{"paper_id":"2daf1bb7-ad81-41fd-90be-3115587b956c","body_text":"Clin. Exp. Obstet. Gynecol. 2024; 51(11): 248\nhttps://doi.org/10.31083/j.ceog5111248\nCopyright: © 2024 The Author(s). Published by IMR Press.\nThis is an open access article under the CC BY 4.0 license .\nPublisher’s Note: IMR Press stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nOriginal Research\nRisk Factors and a Predictive Model for the Co-Occurrence of\nEndometrial Polyps in Patients with Endometriosis: A Retrospective\nStudy\nZhi-Min Song1,†, Xiao-Jie Wan1,†, Jian-Peng Chen 1,2, Tao Zhang1, Jie Luo 1,\nJian-Hong Zhou1,3,*, Jing-Yi Li1,2,3,*\n1Department of Obstetrics and Gynecology, Women’s Hospital, Zhejiang University School of Medicine, 310006 Hangzhou, Zhejiang, China\n2Key Laboratory of Reproductive Genetics (Ministry of Education), Women’s Hospital, Zhejiang University School of Medicine, 310006 Hangzhou,\nZhejiang, China\n3Department of Reproductive Endocrinology, Women’s Hospital, Zhejiang University School of Medicine, 310006 Hangzhou, Zhejiang, China\n*Correspondence: zhoujh1117@zju.edu.cn (Jian-Hong Zhou); 06yxsyljy@zju.edu.cn (Jing-Yi Li)\n†These authors contributed equally.\nAcademic Editor: V alerio Gaetano V ellone\nSubmitted: 6 May 2024 Revised: 1 September 2024 Accepted: 11 September 2024 Published: 18 November 2024\nAbstract\nBackground: The incidence of endometrial polyps (EPs) is higher in patients with endometriosis (EM) compared to the general pop-\nulation. This study aims to analyze the various indices in EM patients with and without EPs and to establish an effective combined\nprediction model to predict the presence of EPs in EM patients. Method: This retrospective study included 1250 EM patients. Logis-\ntic regression analysis was employed to develop a combined diagnostic model. Results: Compared to EM patients without EPs, those\nwith EPs had significantly higher age, gravidity, parity, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure\n(DBP), luteinizing hormone (LH), estradiol (E 2), platelet (PLT), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C),\nlow-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), and significantly lower hemoglobin (HGB) and white blood\ncells (WBCs) ( p < 0.05). After adjusting for potential confounding factors, a prediction model for the presence of EPs in EM patients\nwas developed based on BMI, DBP , gravidity, parity, LH, WBCs, HGB, TC, and FPG. The receiver operating characteristic (ROC) area\nunder the curve (AUC) for the combined diagnostic model was 0.78 (95% confidence interval (95% CI): 0.75–0.82, p < 0.001). The\nsensitivity, specificity, cut-off value, and Y ouden index of the model were 77.6%, 66.1%, 0.159, and 0.437, respectively. Conclusions:\nMetabolic alterations were found to be associated with the presence of EPs in EM patients. The diagnostic model based on these potential\nrisk factors may offer a novel approach for the early diagnosis and targeted treatment of EPs in EM patients.\nKeywords: endometrial polyps; endometriosis; prediction model\n1. Introduction\nEndometriosis (EM) is a gynecological condition af-\nfecting over 170 million women worldwide [ 1], and has a\nprevalence ranging from 6–10% in the general population\n[2]. It is characterized by the abnormal growth of endome-\ntrial tissue (glands and stroma) outside the uterus, typically\nin areas such as the ovaries, fallopian tubes, and pelvic cav-\nity. EM is known to be estrogen-dependent. Symptoms\noften include dysmenorrhea, abnormal menstruation, dys-\npareunia, and infertility. It is estimated that between 25%\nto 50% of patients undergoing fertility treatments have a\nhistory of EM, as it often correlates with a reduction in ovar-\nian reserve [ 3]. Patients with EM often endure both phys-\nical and mental challenges, including depression and anxi-\nety, which significantly impact their quality of life. These\nstruggles also contribute to a substantial economic burden\non both individuals and communities.