Chronic endometritis increases the recurrence of endometrial polyps in premenopausal women after hysteroscopic polypectomy

Chronic endometritis increases the recurrence of endometrial polyps in premenopausal women after hysteroscopic polypectomy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Chronic endometritis increases the recurrence of endometrial polyps in premenopausal women after hysteroscopic polypectomy Jing Huang, Xin Yu, Yue Liu, Chengchao Du, Honggui Zhou, Yamei Yang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1578380/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: To evaluate the impact of chronic endometritis (CE) on the recurrence of endometrial polyps (EPs) in premenopausal women who underwent hysteroscopic polypectomy. Methods: We conducted a retrospective observational cohort study in a university-affiliated hospital. Premenopausal women who underwent hysteroscopic polypectomy were enrolled, and those with definite confounding factors for polyp recurrence, including endometriosis and previous polypectomy history were excluded. A total of 233 women were enrolled in this study, including 64 cases (27.5%) with CE and 169 cases (72.5%) without CE. Comparison of the recurrence rate of EPs was performed in women with or without CE at each monitoring stage (i.e., at 3, 6, 9 and 12 months) after hysteroscopic polypectomy. Result(s): The EPs recurrence rates at one year in patients with and without CE were 26.6% (95% confidence interval [CI] 15.8%–37.4%) and 9.5% (95% CI 5.0%–14.0%), respectively, with an overall cure rate of 14.2% (95% CI 9.7%–18.7%). The hazard ratio (HR) for EPs recurrence in the EPs with CE cohort versus the EPs without CE cohort was 3.08 (95% CI 1.56-6.09) (P=0.001). Similarly, the EPs recurrence rate was significantly higher in women with CE than in those without CE at each monitoring stage (i.e., 3, 6, and 9 months). CE and multiple EPs were risk factors for polyp recurrence. The HR for EPs recurrence in the EPs with CE cohort compared with the EPs without CE cohort was 3.06, after adjustment for the number of polyps. Conclusion(s): CE was a harmful factor for the recurrence of EPs in premenopausal women after hysteroscopic polypectomy. Thus, routine screening for CE are needed, and unlike unchangeable factors, CE can be changed by antibiotics treatment. Frequent monitoring was needed for multiple EPs as the number of EPs also contributed to polyp recurrence. Recurrence chronic endometritis endometrial polyps hysteroscopic polypectomy risk factor Figures Figure 1 Introduction Endometrial polyps (EPs) represent a common benign gynecological condition that manifests via excessive local hyperplasia of the interstitial and endometrial glands. The prevalence of EPs ranges from 7.8–34.9% across different populations [ 1 ]. Many studies have shown that a transient, repetitive and persistent impaired inflammatory state of the endometrium (IISE) is a major factor for most problematic disorders in gynecology, including EPs [ 2 ]. EPs are commonly associated with chronic endometritis (CE) in premenopausal women suffering from abnormal uterine bleeding (AUB) [ 3 ]. The prevalence of CE in premenopausal women with AUB or reproductive failure on EPs is increased, with one clinical trial of 209 cases reporting a prevalence of 28.7% [ 4 ]. CE involves persistent local inflammation of endometrium, characterized by the presence of plasma cells infiltrating the interstitium [ 5 , 6 ]. CE is usually asymptomatic or presents only with mild symptoms, such as AUB, pelvic pain, dyspareunia and leucorrhea, as well as infertility and miscarriage, all of which are very similar to the symptoms of EPs [ 7 ]. However, the spontaneous cure rate for CE is very low, with a randomized clinical trial reporting a rate of only 12.7% [ 8 ]. The optimal treatment currently for CE is oral antibiotics [ 9 , 10 ]. EPs are associated with AUB, infertility and recurrent reproductive failure [ 1 , 11 , 12 ]. Hysteroscopic polypectomy has always been considered the gold standard treatment for EPs [ 12 , 13 ]. Across several studies, the recurrence rate of EPs within 12 months after hysteroscopic polypectomy has ranged widely from 5.6–31.4% [ 14 – 16 ]. A large number of EPs, endometriosis and previous polypectomy history are established independent risk factors for the recurrence of polyps [ 15 , 16 ]. In addition, late menopause and obesity increase the occurrence of EPs [ 17 ]. However, the factors influencing the recurrence potential of EPs after hysteroscopic polypectomy remain rather controversial. In the present retrospective cohort study, we investigated whether CE increased the recurrence of EPs in premenopausal women after hysteroscopic polypectomy. Materials And Methods Study Design Hysteroscopic polypectomy patients with 12 months of follow-up data were enrolled, and those with definite confounding factors for polyp recurrence, including endometriosis and previous polypectomy history were excluded. A total of 233 premenopausal women after hysteroscopic polypectomy were enrolled in this study, including 64 cases with CE and 169 cases without CE. Comparison of the recurrence rate of EPs was performed in women with and without CE at each monitoring stage (i.e., at 3, 6, 9 and 12 months). The expression of CD138 in the endometrium was analyzed by immunohistochemistry to identify CE. Participants Participants involved in this retrospective cohort study were premenopausal women (18–50 years) with data from 12 months of follow-up after treatment with hysteroscopic polypectomy in the follicular phase between January 2019 and January 2020 at the Department of Obstetrics and Gynecology, Affiliated Hospital of North Sichuan Medical College (China). Institutional Review Board approval was obtained from the Ethics Committee of the Affiliated Hospital of North Sichuan Medical College (China) at January 2019 before the experiment was started (2019ER(R)017). All patients signed a written informed consent form, and this study was conducted in accordance with the principles of the Declaration of Helsinki. The exclusion criteria were inflammatory disease (PID) occurring in the 12 months after hysteroscopic polypectomy and the use of hormone therapy or antibiotics. Hysteroscopic resection and endometrial biopsy Hysteroscopic polypectomy was conducted in the follicular phase with a bipolar plasmakinetic resection system under intravenous anesthesia using a 3-mm 15° inside rigid hysteroscope and a 8.5-mm outside sheath (Olympus, Tokyo, Japan). All operations were done by the same physician (DC Qu). Endometrial samples were obtained visually using an unpowered plasma cutting ring from the upper uterine cavity, while hysteroscopic polypectomy was performed to remove local polyps. Immunohistochemistry A histopathology consultant performed immunohistochemical detection of CD138 on the endometrial specimen slices as previously described [ 18 , 19 ]. The clone of anti-CD138 monoclonal antibody used in our study was MI15 Cell Marque (Fuzhou Maixin Biotechnology Co., Ltd., Fuzhou, China). At least 50 high-power fields were examined for each specimen. CD138 expression was classified as positive if one or more positively stained plasma cells were identified per 10 high power fields and negative if less than one positively