaries and the ovarian fossae [3-5]. Typical \nsymptoms are dysmenorrhea, cyclical and acyclical pelvic pain, and \ninfertility [6]. As the intensity of symptoms does not correlate with \nextending of infestation it often takes several years until the diagnosis \nis made [7-9]. Today’s gold standard to detect peritoneal EM is by \nlaparoscopy [10-12]. But within this technique small EM lesions may \nbe overlooked.\nAs the pathogenesis of EM has not been clarified and probably \ncannot be described by only one theory, we were wondering which \npart of the OME lesions take it in. We chose to concentrate on the \nimpact of the peritoneal fluid, which is known to have several spaces \nin the peritoneal cavity where it is more present. One of these spaces \nis the right paracolic gutter, which is why we decided to examine \nthe difference between the right and left paracolic gutters for the \noccurrence of OME [13,14]. OME was first described in 1986 by \nResearch Article\nCharacterisation of Microscopic Changes in \nMacroscopically Unaffected Peritoneum in Women \nwith and without Endometriosis\nMira Luhmann, Vito Chiantera, Jalid Sehouli and Sylvia Mechsner*\nEndometriosis Centre Charité, Department of Gynaecology, Charité, Campus Virchow Clinic, Berlin, Germany\n*Corresponding author: Sylvia Mechsner, Endometriosis Centre Charité, Department of Gynaecology, Charité, Campus Virchow Clinic, Berlin, Germany\nReceived: February 23, 2021; Accepted: March 03, 2021; Published: March 29, 2021\nMurphy et al. [15]. It is defined by the presence of endometriosis \nin macroscopically normal-looking tissue. Even though there have \nbeen further studies, the meaning of OME is still unclear. Firstly, it \ncould have an important status in the pathogenesis of endometriosis. \nSecondly, it could also be a physiological phenomenon with no \ndisease value. To find out more about the clinical relevance of OME \nwe histologically examined tissue specimens derived from visually \nnormal peritoneum of the paracolic gutters of women with and \nwithout EM to detect the possible occurrence of OME. Due to the fact, \nthat endometriotic lesions are associated with the local inflammatory \nresponse we also investigated the occurrence of IC and angiogenesis \nin this tissue.\nMaterials and Methods\nSubjects\nDuring the period between 2013 and 2016, peritoneal biopsy \nsamples from 64 women with visible endometriosis and 22 women \nwithout visible endometriosis were collected during laparoscopy. The \ninstitute of pathology made the diagnostic assurance by histological \nexamination. The most common reason for the operations in women \nwith EM was EM resection. For women without EM, it was resection of \nfibroids. With the knowledge of the influence the peritoneal fluid has \nAbstract\nStudy question: Is there a difference in the occurrence of occult microscopic endometriotic lesions in normal peritoneum between women with and \nwithout endometriosis and if so are there other differences in the structure of the peritoneum between these groups?\nIntroduction: Occult Microscopically Endometriosis (OME) was firstly described by Murphy et al. in 1986. Since then there has been more research \non the topic but without finding any conclusions about the clinical significance. Therefore, OME could be a physiological phenomenon that occurs in \nwomen with and without endometriosis (EM) or it could also be an early stage of real EM lesions.\nMethods: For this study, we surgically removed the macroscopically unaffected peritoenum from the left and/or right paracolic gutter from 64 \nwomen with and 22 women without EM. The tissue was then immunohistochemically stained with antibodies of an Estrogen Receptor Alpha (ERa), a \nProgesterone Receptor (PR), Cytokeratin, CD10, and Anti-Smooth Muscle Cell Actin (ASMA).\nResults: OME lesions were found in five of the 86 patients (5, 81%). One of these lesions was found in a woman without EM which is 4, 5% of the control \ngroup. In the group of women with EM, there were four patients with OME lesions which is 6, 3% of the cohort, so there was no statistically significant \ndifference between these groups. Besides the OME lesions, there were immune cells found in the tissue of 12 women with EM (18, 8% of the EM cohort) \nbut none in the control group. These findings did not correlate with the OME lesions.