\nEndometrial polyps (EPs) are characterized by the\novergrowth of endometrial glands and stroma within the\nuterine cavity [ 4]. These polyps can vary in size, ranging\nfrom tiny fractions of a millimeter to several centimeters in\ndiameter, and are commonly observed in women aged 40\nto 49 years. They are detected in approximately 10 percent\nof women during autopsy [ 5]. Patients with EPs may be\nasymptomatic, but the most common symptom is abnormal\nuterine bleeding, which does not correlate with the size or\ngrowth rate of EPs [ 6]. Other rare symptoms that may be\nassociated with EPs include abdominal pain, pelvic pain,\nand infertility. In asymptomatic patients, EPs may regress\nspontaneously with menstruation. Hysteroscopic excision\nis recommended as a safe and efficient treatment for symp-\ntomatic women, as well as for those in the perimenopause\nand postmenopausal stages [ 7].\nIn clinical practice, we observed a higher incidence\nof EPs in patients with EM. Considering the common ab-\nnormalities in the biological behavior of endometrial cells,\nwe hypothesize a relationship between the development of\nthese two diseases. Previous study has reported a higher oc-\ncurrence of EPs in women with EM who also experience in-\n\nFig. 1. Flowchart of the retrospective study design. EM, endometriosis; EPs, endometrial polyps.\nfertility [8]. EPs were detected by hysteroscopy in 47.83%\nof the EM group and 29.82% of the control group among\ninfertile patients [9]. Both conditions involve excessive en-\ndometrial growth, and various mechanisms contribute to the\nassociation between EM and EPs. At present, the pathogen-\nesis of EM and EPs remains unclear. Furthermore, there\nis currently no noninvasive test that can fully confirm the\npresence of polyps in patients with EM.\nOur study conducted a retrospective analysis of the\nclinical characteristics of EM patients, comparing those\nwith and without EPs. Additionally, we developed a predic-\ntive model to identify the presence of EPs in EM patients.\nThis model provides insights into the mechanisms underly-\ning the co-occurrence of polyps in patients with EM.\n2. Materials and Methods\nThis retrospective case-control study was conducted\nat the Women’s Hospital, Zhejiang University School of\nMedicine, China, and was approved by the Institutional\nEthics Committee. Subjects were identified from the elec-\ntronic medical record system of Women’s Hospital, Zhe-\njiang University School of Medicine, covering the period\nfrom August 1, 2020 to July 31, 2021. A cohort of 1250 EM\npatients who underwent surgical interventions at this hos-\npital was included in the study, and their clinical data were\nincluded in the final statistical analysis (Fig. 1). All pa-\ntients underwent laparoscopic resection of ectopic lesions.\nIf B-mode ultrasound indicated the presence of EPs before\nsurgery, simultaneous hysteroscopy was performed, and the\ndiagnoses of EM and EPs were pathologically confirmed.\nPatients scheduled for surgery were hospitalized within 3–\n7 days of the onset of their menstrual cycle, without con-\nsidering hormone replacement therapy. Age, body weight,\nheight, fertility status, blood pressure, and laboratory in-\ndices were extracted from medical records. Reproductive\nhistory was self-reported, and baseline clinical characteris-\ntics were assessed at hospital admission. This encompassed\nvarious factors such as body weight, height, and blood pres-\nsure. Body mass index (BMI) was determined by divid-\ning weight in kilograms by the square of height in meters.\nAccording to Chinese adult criteria, BMI categories were\nclassified as follows: underweight ( <18.5 kg/m 2), normal\nweight (18.5–23.9 kg/m 2), overweight (24.0–27.9 kg/m 2),\nand obesity (≥28 kg/m2) [10].