stained plasma cell was identified per 10 high power fields [ 18 , 19 ]. Follow up Women who underwent hysteroscopic polypectomy at our hysteroscopic center were surveilled routinely. Transvaginal ultrasonography was performed to evaluate the uterine cavity condition at 3, 6, 9 and 12 months after hysteroscopic polypectomy. Women without the full 12 months of surveillance data were not enrolled in this study. Power calculation The retrospective cohort study included 64 experimental subjects, 169 control subjects, an accrual interval of 12 months, and additional follow-up after the accrual interval of 12 months. The recurrence rates were 26.6% in the experimental group and 9.5% in the control group. With type I error of 0.05, the statistical power can reach 0.9. Statistical analyses For all statistical analyses, we used SPSS version 22.0 (SPSS, Inc, Chicago, IL, USA), and a P value < 0.05 was considered to be statistically significant. After analyzing the distribution of the data and confirming that the age and body mass index (BMI) of the population were not normally distributed, we adopted the Mann-Whitney U test to analyze age and BMI expressed as median (interquartile range). Categoric variables were compared using the chi-square test. The chi-square test was used to compare the recurrence of EPs between each group at each stage. The Kaplan–Meier method with the log-rank test was used to estimate recurrence-free survival and to compare recurrence rates between the two groups. Cox regression models were used to compare the recurrence risk of the two groups in both univariate and multivariate analyses. Factors for which P < 0.05 on univariate analyses were included in the subsequent multivariable model. Results Comparison of general and clinical features of EPs patients with and without CE A total of 233 women with 12 months follow-up data after hysteroscopic polypectomy for EPs treatment were enrolled in this study, including 64 cases with CE and 169 cases without CE. Thus, the prevalence of CE in the population was 27.5% (64/233). The demographic details and clinical features of the two groups of patients are shown in Table 1 . No statistically significant differences in demographic details and clinical features were found between the two groups of patients (all P > 0.05). Table 1 Baseline demographics of the enrolled patients. Characteristics EPs with CE (n = 64) EPs without CE (n = 169) P value Age, y (median (Q3-Q1)) 33 (9) 34 (8) 0.092 BMI, kg/m 2 (median (Q3-Q1)) 21.7 (3.9) 22.4 (4.0) 0.120 Polyp number, n (%) 0.713 Solitary 17 (26.6%) 49 (29.0%) Multiple 47 (73.4%) 120 (71.0%) Polyp size (cm), n (%) 0.314 ≤ 1 12 (18.8%) 20 (11.8%) > 1, ≤2 49 (76.6%) 136 (80.5%) > 2 3 (4.7%) 13 (7.7%) Note: EPs - endometrial polyps; CE - chronic endometritis; BMI - body mass index. Comparison of EPs recurrence rate between patients with and without CE During the 12-month follow-up, a total of 33 women experienced EPs recurrence, including 17 cases with CE and 16 cases without CE. The recurrence rates of EPs with CE and without CE were 26.6% (95% confidence interval [CI] 15.8–37.4%) and 9.5% (95% CI 5.0–14.0%), respectively, with an overall cure rate of 14.2% (95% CI 9.7–18.7%) (Fig. 1 ). The EPs recurrence rate was higher in patients with CE (P = 0.001). The HR for EPs recurrence in the EPs with CE cohort versus the EPs without CE cohort was 3.08 (95% CI 1.56–6.09, P < 0.01; Table 2 ). Table 2 Risk factors for recurrence of EPs from univariate and multivariate analyses. Characteristics HR (95%CI) P value Univariate analysis Age 1.00 (0.95–1.06) 0.996 BMI 0.93 (0.81–1.05) 0.245 Polyp size (cm) (vs. ≤1) > 1, ≤2 1.54 (0.16–14.80) 0.709 > 2 2.57 (0.35–18.89) 0.353 Multiple EPs vs. solitary EP 3.02 (1.06–8.60) 0.038 CE 3.08 (1.56–6.09) 0.001 Multivariate analysis CE 3.06 (1.54–6.05) 0.001 Multiple EPs vs. solitary EP 2.99 (1.05–8.91) 0.040 Note: BMI - body mass index; EPs - endometrial polyps; EP - endometrial polyp; CE - chronic endometritis. Similarly, in the group with CE, there were 5 cases of EPs recurrence at 3 months, 10 cases at 6 months, and 14 cases at 9 months. In the group without CE, there were 2 cases of EPs recurrence at 3 months, 7 cases at 6 months, and 12 cases at 9 months. The recurrence rates of EPs were significantly higher in women with CE than in those without CE at every monitoring stage, i.e., 7.8% (95% CI 1.1–14.5%) vs. 1.2% (95% CI -0.4–2.8%, P = 0.018) at 3 months, 15.6% (95% CI 6.8–24.4%) vs. 4.1% (95% CI 1.2–7.0%, P = 0.003) at 6 months, and 21.9% (95% CI 11.7–32.1%) vs. 7.1% (95% CI 3.2–11.0%, P = 0.001) at 9 months (Fig. 1 ). Factors associated with recurrence of EPs Univariate and multivariate Cox regression models were used to assess the factors associated with the recurrence of EPs. Univariate analysis showed that the recurrence of EPs was not affected by age, BMI, or polyp size, but significantly higher EPs recurrence rates were observed in women with multiple EPs or with CE compared with the rates in patients without the respective conditions (Table 2 , P < 0.05 and P < 0.05, respectively). Multivariate analysis confirmed that CE was a harmful factor for the recurrence of EPs (HR 3.06, 95% CI 1.54–6.05, P = 0.001). In addition, as previously mentioned [ 15 , 16 ], the presence of multiple EPs also contributed to the recurrence of EPs (HR 2.99, 95% CI 1.05–8.91, P = 0.040). Discussion The reported recurrence rate of EPs after hysteroscopic polypectomy had varied widely [ 14 – 16 ], and the factors influencing the recurrence potential of EPs after hysteroscopic polypectomy were still controversial. Furthermore, the known definite independent risk factors are almost unchangeable, such as the number of polyps and previous polypectomy history. In this study, the overall recurrence rate of EPs in premenopausal women was 14.2% at 12 months after hysteroscopic polypectomy, which is consistent with rates reported in previous studies [ 14 , 20 – 22 ]. Although, after subgroup analysis according to CE, the recurrence rate of EPs in premenopausal women increased to 26.6%, and CE played a harmful role in the recurrence of EPs. To the best of our knowledge, our study is the first to report the effect of CE. Similarly, the recurrence rate of EPs was significantly higher in women with CE than in those without CE at each monitoring stage, i.e., 7.8% vs. 1.2% at 3 months, 15.6% vs. 4.1% at 6 months, and 21.9% vs. 7.1% at 9 months. This may be a possible explanation for the wide range of the EPs recurrence rates (5.6–31.4%) previously reported during 1-year follow-up [ 14 – 16 ]. CE may have been a concealed factor for the recurrence of EPs. The underlying mechanism of the harmful effects of CE is currently unknown. One possible explanation is that the vessel axis of EPs may actually originate from the evolution of vascular changes associated with endometritis [ 23 ]. In addition, persistent IISE is a major factor for the occurrence of EPs, as CE participates in the pathogenesis of EPs [ 2 ]. CE is a disease involving destruction of the homeostasis between microorganisms in the endometrium and the host immune system. The most common bacterial pathogens causing CE are reported to be Enterobacteriaceae , Enterococcus , Streptococcus , Staphylococcus , Mycoplasma , and Ureaplasma [ 24 ]. Similarly, another study found