{"paper_id":"dcfc63a9-1cde-4d5d-81d2-0675d454fd28","body_text":"REVIEW Open Access\n© The Author(s) 2024. Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, \nsharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and \nthe source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this \narticle are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included \nin the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will \nneed to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The \nCreative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available \nin this article, unless otherwise stated in a credit line to the data.\nLi et al. BMC Women's Health          (2024) 24:403 \nhttps://doi.org/10.1186/s12905-024-03245-2\nBMC Women's Health\n†Jingjing Li and Jiajia Wei are joint first authors.\n*Correspondence:\nLi Fan\n13481279166@163.com\n1Department of Gynecology, Liuzhou Maternity and Child Healthcare \nHospital, No. 50, Boyuan Avenue, Yufeng District, Liuzhou City, Guangxi, \nChina\nAbstract\nBackground To explore the incidence of chronic endometritis (CE) in patients with infertility and different forms of \nadenomyosis and analyze potential high-risk factors for infection.\nMethods This retrospective cohort study included 154 patients with infertility in the Liuzhou Maternity and Child \nHealthcare Hospital. Among them, 77 patients with adenomyosis were divided into four subgroups based on \nmagnetic resonance imaging (MRI): internal, exterior, intramural, and full-thickness. Meanwhile, 77 patients did not \nhave adenomyosis. Hysteroscopy and endometrial biopsy were performed in the proliferative phase. The main \noutcome measures were the morphology of the endometrium, syndecan-1 (CD138) immunohistochemical staining, \nclinical characteristics, and prevalence of CE in the adenomyosis subgroups.\nResults In comparison to the non-adenomyosis group, the adenomyosis group had significantly higher body \nmass index (BMI) and CA125 levels. The menstrual cycle in the adenomyosis group was significantly shorter, and \nmenarche was significantly earlier. In comparison to the non-adenomyosis group, the adenomyosis group had a \nsignificantly higher diagnostic rate of CE (75.3% vs. 46.8% according to hysteroscopy and 74.0% vs. 33.8% according to \nhistopathology, both with p < .050). The incidence of CE was significantly lower in patients with internal adenomyosis \nwhen compared with the other three subgroups. Increased BMI contributed to a higher risk of CE.\nConclusions The prevalence of CE was significantly higher in patients with adenomyosis and infertility. The \ndifferences in the incidence of CE are closely associated with the classification of adenomyosis. When patients with \ninfertility are diagnosed with adenomyosis, it is recommended to identify the subtype and screen for endometritis.\nSummary\nThe prevalence of CE in patients with adenomyosis and infertility is significantly higher and differences in the \nincidence of CE are closely associated with the classification of adenomyosis.\nKeywords Adenomyosis, CD138, Chronic endometritis, Hysteroscopy, Infertility\nPrevalence and risk factors for chronic \nendometritis in patients with adenomyosis \nand infertility: a retrospective cohort study\nJingjing Li1†, Jiajia Wei1†, Saiqiong Chen1, Xindan Wang1, Jing Chen1, Dingyuan Zeng1 and Li Fan1*\n\nPage 2 of 8\nLi et al. BMC Women's Health          (2024) 24:403 \nBackground\nChronic endometritis (CE) is a type of endometrial \ninflammation characterized by plasma cell incursion \ninto the endometrial matrix region [ 1]. Although CE \nis frequently silent or presents as non-specific clini -\ncal symptoms such as abnormal uterine bleeding, pelvic \ndiscomfort, leukorrhea, and minor gastrointestinal dis -\ncomfort, it may cause decreased fertility and impede the \nimplantation of embryos [ 2– 5]. Women who are infertile \nand have a history of