Association between endometrial polyps and chronic endometritis

Chronic endometritis (CE) is a persistent inflammatory disorder of the endometrium. It is now diagnosed by observing the presence of plasma cell infiltration in the stromal tissue of the endometrium [,]. The development of CE may be caused by changes in the quality and quantity of the microorganisms in the endometrium [,]. Endometrial polyps (EPs) are characterized by their confined nature, as they are either sessile or pedunculated extensions of the endometrial mucosa []. This study aimed to examine the potential correlation between EPs and CE since the link between these two conditions remains uncertain. Patients and methods This prospective cohort study was carried out on 60 women, aged from 20 to 50 years old, diagnosed to have EP either by three dimensional (3D) transvaginal ultrasound with color doppler, during a diagnostic workup for abnormal uterine bleeding (AUB), infertility, or accidently discovered by ultrasound. The study was done from November 2022 to November 2023 after approval from the Ethical Committee Tanta University Hospitals, Egypt (approval code: 35941/10/22). An informed written consent was obtained from the patient or relatives of the patients. Exclusion criteria were history of steroid or antibiotic treatment for CE within the last 3 months, submucosal uterine fibroids, women on hormonal contraception or IUCD, previous D and C biopsy that revealed atypical hyperplasia and ultrasound criteria suspicious of malignancy such as: (thick inhomogenous endometrium with cystic irregular areas, subendometrial hypervascularity, large solid lesion with inhomogeneous echogenicity and intracavitary fluid). All patients were subjected to complete history taking such as analysis of the presenting complaint as: AUB: either heavy menstrual bleeding, intermenstrual bleeding, or cycle irregularities. Infertility: either primary or secondary infertility and any other possible infertility causes. History of steroid or antibiotic treatment. Previous D and C biopsy or polypectomy. History of previous pelvic infection. Comorbidities for any anesthesia contraindication as uncontrolled diabetes mellitus, cardiac, hepatic, and renal patients), full general examination [Vital signs, body mass index (BMI), dyspnea, pallor (as in cases of AUB with anemia), jaundice (in hepatic patients), and any masses. Skin: any manifestations of bleeding tendency. Systemic examination for any anesthesia risk: as thyroid, liver, kidneys, DVT, or cardiac patients], abdominal examination, gynecological examination [inspection of external genitalia, vagina, and cervix (tight or opened) using cusco speculum examination for manifestations of infection, protruding polyps from the cervix, and any other abnormalities in uterus and/or adenxia. Bimanual examination for tenderness and signs of infection, any masses either uterine, adenxial and pelvic, and any other abnormalities] and laboratory investigations [complete blood count, urine analysis, renal function tests, liver function tests, coagulation profile, serum pregnancy test, and inflammatory markers such as: (erythrocyte sedimentation rate and C-reactive protein)]. Ultrasound: 3D transvaginal ultrasound screening, performed during the second half of menstrual cycle and confirmed immediately postmenstrual for: exploration of uterine cavity and endometrial thickness. Confirmation of the presence of EPs with their site, size, and number. Exclusion of other uterine lesions. Figure 1. Also, using color-flow or power Doppler may demonstrate the single feeding vessel typical of EPs or subendometrial blood vessels. Preoperative preparation Premedication: all cases were given IV Ampicillin/sulbactam 1500 mg vial preoperatively, and sublingual misoprostol tablet (Cytotec 200 μg) before intervention as a preprocedural cervical preparation in cases with tight cervix. As regards anesthesia, preoperative fasting. Operative procedure: hysteroscopy (Operative hysteroscopy, KARL STORZ Germany 26040EB). A hysteroscope was performed in the proliferative phase (on Days 6–12 of the menstrual cycle), as the endometrium is thin facilitating intracavity viewing, and pregnancy was ruled out. To evaluate EP (site and size) and any other lesions. In women with irregular uterine bleeding, the ideal time for the procedure is unpredictable. Figure 2. The patient was put in a lithotomy position; the perineum should be at the edge of the table with the sacrum well supported. Painting and draping towels with support of both legs according to standard surgical techniques. General anesthesia with the use of muscle relaxants and intubation. Inspection of the polyps and any associated lesions: site and size. Type (either sessile or pedunculated). Either single or polypoid endometrium. Inspection of associated pathology in endometrium: especially CE. Criteria of Chronic endometritis diagnosis CE is characterized by the presence of bright red endometrial areas with white central dots. These areas are distributed either focally or diffusely across the endometrial surface, resembling a strawberry pattern. Additionally, there is hyperemia, stromal edema, micropolyps, and intrauterine synechiae. Polypectomy and endometrial D and C biopsy: hysteroscopic removal of intrauterine polyps was performed using a range of devices, including microscissors for instances of infertility, gripping forceps, or electrosurgery using either a monopolar probe or a resectoscope. Polypectomy was conducted for tiny or thin stalk polyps using either microscissors, gripping forceps, or a monopolar electrode using an operating hysteroscope. Resectoscope was used to remove polyps that had a wide base or were big. All patients made a comprehensive effort to remove intrauterine polyps. The polypectomy procedure was performed until a clear and comprehensive view of the endometrial cavity was seen, and both tubal ostia were visible after reassessing the endocervix and cervical canal. The biopsies were promptly immersed in a 10% neutral buffered formalin solution to facilitate fixation at ambient temperature. Subsequently, they were embedded in paraffin wax to facilitate further pathological tests. Recovery from hysteroscopy: patients were required to undergo a period of rest until the symptoms of anesthesia had subsided, after which they were often permitted to return home on the same day. Experiencing menstrual cramps and occasional spotting or bleeding for a few days after a hysteroscopy is a common occurrence. To alleviate these symptoms, one may simply take over-the-counter medicines like paracetamol or ibuprofen and use sanitary pads until the bleeding ceases. Patients with CE were administered ciprofloxacin 500 mg twice daily for a duration of 10 days or Doxycycline 100 mg twice daily for a duration of 14 days as part of their postoperative antibiotic treatment. Sample size calculation The researchers used the Epi-info software statistical program, developed by the WHO and the Center for Disease Control and Prevention in Atlanta, Georgia, USA, version 2002, to determine the sample size and conduct power analysis. The criteria used for the computation of sample size were as follows: the estimated prevalence of CE among patients with EPs is reported to be 70% with a 95% confidence level, accompanied by a margin of error of 15% (55%–85%). The determined sample size was N=36. To address the issue of incomplete findings, the researcher intends to augment the sample size to 60 instances. Statistical analysis SPSS v26 (IBM Inc., Chicago, IL, USA) was used for conducting statistical analysis. The normality of the data distribution was assessed using the Shapiro–Wilks test and histograms. The study used quantitative parametric data, namely the mean and standard deviation (SD), and employed a paired T-test for analysis. The study used quantitative nonparametric data, namely the median and interquartile range (IQR), for presentation. The frequency and percentage (%) of qualitative variables were reported and subjected to analysis using the χ2 test. A statistically significant result was defined as a two-tailed P value less than 0.05.