that the most abundant genus in the microbiota of endometrium with CE is non- Lactobacillus [ 25 ]. Antibiotics are effective for treating CE [ 8 , 19 , 26 – 28 ], as it is caused by bacterial pathogens. Although CE was an independent risk factor for polyp recurrence, unlike unchangeable factors, CE can be changed by treatment of antibiotic. In this retrospective cohort study of 233 participants who underwent hysteroscopic polypectomy as treatment for EPs, polyp recurrence rates were significantly higher in women with CE than in those without CE at each monitoring stage, i.e., at 3, 6, 9 and 12 months. These findings indicate a harmful role of CE in the recurrence of EPs in premenopausal women after hysteroscopic polypectomy. The HR for EPs recurrence in the EPs with CE cohort compared with the EPs without CE cohort was 3.06, after adjustment for the number of polyps. Our study demonstrated CE and the number of polyps were risk factors for the recurrence of EPs in premenopausal women after hysteroscopic polypectomy. CE can be diagnosed easily when undergoing hysteroscopic polypectomy, and be treated with empirical use of antibiotic. Thus, we suggest that women undergo an examination for CE when undergoing hysteroscopic polypectomy and receive treatment for CE once a diagnosis is made. Frequent monitoring was needed for multiple polyps after hysteroscopic polypectomy. In the current study, to better evaluate the impact of CE on polyp recurrence, patients with definite external confounding factors for polyp recurrence, including endometriosis and previous polypectomy history, were excluded. The recurrence of EPs was not affected by age, BMI, or polyp size, which are consistent with previous studies [ 15 , 16 ]. There are some limitations in this study. For example, because this was a retrospective review, we could not take into account enough factors affecting the recurrence of EPs, and other concealed factors need to be explored. Furthermore, CE treated with antibiotic cohort was not included in our study, we do not know whether the effect of CE on the recurrence of EPs can be eliminated when treated with antibiotic. Conclusion In conclusion, this study demonstrated that CE was a harmful factor for the recurrence of EPs in premenopausal women after hysteroscopic polypectomy. Thus, routine screening and treatment are needed for CE. Multiple EPs also contributed to polyp recurrence. The role of CE in the recurrence of EPs needs to be further confirmed by randomized trials with a large sample size, and the potential mechanism of the harmful effects of CE remains to be investigated. Declarations Acknowledgments The authors thank Wei Xu for processing statistical data. Author contributions DQ and JH designed most of the investigation, data analysis and wrote the manuscript; XY and YL performed most of the investigation; CD and YY contributed to data curation; DQ and HZ contributed to interpretation of the data and analyses. All of the authors have read and approved the manuscript. Funding information The work was supported by the Bureau of Science and Technology Nanchong City (19SXHZ0338) and Sichuan Science and Technology Program (2018SZ0264). Data Availability The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.. Compliance with Ethical Standards Conflicts of Interest The authors declare that they have no conflict of interest. Ethics Approval All procedures performed were ethically approved. Consent for Publication All involved consented to publication. Code Availability Not applicable. References Clark TJ, Stevenson H. Endometrial Polyps and Abnormal Uterine Bleeding (AUB-P): What is the relationship, how are they diagnosed and how are they treated? Best Pract Res Clin Obstet Gynaecol. 2017;40:89–104. Drizi A, Djokovic D, Laganà AS, van Herendael B. Impaired inflammatory state of the endometrium: a multifaceted approach to endometrial inflammation. Current insights and future directions. Prz Menopauzalny. 2020;19(2):90–100. Cicinelli E, Bettocchi S, de Ziegler D, Loizzi V, Cormio G, Marinaccio M, et al. Chronic Endometritis, a Common Disease Hidden Behind Endometrial Polyps in Premenopausal Women: First Evidence From a Case-Control Study. J Minim Invasive Gynecol. 2019;26(7):1346–50. Song D, Feng X, Zhang Q, Xia E, Xiao Y, Xie W, et al. Prevalence and confounders of chronic endometritis in premenopausal women with abnormal bleeding or reproductive failure. Reprod Biomed Online. 2018;36(1):78–83. Kitaya K, Takeuchi T, Mizuta S, Matsubayashi H, Ishikawa T. Endometritis: new time, new concepts. Fertil Steril. 2018;110(3):344–50. Puente E, Alonso L, Laganà AS, Ghezzi F, Casarin J, Carugno J. Chronic Endometritis: Old Problem, Novel Insights and Future Challenges. Int J Fertil Steril. 2020;13(4):250–6. Kasius JC, Fatemi HM, Bourgain C, Sie-Go DM, Eijkemans RJ, Fauser BC, et al. The impact of chronic endometritis on reproductive outcome. Fertil Steril. 2011;96(6):1451–6. Dongmei S. RCT(Randomized Clinical Trial) of Antibiotic Therapy in Chronic Endometritis - Full Text View - ClinicalTrials.gov: NIH: U.S. National Library of Medicine 2016. Cicinelli E, Matteo M, Tinelli R, Lepera A, Alfonso R, Indraccolo U, et al. Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy. Hum Reprod. 2015;30(2):323–30. Cicinelli E, Matteo M, Trojano G, Mitola PC, Tinelli R, Vitagliano A. Chronic endometritis in patients with unexplained infertility: Prevalence and effects of antibiotic treatment on spontaneous conception. Am J Reprod Immunol. 2018;79(1). Nijkang NP, Anderson L, Markham R, Manconi F. Endometrial polyps: Pathogenesis, sequelae and treatment. SAGE Open Med. 2019;7:2050312119848247. Sheng KK, Lyons SD. To treat or not to treat? An evidence-based practice guide for the management of endometrial polyps. Climacteric. 2020;23(4):336–42. American Association of Gynecologic Laparoscopists. AAGL practice report: practice guidelines for the diagnosis and management of endometrial polyps. J Minim Invasive Gynecol. 2012;19(1):3–10. Ciscato A, Zare SY, Fadare O. The significance of recurrence in endometrial polyps: a clinicopathologic analysis. Hum Pathol. 2020;100:38–44. Gu F, Zhang H, Ruan S, Li J, Liu X, Xu Y, et al. High number of endometrial polyps is a strong predictor of recurrence: findings of a prospective cohort study in reproductive-age women. Fertil Steril. 2018;109(3):493–500. Yang JH, Chen CD, Chen SU, Yang YS, Chen MJ. Factors Influencing the Recurrence Potential of Benign Endometrial Polyps after Hysteroscopic Polypectomy. PLoS One. 2015;10(12):e0144857. Oguz S, Sargin A, Kelekci S, Aytan H, Tapisiz OL, Mollamahmutoglu L. The role of hormone replacement therapy in endometrial polyp formation. Maturitas. 2005;50(3):231–6. Song D, Li TC, Zhang Y, Feng X, Xia E, Huang X, et al. Correlation between hysteroscopy findings and chronic endometritis. Fertil Steril. 2019;111(4):772–9. Qu D, Yang M, Tong L, Yu X, Jing Q, Yang Y, et al. Combination of Dydrogesterone and Antibiotic Versus Antibiotic Alone for Chronic Endometritis: a Randomized Controlled Trial Study. Reprod Sci. 2021. Wang Y, Yang M, Huang X, Li X, Lin E, Feng Y. Prevention of Benign Endometrial Polyp Recurrence Using a Levonorgestrel-releasing Intrauterine System in Premenopausal Patients: A Retrospective Cohort Study. J Minim Invasive Gynecol. 