endometriosis, recurrent pregnancy \nloss (RPL), and repeated implantation failure (RIF) are at \na higher risk of developing CE. Recently, the incidence \nrate of CE is 14–42% in cases of RIF and 27–57.8% in \ncases of RPL [ 6]. Traditionally, CE is diagnosed by endo -\nmetrial sample histopathology analysis, hysteroscopy, \nand microbiological culture. Plasma cell identification \nthrough histological analysis of endometrial biopsies is \nthe gold standard for diagnosis [ 7, 8]. Emerging evidence \nsuggest that no fewer than five plasma cells for each high-\npower field (HPF) could accurately characterize a CE \ndiagnosis with important clinical ramifications [9, 10].\nAdenomyosis refers to pathological changes result -\ning in the thickening of the inner myometrium, while \nthe endometrium is proliferative. The incidence of this \ndisease in women at childbearing age ranges from 20 to \n25% [11– 13]. Over 50% of patients experience abnormal \nhemorrhage, pelvic pain, and fertility problems [ 5, 6, \n14]. Adenomyosis is an occasionally chronic, immuno-\ninflammatory illness, involving multiple inflammatory \nfactors, including TNF-α in the focal tissues, IL-1β, IL-6, \nand IL-8 [ 15]. A multicenter cohort study conducted in \nJapan reported that patients with diffuse adenomyosis \nhad a greater prevalence of uterine infection; however, \nthe study did not investigate whether these women had \nconcurrent CE [ 16]. Through cross-sectional research, \nKhan et al. reported that the varying prevalence of CE \nin various types of adenomyosis could contribute to \nunfavorable reproductive outcomes [ 17]. Nevertheless, \nlittle data is available on the prevalence of CE in adeno -\nmyosis and patients who are infertile. This retrospective \nstudy aimed to explore the hysteroscopic characteristics \nof patients with infertility and adenomyosis combined \nwith CE, and the correlation between CE and infertility \nin these patients.\nMaterials and methods\nEthical considerations\nThis study was approved by the ethics committee of our \ninstitution (No. KS-LS-2023-001). The need for informed \nconsent was waived due to the retrospective nature of the \nstudy.\nPatients\nWe retrospectively reviewed 154 patients with infertil -\nity who underwent hysteroscopy procedures at Liuzhou \nMaternal and Child Health Care Hospital in Guangxi, \nChina, between January 2020 and June 2023. Overall, \n77 patients were diagnosed with adenomyosis, and the \nremaining 77 patients did not have adenomyosis, which \nwas confirmed by histology or imaging.\nThe inclusion criteria included (i) age between 18 and \n45 years; (ii) confirmed infertility (unable to conceive \nafter a year of consistent sexual activity without using \ncontraception); (iii) without a contraindication for sur -\ngery (e.g., serious cardiovascular disease, coagulopathy, \nor acute reproductive tract infection); and (iv) access to \nthorough medical information.\nThe exclusion criteria included: (i) history of antibiotic \nor anti-inflammatory medication use within 3 months \nbefore surgery; (ii) history of hysteroscopy within 3 \nmonths before surgery; (iii) history of intrauterine adhe -\nsions; (iv) history of uterine anomalies, submucous myo -\nmas, endometrial polyps, intrauterine hyperplasia, and \nendometrial tuberculosis; and (v) diagnosed malignant \nuterine tumor.\nAs reported previously [ 18], all patients with adeno -\nmyosis underwent 1.5T MRI for evaluation for at least \n6 months before hysteroscopic surgery. MRI is consid -\nered the gold standard for the noninvasive identification \nof adenomyosis in patients with infertility [ 19] and can \nclearly demonstrate the presence of adenomyosis with \neither symmetric or asymmetric lesions in the internal or \nexterior layers of the myometrium [20]. The normal junc-\ntional zone (JZ) is located immediately beneath the endo-\nmetrium and represents the innermost compact layer of \nthe myometrium [ 21]. Patients with adenomyosis may \nexhibit focal or diffuse JZ hypertrophy. A JZ thickness of \n12 mm or greater is the most frequently used threshold \nfor diagnosis of adenomyosis, while a measurement of \nless than 8  mm has a high negative predictive value for \nthe presence of the disorder [ 22, 23]. Based on the rela -\ntionship between the adenomyotic lesion, uterine serosa, \nand endometrium, 77 patients with adenomyosis were \nclassified into four subgroups: internal, exterior, intramu-\nral, and full-thickness.