\n\nARCH Women Health Care, Volume 4(1): 2–5, 2021 \nSylvia Mechsner (2021) Characterisation of Microscopic Changes in Macroscopically Unaffected Peritoneum in Women with and without \nEndometriosis\non the distribution of EM lesions, we chose to collect tissue from the \nright and left paracolic gutters. The goal was to see if the distribution \nof OME lesions is also influenced by it. All biopsy specimens were \ncollected in accordance with the patients and were approved by the \nguidelines of the ethics committee. In Table 1 you can find the clinical \nprofiles of the two groups.\nWith EM n (%) Without EM n (%)\nNumber 64 22\nAge Mean Range 29,9 years 18-47 36,4 years 18-50\nOral Contraceptives (OC) 24 (37,5) 4 (18,2)\nMenstrual cycle\nMenstruation \nProliferation \nSecretion\nNo Cycle (due to OC) \nUnknown\n7 (10,9)\n6 (9,4)\n14 (21,9)\n24 (37,5)\n13 (20,3)\n0 (0)\n3 (13,64)\n3 (13,64)\n4 (18,18)\n12 (54,54)\nCoexisting diseases\nAdenomyosis (AM) \nMyoma (UM) \nSterility\nHypothyroidism\n43 (67,2)\n9 (14,1)\n10 (15,6)\n8 (12,5)\n0 (0)\n12 (54,5)\n1 (4,5)\n4 (18,2)\nTable 1: Subjects.\nAntibodies\nWe performed immunohistochemical studies to investigate \nimmunoreaction of target antigens in the serial sections of biopsies \nusing the following antibodies: PR (Progesterone receptor), ERa \n(Estrogen receptor alpha), CD 10 (stromal cell marker), ASMA (Anti-\nSmooth Muscle Cell Actin), and Cytokeratin (glandular cell marker). \nNon-immune mouse immunoglobulin (IgG) antibody was used as a \nnegative control. The detailed names, dilutions, and manufacturers are \ngiven in Table 2.\nImmunohistochemistry\nFirstly, we prepared 2 µm thick paraffin-embedded tissue slides \nwhich were then deparaffinized in xylene and ethanol. After that, they \nwere either treated with Target-Retrieval-Solution (pH 9) or citrate \nbuffer (pH 6) – depending on the antigen we were planning to use on \nit. Subsequently, the slides were incubated with the primary antibodies \nfor 1 hour at room temperature and then for another hour with the \nbiotin secondary antibody (Table 2), followed by incubation with \navidin–peroxidase for 30 min and finally visualized with Fast Red \nChromogen System (PR, ERa, CD10, Cytokeratin) or SIGMAFAST \n(ASMA). Finally, the tissue sections were counterstained with Mayer’s \nhematoxylene, cleared in aqua dest, and mounted.\nStatistical Analysis\nAll data were analyzed by SSPS program, using exclusively \nmetrical variables in independent samples. All groups to be compared \nin the evaluation were checked for normal distribution. Subsequently, \nthe statistical test to be used was determined. If two samples were \npresent, the Chi-square test or the Mann-Whitney test was carried out \nfor normally distributed and non-normally distributed samples. The \nt-test was not used due to the small number of cases. A value of P < \n0.05 was considered to be statistically significant.\nResults\nThe Occurrence of OME Lesions\nIn total, we found 5 OME lesions, which is 5, 81% of all patients. \nThree of these lesions contained at least one glandular cell whereas the \nother two lesions contained stromal cells. There was only one lesion, \nwhich contained all three parts of a typical EM lesion (glandular cells, \nstromal cells, and smooth muscle cells (SMC)) (Figure 1). A summary \nof these results can be found in Table 3. Furthermore, the clinical \nprofiles of patients with OME are given in Table 4.\nFour of these lesions were found in the right paracolic gutter with \nonly one on the left side while four of those lesions were also found in \npatients with EM with only one found in a woman of the control group. \nFor the group of patients with EM that is a proportion of 6, 3% and for \nthe control group, it is a proportion of 4, 5%. A statistical evaluation \nwas carried out using the chi-square test. This calculation resulted in \nName of antibody Dilution Manufacturer\nMs anti- Progesteron-R Dako PgR 1:50 Dako, Denmark\nMs anti-ER-alpha 1D5 1:60 Dako, Denmark\nMs ASMA abcam 1A4 1:50 Abcam, UK\nMs anti-CD10 ab951 1:50 Dako, Denmark\nAnti-Cytokeratin MNF116 Dako 1:50 Dako, Denmark\nBiotin-SP-conjugated AddiniPure Rabbit Anti-Mouse IgG 1:400 Dianova, USA\nTable 2: Antibodies.