2020;27(6):1281–6. Ceci O, Franchini M, Cardinale S, Cannone R, Giarrè G, Fascilla FD, et al. Comparison of endometrial polyp recurrence in fertile women after office hysteroscopic endometrial polypectomy using two widely spread techniques. J Obstet Gynaecol Res. 2020;46(10):2084–91. Li F, Wei S, Yang S, Liu Z, Nan F. Post hysteroscopic progesterone hormone therapy in the treatment of endometrial polyps. Pak J Med Sci. 2018;34(5):1267–71. Carvalho FM, Aguiar FN, Tomioka R, de Oliveira RM, Frantz N, Ueno J. Functional endometrial polyps in infertile asymptomatic patients: a possible evolution of vascular changes secondary to endometritis. Eur J Obstet Gynecol Reprod Biol. 2013;170(1):152–6. Moreno I, Cicinelli E, Garcia-Grau I, Gonzalez-Monfort M, Bau D, Vilella F, et al. The diagnosis of chronic endometritis in infertile asymptomatic women: a comparative study of histology, microbial cultures, hysteroscopy, and molecular microbiology. Am J Obstet Gynecol. 2018;218(6):602 .e1-.e16 . Liu Y, Ko EY, Wong KK, Chen X, Cheung WC, Law TS, et al. Endometrial microbiota in infertile women with and without chronic endometritis as diagnosed using a quantitative and reference range-based method. Fertil Steril. 2019;112(4):707 – 17.e1. Johnston-MacAnanny EB, Hartnett J, Engmann LL, Nulsen JC, Sanders MM, Benadiva CA. Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization. Fertil Steril. 2010;93(2):437–41. McQueen DB, Bernardi LA, Stephenson MD. Chronic endometritis in women with recurrent early pregnancy loss and/or fetal demise. Fertil Steril. 2014;101(4):1026–30. Kitaya K, Matsubayashi H, Takaya Y, Nishiyama R, Yamaguchi K, Takeuchi T, et al. Live birth rate following oral antibiotic treatment for chronic endometritis in infertile women with repeated implantation failure. Am J Reprod Immunol. 2017;78(5). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1578380","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":100528643,"identity":"f4720f67-1010-4362-b7c1-dcdfcfee0b6d","order_by":0,"name":"Jing Huang","email":"","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Huang","suffix":""},{"id":100528644,"identity":"bd17f18d-8554-4efd-97c6-175e3c470259","order_by":1,"name":"Xin Yu","email":"","orcid":"","institution":"LongQuanYi District of maternity and child health care hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Yu","suffix":""},{"id":100528645,"identity":"5f845d96-495b-4e97-9ce0-4db3759d1383","order_by":2,"name":"Yue Liu","email":"","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yue","middleName":"","lastName":"Liu","suffix":""},{"id":100528646,"identity":"fa5e9a29-a3aa-4547-a35e-d0db9b9c21cb","order_by":3,"name":"Chengchao Du","email":"","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chengchao","middleName":"","lastName":"Du","suffix":""},{"id":100528647,"identity":"b1c2e134-9c6a-434b-8861-ab795f1e1838","order_by":4,"name":"Honggui Zhou","email":"","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Honggui","middleName":"","lastName":"Zhou","suffix":""},{"id":100528648,"identity":"4145612a-cf2d-4a10-8402-68d871f47efd","order_by":5,"name":"Yamei Yang","email":"","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yamei","middleName":"","lastName":"Yang","suffix":""},{"id":100528649,"identity":"72b90435-ad2a-4e71-8abd-80985892b4bf","order_by":6,"name":"Dacheng Qu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIiWNgGAWjYFCCBOYHH//UyNm3Nx848OEHcVrYDGc2HDM24DmWeHBmD3FaGKR5G5gTN0jkGB/mYCNCA9/x5AcGvDvYjM0lcj4cZuBhkOcXO4Bfi+SZZwYPJM/IyFn2vN1wuMCCwXDm7AT8Wgxu5DAYGLCxGTMcz91weAYPQ4LBbSK0SCSwMSc2HMh5cJiHjVgtB9uA3j+Rw0CcFqBfzAwbzhwzluw5ZgAMZAnCfgGG2OPHfypq5PjZmx9/+PDDRp5fmoAWhgOoXAkCyrFoGQWjYBSMglGACQB7SE56RpLJigAAAABJRU5ErkJggg==","orcid":"","institution":"Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Dacheng","middleName":"","lastName":"Qu","suffix":""}],"badges":[],"createdAt":"2022-04-20 22:44:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1578380/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1578380/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":20748452,"identity":"39e78202-460d-4208-92ab-05c935bb9685","added_by":"auto","created_at":"2022-04-25 21:39:42","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":36696,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of EPs recurrence rates between the patient groups with and without CE at each monitoring stage over the 12-month follow-up (all P\u0026lt;.05 at 3, 6, 9 and 12 months). Values are rate (95% confidence interval). EPs - endometrial polyps; CE - chronic endometritis.\u003c/p\u003e","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-1578380/v1/bf5de3769835f495cdbe0c81.png"},{"id":26047343,"identity":"f7ccdb7f-11fb-49e2-85e9-d89eafcc860e","added_by":"auto","created_at":"2022-09-05 04:29:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":403617,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1578380/v1/6389adf9-5c79-43b7-a2c2-e722ab3b9af3.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Chronic endometritis increases the recurrence of endometrial polyps in premenopausal women after hysteroscopic polypectomy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEndometrial polyps (EPs) represent a common benign gynecological condition that manifests via excessive local hyperplasia of the interstitial and endometrial glands. The prevalence of EPs ranges from 7.8\u0026ndash;34.9% across different populations [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Many studies have shown that a transient, repetitive and persistent impaired inflammatory state of the endometrium (IISE) is a major factor for most problematic disorders in gynecology, including EPs [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. EPs are commonly associated with chronic endometritis (CE) in premenopausal women suffering from abnormal uterine bleeding (AUB) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The prevalence of CE in premenopausal women with AUB or reproductive failure on EPs is increased, with one clinical trial of 209 cases reporting a prevalence of 28.7% [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCE involves persistent local inflammation of endometrium, characterized by the presence of plasma cells infiltrating the interstitium [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. CE is usually asymptomatic or presents only with mild symptoms, such as AUB, pelvic pain, dyspareunia and leucorrhea, as well as infertility and miscarriage, all of which are very similar to the symptoms of EPs [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, the spontaneous cure rate for CE is very low, with a randomized clinical trial reporting a rate of only 12.7% [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The optimal treatment currently for CE is oral antibiotics [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEPs are associated with AUB, infertility and recurrent reproductive failure [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Hysteroscopic polypectomy has always been considered the gold standard treatment for EPs [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Across several studies, the recurrence rate of EPs within 12 months after hysteroscopic polypectomy has ranged widely from 5.6\u0026ndash;31.4% [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. A large number of EPs, endometriosis and previous polypectomy history are established independent risk factors for the recurrence of polyps [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In addition, late menopause and obesity increase the occurrence of EPs [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. However, the factors influencing the recurrence potential of EPs after hysteroscopic polypectomy remain rather controversial.