\nUpon hospital admission, a routine blood examina-\ntion, glucose and lipid metabolism parameters, and repro-\nductive endocrine hormone measurements were conducted\non peripheral blood collected from all subjects. Partici-\npants fasted for at least 8 h before blood sampling. The\nevaluated indices included serum levels of hemoglobin\n(HGB), white blood cells (WBCs), platelet (PLT), fast-\ning plasma glucose (FPG), high-density lipoprotein choles-\nterol (HDL-C), low-density lipoprotein cholesterol (LDL-\nC), total cholesterol (TC), triglycerides (TG), estradiol\n(E2), follicle-stimulating hormone (FSH), luteinizing hor-\nmone (LH), prolactin (PRL), and anti-Müllerian hormone\n(AMH). All measurements were conducted utilizing a\nRoche Modular Analytics E170 fully automated analyzer\n(Roche Diagnostics, Mannheim, Germany). All patients\nunderwent ultrasound examinations after admission, and\nthose with ultrasound findings suggestive of EPs were con-\nfirmed to exhibit EPs during hysteroscopy. Postoperative\npathology confirmed the diagnosis of EPs in all 248 EM\npatients, while 1002 patients were diagnosed without EPs.\nStatistical analyses were conducted using SPSS for\nWindows (V ersion 24.0., IBM Corp., Armonk, NY , USA),\nwith statistical significance set at a two-sided p < 0.05.\nContinuous variables were expressed as mean ± standard\n2\n\n\nTable 1. The baseline clinical characteristics of the EM group and EM combined with EPs group a.\nEM group (n = 1002) EM combined with EPs group (n = 248) p-value\nAge (years) 32.3 ± 5.0 35.4 ± 7.5 <0.001\nHeight (cm) 160.5 ± 7.0 161.3 ± 4.7 0.088\nWeight (kg) 54.7 ± 7.5 57.4 ± 7.5 <0.001\nBMI (kg/m2) 21.2 ± 2.8 22.4 ± 2.9 <0.001\n<18.5 (n = 154) 137 (13.7%) 17 (6.9%) 0.003\n≥18.5 to <24 (n = 881) 719 (71.8%) 162 (65.3%) 0.047\n≥24 to <28 (n = 188) 132 (13.2%) 56 (22.6%) <0.001\n≥28 (n = 27) 14 (1.4%) 13 (5.2%) <0.001\nSBP (mmHg) 115.0 ± 10.8 117.8 ± 11.7 0.001\nDBP (mmHg) 71.2 ± 8.4 74.5 ± 9.0 <0.001\nParity 0 (0, 0) 0 (0, 1) <0.001\nAbortion 0 (0, 1) 0 (0, 1) 0.931\nGravidity 0 (0, 1) 1 (0, 2) <0.001\na Continuous variables are presented as mean ± standard deviation (SD), and skewed variables are presented\nas the median (interquartile range). Student’s t-test for independent samples was used for normally distributed\ncontinuous variables, and the Chi-squared ( χ2) test for categorical variables.\nBMI, body mass index; EPs, endometrial polyps; EM, endometriosis; SBP , systolic blood pressure; DBP ,\ndiastolic blood pressure.\ndeviation (SD), while skewed variables are presented as\nmedian (interquartile range) and use non-parametric test\n(Mann-Whitney U test). Student’s t-test for independent\nsamples was employed for normally distributed continuous\nvariables, and the Chi-squared (χ2) test was applied for cat-\negorical variables.\nLogistic regression analysis, utilizing the Enter\nmethod, was employed to investigate the risk factors asso-\nciated with the concurrent presence of EPs in EM patients.\nA prediction model was also constructed. Receiver oper-\nating characteristic (ROC) curve analysis was used to as-\nsess the performance of this predictive model. The Y ouden\nindex, representing the maximum sum of sensitivity and\nspecificity across all feasible cut-off points, was mathemat-\nically defined as J = sensitivity + specificity – 1 [ 11].\n3. Results\nOur study included 248 EM patients with EPs and\n1002 EM patients without EPs. Table 1 presents the base-\nline clinical characteristics of the participants. Participants\nin the EM combined with EPs group exhibited older age\n(35.4 years vs. 32.3 years, p < 0.001), higher gravidity (1\nvs. 0, p < 0.001), parity (0 vs. 0, p < 0.001), higher mean\nBMI (22.4 kg/m 2 vs. 21.2 kg/m 2, p < 0.001), higher sys-\ntolic blood pressure (SBP) (117.8 mmHg vs. 115.0 mmHg,\np = 0.001), and higher diastolic blood pressure (DBP) (74.5\nmmHg vs. 71.2 mmHg, p < 0.001). There was no statisti-\ncally significant difference observed in height and abortion\nbetween the two groups ( p = 0.088 and p = 0.931, respec-\ntively).\nAs shown in Table 2, the PLT count (245.6 × 109/L\nvs. 256.6 × 109/L, p = 0.016), TC (4.4 mmol/L vs. 4.6\nmmol/L, p = 0.004), LDL-C (2.6 mmol/L vs. 2.8 mmol/L, p\n< 0.001), LH (5.1 IU/L vs. 7.8 IU/L, p < 0.001), E2 (132.8\npmol/L vs. 198.9 pmol/L, p < 0.001) and FPG (5.1 mmol/L\nvs. 5.4 mmol/L, p < 0.001) were significantly higher in the\nEM combined with EPs group compared to the EM group.