\n \n \n \n \nA B\nFigure 1: OME lesion 03, which contains all three parts of an EM lesion. A: Cytokeratin; B: ASMA.\n\nARCH Women Health Care, Volume 4(1): 3–5, 2021 \nSylvia Mechsner (2021) Characterisation of Microscopic Changes in Macroscopically Unaffected Peritoneum in Women with and without \nEndometriosis\na p-value of 0.768 and therefore shows no statistical relevance of the \nprobability of occurrence of OME between the two groups of patients.\nOME lesion 01 02 03 04 05\nGlandular cells Ye s Ye s Ye s No No\nStromal cells No No Ye s Ye s Ye s\nSMCs Ye s Ye s Ye s No No\nSize in µm 88 x 30 328 x 75 310 x 312 222 x 62 337 x 140\nTable 3: Summary of OME lesions.\nOME lesion 01 02 03 04 05\nEM No Ye s Ye s Ye s Ye s\nMenstrual cycle Proliferative Menstruation Unknown Proliferative No Cycle\nOC No No No No Ye s\nAge (years) 45 38 45 36 25\nHistory UM AM, Sterility AM AM, UM AM\nSide Right Right Right Right Left\nCell type in OME Glandular \ncells\nGlandular \ncells\nGlandular \ncells\nStromal \ncells\nStromal \ncells\nTable 4: Clinical profiles of patients with OME.\nThe Occurrence of Immune Cells in Peritoneal Tissue\nBesides the OME lesions, we also detected some groups of \nimmune cells. These cells were seen in the immunostaining pattern \nof CD10. In total there were 12 patients who had such groups \n(containing lymphocytes and granulocytes) in their peritoneal tissue. \nAll of these patients were in the EM group and no inflammatory signs \ncould be found in the control group. In the group of women with \nEM there were 18,8% demonstrably affected by inflammation of the \nperitoneum. The p-value of 0.029, determined using a chi-square test, \nshows the statistical relevance of this result.\nThe Occurrence of Blood Vessels in Peritoneal Tissue\nTo find out if the process of neoangiogenesis takes part in the \ndevelopment of OME we examined all tissue specimens for blood \nvessels. To take into account the difference in the size of the samples, \nthe vessel density was determined using the hot-spot method.\nIn women with EM we found a slightly higher density than in \nwomen without EM (1, 74 vessels per mm2 in women with EM versus \n1.66 vessels per mm2 in women without EM). However, this difference \nis with a p-value of 0.519 determined using a Mann-Whitney U test \nnot statistically relevant.\nDiscussion\nThere has been more research done on this topic since Murphy et \nal. first described the occurrence of OME lesions in 1986. Synoptically \nthis has all but confirmed the presence of OME. However, in the study \nof Redwine and Y okom, it was the other way around and they found \nOME to be more common in women without EM. It is important to \npoint out that this study only used a small control group consisting of \n10 women, which limits the meaningfulness of it [16-22]. Nevertheless, \nthere has not been a statistical significance in the occurrence of OME \nbetween women with and without EM in any of the studies. Table 5 \nshows a summary of all the studies about OME.\nEven though there is no significant difference between the \noccurrence rate of OME in this study compared to Nisolle, Balasch, \nand Kahn, et al. there are reasons why they found a higher rate. First \nof all the technical possibilities were significantly improved in the last \nfew years. Furthermore and more interestingly, we examined tissue \nfrom the paracolic gutters, which is not known to be one of the most \ncommon sites for EM. In contrast, all the other authors decided to take \ntissues from sites of the peritoneum where EM is very likely to find in \nthe pelvis [6,13,23].\nThe Meaning of OME\nThere are two potential meanings of OME. Firstly, it could be an \nearly stage of a “real” EM lesion. In that case, it would be involved in the \ndevelopment and eventually even in the persistence and recurrence of \nEM after a successful treatment. Secondly, it could also be a physiological \nphenomenon in which endometrial cells settle in the peritoneum but \nlater get broken down by the immune system. In that case, it would not \nhave anything to do with the development of a “real” EM lesion.\nThe first case could explain why up to 50% of patients who \nunderwent surgical EM resection, have a recurrence of complaints \nand “new” EM lesions within 5 years [24,25]. The opinion of Kahn et \nal. that OME lesions are biologically active and have growth potential \nwould support this theory [22].