\nEvery surgical operation was performed under general \nanesthesia and by experienced gynecological surgeons. \nAll the surgeries were performed in the follicular phase \nof the menstrual cycle using a rigid hysteroscope (KMS, \nHunan, China). An advancing hysteroscope was used \nto carefully examine the front and back walls, two flank \nwalls, two sides of the cervix, and cervical mucosa across \nendometrial surfaces throughout this assessment. This \ntechnique allowed for a close inspection of potential mac-\nroscopic indicators for CE, such as uterine cavity mor -\nphology, intima thickness, color, elasticity, smoothness, \n\nPage 3 of 8\nLi et al. BMC Women's Health          (2024) 24:403 \nglands, stroma, and oviductal orifice [ 24]. Discrete or \nwidespread micropolyps, stromal edema, and generalized \nperiglandular hyperemia were the signs observed dur -\ning hysteroscopy to identify CE [ 25– 27]. An endometrial \nbiopsy was performed at the end of the procedure. The \nformalin-fixed biopsy samples were sent to the Depart -\nment of Pathology for a histological assessment. The \npresence of at least five plasma cells in the endometrial \nstroma per ten HPF confirmed a CE diagnosis following \nan immunohistochemistry (IHC) labeling using a CD138 \nantibody [9, 10].\nStatistical analysis\nStatistical analysis and graphical representations were \nperformed using SPSS 26.0 (SPSS Inc., Chicago, IL). Nor -\nmal distribution data are displayed as mean ± SD, whereas \nskewed distribution data are displayed as median and \ninterquartile range. To contrast different grouping vari -\nables, one-way analysis of variance or the Kruskal-Wallis \ntest was performed. To ascertain the distinctions among \nsubgroups, a post-hoc test was carried out when there \nwas a significant difference. Count data are reported as \npercentages (%), and the chi-square test or Fisher’s exact \ntest was carried out. Subgroup differences were con -\nfirmed using a post-hoc Bonferroni test when there was \na significant difference. Univariate and multivariate logis-\ntic regression analyses were performed to examine the \nfactors influencing CE. Statistical significance was set at \np < .050.\nResults\nClinical parameters\nA total of 77 patients were assigned to the cohort with \nadenomyosis, while another 77 cases were assigned to \nthe cohort without adenomyosis. Table  1 presents the \nresearch population’s demographic characteristics. No \nstatistically significant differences in the length of infer -\ntility, infertility history, time of pregnancy, abortion, and \ndelivery, anti-Müllerian hormone (AMH) levels, or the \npresence of hydrosalpinx were observed between the two \ngroups. Considerable variations were observed in age at \nmenarche, length of menstrual cycle, body mass index \n(BMI), and CA125 levels across both cohorts. In com -\nparison to the non-adenomyosis group, the adenomyosis \ngroup had significantly higher BMI and CA125 levels, \nalthough the menstrual cycle was significantly shorter \nand the age at menarche was significantly lower (Table 1).