\nIn contrast, HGB (121.9 g/L vs. 126.3 g/L, p < 0.001) and\nWBCs (5.9 × 109/L vs. 6.4 × 109/L, p = 0.002) were sig-\nnificantly higher in the EM group. There were no statis-\ntically significant differences in PRL, FSH, TG, HDL-C,\nand AMH between the two groups ( p = 0.790, p = 0.938, p\n= 0.096, p = 0.398 and p = 0.816, respectively).\nAfter adjusting for potential confounding factors (age,\nSBP , E2, LDL-C), logistic regression analysis employing\nthe enter method, revealed significant correlations between\nthe incidence of EPs in patients with EM and several fac-\ntors, including BMI, DBP , parity, gravidity, WBCs, HGB,\nLH, FPG, and TC ( p < 0.001 for BMI, DBP , parity, gra-\nvidity, LH; p = 0.024 for WBCs; p = 0.011 for HGB; p =\n0.010 for FPG; and p = 0.008 for TC). A combined pre-\ndiction model based on BMI, DBP , gravidity, parity, LH,\nWBCs, HGB, TC, and FPG was established (Table 3). Us-\ning the EM group as a reference, we plotted the ROC curve\nto analyze the diagnostic efficacy of the combined model.\nThe ROC curve demonstrated that the combined diagnostic\nmodel had an area under the curve (AUC) of 0.78 (0.75–\n0.82, p < 0.001) (Fig. 2). The optimal cut-off point was de-\ntermined as the point on the ROC curve closest to the (0, 1)\npoint. The optimal cut-off value, determined as 0.159 with\na Y ouden index of 0.437, provided the best balance between\nsensitivity (77.6%) and specificity (66.1%), as shown in Ta-\nble 4.\n3\n\nTable 2. Laboratory indeces of the EM group and EM combined with EPs group.\nIndeces EM group (n = 1002) EM combined with EPs group (n = 248) p-value\nPRL (ng/mL) 14.6 (0.0, 21.5) 16.6 (12.3, 23.4) 0.790\nLH (IU/L) 5.1 (3.7, 7.0) 7.8 (5.4, 11.1) <0.001\nFSH (IU/L) 7.0 (5.7,8.7) 6.2 (5.1, 8.1) 0.938\nE2 (pmol/L) 132.8 (94.8, 182.8) 198.9 (113.0, 389.0) <0.001\nWBCs (109/L) 6.4 ± 2.3 5.9 ± 1.8 0.002\nPLT (109/L) 245.6 ± 63.0 256.6 ± 69.0 0.016\nHGB (g/L) 126.3 ± 12.5 121.9 ± 14.5 <0.001\nTG (mmol/L) 0.9 (0.7, 2.0) 1.0 (0.7, 1.3) 0.096\nTC (mmol/L) 4.4 ± 0.8 4.6 ± 0.8 0.004\nLDL-C (mmol/L) 2.6 ± 0.7 2.8 ± 0.6 <0.001\nHDL-C (mmol/L) 1.4 ± 0.3 1.4 ± 0.4 0.398\nFPG (mmol/L) 5.1 ± 0.7 5.4 ± 1.1 <0.001\nAMH (ng/mL) 2.1 (1.1–3.7) 2.2 (1.1–3.7) 0.816\nSteroid hormone levels measured in 3–7 days after the onset of menstrual cycle, without considering\nhormone replacement therapy.\nEPs, endometrial polyps; EM, endometriosis; HGB, hemoglobin; WBCs, white blood cells; PLT,\nplatelet; FPG, fasting plasma glucose; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-\ndensity lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides; E 2, estradiol; FSH, follicle-\nstimulating hormone; PRL, prolactin; LH, luteinizing hormone; AMH, anti-Müllerian hormone.\nFig. 2. ROC curve for the prediction model based on BMI, DBP, gravidity, parity, WBCs, HGB, TC, FPG and LH. AUC, area\nunder the curve; ROC, receiver operating characteristic; BMI, body mass index; DBP , diastolic blood pressure; WBCs, white blood cells;\nHGB, hemoglobin; TC, total cholesterol; FPG, fasting plasma glucose; LH, luteinizing hormone; CI, confidence interval.\n4. Discussion\nIn this study, we conducted a retrospective analysis to\ncompare the differences in laboratory indices and baseline\nclinical features between EM patients with and without EPs.\nAfter adjusting for potential confounding factors, we devel-\noped a prediction model incorporating BMI, DBP , gravid-\nity, parity, WBCs, HGB, TC, FPG, and LH to predict the\nconcurrent presence of EPs in patients with EM. The ROC\ncurve for this combined diagnostic model yielded an AUC\nof 0.78, with sensitivity of 77.6%, specificity of 66.1%, cut-\noff value of 0.159, and Y ouden index of 0.437.\n4.1 Evidence for the Co-Occurrence of EPs in EM Patients\nA 2015 meta-analysis involving 2896 women sug-\ngested a higher risk of EPs in women with EM compared\nto those without, with a pooled relative risk (RR) 2.81 and\n95% confidence interval (95% CI): 2.48–3.18. Previous\nstudies have recommended hysteroscopy for infertile pa-\n4\n\n\nTable 3. Logistic regression to construct the prediction model.