\nOn the other hand, the fact that the prevalence of OME in women \nwith and without EM is almost the same suggests that OME lesions \nhave no influence on the development of EM or only in connection \nwith other influencing factors that have not yet been finally clarified.\nStudy Ye a r Operation Localization of removed tissue Frequency of OME in patients with EM Frequency of OME in \npatients without EM\nMurphy et al. 1986 Laparotomie Cul-de-sac 25% -\nRedwine 1988 Laparoscopy Posterior pelvic peritoneum 0% 0%\nRedwine, Y ocom 1990 Laparoscopy Cul-de-sac, Sacrouterine ligaments, Broad \nligaments 4,4% 10%\nNisolle et al. 1990 Laparoscopy Sacrouterine ligaments 13% 6%\nNezhat et al. 1991 Laparoscopy Peritoneum, 3-5 cm next to EM lesions 15% (clin. diagnosis) vs. 3,9% (histolog. diagnosis) 0%\nBalasch et al. 1996 Laparoscopy Sacrouterine ligaments 11% 6%\nKahn et al. 2014 Laparoscopy Pouch of Douglas, Uterovesicle space, \nSacrouterine ligaments 15% 6,4%\nTable 5: Summary of results of studies about OME [16-22].\n\nARCH Women Health Care, Volume 4(1): 4–5, 2021 \nSylvia Mechsner (2021) Characterisation of Microscopic Changes in Macroscopically Unaffected Peritoneum in Women with and without \nEndometriosis\nDistribution of OME Lesions\nThe peritoneal fluid has a typical distribution in the peritoneal \ncavity. Due to the force of gravity, it is usually located in deeper \nlocations such as the Pouch of Douglas. However, negative intracranial \npressures during inspiration and the influence of peristalsis regularly \nlead to a cranial flow of the peritoneal fluid. Therefore, the fluid runs \nover the paracolic gutters. The majority of the peritoneal fluid runs \nover the right paracolic gutter, as it is deeper than the left paracolic \ngutter. In this way, the fluid reaches the subdiaphragmatic space on \nthe right side and from there is directed back into the deeper areas \nvia the inframesocolic compartment. This circulation of the PF in the \nperitoneal cavity results in four places where it is particularly frequent/\nlong [13,26]. As one of these places is the right paracolic gutter, we \ndecided to examine both of the paracolic gutters to see if there is a \ndifference in the occurrence of OME lesions. In this study the lesions \nwere distributed in a 4: 1 ratio (right: left) in the paracolic gutters. This \nresult suggests that the development of the lesions is justified or at least \nencouraged by the influence of the peritoneal fluid, their composition, \nand their flow directions [13,14,27]. Therefore, one could either \nsupport Sampson’s theory or say that retrograde menstruation causes \nendometrial cells to enter the PF and adhere to the peritoneum as they \ncirculate, and assume that growth factors, angiogenesis factors, and \ninflammatory factors contained in the PF promote the development \nof OME lesions [27-29].\nImmune Cells\nInterestingly, when comparing the specimens in the paracolic \ngutters of women with and without EM, it became clear that \nimmune cells were only found in tissue samples from patients with \nEM. The associations of immune cells could be an expression of the \ninflammatory response in the context of EM and OME lesions that \nhave been eliminated by the immune system. However, since they \ntended to be found more often on the left side and OME lesions as well \nas normal EM lesions are mainly located in the right paracolic gutter, \nit can be assumed that there are inflammatory processes in the entire \nperitoneal tissue of women with EM. A study by Scheerer et al. from \n2016 also found a significantly more frequent occurrence of immune \ncells in the peritoneal tissue of women with endometriosis compared \nto women without endometriosis [30].\nThe question of whether the peritoneum becomes flammable \nthrough the EM, or whether the peritoneum is more likely to \ndevelop EM lesions due to its inflammatory consideration is still \nopen. However, five women with inflammatory tissue were under the \ninfluence of OC at the time of surgery. This medication can prevent \nthe progression of EM lesions and improve the symptoms. However, \nthis is not the case for all patients who take OC, and often after the \npills have been discontinued the symptoms recur quickly [31,32]. This \ncould be because the peritoneum is less penetrated by EM lesions, \nbut it is still affected by inflammatory processes and may therefore \npromote the formation or regrowth of regressed lesions.