{"paper_id":"7baffa2f-4d9e-40c4-82bf-318261b085c0","body_text":"Volume 9 • Issue 6 • 10001253J Clin Case Rep, an open access journal\nISSN: 2165-7920\nAbdel-Gadir, J Clin Case Rep 2019, 9:6\nOpen AccessResearch Article\nJournal of Clinical Case ReportsJournal of Clinical Case Reports\nISSN: 2165-7920\nChromohysteroscopy and Laparoscopy Findings in Infertile Patients with \nPersistent Midluteal Phase Central Endometrial Echo\nAbdel-Gadir A*\nDivision of Gynaecology and Reproductive Medicine and Surgery, Al-Salam International Hospital, Al-Messila Clinics Tower, Port Sayeed Road, Kuwait\nAbstract\nObjective: To study the relationship between persistent midluteal central endometrial echo versus polycystic \novaries and chromohysteroscopy and laparoscopy findings in infertile patients with regular menstruation.\nMaterial and methods: 164 infertile patients with regular menstruation were investigated with ultrasound \nmonitored cycles followed by chromohysteroscopy and laparoscopy. Persistent midluteal central endometrial echo \nwas assessed against presence of polycystic ovaries, micropolyps and deep endometrial staining with methylene \nblue and presence of endometriosis diagnosed laparoscopically. \nResults: 51 patients (31.1%) showed persistent central midluteal endometrial echo and 72 (43.9%) showed \npolycystic ovaries. During chromohysteroscopy 21 patients (12.8%) showed micropolyps and 26 (15.9%) showed \ndeep endometrial staining with methylene blue. Moreover, 30/51 patients with central midluteal endometrial echo \n(58.8%) showed polycystic ovaries versus 42/113 patients (37.2%) with homogeneous endometrium, p=0.011. \nFurthermore, 18/51 patients (35.3%) with central endometrial echo showed dark endometrial discolouration with \nmethylene blue versus 08/113 patients (7.1%) with homogenous endometrium, p<0.001. Similarly, 14/51 patients \n(27.5%) with central midluteal endometrial echo showed micropolyps versus 7/113 (6.2%) with homogeneous \nendometrium, p=0.001. Polycystic ovaries showed no significant association with either sign of chronic endometritis. \nDuring laparoscopy, 31/164 patients (18.9%) showed pelvic endometriosis. 14 of them (45.2%) developed deep \nendometrial discolouration with methylene blue versus 12/113 patients (9.0%) without endometriosis, p<0.001. \nLikewise, 21/31 patients with endometriosis (67.7%) had central midluteal endometrial echo versus 30/133 patients \n(22.6%) with no endometriosis, p<0.001. This association was maintained after excluding patients with chronic \nendometritis.   \nConclusion: Persistent midluteal central endometrial echo might reflect chronic endometritis as it was significantly \nassociated with deep endometrial discolouration with methylene blue and micropolyps. The significant association \nbetween endometriosis and midluteal central endometrial echo in cases with and without chronic endometritis \nindicated that endometriosis might affect the endometrium through more than one mechanism. Conversely, the \nassociation of polycystic ovaries with midluteal endometrial echo was independent of chronic endometritis.\nKeywords: Mid luteal central endometrial echo; Chronic \nendometritis; Endometriosis\nIntroduction\nChronic endometritis was a neglected diagnosis in gynaecological \npractice but has recently emerged as an important factor associated \nwith implantation failure, repeated miscarriages and neonatal problems \n[1,2]. Women with histopathological diagnosis of chronic endometritis \nwere shown to have lower implantation rates in subsequent in vitro \nfertilisation and embryo transfer cycles (IVF-ET) [3]. A recent pro-\nspective study showed chronic endometritis in 14% of patients with \nrecurrent implantation failure and 27% of patients with recurrent \npregnancy loss [4]. On the positive side, treatment of chronic \nendometritis resulted in successful pregnancies after IVF-ET in patients \nwho had recurrent implantation failures in the past [5]. Furthermore, \nchronic endometritis was found to be highly prevalent in patients \nwith unexplained infertility and its treatment improved spontaneous \npregnancy and live birth rates [6]. An interesting study reported chronic \nendometritis in 52.94% of patients with endometriosis compared to \n27.02% of patients with no endometriosis p=0.05. [7].  \nRecent studies showed the accuracy of fluid hysteroscopy \nexceeded 90% in diagnosing chronic endometritis compared \nto histological examination. It also had higher sensitivity than \nendometrial microbiological examinations [8-10]. Yet again using \nchromohysteroscopy further improved the diagnostic power of \nhysteroscopy. Instillation of methylene blue before hysteroscopic \nexamination of the uterine cavity increased the efficacy for diagnosing \n*Corresponding author: Abdel-Gadir A, Division of Gynaecology and Reproductive \nMedicine and Surgery, Al-Salam International Hospital, Al-Messila Clinics Tower, Port \nSayeed Road, Kuwait, Tel: 096522232006; E-mail: prof.gadir@gmail.com\nReceived May 30, 2019; Accepted June 06, 2019; Published June 13, 2019\nCitation: Abdel-Gadir A (2019) Chromohysteroscopy and Laparoscopy Findings in \nInfertile Patients with Persistent Midluteal Phase Central Endometrial Echo. J Clin \nCase Rep 9: 1253.\nCopyright: © 2019 Abdel-Gadir A. This is an open-access article distributed under \nthe terms of the Creative Commons Attribution License, which permits unrestricted \nuse, distribution, and reproduction in any medium, provided the original author and \nsource are credited.\nabnormal endometrium and targeting endometrial biopsies [11]. This \nwas confirmed by another study which showed chromohysteroscopy \nto be more effective in detecting endometrial pathology than blind \nendometrial sampling [12]. At the same time, chromohysteroscopy \ncould give reassuring results as diffuse light blue staining without dark \nareas strongly indicated normal endometrium free of endometritis [13].  \nAll studies reporting on chronic endometritis relied on different \nhysteroscopic appearances summarised recently by an international \nrandomised controlled observer study [14]. Historically, micropolyps, \nintense discolouration of the endometrium with methylene blue or \ntoluidine blue during chromohysteroscopy and laboratory studies \non endometrial biopsies were the main diagnostic tools. There was \nno study which showed specific ultrasonic characteristics of chronic \nendometritis in relation to infertility, reduced implantation rates or \nrecurrent miscarriages. A recent transvaginal ultrasound study with \nsaline infusion sonohysterography failed to diagnose micropolyps in \n81 patients investigated for abnormal uterine bleeding, infertility and \n\nCitation: Abdel-Gadir A (2019) Chromohysteroscopy and Laparoscopy Findings in Infertile Patients with Persistent Midluteal Phase Central \nEndometrial Echo. J Clin Case Rep 9: 1253.\nPage 2 of 4\nVolume 9 • Issue 6 • 10001253J Clin Case Rep, an open access journal\nISSN: 2165-7920\nrepeated miscarriages [15]. Nevertheless, nonhomogeneous midluteal \nphase endometrial patterns were reported to be associated with lower \nimplantation rate during assisted reproduction treatment cycles \n[16,17]. Similarly, a recent study reported persistent midluteal central \nendometrial echo in 26 of 72 infertile regularly menstruating patients \n(36.1%) investigated with repeated ultrasound scan examinations \n[18]. Local factors were postulated to be important in this respect as \nendometrial thickness, uterine arteries blood flow and midluteal serum \nprogesterone levels did not correlate to the presence of the persistent \nmidluteal central endometrial echo. \nIn the current study I looked at a possible association between \nultrasonically diagnosed persistent midluteal central endometrial \necho against polycystic ovaries and signs of chronic endometritis \ndiagnosed during chromohysteroscopy. I also investigated whether \nlaparoscopy could add useful information in relation to this problem, \nas endometriosis was shown previously to be associated with chronic \nendometritis [7].\nMaterial and Methods\nA total of 164 infertile patients with regular menstrual cycles were \nmonitored with repeated ultrasound scan examinations during a whole \ncycle. This was followed by chromohysteroscopy with methylene \nblue and diagnostic laparoscopy during the early follicular phase of \na subsequent cycle. All procedures were done as part of the routine \nclinical assessment for infertility. Presence of polycystic ovaries, \nchromohysteroscopic signs of chronic endometritis and presence \nof laparoscopically diagnosed endometriosis were noted. They were \nassessed against the ultrasound diagnosis of persistent midluteal central \nendometrial echo. All patients consented to have their nonidentifying \ninformation used for teaching and research purposes. Patients with \nsubmucous fibroids or history of previous uterine surgery were not \nincluded in the study.