\nParameters β coefficient p-value OR 95% CI\nBMI 0.108 <0.001 1.114 1.051–1.180\nDBP 0.036 <0.001 1.036 1.016–1.057\nParity 1.690 <0.001 5.422 3.452–8.514\nGravidity –0.541 <0.001 0.582 0.461–0.734\nLH 0.038 <0.001 1.039 1.021–1.057\nWBCs –0.088 0.024 0.915 0.848–0.988\nHGB –0.015 0.011 0.985 0.974–0.997\nTC 0.255 0.008 1.290 1.068–1.558\nFPG 0.243 0.010 1.275 1.059–1.534\nConstant –6.860\nOR, odds ratio; CI, confidence interval; BMI, body mass index;\nDBP , diastolic blood pressure; WBCs, white blood cells; LH,\nluteinizing hormone; HGB, hemoglobin; TC, total cholesterol;\nFPG, fasting plasma glucose.\nTable 4. Y ouden index of the prediction model.\nCut-off point Sensitivity Specificity Y ouden index*\np-value 0.159 77.6% 66.1% 0.437\n*Y ouden index formula is defined as J = sensitivity + specificity – 1.\ntients with EM [12,13]. In our clinical experience, while we\ncannot provide exact data in this study, many EM patients\nadmitted for surgery concurrently present with EPs, as iden-\ntified by B-mode ultrasonography during routine preopera-\ntive exams. This discovery impacts surgical plans, neces-\nsitating both laparoscopic and hysteroscopic approaches,\nthereby increasing the complexity and duration of the pro-\ncedure.\n4.2 Metabolic Alterations in EPs and EM\nMetabolic alterations, including changes in various\nenergy-related, ketogenic, and glucogenic metabolites,\nhave been reported to at different stages of EM [ 14]. Glu-\ncose metabolism is generally believed to be increased in\nEM patients [ 15], accompanied by increased levels of TG,\nTC, and LDL-C, rendering them more prone to hyperc-\nholesterolemia and hypertension [ 16,17]. Additionally, a\nhigher BMI has been associated with a reduced risk of EM\n[18]. In contrast, risk factors for EPs include advanced age,\ntamoxifen use, inflammation, obesity, hypertension, dia-\nbetes, endocrine dysfunction, and altered estrogen secretion\n[4,6]. Metabolic parameters such as BMI, insulin levels,\nwaist circumference (WC), and the homeostatic model as-\nsessment of insulin resistance (HOMA-IR) have also been\ncorrelated with the presence of EPs [ 19]. In summary,\nboth EM and EPs, which are prevalent in women of child-\nbearing age, exhibit abnormal biological behavior of en-\ndometrial cells [20,21] and metabolism disorders [ 22]. EPs\nare primarily associated with dysregulated lipid metabolism\nand increased BMI, while EM is linked to impaired glu-\ncose metabolism and decreased BMI. Based on the above-\ndescribed clinical observation and similarities analogy in\nthe pathogenesis in EM and EPs, we propose the following\nhypothesis: metabolic dysregulation may play a significant\nrole in the development of both conditions, with potential\ndifferences in metabolic profiles between EM patients with\nand without EPs. However, few studies have examined the\ndifferences in metabolic markers between these two groups.\nIdentifying these metabolic disparities could facilitate early\ndiagnosis and development of tailored treatment strategies\nfor EPs in individuals with EM. Our findings show that EM\npatients with EPs had significantly higher BMI, SBP , DBP ,\nTC, LDL-C, FPG, and PLT compared to those without EPs.\nHowever, our metabolic indicators may not fully capture\nthe alterations in metabolic profile. Further research is war-\nranted to elucidate the precise mechanisms underlying these\nmetabolic differences and their roles in the development of\nEPs among individuals with EM.\n4.3 Steroid Hormone Dysregulation in EPs and EM\nIt was well known that elevated levels of E 2 is one\nof the contributing factors to EM. Exposure to diethyl-\nstilbestrol and an early age at menarche have been re-\nported to correlate with an increased risk of EM [ 23]. An\nearly age at menarche indicates an earlier onset of ovula-\ntion and prolonged exposure to estrogen and progesterone.\nEM is dependent on estrogen for its continued growth.