\nHysteroscopic features and CD138 immunohistochemical \nstaining\nCompared with the non-adenomyosis group, the adeno -\nmyosis group had a higher diagnostic rate of CE (75.3% \nvs. 46.8% according to hysteroscopy and 74.0% vs. 33.8% \naccording to histopathology, both p < .050). Each hys -\nteroscopic feature associated with CE was analyzed \nindividually. In patients with adenomyosis, the primary \nmanifestation linked to a hysteroscopic diagnosis of CE \nwas the presence of micropolyps, while in patients with -\nout adenomyosis, it was hyperemia. Micropolyps were \ndetected in 51.7% of cases in the adenomyosis cohort \nand 27.8% in the non-adenomyosis cohort, indicating \na considerably higher incidence of micropolyps in the \nadenomyosis group ( p < .050). The prevalence of edema, \nhyperplasia, or hyperemia did not significantly differ \nbetween the two cohorts (Table 2). Additionally, the inci-\ndence of CE in patients with internal adenomyosis was \nsignificantly lower than in the other three types, as deter -\nmined by hysteroscopy or histopathology (Table 3).\nLogistic regression analysis of variables affecting CE in \npatients with adenomyosis\nBased on histopathology, the 77 patients with adenomyo-\nsis were divided into two groups: 20 without CE (non-CE \ngroup) and 57 with CE (CE group). The risk variables for \nCE were investigated using univariate logistic regres -\nsion analysis. No significant correlation was observed \nbetween patient age, AMH level, pregnancy frequency, \npresence of endometriosis, presence of hydrosalpinx, \nhistory of uterine cavity surgery, or lesion number or \nTable 1 Clinical characteristics of patients (AM and non-AM \ncohorts)\nVariable AM \ncohort(n = 77)\nNon-AM \ncohort(n = 77)\nP \nvalue\nAge(years) 36.0(32.5, 39.0) 36.0(33.0, 39.5) 0.500\nAge of menarche 12.0(11.0,12.0) 13.0(12.0,13.0) 0.000\nmenstrual cycle(days) 28.0(26.3,29.0) 29.0(28.0,30.0) 0.000\nBMI (kg/m2) 26.8(24.7,30.4) 25.5(23.7,27.9) 0.017\nLength of infertility(years) 4.0(3.0,5.5) 4.0(2.0,6.0) 0.339\nInfertility 0.164\nPrimary infertility(%) 36.4%(28/77) 26.0%(20/77)\nSecondary infertility(%) 63.6%(49/77) 74.0%(57/77)\nPregnancy(n) 1.0(0.0,3.0) 1.0(0.0,3.0) 0.453\nAbortion(n) 1.0(0.0,3.0) 1.0(0.0,3.0) 0.562\nDelivery(n) 0.0(0.0,1.0) 0.0(0.0,1.0) 0.185\nAMH(ng/ml) 2.7(2.0,3.9) 2.7(2.2,3.7) 0.533\nCA125(U/ml) 39.0(0.35.0,50.0) 15.0(9.5,20.0) 0.000\nPresence of \nhydrosalpinx(%)\n48.1%(37/77) 33.8%(26/77) 0.071\nTable 2 The diagnosis of CE based on hysteroscopy and \nhistopathology (AM and non-AM cohorts)\nVariable AM \ncohort(n = 77)\nNon- AM \ncohort(n = 77)\nP \nvalue\nHysteroscopy(+)(%) 75.3%(58/77) 46.8%(36/77) 0.000\nHyperemic(%) 36.2%(21/58) 47.2%(17/36) 0.290\nMicropolyps(%) 51.7%(30/58) 27.8%(10/36) 0.022\nEdema hyperplasia(%) 34.5%(20/58) 38.9%(14/36) 0.667\nCD138 IHC(+)(%) 74.0%(57/77) 33.8%(26/77) 0.000\n\nPage 4 of 8\nLi et al. BMC Women's Health          (2024) 24:403 \nlocation. However, notable distinctions were observed \nbetween the CE and non-CE groups regarding patient \nBMI, CA125 levels, frequency of abortions, and adeno -\nmyosis type (internal vs. full-thickness).\nWe evaluated the associations between BMI, CA125 \nlevels, abortion frequency, adenomyosis type, and CE \npredisposing factors to validate the findings of the uni -\nvariate logistic regression analysis. Compared to patients \nwith internal adenomyosis, those with full-thickness ade -\nnomyosis had a significantly higher CE rate (Table 4).\nUsing receiver operating characteristic (ROC) curves, \nwe examined the connection between BMI and CE \nrates. Based on the information, BMI had the highest \nYouden Index (26.07) for age. Our findings showed that \npatients’ CE rates were significantly higher in those with \na BMI > 26.07 kg/m2 (Fig. 1).