\u003c/p\u003e \u003cp\u003eIn the present retrospective cohort study, we investigated whether CE increased the recurrence of EPs in premenopausal women after hysteroscopic polypectomy.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eHysteroscopic polypectomy patients with 12 months of follow-up data were enrolled, and those with definite confounding factors for polyp recurrence, including endometriosis and previous polypectomy history were excluded. A total of 233 premenopausal women after hysteroscopic polypectomy were enrolled in this study, including 64 cases with CE and 169 cases without CE. Comparison of the recurrence rate of EPs was performed in women with and without CE at each monitoring stage (i.e., at 3, 6, 9 and 12 months). The expression of CD138 in the endometrium was analyzed by immunohistochemistry to identify CE.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u003c/h2\u003e \u003cp\u003e Participants involved in this retrospective cohort study were premenopausal women (18\u0026ndash;50 years) with data from 12 months of follow-up after treatment with hysteroscopic polypectomy in the follicular phase between January 2019 and January 2020 at the Department of Obstetrics and Gynecology, Affiliated Hospital of North Sichuan Medical College (China). Institutional Review Board approval was obtained from the Ethics Committee of the Affiliated Hospital of North Sichuan Medical College (China) at January 2019 before the experiment was started (2019ER(R)017). All patients signed a written informed consent form, and this study was conducted in accordance with the principles of the Declaration of Helsinki. The exclusion criteria were inflammatory disease (PID) occurring in the 12 months after hysteroscopic polypectomy and the use of hormone therapy or antibiotics.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eHysteroscopic resection and endometrial biopsy\u003c/h2\u003e \u003cp\u003eHysteroscopic polypectomy was conducted in the follicular phase with a bipolar plasmakinetic resection system under intravenous anesthesia using a 3-mm 15\u0026deg; inside rigid hysteroscope and a 8.5-mm outside sheath (Olympus, Tokyo, Japan).\u003c/p\u003e \u003cp\u003eAll operations were done by the same physician (DC Qu). Endometrial samples were obtained visually using an unpowered plasma cutting ring from the upper uterine cavity, while hysteroscopic polypectomy was performed to remove local polyps.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eImmunohistochemistry\u003c/h2\u003e \u003cp\u003eA histopathology consultant performed immunohistochemical detection of CD138 on the endometrial specimen slices as previously described [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The clone of anti-CD138 monoclonal antibody used in our study was MI15 Cell Marque (Fuzhou Maixin Biotechnology Co., Ltd., Fuzhou, China). At least 50 high-power fields were examined for each specimen. CD138 expression was classified as positive if one or more positively stained plasma cells were identified per 10 high power fields and negative if less than one positively stained plasma cell was identified per 10 high power fields [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eFollow up\u003c/h2\u003e \u003cp\u003eWomen who underwent hysteroscopic polypectomy at our hysteroscopic center were surveilled routinely. Transvaginal ultrasonography was performed to evaluate the uterine cavity condition at 3, 6, 9 and 12 months after hysteroscopic polypectomy. Women without the full 12 months of surveillance data were not enrolled in this study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePower calculation\u003c/h2\u003e \u003cp\u003eThe retrospective cohort study included 64 experimental subjects, 169 control subjects, an accrual interval of 12 months, and additional follow-up after the accrual interval of 12 months. The recurrence rates were 26.6% in the experimental group and 9.5% in the control group. With type I error of 0.05, the statistical power can reach 0.9.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analyses\u003c/h2\u003e \u003cp\u003eFor all statistical analyses, we used SPSS version 22.0 (SPSS, Inc, Chicago, IL, USA), and a P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered to be statistically significant. After analyzing the distribution of the data and confirming that the age and body mass index (BMI) of the population were not normally distributed, we adopted the Mann-Whitney U test to analyze age and BMI expressed as median (interquartile range). Categoric variables were compared using the chi-square test. The chi-square test was used to compare the recurrence of EPs between each group at each stage. The Kaplan\u0026ndash;Meier method with the log-rank test was used to estimate recurrence-free survival and to compare recurrence rates between the two groups. Cox regression models were used to compare the recurrence risk of the two groups in both univariate and multivariate analyses. Factors for which P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 on univariate analyses were included in the subsequent multivariable model.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eComparison of general and clinical features of EPs patients with and without CE\u003c/h2\u003e \u003cp\u003eA total of 233 women with 12 months follow-up data after hysteroscopic polypectomy for EPs treatment were enrolled in this study, including 64 cases with CE and 169 cases without CE. Thus, the prevalence of CE in the population was 27.5% (64/233). The demographic details and clinical features of the two groups of patients are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. No statistically significant differences in demographic details and clinical features were found between the two groups of patients (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline demographics of the enrolled patients.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEPs with CE (n\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEPs without CE (n\u0026thinsp;=\u0026thinsp;169)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, y (median (Q3-Q1))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.092\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, kg/m\u003csup\u003e2\u003c/sup\u003e (median (Q3-Q1))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.7 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.4 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.120\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolyp number, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.713\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSolitary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (26.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (29.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47 (73.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e120 (71.