\nCross tabulation with chi square test and binary logistic regression \nanalysis were used as appropriate. The Mann-Whitney U test was used \nfor nonparametric data. The Statical Package for Social Sciences (IBM \nSPSS) was used for data analysis. P<0.05 was used to indicate statistical \nsignificance with an observed power=0.8.\nResults\nDuring ultrasound monitored cycles, 51 patients (31.1%) showed \npersistent central midluteal endometrial echo and 72 (43.9%) showed \npolycystic ovaries. During chromohysteroscopy 21 patients (12.8%) \nshowed micropolyps and 26 (15.9%) showed deep endometrial \nstaining with methylene blue. Figures 1 and 2 show samples of the \ncases seen. Moreover, 30/72 patients with polycystic ovaries (41.7%) \nshowed central endometrial echo versus 21/92 patients (22.0%) with \nnormal ovaries, p=0.011. Furthermore, 18/51 (35.3%) patients with \ncentral endometrial echo showed dark endometrial discolouration \nwith methylene blue versus 08/113 patients (7.1%) with homogenous \nluteal endometrium, p<0.001. Similarly, 14/51 (27.5%) patients with \nFigure 1: (A) A hysteroscopic panoramic view of a uterine cavity with hyperaemic area involving the left sidewall and parts of the posterior wall and fundus. (B) A \nmagnified view of the left sidewall of the same uterus showing micropolyps.\nFigure 2: Hysteroscopic views of an inflamed uterine cavity before (A) and after instillation of methylene blue (B). Note the wide distribution of deeply stained \nendometrium almost mirroring the hyperaemic area in image (A).\n\nCitation: Abdel-Gadir A (2019) Chromohysteroscopy and Laparoscopy Findings in Infertile Patients with Persistent Midluteal Phase Central \nEndometrial Echo. J Clin Case Rep 9: 1253.\nPage 3 of 4\nVolume 9 • Issue 6 • 10001253J Clin Case Rep, an open access journal\nISSN: 2165-7920\npersistent midluteal endometrial echo showed micropolyps versus \n7/113 patients (6.2%) with homogeneous luteal endometrium, p=0.001. \nDuring laparoscopy, 31/164 patients (18.9%) showed pelvic \nendometriosis. Deep endometrial discolouration with methylene blue \nwas seen in 14/31 patients (45.2%) with endometriosis versus 12/113 \npatients (9.0%) without endometriosis, p<0.001. Comparably, 10/31 \npatients with endometriosis (32.3%) showed endometrial micropolyps \nversus 11/133 patients (8.3%) with no endometriosis, p=0.001. \nPersistent central endometrial echo was seen in 21/31 patients (67.7%) \nwith endometriosis compared to 30/133 patients (22.6%) with no \nendometriosis, p<0.001. This association was maintained even after \nexcluding cases with chronic endometritis. In patients with no sign \nof endometritis, 9/16 patients (56.3%) with endometriosis showed \ncentral endometrial echo versus 23/121 patients (19.0%) with no \nendometriosis, p=0.003. \nUnlike endometriosis there was no significant association between \nPCO and hysteroscopic signs of chronic endometritis. 12/72 patients \nwith PCO (16.7%) showed micropolyps versus 9/92 patients (9.8%) \nwith normal ovaries, p=0.241. The equivalent numbers for patients with \ndeep endometrial staining with methylene blue were 15/72 (20.8%) and \n11/92 (12.0%) for patients with PCO and normal ovaries respectively \np=0.136. Furthermore, crosstabulation with chi square test showed no \nassociation between endometriosis and polycystic ovaries in the whole \ngroup. 17/72 patients with PCO had endometriosis (23.6%) versus \n14/92 patients (15.2%) with no PCO, p=0.228.