\nDiscussion\nThis study compared the uterine cavity conditions of \npatients with and without adenomyosis and confirmed \nthe presence of endometritis through histopathologi -\ncal and immunohistochemical analyses. Adenomyosis \nis being discovered in infertile women more frequently \nas a result of the current tendency of women delaying \npregnancy until their late thirties or early forties [ 13]. \nPrevious studies have suggested that multiple parity is a \nprotective factor against adenomyosis, whereas a short \nmenstruation cycle, early age of menarche, history of \ndepression, and increased BMI are considered promoting \nfactors [ 28– 30]. Our study found that the BMI and \nCA125 levels were significantly higher in the adenomyo -\nsis cohort than in the non-adenomyosis cohort. However, \nthe age at menarche was significantly lower, and the men-\nstrual cycle was significantly shorter, which supports the \nfindings of previous studies. In our opinion, early men -\narche can be interpreted as a surrogate indicator of high \nlevels of pro-inflammatory estrogen exposure during \ndevelopment [ 31], and recurrent menstruation-induced \nimpaired spontaneous decidualization could increase the \nlikelihood of adenomyosis development.\nThe exact mechanism behind the correlation between \ninfertility and adenomyosis remains elusive. Neverthe -\nless, several hypotheses have been proposed to address \nthis association, including altered endometrial function/\nreceptivity, impairment of utero-tubal sperm transport, \nmenstrual cycle disruption, local inflammation trig -\ngered by adenomyosis, and dysregulation of local hor -\nmone metabolism, culminating in a hyperestrogenic \nlocal environment [ 32]. The incidence of CE brought \non by intrauterine microbial infections may be linked to \npoor reproductive outcomes in women with adenomyo -\nsis [17]. Several recent investigations have demonstrated \nthat women with and without adenomyosis have distinct \nvaginal microbiota patterns [33]. Notably, adenomyosis is \nassociated with a distinctive endometrial microbiota pro-\nfile, with certain pathogenic bacteria such as Citrobacter \nfreundii, Prevotella copri, and Burkholderia cepacia being \nimplicated [34]. The activation of cytokines that promote \nTable 3 Comparison of incidence of CE in patients with different types of adenomyosis\nParameter Internal(n = 25) External(n = 17) Intramural(n = 10) Full-thickness(n = 25) P\nHysteroscopy(+)(%) 56.0%(14/25)a 76.5%(13/17) 100%(10/10) 84.0%(21/25) 0.026\nCD138 IHC(+)(%) 48.0%(12/25)a 82.4%(14/17) 90.0%(9/10) 88.0%(22/25) 0.006\nNotes: a. Indicates a significant difference between patients with internal adenomyosis and patients with external, intramural, and full-thickness adenomyosis \n(p < .05).\nTable 4 Univarlate and multivariate logistic regresslon analysis of factors influencing CE\nVariable Univariate logistic OR (95%CI) P Multivariate logistic OR (95%CI) P\nAge(years) 1.036 0.541 - -\nBMI (kg/m2) 1.594 0.000 1.535 0.007\nAMH(ng/ml) 1.017 0.944 - -\nCA125(U/ml) 1.090 0.011 1.087 0.093\nPregnancy frequency 0.796 0.072 - -\nAbortion frequency 0.718 0.021 0.660 0.053\nPresence of endometriosis 0.549 0.280 - -\nPresence of hydrosalpinx积水 0.847 0.751 - -\nHistory of uterine cavity surgery frequency 0.830 0.171 - -\nType of adenomyosis (vs. Full-thickness)\nInternal 0.128 0.007 0.116 0.030\nExternal 0.192 0.039 0.375 0.315\nIntramural 0.635 0.643 0.149 0.126\nLocation of lesions(vs. Fundus)\nAnterior 1.038 0.954 - -\nPosterior 0.677 0.551 - -\n\nPage 5 of 8\nLi et al. BMC Women's Health          (2024) 24:403 \ninflammation, coupled with the production of virulence \nfactors by specific endometrial microbiota, subsequently \ninfluences various cellular processes, including inflam -\nmation, immunoregulation, survival, proliferation, inva -\nsion, and angiogenesis of endometrial cells. [ 35– 37]. \nBased on available data, the association between adeno -\nmyosis and poor reproductive outcomes may be attrib -\nuted to the destruction of the microvillus and axonemal \nalteration within the apical endometrium due to endo -\nmetrial inflammation [ 38]. Currently, CE diagnosis is \nbased on the results of endometrial biopsy and hystero -\nscopic examination. Despite having limited participants, \nour study provides a deeper understanding of the preva -\nlence