\nAmount of Blood Vessels\nThe pathogenesis of EM is known to be influenced by VEGF \n[33]. The growth factor leads to an increased blood flow to the tissue \npermeated by EM and thereby promotes the progression of the lesions \n[34]. In this study, there was no statistically relevant difference in the \nvascular density between women with and without EM. Furthermore, \nno relevantly increased vessel density could be found in the tissue \npieces in which there were OME lesions. Therefore, they did not seem \nto be associated with neoangiogenesis. In contrast to the samples \nwith OME lesions, however, an increased vascular density was \nfound in samples with immune cells, which corresponds to a typical \ninflammatory reaction.\nConclusion\nIn this study, a few cases of OME were detected in both women with \nand without EM. There was no significant difference in the frequency \nof occurrence between the two cohorts. An important significant \ndifference in the peritoneal tissue of women with EM compared to \nthat of women without EM was the appearance of immune cells, \nwhich were only found in women with EM. Both lymphocytes and \ngranulocytes were found, which, however, were in no case associated \nwith an OME lesion in this study. These tissue samples also had an \nincreased average number of vessels, which can be easily reconciled \nwith an inflammatory reaction. Even though this result was not \nsignificant, it does show a certain trend.\nAs OME occurs in both tissue samples from women with and tissue \nsamples from women without EM, it is likely that it is a physiological \nphenomenon in which endometrial cells settle in the peritoneum and \nare subsequently cleared by the immune system. The found hormone \nreceptor status with a predominance of PR over ER of these lesions \nalso supports this theory.\nConcerning the causality of the inflammatory changes in the \nperitoneal tissue of women with EM, further research is required to \nbe able to offer patients better and long-term successful therapeutic \noptions.\nReferences\n1. Laschke MW , Menger MD (2016) The gut microbiota: a puppet master in the \npathogenesis of endometriosis? Am J Obstet Gynecol 215: e1-4. [crossref]\n2. O DF , Roskams T, Van den Eynde K, Vanhie A, Peterse DP , et al. (2016) The Presence \nof Endometrial Cells in Peritoneal Fluid of Women With and Without Endometriosis. \nReprod Sci 24: 242-251. [crossref]\n3. Barcena de Arellano ML, Gericke J, Reichelt U, Okuducu AF , Ebert AD, et al. (2011) \nImmunohistochemical characterization of endometriosis-associated smooth muscle \ncells in human peritoneal endometriotic lesions. Hum Reprod 26: 2721-2730. [crossref]\n4. Fukunaga M (2000) Smooth muscle metaplasia in ovarian endometriosis. \nHistopathology 36: 348-352. [crossref]\n5. Prevalence and anatomical distribution of endometriosis in women with selected \ngynaecological conditions: results from a multicentric Italian study. Gruppo italiano \nper lo studio dell’ endometriosi. Hum Reprod 9: 1158-1162. [crossref]\n6. Imesch P , Fink D (2016) [Endometriosis Update 2016]. Praxis (Bern 1994) 105: 253-\n257. [crossref]\n7. Rizner TL (2015) Diagnostic potential of peritoneal fluid biomarkers of \nendometriosis. Expert Rev Mol Diagn 15: 557-580. [crossref]\n8. Kavoussi SK, Lim CS, Skinner BD, Lebovic DI, As-Sanie S (2016) New paradigms \nin the diagnosis and management of endometriosis. Curr Opin Obstet Gynecol  28: \n267-276. [crossref]\n9. Burney RO, Giudice LC (2012) Pathogenesis and pathophysiology of endometriosis. \nFertil Steril 98: 511-519. [crossref]\n\nARCH Women Health Care, Volume 4(1): 5–5, 2021 \nSylvia Mechsner (2021) Characterisation of Microscopic Changes in Macroscopically Unaffected Peritoneum in Women with and without \nEndometriosis\n10. Wanyonyi SZ, Sequeira E, Mukono SG (2011) Correlation between laparoscopic and \nhistopathologic diagnosis of endometriosis. Int J Gynaecol Obstet 115: 273-276. [crossref]\n11. Practice Committee of the American Society for Reproductive, M., Treatment of \npelvic pain associated with endometriosis: a committee opinion. Fertil Steril 101: \n927-935. [crossref]\n12. Giudice LC, Kao LC (2004) Endometriosis. Lancet 364: 1789-1799.