\nNext step I used polycystic ovaries and endometriosis as \nindependent factors against the persistent central midluteal \nendometrial echo in a binary logistic regression analysis. Both showed \nsignificant association with the abnormal endometrial echo. However, \nthe odds ratio (exponentiation of the B coefficient) of endometriosis \nwas 3.04 times that of polycystic ovaries (Table 1). This represented \na higher likelihood of endometriosis to affect the endometrium \nthan PCO. Next, I introduced deep methylene blue staining of the \nendometrium as a sign of chronic endometritis as a third independent \nfactor in the logistic regression equation as shown in Table 2. Each \nfactor proved to have significant and independent association with the \npersistent midluteal central endometrial echo. However, endometriosis \nretained the highest exponentiation coefficient (odds ratio) followed \nby chronic endometritis, then polycystic ovaries. Nevertheless, there \nwas 30.5% reduction in endometriosis odds ratio after introducing \nchronic endometritis in the logistic regression equation. This difference \nrepresented the contribution of chronic endometritis to the total \nnegative effect of endometriosis on the midluteal phase endometrium. \nOn the other hand, the odds ratio of polycystic ovaries changed by only \n4.6% after including chronic endometritis in the equation as shown by \nthe corresponding figures in Tables 1 and 2. \nLast I assessed the association of age and body mass index (BMI) \nto the presence of central endometrial echo. Both parameters did not \nshow normal distribution using Shapiro-Wilk test (p<0.001 for BMI \nand p=0.011 for age). Accordingly, non-parametric analysis was done \nusing Mann-Whitney U test. Both parameters showed no significant \nassociation with the central endometrial echo. The mean rank and \nsum of ranks for age were 82.95 and 4230.50 respectively for patients \nwith central endometrial echo. The equivalent figures for patients \nwho did not show central endometrial echo were 82.30 and 9299.50 \nrespectively. The Mann Whitney U test was 2858.500, Z was -.082 and \nthe 2 tailed significance tests =.935. The equivalent mean rank and \nsum of ranks for BMI were 80.17 and 4088.50 respectively for women \nwith central endometrial echo. The corresponding figures for women \nwith no similar endometrial echo were 83.55 and 9441.50 respectively. \nThe Mann-Whitney U test was 2762.500, Z was -.425 and 2-tailed \nsignificance =.671. \nDiscussion\nThis study showed significant association between persistent \nmidluteal central endometrial echo with signs of chronic endometritis, \npolycystic ovaries and endometriosis. It also showed significant \nassociation between endometriosis with micropolyps and deep \nendometrial discolouration with methylene blue. This confirmed \na previous finding which showed significant association between \nendometriosis and chronic endometritis [7]. Despite the highly \nsignificant association between the two, endometriosis and chronic \nendometritis maintained an independent significant association to \nmidluteal central endometrial echo as shown by logistic regression \nanalysis. Also, endometriosis had significant association with the \nVariables B S.E. Wald df P value Exp(B) 95% C.I. for Exp (B)\nLower Upper\nPCO 0.824 0.371 4.929 1 0.026 2.28 1.101 4.721\nEndometriosis 1.939 0.445 19.001 1 0 6.95 2.907 16.619\nConstant -3.907 0.998 15.321 1 0 0.02\nB: Coefficient for the constant in the null model; SE: Standard error around the coefficient for the constant; Wald: Wald chi-square tests the null hypothesis that the constant \nequals 0; df: Degrees of freedom for the Wald chi-square test; Exp (B): Exponentiation of the B coefficient; which is the odds ratio; 95% C.I. for Exp (B): 95% confidence \ninterval for the odds ratio.\nTable 1: Shows both polycystic ovaries and endometriosis were significantly associated to persistent midluteal central endometrial echo after binary logistic regression analysis.\nVariables B S.E. Wald df P value Exp(B) 95% C.I. for Exp (B)\nLower Upper\nPCO 0.777 0.382 4.129 1 0.042 2.174 1.028 4.599\nEndometriosis 1.575 0.476 10.961 1 0.001 4.831 1.902 12.275\nEndometritis 1.452 0.519 7.822 1 0.005 4.273 1.544 11.822\nConstant -5.845 1.329 19.339 1 0 0.003\nB: Coefficient for the constant in the null model; SE: Standard error around the coefficient for the constant; Wald: Wald chi-square tests the null hypothesis that the constant \nequals 0; df: Degrees of freedom for the Wald chi-square test; Exp (B): Exponentiation of the B coefficient; which is the odds ratio; 95% C.I. for Exp (B): 95% confidence \ninterval for the odds ratio.\nTable 2: Shows the result of logistic regression analysis when chronic endometritis was included in the equation together with polycystic ovaries and endometriosis. \nEndometriosis had the highest exponentiation coefficient (odds ratio) followed by endometritis then polycystic ovaries. Despite the significant association between \nendometriosis and chronic endometritis shown by this study, each of them maintained an independent high significant association to the persistent midluteal endometrial \necho in logistic regression analysis.