of endometritis in patients with adenomyosis and \ninfertility. Our findings demonstrated that compared to \nthe non-adenomyosis group, the adenomyosis group had \na significantly higher prevalence of CE. According to \nKhan et al., women with adenomyosis had a higher inci -\ndence of CE (about 60%) than those with uterine myo -\nmas (10%) [ 17]. In contrast, both cohort groups showed \na higher prevalence of CE, confirming high prevalence \nof CE in low-fertility population. However, there was a \nlack of consensus between histological and hysteroscopic \nfindings in each investigation (with agreement ranging \nfrom 46.5 to 95% for CE diagnosis or exclusion) (34). \nEven in instances where hysteroscopic indications of CE \nare present, confirmation through endometrial biopsy \nand histological analysis remains imperative. Histology \nremains the gold standard diagnostic approach owing to \ndiscrepancies frequently observed between hysteroscopy \nand histopathology outcomes among patients. Conse -\nquently, relying solely on positive hysteroscopic findings \nwithout histological verification may lead to erroneous \nCE diagnoses, potentially resulting in overdiagnosis [39].\nOur results also showed that the main presentation of \na hysteroscopic diagnosis of CE in patients with adeno -\nmyosis was micropolyps, whereas that in the non-adeno -\nmyosis group was hyperemia. Micropolyps are recently \ndiscovered tiny intrauterine growths < 1  mm in size \nand have a unique connective vascular axis that can be \nfound across the endometrial surface or in specific loca -\ntions [26]. The histological examination of the connective \naxis of micropolyps reveals the presence of inflamma -\ntory cell accumulation; furthermore, it is proposed that \nFig. 1 Receiver operating characteristic curves\n \n\nPage 6 of 8\nLi et al. BMC Women's Health          (2024) 24:403 \nmicropolyps signify an endometrial proliferative stimulus \nowing to an increased level of inflammation [ 26, 27]. It \nis speculated that the appearance of micropolyp features \nmay be related to changes in endometrial receptors in \npatients with adenomyosis. Estrogen receptor expres -\nsion increases with an increase in inflammation, whereas \nprogesterone receptor expression decreases in the bor -\nder area, inducing progesterone resistance [ 40], damag -\ning endometrial health, and leading to local tissue edema \nand proliferation. However, the specific pathological and \nphysiological changes require further exploration.\nBased on the findings of previous studies, the differ -\nent subtypes may represent heterogeneous etiologies \nand pathogenesis. Intrinsic adenomyosis may occur \nwhen the endometrium traverses directly into the inner \nand medial myometrium. External adenomyosis may \noccur as a consequence of direct invasion of the serosa \nby extrauterine endometriosis. Intramural adenomyosis \nmay be caused by metaplasia or epithelial-mesenchymal \ntransition (EMT). A diverse combination of different \ntypes of advanced disease may result in full-thickness \nadenomyosis [ 41]. Prior research [ 18] has established a \nstrong correlation between variations in clinical mani -\nfestation and pregnancy outcomes and the classifica -\ntion of adenomyosis. Consequently, it is indisputable \nthat diverse treatment approaches and subtype-specific \nadenomyosis analysis must be considered when analyz -\ning the impact of adenomyosis on pregnancy outcomes. \nIn this study, patients with internal adenomyosis had the \nlowest incidence of CE. Additionally, the incidence of CE \nwas found to be influenced by the type of adenomyosis, \nas indicated by the multivariate logistic regression analy -\nsis. Compared with patients with internal adenomyosis, \nthose with full-thickness adenomyosis had a significantly \nhigher CE rate. As adenomyotic lesions progress and \nbecome stiffer due to increased fibrosis, pro-fibrotic