\nThe onset of EPs may involve both estrogen-related and\nnon-estrogen-related pathways, with potential overlap be-\ntween these mechanisms. On the other hand, rearrange-\nments within the family of high mobility group (HMG) tran-\nscription factors, potentially resulting from a mechanism in-\nvolving aromatase-dependent focal hyperestrogenism, have\nbeen identified in EPs. Immunohistochemistry has revealed\nincreased estrogen receptor expression in EPs [ 24], further\nelucidating hormonal imbalances present in these lesions.\nWhile EM may result from prolonged or heightened estro-\ngen exposure, EPs primarily arise from focal hyperestro-\ngenism. However, research on the distinct hormonal patho-\ngenesis of EM and EPs is currently lacking. The prevalence\nof EM and EPs in adolescence is very low; however, a cor-\nrelation exists with steroid hormone levels. Diagnosing EM\nin adolescents poses a clinical challenge due to prolonged\ndelays in diagnosis. However, early imaging interventions\ncan help in mitigate this delay, particularly in young pa-\ntients exhibiting suggestive symptoms, such as severe men-\nstrual cramps or abnormal uterine bleeding [ 25,26].\nOur study found that patients with EM combined with\nEPs had higher levels of LH and E 2 compared to EM-only\npatients, warranting further investigation into the underly-\ning pathogenesis. Additionally, AMH levels were similar in\nboth groups, indicating no significant difference in ovarian\nreserve function and suggesting that variations in ovarian\nreserve contribute minimally to the pathogenesis of EP in\npatients with EM.\n5\n\n4.4 Inflammation Indices in EPs and EM\nThere may be a dependent relationship between\nchronic endometritis (CE) and EPs in premenopausal\nwomen [ 27]. The inflammatory response in patients with\nEM can impact glucose and lipid metabolism [16], although\nstudies on systemic inflammatory markers are limited. A\nstudy published in 2016 found that in both EM patients\nand the control group exhibited largely similar profiles of\nthree categories of molecules associated with systemic in-\nflammation: oxylipins, immunomodulatory proteins, and\nC-reactive protein (CRP) [ 28]. Interestingly, we observed\nhigher PLT levels, lower HGB, and lower WBCs in EM pa-\ntients with EPs compared to those without EPs for the first\ntime. Lower WBCs counts reflect abnormal immune func-\ntion and a different inflammatory state in EM patients with\nEPs. On the other hand, lower HGB may contribute to a\nhigher risk of anemia, indicating dysregulated inflamma-\ntion and immune response in EM patients with EPs. Col-\nlectively, these findings suggest a potential role of systemic\ninflammation in the development of EPs in individuals with\nEM.\nAs demonstrated above, we have identified numerous\ndifferences between EM patients with and without EPs. The\nconvergence of these various factors strongly suggests the\npotential role of steroid hormones and inflammation in the\ndevelopment of EM [ 29]. In order to develop a more pre-\ncise treatment strategy for EM patients, we established a\nmodel based on these different indices to predict the pres-\nence of EPs in patients with EM. Although this prediction\nmodel has not been fully validated in infertile patients, it\nstill provides valuable insights. Patients with EM preparing\nfor surgery can undergo hysteroscopy if they meet the crite-\nria of this prediction model, thus avoiding a second anesthe-\nsia and surgery. Hysteroscopy is clinically recommended\nfor infertile patients with EM who are planning to undergo\nlaparoscopic surgery. However, as an invasive procedure,\nhysteroscopic surgery carries risks, including water intoxi-\ncation and uterine perforation. Furthermore, postoperative\nrisks, including pelvic infection, intrauterine adhesion, cer-\nvical adhesion and cervical incompetence, may adversely\naffect subsequent pregnancy process. Our prediction model\noffers a strategy for early diagnosis and targeted treatment\nof patients with EM, potentially reducing unnecessary hys-\nteroscopies, safeguarding fertility, and improving repro-\nductive outcomes. Further studies using in vivo and in vitro\nmodels may help elucidate the pathogenesis of EPs in EM\npatients and identify potential therapeutic targets.