\n\nCitation: Abdel-Gadir A (2019) Chromohysteroscopy and Laparoscopy Findings in Infertile Patients with Persistent Midluteal Phase Central \nEndometrial Echo. J Clin Case Rep 9: 1253.\nPage 4 of 4\nVolume 9 • Issue 6 • 10001253J Clin Case Rep, an open access journal\nISSN: 2165-7920\nsame echo even after controlling for signs of chronic endometritis. \nThis suggested that endometriosis might also affect the luteal phase \nendometrium by another mechanism other than chronic endometritis. \nLessey [19] reported low expression of secretory phase endometrial cells \nintegrins (adhesion molecules) in some women with endometriosis. This \nwas seen more often in minimal and mild endometriosis compared to \nthe more severe grades despite the endometrium being histologically in \nphase. The same author reported increased endometrial integrins levels \nafter treatment of endometriosis. Accordingly, chronic endometritis \nand low levels of luteal phase endometrial integrins might be separately \nresponsible for the midluteal unfavourable endometrium represented \nby the persistent central echo. On the other hand, the corresponding \nassociation of polycystic ovaries with the midluteal phase endometrial \necho proved to be independent of chronic endometritis. This might be \naffected through local endometrial hyperandrogenisation as postulated \nbefore [18]. Unexpectedly, neither age nor BMI showed significant \nassociation with the central endometrial echo. \nConclusion\nPersistent midluteal central endometrial echo might reflect \nchronic endometritis as shown by its significant association with deep \nendometrial discolouration with methylene blue and micropolyps. \nThe likelihood of endometriosis to negatively affect the endometrium \nproved to be higher than PCO. Beside its negative effect on endometrial \nintegrins levels, endometriosis might affect endometrial function \nby causing chronic endometritis. On the other hand, the significant \nassociation of polycystic ovaries with midluteal central endometrial \necho was independent of chronic endometritis. Age and BMI had no \neffect on midluteal endometrial texture.\nReferences\n1. Kitaya K, Matsubayashi H, Yamaguchi K, Nishiyama R, Takaya Y, et al. (2016) \nChronic endometritis: Potential cause of infertility and obstetric and neonatal \ncomplications. Am J Reprod Immunol 75: 13-22. \n2. Romero R, Espinoza J, Mazor M (2004) Can endometrial infection/inflammation \nexplain implantation failure, spontaneous abortion, and preterm birth after in \nvitro fertilization? Fertil Steril 82: 799-804.\n3. Johnston-MacAnanny EB, Hartnett J, Engmann LL, Nulsen JC, Sanders M, et \nal. (2010) Chronic endometritis is a frequent finding in women with recurrent \nimplantation failure after in vitro fertilization. Fertil Steril 93: 437-441.\n4. Bouet PE, El Hachem H, Monceau E, Gariepy G, Kadoch IJ, et al. (2016) \nChronic endometritis in women with recurrent pregnancy loss and recurrent \nimplantation failure: Prevalence and role of office hysteroscopy and \nimmunohistochemistry in diagnosis. Fertil Steril 105: 106-110.\n5. Vitagliano A, Saccardi C, Noventa M, Sardo ADS, Saccone G, et al. 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Abdel-Gadir A (2019) Factors and clinical scenarios possibly related to \nendometrial micropolyps and chronic endometritis. J Clin Case Rep 9: 1225. \n16. Oliveira JB, Baruffi RL, Mauri AL, Petersen CG, Borges MC, et al. (1997) \nEndometrial ultrasonography as a predictor of pregnancy in an invitro \nfertilization programme after ovarian stimulation and gonadotrophin releasing \nhormone and gonadotrophins. Hum Reprod 12: 2515-2518.\n17. Check JH, Dietterich C, Lurie D (2000) Non-homogeneous hyperechogenic \npattern 3 days after embryo transfer is associated with lower pregnancy rates. \nHum Reprod 15: 1069-1074.\n18. Abdel-Gadir A (2019) Persistence of the central endometrial echo during the \nmidluteal phase of the cycle. J Clin Case Rep 9: 1228. \n19. Lessey BA (2002) Implantation defects in infertile women with endometriosis. \nAnn NY Acad Sci 955: 265-280.","source_license":"CC0","license_restricted":false}