\n13. Levy AD, Shaw JC, Sobin LH (2009) Secondary tumors and tumorlike lesions of the \nperitoneal cavity: imaging features with pathologic correlation. Radiographics  29: \n347-373. [crossref]\n14. Meyers MA (1973) Distribution of intra-abdominal malignant seeding: dependency \non dynamics of flow of ascitic fluid. Am J Roentgenol Radium Ther Nucl Med 119: \n198-206. [crossref]\n15. Hopton EN, Redwine DB (2014) Eyes wide shut: the illusory tale of ‘occult’ \nmicroscopic endometriosis. Hum Reprod 29: 384-387. [crossref]\n16. Murphy AA, Green WR, Bobbie D, dela Cruz ZC, Rock JA (1986) Unsuspected \nendometriosis documented by scanning electron microscopy in visually normal \nperitoneum. Fertil Steril 46: 522-524. [crossref]\n17. Redwine DB (1988) Is “microscopic” peritoneal endometriosis invisible? Fertil Steril \n50: 665-666. [crossref]\n18. Redwine DB, Y ocom LB (1990) A serial section study of visually normal pelvic \nperitoneum in patients with endometriosis. Fertil Steril 54: 648-651. [crossref]\n19. Nisolle M, Paindaveine B, Bourdon A, Berlière M, Casanas-Roux F , et al. (1990) \nHistologic study of peritoneal endometriosis in infertile women. Fertil Steril 53: 984-\n988. [crossref]\n20. Nezhat F , Allan CJ, Nezhat C, Martin DC (1991) Nonvisualized endometriosis at \nlaparoscopy. Int J Fertil 36: 340-343. [crossref]\n21. Balasch J, Creus M, Fábregues F , Carmona F , Ordi J, et al. (1996) Visible and non-\nvisible endometriosis at laparoscopy in fertile and infertile women and in patients \nwith chronic pelvic pain: a prospective study. Hum Reprod 11: 387-391. [crossref]\n22. Khan KN, et al. (2014) Occult microscopic endometriosis: undetectable by \nlaparoscopy in normal peritoneum. Hum Reprod 29: 462-472.\n23. Chiantera V , Dessole M, Petrillo M, Lucidi A, Frangini S, et al. (2016) Laparoscopic \nEn Bloc Right Diaphragmatic Peritonectomy for Diaphragmatic Endometriosis \nAccording to the Sugarbaker Technique. J Minim Invasive Gynecol 23: 198-205. \n[crossref]\n24. Vlek SL, et al. (2016) Laparoscopic Imaging Techniques in Endometriosis Therapy: A \nSystematic Review. J Minim Invasive Gynecol 23: 886-892.\n25. Zhu L, Lier MC, Ankersmit M, Ket JC, Dekker JJ, et al. (2019) Comparisons of the \nefficacy and recurrence of adenomyomectomy for severe uterine diffuse adenomyosis \nvia laparotomy versus laparoscopy: a long-term result in a single institution. J Pain \nRes 12: 1917-1924. [crossref]\n26. Bricou A, Batt RE, Chapron C (2008) Peritoneal fluid flow influences anatomical \ndistribution of endometriotic lesions: why Sampson seems to be right. Eur J Obstet \nGynecol Reprod Biol 138: 127-134. [crossref]\n27. Koninckx PR, Kennedy SH, Barlow DH (1998) Endometriotic disease: the role of \nperitoneal fluid. Hum Reprod Update 4: 741-751. [crossref]\n28. Sasson IE, Taylor HS (2008) Stem cells and the pathogenesis of endometriosis. Ann N \nY Acad Sci 1127: 106-115. [crossref]\n29. Gazvani R, Templeton A (2002) Peritoneal environment, cytokines and angiogenesis \nin the pathophysiology of endometriosis. Reproduction 123: 217-226. [crossref]\n30. Scheerer C, Bauer P , Chiantera V , Sehouli J, Kaufmann A, et al. (2016) Characterization \nof endometriosis- associated immune cell infiltrates (EMaICI). Arch Gynecol Obstet  \n294: 657-664. [crossref]\n31. Lindsay SF , Luciano DE, Luciano AA (2015) Emerging therapy for endometriosis. \nExpert Opin Emerg Drugs 20: 449-461. [crossref]\n32. Schweppe KW (2005) [Guidelines for the use of GnRH-analogues in the treatment of \nendometriosis]. Zentralbl Gynakol 127: 308-313. [crossref]\n33. Liu S, Xin X, Hua T, Shi R, Chi S, et al. (2016) Efficacy of Anti-VEGF/VEGFR Agents \non Animal Models of Endometriosis: A Systematic Review and Meta-Analysis. PLoS \nOne 11: e0166658. [crossref]\n34. Burney RO, Giudice LC (2012) Pathogenesis and pathophysiology of endometriosis. \nFertil Steril 98: 511-519. [crossref]\nCitation:\nLuhmann M, Chiantera V , Sehouli J, Mechsner S (2021) Characterisation of Microscopic Changes in Macroscopically Unaffected Peritoneum in Women with and \nwithout Endometriosis. ARCH Women Health Care Volume 4(1): 1-5.","source_license":"CC0","license_restricted":false}