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolyp size (cm), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.314\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (18.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (11.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;1, \u0026le;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (76.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e136 (80.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (4.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eNote: EPs - endometrial polyps; CE - chronic endometritis; BMI - body mass index.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eComparison of EPs recurrence rate between patients with and without CE\u003c/h2\u003e \u003cp\u003eDuring the 12-month follow-up, a total of 33 women experienced EPs recurrence, including 17 cases with CE and 16 cases without CE. The recurrence rates of EPs with CE and without CE were 26.6% (95% confidence interval [CI] 15.8\u0026ndash;37.4%) and 9.5% (95% CI 5.0\u0026ndash;14.0%), respectively, with an overall cure rate of 14.2% (95% CI 9.7\u0026ndash;18.7%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The EPs recurrence rate was higher in patients with CE (P\u0026thinsp;=\u0026thinsp;0.001). The HR for EPs recurrence in the EPs with CE cohort versus the EPs without CE cohort was 3.08 (95% CI 1.56\u0026ndash;6.09, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRisk factors for recurrence of EPs from univariate and multivariate analyses.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHR (95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnivariate analysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.00 (0.95\u0026ndash;1.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.996\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.93 (0.81\u0026ndash;1.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.245\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolyp size (cm) (vs. \u0026le;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;1, \u0026le;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.54 (0.16\u0026ndash;14.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.709\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.57 (0.35\u0026ndash;18.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.353\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple EPs vs. solitary EP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.02 (1.06\u0026ndash;8.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.08 (1.56\u0026ndash;6.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultivariate analysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.06 (1.54\u0026ndash;6.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple EPs vs. solitary EP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.99 (1.05\u0026ndash;8.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.040\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eNote: BMI - body mass index; EPs - endometrial polyps; EP - endometrial polyp; CE - chronic endometritis.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eSimilarly, in the group with CE, there were 5 cases of EPs recurrence at 3 months, 10 cases at 6 months, and 14 cases at 9 months. In the group without CE, there were 2 cases of EPs recurrence at 3 months, 7 cases at 6 months, and 12 cases at 9 months. The recurrence rates of EPs were significantly higher in women with CE than in those without CE at every monitoring stage, i.e., 7.8% (95% CI 1.1\u0026ndash;14.5%) vs. 1.2% (95% CI -0.4\u0026ndash;2.8%, P\u0026thinsp;=\u0026thinsp;0.018) at 3 months, 15.6% (95% CI 6.8\u0026ndash;24.4%) vs. 4.1% (95% CI 1.2\u0026ndash;7.0%, P\u0026thinsp;=\u0026thinsp;0.003) at 6 months, and 21.9% (95% CI 11.7\u0026ndash;32.1%) vs. 7.1% (95% CI 3.2\u0026ndash;11.0%, P\u0026thinsp;=\u0026thinsp;0.001) at 9 months (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eFactors associated with recurrence of EPs\u003c/h2\u003e \u003cp\u003eUnivariate and multivariate Cox regression models were used to assess the factors associated with the recurrence of EPs. Univariate analysis showed that the recurrence of EPs was not affected by age, BMI, or polyp size, but significantly higher EPs recurrence rates were observed in women with multiple EPs or with CE compared with the rates in patients without the respective conditions (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 and P\u0026thinsp;\u0026lt;\u0026thinsp;0.05, respectively). Multivariate analysis confirmed that CE was a harmful factor for the recurrence of EPs (HR 3.06, 95% CI 1.54\u0026ndash;6.05, P\u0026thinsp;=\u0026thinsp;0.001). In addition, as previously mentioned [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], the presence of multiple EPs also contributed to the recurrence of EPs (HR 2.99, 95% CI 1.05\u0026ndash;8.91, P\u0026thinsp;=\u0026thinsp;0.040).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe reported recurrence rate of EPs after hysteroscopic polypectomy had varied widely [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], and the factors influencing the recurrence potential of EPs after hysteroscopic polypectomy were still controversial. Furthermore, the known definite independent risk factors are almost unchangeable, such as the number of polyps and previous polypectomy history.\u003c/p\u003e \u003cp\u003eIn this study, the overall recurrence rate of EPs in premenopausal women was 14.2% at 12 months after hysteroscopic polypectomy, which is consistent with rates reported in previous studies [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Although, after subgroup analysis according to CE, the recurrence rate of EPs in premenopausal women increased to 26.6%, and CE played a harmful role in the recurrence of EPs. To the best of our knowledge, our study is the first to report the effect of CE. Similarly, the recurrence rate of EPs was significantly higher in women with CE than in those without CE at each monitoring stage, i.e., 7.8% vs. 1.2% at 3 months, 15.6% vs. 4.1% at 6 months, and 21.9% vs. 7.1% at 9 months. This may be a possible explanation for the wide range of the EPs recurrence rates (5.6\u0026ndash;31.4%) previously reported during 1-year follow-up [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. CE may have been a concealed factor for the recurrence of EPs. The underlying mechanism of the harmful effects of CE is currently unknown. One possible explanation is that the vessel axis of EPs may actually originate from the evolution of vascular changes associated with endometritis [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In addition, persistent IISE is a major factor for the occurrence of EPs, as CE participates in the pathogenesis of EPs [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCE is a disease involving destruction of the homeostasis between microorganisms in the endometrium and the host immune system. The most common bacterial pathogens causing CE are reported to be \u003cem\u003eEnterobacteriaceae\u003c/em\u003e, \u003cem\u003eEnterococcus\u003c/em\u003e, \u003cem\u003eStreptococcus\u003c/em\u003e, \u003cem\u003eStaphylococcus\u003c/em\u003e, \u003cem\u003eMycoplasma\u003c/em\u003e, and \u003cem\u003eUreaplasma\u003c/em\u003e [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Similarly, another study found that the most abundant genus in the microbiota of endometrium with CE is non-\u003cem\u003eLactobacillus\u003c/em\u003e [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Antibiotics are effective for treating CE [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], as it is caused by bacterial pathogens. Although CE was an independent risk factor for polyp recurrence, unlike unchangeable factors, CE can be changed by treatment of antibiotic.