mol-\necules originating from the lesions migrate toward the \nadjacent endometrial-myometrial interface [ 42]. EMT \nand fibroblast-to-myofibroblast trans-differentiation \nare facilitated by macrophage-secreted inflammatory \ncytokines and growth factors, which ultimately result in \nlesion invasion and fibrosis [43]. The pain associated with \nadenomyosis was found to be positively correlated with \nthe quantity of accumulated macrophages [ 44]. Based on \nour previous findings, patients with full-thickness ade -\nnomyosis experienced more menstrual discomfort than \nthose with internal adenomyosis [ 18]. Combining the \nabove mechanisms and clinical manifestations may help \nexplain this phenomenon. Conversely, Khan et al. discov-\nered that intrinsic adenomyosis had a considerably higher \ntissue infiltration of macrophages in the endometria than \nextrinsic adenomyosis. However, a lack of substantial dif-\nferentiation in the incidence of CE was seen between the \ntwo adenomyosis types. Similarly, in endometria from \nwomen with various forms of adenomyosis, there were no \nappreciable variations in the location of CD138-stained \nplasma cells [ 17]. The endometrial regions and phases \nof the menstrual cycle of the samples may account for \nthese variations. Epithelial cells derived from the secre -\ntory phase endometrium of adenomyotic uteri exhibited \ndecreased levels of pro-inflammatory cytokines in vitro. \nThis finding may indicate that stromal cells present in \nadenomyosis lesions, specifically during the proliferative \nphase, play a significant role in mediating the locally dys -\nregulated immunological reaction [ 45]. Incidence of CE \nwas found to be considerably higher on the homolateral \nside compared to the contralateral side in patients with \nlocalized adenomyosis [ 17]. All our research samples \nwere in the proliferative phase, but there were no spe -\ncific endometrial regions. This study offers an exhaustive \nfoundation for subsequent investigations in this field.\nWomen with uncontrolled endometrial inflamma -\ntion are prone to developing adenomyosis, the central \ncomponent of uterine adenomyotic lesions. However, \nthe causal relationship between adenomyosis and CE \nremains unclear, and a comprehensive assessment of \nits effects on female fertility is required. Using univari -\nate and multivariate analyses, we investigated the fac -\ntors that contribute to CE in patients with adenomyosis \nand infertility. Multiple logistic regression analysis find -\nings indicated that BMI influences the incidence of CE \nin addition to adenomyosis type. One case-control study \nshowed that overweight or obese women had a higher \nrisk of developing adenomyosis [ 46]. Women diagnosed \nwith adenomyosis were more prone to central obesity \nand had reduced levels of high-density lipoprotein C, \naccording to recent research examining the individual \ncomponents of metabolic syndrome [ 47]. In a study on \npolycystic ovary syndrome (PCOS), it was found that \nobesity increases both hyperandrogenism and low-grade \ninflammation in patients with PCOS [ 48]. The degree of \nobesity has a major impact on the reproductive system in \nwomen. Increased endometrial levels of free fatty acids \ncan negatively impact endometrial function in obese \nPCOS patients [ 49]. Weight loss is a well-known ele -\nment in restoring endometrial function [ 50]. Our study \nrevealed a significantly higher CE incidence in patients \nwith a BMI > 26.07 kg/m2 based on ROC curves, and we \nhypothesized that BMI may have a predictive role in the \nCE incidence rate in adenomyosis, and weight loss may \nreduce the incidence of adenomyosis and CE. However, \nmore studies on metabolic risk factors related to adeno -\nmyosis must be conducted to confirm this hypothesis.