\n4.5 Strengths and Limitations\nThe strengths of this study lie in its thorough analysis\nof the differences between EM patients with and without\nEPs, as well as in the establishment of an efficient com-\nbined prediction model. This model predicts the presence\nof EPs in patients with EM for the first time, providing valu-\nable insights into diagnostic and treatment strategies. The\nprimary limitation is the lack of accurate incidence rates of\nEPs in patients with EM. The absence of precise data may\naffect the generalizability of the findings and the reliability\nof the prediction model. The large number of included pa-\ntients facilitates the identification of statistically significant\ndifferences, which may not always translate to clinical sig-\nnificance. Additionally, we did not consider the severity or\nstage of EM and the size of EPs due to the limited number\nof subjects. Further investigations with larger sample sizes\nare warranted to explore whether the severity of EM corre-\nlates with the incidence of EPs. This could provide deeper\ninsights into the relationship between these two conditions\nand assist in refining diagnostic and management strategies.\n5. Conclusions\nCertain metabolic alterations were associated with the\npresence of EPs in patients with EM. The development of a\ndiagnostic model incorporating these potential risk factors\ncould offer a novel approach for the early detection and tar-\ngeted treatment of EPs in individuals with EM.\nAbbreviations\nEPs, endometrial polyps; EMs, endometriosis; BMI,\nbody mass index; SBP , systolic blood pressure; DBP , dias-\ntolic blood pressure; LH, luteinizing hormone; E 2, estra-\ndiol; PLT, platelet; TC, total cholesterol; LDL-C, low-\ndensity lipoprotein cholesterol; FPG, fasting plasma glu-\ncose; HGB, hemoglobin; WBCs, white blood cells; ROC,\nreceiver operating characteristic; AUC, area under the\ncurve; HOMA-IR, homeostatic model assessment of in-\nsulin resistance; HMG, high mobility group; AMH, anti-\nMüllerian hormone; CE, chronic endometritis; CRP , C-\nreactive protein.\nAvailability of Data and Materials\nThe datasets used and analyzed during the current\nstudy are available from the corresponding author on rea-\nsonable request.\nAuthor Contributions\nJYL and JHZ designed the study. XJW, JL and JPC\nsupervised the laboratory exams and data collection. ZMS\nand TZ analyzed and interpreted the data. ZMS and JYL\nwrote the first draft of the paper. JYL edited the paper. All\nauthors contributed to editorial changes in the manuscript.\nAll authors read and approved the final manuscript. All au-\nthors have participated sufficiently in the work and agreed\nto be accountable for all aspects of the work.\nEthics Approval and Consent to Participate\nThis retrospective study was approved by the ethics\ncommittee of the Women’s Hospital, Zhejiang University\nSchool of Medicine (IRB-20220207-R). This article does\nnot contain any studies with animals performed by any of\nthe authors. Furthermore, the consent of the study partici-\npants was deemed unnecessary as the study only involves\n6\n\n\nthe retrospective review of the medical database. The need\nof informed consent was waived by the ethics committee\n(Medical Ethics Committee of the Women’s Hospital, Zhe-\njiang University School of Medicine) for this retrospective\nstudy. We confirm that all methods were performed in ac-\ncordance with the 1964 Declaration of Helsinki and its later\namendments.\nAcknowledgment\nWe thank all the patients and their families for their\ncooperation and contribution.\nFunding\nThis study was funded by the National Natural Sci-\nence Foundation of China (No. 82001537), the Funda-\nmental Research Funds for the Central Universities (No.\n2021FZZX003-02-18) and Zhejiang University Education\nFoundation Global Partnership Fund.\nConflict of Interest\nThe authors declare no conflict of interest.\nReferences\n[1] Della Corte L, Di Filippo C, Gabrielli O, Reppuccia S, La Rosa\nVL, Ragusa R, et al. The Burden of Endometriosis on Women’s\nLifespan: A Narrative Overview on Quality of Life and Psy-\nchosocial Wellbeing. 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