\u003c/p\u003e \u003cp\u003eIn this retrospective cohort study of 233 participants who underwent hysteroscopic polypectomy as treatment for EPs, polyp recurrence rates were significantly higher in women with CE than in those without CE at each monitoring stage, i.e., at 3, 6, 9 and 12 months. These findings indicate a harmful role of CE in the recurrence of EPs in premenopausal women after hysteroscopic polypectomy. The HR for EPs recurrence in the EPs with CE cohort compared with the EPs without CE cohort was 3.06, after adjustment for the number of polyps.\u003c/p\u003e \u003cp\u003eOur study demonstrated CE and the number of polyps were risk factors for the recurrence of EPs in premenopausal women after hysteroscopic polypectomy. CE can be diagnosed easily when undergoing hysteroscopic polypectomy, and be treated with empirical use of antibiotic. Thus, we suggest that women undergo an examination for CE when undergoing hysteroscopic polypectomy and receive treatment for CE once a diagnosis is made. Frequent monitoring was needed for multiple polyps after hysteroscopic polypectomy.\u003c/p\u003e \u003cp\u003eIn the current study, to better evaluate the impact of CE on polyp recurrence, patients with definite external confounding factors for polyp recurrence, including endometriosis and previous polypectomy history, were excluded. The recurrence of EPs was not affected by age, BMI, or polyp size, which are consistent with previous studies [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere are some limitations in this study. For example, because this was a retrospective review, we could not take into account enough factors affecting the recurrence of EPs, and other concealed factors need to be explored. Furthermore, CE treated with antibiotic cohort was not included in our study, we do not know whether the effect of CE on the recurrence of EPs can be eliminated when treated with antibiotic.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, this study demonstrated that CE was a harmful factor for the recurrence of EPs in premenopausal women after hysteroscopic polypectomy. Thus, routine screening and treatment are needed for CE. Multiple EPs also contributed to polyp recurrence. The role of CE in the recurrence of EPs needs to be further confirmed by randomized trials with a large sample size, and the potential mechanism of the harmful effects of CE remains to be investigated.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAcknowledgments\u003c/h2\u003e\n\u003cp\u003eThe authors thank Wei Xu for processing statistical data.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eAuthor contributions\u003c/h2\u003e\n\u003cp\u003eDQ and JH designed most of the investigation, data analysis and wrote the manuscript; XY and YL performed most of the investigation; CD and YY contributed to data curation; DQ and HZ contributed to interpretation of the data and analyses. All of the authors have read and approved the manuscript.\u003c/p\u003e\n\u003ch2\u003eFunding information\u003c/h2\u003e\n\u003cp\u003eThe work was supported by the Bureau of Science and Technology Nanchong City (19SXHZ0338) and Sichuan Science and Technology Program (2018SZ0264).\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study available from the corresponding author on reasonable request..\u003c/p\u003e\n\u003ch2\u003eCompliance with Ethical Standards\u003c/h2\u003e\n\u003ch2\u003eConflicts of Interest\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003ch2\u003eEthics Approval\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eAll procedures performed were ethically approved.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eConsent for Publication\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eAll involved consented to publication.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003eCode Availability\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eClark TJ, Stevenson H. Endometrial Polyps and Abnormal Uterine Bleeding (AUB-P): What is the relationship, how are they diagnosed and how are they treated? Best Pract Res Clin Obstet Gynaecol. 2017;40:89\u0026ndash;104.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDrizi A, Djokovic D, Lagan\u0026agrave; AS, van Herendael B. Impaired inflammatory state of the endometrium: a multifaceted approach to endometrial inflammation. Current insights and future directions. Prz Menopauzalny. 2020;19(2):90\u0026ndash;100.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCicinelli E, Bettocchi S, de Ziegler D, Loizzi V, Cormio G, Marinaccio M, et al. Chronic Endometritis, a Common Disease Hidden Behind Endometrial Polyps in Premenopausal Women: First Evidence From a Case-Control Study. J Minim Invasive Gynecol. 2019;26(7):1346\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSong D, Feng X, Zhang Q, Xia E, Xiao Y, Xie W, et al. Prevalence and confounders of chronic endometritis in premenopausal women with abnormal bleeding or reproductive failure. Reprod Biomed Online. 2018;36(1):78\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKitaya K, Takeuchi T, Mizuta S, Matsubayashi H, Ishikawa T. Endometritis: new time, new concepts. Fertil Steril. 2018;110(3):344\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePuente E, Alonso L, Lagan\u0026agrave; AS, Ghezzi F, Casarin J, Carugno J. Chronic Endometritis: Old Problem, Novel Insights and Future Challenges. Int J Fertil Steril. 2020;13(4):250\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKasius JC, Fatemi HM, Bourgain C, Sie-Go DM, Eijkemans RJ, Fauser BC, et al. The impact of chronic endometritis on reproductive outcome. Fertil Steril. 2011;96(6):1451\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDongmei S. RCT(Randomized Clinical Trial) of Antibiotic Therapy in Chronic Endometritis - Full Text View - ClinicalTrials.gov: NIH: U.S. National Library of Medicine 2016.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCicinelli E, Matteo M, Tinelli R, Lepera A, Alfonso R, Indraccolo U, et al. Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy. Hum Reprod. 2015;30(2):323\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCicinelli E, Matteo M, Trojano G, Mitola PC, Tinelli R, Vitagliano A. Chronic endometritis in patients with unexplained infertility: Prevalence and effects of antibiotic treatment on spontaneous conception. Am J Reprod Immunol. 2018;79(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNijkang NP, Anderson L, Markham R, Manconi F. Endometrial polyps: Pathogenesis, sequelae and treatment. SAGE Open Med. 2019;7:2050312119848247.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSheng KK, Lyons SD. To treat or not to treat? An evidence-based practice guide for the management of endometrial polyps. Climacteric. 