\nThe design of this study had some limitations. First, the \nstudy examined patients’ observations from a single loca-\ntion and was restricted to certain types of samples. Future \nresearch should consider different menstrual cycle stages, \nand endometrial regions of the uterine cavity should be \n\nPage 7 of 8\nLi et al. BMC Women's Health          (2024) 24:403 \ndistinguished and detected during sampling. Second, \nhysteroscopy and endometrial biopsy were performed \nby different physicians, possibly introducing heterogene -\nity. Our current research has opened new directions for \nexploring the exact mechanism and causal relationship \nbetween CE and adenomyosis, as well as their impact on \nfertility outcomes. Further research using larger sample \nsizes and more comprehensive data is required to vali -\ndate the correlation between CE and adenomyosis in \npatients with infertility.\nConclusions\nWe retrospectively studied incidence of CE in patients \nwith infertility with different forms of adenomyosis and \nattempted to explore the related high-risk factors. The \nprevalence of CE is significantly higher in patients with \nadenomyosis and infertility. The differences in the inci -\ndence of CE are closely associated with the classification \nof adenomyosis. When patients with infertility are diag -\nnosed with adenomyosis, it is recommended to clarify \nthe classification and screen for endometritis. Further \nresearch is required to explore the mechanisms underly -\ning these effects.\nAbbreviations\nCE  chronic endometritis\nMRI  magnetic resonance imaging\nBMI  body mass index\nRPL  recurrent pregnancy loss\nRIF  repeated implantation failure\nHPF  High-power field\nIHC  immunohistochemistry\nAMH  anti-Müllerian hormone\nROC  receiver operating characteristic\nEMT  epithelial-mesenchymal transition\nPCOS  polycystic ovary syndrome\nAcknowledgements\nNot applicable.\nAuthor contributions\nDingyuan Zeng and Li Fan designed the study. Jingjing Li and Jiajia Wei \ncontributed to data collection, data analysis, and writing the manuscript. Both \nJingjing Li and Jiajia Wei contributed equally to this study. Saiqiong Chen \nand Jing Chen contributed to data collection. Saiqiong Chen, Xindan Wang, \nand Jing Chen performed the surgical procedures. All authors reviewed the \nmanuscript and approved the final version of the manuscript for publication.\nFunding\nThis study was funded by the Guangxi Science and Technology Plan Project \nunder a Grant from the Guangxi Clinical Research Center for Obstetrics \nand Gynecology (Grant No. GuiKe AD22035223), and the Key Research and \nDevelopment Program of Guangxi (Grant No. Guike AB18126056). The funders \nhad no role in study design, data collection and analysis, decision to publish, \nor preparation of the manuscript.\nData availability\nThe datasets used and/or analysed during the current study available from the \ncorresponding author on reasonable request.\nDeclarations\nEthics approval and consent to participate\nThis study was approved by the Ethics Committee of Liuzhou Maternal and \nChild Health Care Hospital (Ethics No. KS-LS-2023-001). Written informed \nconsent was obtained from all subjects.\nConsent for publication\nNot applicable.\nCompeting interests\nThe authors declare no competing interests.\nReceived: 23 March 2024 / Accepted: 4 July 2024\nReferences\n1. Michels TC. Chronic endometritis. Am Family Phys. 1995;52(1):217–22.\n2. Bayer-Garner IB, Nickell JA, Korourian S. Routine syndecan-1 immunohisto-\nchemistry aids in the diagnosis of chronic endometritis. Arch Pathol Lab Med. \n2004;128(9):1000–3.\n3. Johnston-MacAnanny EB, Hartnett J, Engmann LL, Nulsen JC, Sanders \nMM, Benadiva CA. Chronic endometritis is a frequent finding in women \nwith recurrent implantation failure after in vitro fertilization. Fertil Steril. \n2010;93(2):437–41.\n4. Vitagliano A, Saccardi C, Noventa M, Di Spiezio Sardo A, Saccone G, Cicinelli \nE, Pizzi S, Andrisani A, Litta PS. 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