2020;23(4):336\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmerican Association of Gynecologic Laparoscopists. AAGL practice report: practice guidelines for the diagnosis and management of endometrial polyps. J Minim Invasive Gynecol. 2012;19(1):3\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCiscato A, Zare SY, Fadare O. The significance of recurrence in endometrial polyps: a clinicopathologic analysis. Hum Pathol. 2020;100:38\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGu F, Zhang H, Ruan S, Li J, Liu X, Xu Y, et al. High number of endometrial polyps is a strong predictor of recurrence: findings of a prospective cohort study in reproductive-age women. Fertil Steril. 2018;109(3):493\u0026ndash;500.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang JH, Chen CD, Chen SU, Yang YS, Chen MJ. Factors Influencing the Recurrence Potential of Benign Endometrial Polyps after Hysteroscopic Polypectomy. PLoS One. 2015;10(12):e0144857.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOguz S, Sargin A, Kelekci S, Aytan H, Tapisiz OL, Mollamahmutoglu L. The role of hormone replacement therapy in endometrial polyp formation. Maturitas. 2005;50(3):231\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSong D, Li TC, Zhang Y, Feng X, Xia E, Huang X, et al. Correlation between hysteroscopy findings and chronic endometritis. Fertil Steril. 2019;111(4):772\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQu D, Yang M, Tong L, Yu X, Jing Q, Yang Y, et al. Combination of Dydrogesterone and Antibiotic Versus Antibiotic Alone for Chronic Endometritis: a Randomized Controlled Trial Study. Reprod Sci. 2021.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang Y, Yang M, Huang X, Li X, Lin E, Feng Y. Prevention of Benign Endometrial Polyp Recurrence Using a Levonorgestrel-releasing Intrauterine System in Premenopausal Patients: A Retrospective Cohort Study. J Minim Invasive Gynecol. 2020;27(6):1281\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCeci O, Franchini M, Cardinale S, Cannone R, Giarr\u0026egrave; G, Fascilla FD, et al. Comparison of endometrial polyp recurrence in fertile women after office hysteroscopic endometrial polypectomy using two widely spread techniques. J Obstet Gynaecol Res. 2020;46(10):2084\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi F, Wei S, Yang S, Liu Z, Nan F. Post hysteroscopic progesterone hormone therapy in the treatment of endometrial polyps. Pak J Med Sci. 2018;34(5):1267\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarvalho FM, Aguiar FN, Tomioka R, de Oliveira RM, Frantz N, Ueno J. Functional endometrial polyps in infertile asymptomatic patients: a possible evolution of vascular changes secondary to endometritis. Eur J Obstet Gynecol Reprod Biol. 2013;170(1):152\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoreno I, Cicinelli E, Garcia-Grau I, Gonzalez-Monfort M, Bau D, Vilella F, et al. The diagnosis of chronic endometritis in infertile asymptomatic women: a comparative study of histology, microbial cultures, hysteroscopy, and molecular microbiology. Am J Obstet Gynecol. 2018;218(6):602\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e.e1-.e16\u003c/span\u003e\u003cspan address=\"http://.e1-.e16\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu Y, Ko EY, Wong KK, Chen X, Cheung WC, Law TS, et al. Endometrial microbiota in infertile women with and without chronic endometritis as diagnosed using a quantitative and reference range-based method. Fertil Steril. 2019;112(4):707 \u0026ndash; 17.e1.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJohnston-MacAnanny EB, Hartnett J, Engmann LL, Nulsen JC, Sanders MM, Benadiva CA. Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization. Fertil Steril. 2010;93(2):437\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcQueen DB, Bernardi LA, Stephenson MD. Chronic endometritis in women with recurrent early pregnancy loss and/or fetal demise. Fertil Steril. 2014;101(4):1026\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKitaya K, Matsubayashi H, Takaya Y, Nishiyama R, Yamaguchi K, Takeuchi T, et al. Live birth rate following oral antibiotic treatment for chronic endometritis in infertile women with repeated implantation failure. Am J Reprod Immunol. 2017;78(5).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Recurrence, chronic endometritis, endometrial polyps, hysteroscopic polypectomy, risk factor","lastPublishedDoi":"10.21203/rs.3.rs-1578380/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1578380/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eTo evaluate the impact of chronic endometritis (CE) on the recurrence of endometrial polyps (EPs) in premenopausal women who underwent hysteroscopic polypectomy.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eWe conducted\u003cstrong\u003e \u003c/strong\u003ea retrospective observational cohort study in a university-affiliated hospital. Premenopausal women who underwent hysteroscopic polypectomy were enrolled, and those with definite confounding factors for polyp recurrence, including endometriosis and previous polypectomy history were excluded. A total of 233 women were enrolled in this study, including 64 cases (27.5%) with CE and 169 cases (72.5%) without CE. Comparison of the recurrence rate of EPs was performed in women with or without CE at each monitoring stage (i.e., at 3, 6, 9 and 12 months) after hysteroscopic polypectomy. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResult(s): \u003c/strong\u003eThe EPs recurrence rates at one year in patients with and without CE were 26.6% (95% confidence interval [CI] 15.8%–37.4%) and 9.5% (95% CI 5.0%–14.0%), respectively, with an overall cure rate of 14.2% (95% CI 9.7%–18.7%). The hazard ratio (HR) for EPs recurrence in the EPs with CE cohort versus the EPs without CE cohort was 3.08 (95% CI 1.56-6.09) (P=0.001). Similarly, the EPs recurrence rate was significantly higher in women with CE than in those without CE at each monitoring stage (i.e., 3, 6, and 9 months). CE and multiple EPs were risk factors for polyp recurrence. The HR for EPs recurrence in the EPs with CE cohort compared with the EPs without CE cohort was 3.06, after adjustment for the number of polyps.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion(s): \u003c/strong\u003eCE was a harmful factor for the recurrence of EPs in premenopausal women after hysteroscopic polypectomy. Thus, routine screening for CE are needed, and unlike unchangeable factors, CE can be changed by antibiotics treatment. Frequent monitoring was needed for multiple EPs as the number of EPs also contributed to polyp recurrence.\u003c/p\u003e","manuscriptTitle":"Chronic endometritis increases the recurrence of endometrial polyps in premenopausal women after hysteroscopic polypectomy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-04-25 21:39:40","doi":"10.21203/rs.3.rs-1578380/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e479cb4d-d644-4e52-a38c-f360c27cbca9","owner":[],"postedDate":"April 25th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-09-05T04:29:08+00:00","versionOfRecord":[],"versionCreatedAt":"2022-04-25 21:39:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1578380","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1578380","identity":"rs-1578380","version":["v1"]},"buildId":"ehx78VzkSd0WSzXnipQa-","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}