The age was with a mean value of 39.7 ± 8.77 years. Obstetric history was nongravid in 10 (16.67%) patients. The median (IQR) of gravidity was 3 (2–4). The median (IQR) of parity was 2 (2–3). The median (IQR) of live birth was 2 (1.75–3). Abortion was one in 15 (25%) patients, two in five (8.33%) patients, and three in two (3.33%) patients. Previous cesarean section was one in nine (15%) patients, two in 11 (18.33%) patients, three in three (5%) patients, and four in one (1.67%) patient. Normal vaginal delivery was one in four (6.67%) patients, two in three (5%) patients, three in seven (11.67%) patients, four in six (10%) patients, five in two (3.33%) patients and six in one (1.67%) patient. AUB occurred in 36 (60%) patients, 1 ry infertility occurred in 10 (16.67%) patients and 2 ry infertility occurred in eight (13.33%) patients and was accidentally discovered in six (10%) patients. Table 1 individuals with CE had a substantially lower age compared with individuals without CE (P value= 0.005). There was no statistically significant difference seen in the clinical presentation between individuals diagnosed with CE and those without CE. Table 2. There was no significant difference observed in the number and size of polyps between individuals diagnosed with CE and those without CE. There were no significant differences seen in the number, size, and form of polyps between individuals diagnosed with CE and those without CE. individuals with CE had a considerably greater prevalence of suspicious manifestations of CE, such as hypereraemia and stromal edema, compared with individuals without CE (P value 0.001). Table 3. Regarding histopathology, simple EP was present in 33 (55%) patients, Adenomyomatous polyp was present in eight (13.33%) patients, angiofibromatous polyp was present in one (1.67%) patients and polypoid endometrial hyperplasia was present in 18 (30%) patients. 15 (25%) patients had CE by histopathology. Table 4. Histopathology of the patients with CE was simple EP with CE in three (20%) patients, simple EP with CE and chronic cervicitis in two (13.33%), simple EPs and EP with chronic cervicitis and CE in one (6.67%) patient, simple EP with disordered proliferative endometrium and CE in one (6.67%) patient, simple EP with disordered proliferative endometrium with CE and chronic cervicitis in one (6.67%) patient, polypoid endometrial hyperplasia with CE six (40%) patients and angiofibromatous polyp with CE in one (6.67%) patient, no atypia or malignancy in all specimens. Histopathology of the patients without CE was simple EP with progestational effect in eight (17.78%) patients, simple EP with cystic changes in one (2.22%) patient, simple EP with proliferative endometrium in 16 (35.56%) patients, adenomyomatus polyp in eight (17.78%) patients and polypoid endometrial hyperplasia in 12 (26.67%) patients, no atypia or malignancy in all specimens. Table 5

EPs are characterized by the presence of regional extensions of endometrial mucosa, which arise due to the excessive proliferation of endometrial glands and stroma around a central vascular region. EP may range in size from a few millimeters to a few centimeters and can be either solitary or numerous, sessile, or pedunculated []. CE is a chronic inflammatory disorder that affects the endometrium across many menstrual cycles. Cervical endometriosis (CE) has a detrimental impact on fertility and is identified in about 30%–60% of women who are infertile and have had recurrent implantation failure []. The current investigation revealed a noteworthy correlation between EPs and CE, with a prevalence of 25% among individuals with polyps and CE. The precise etiology and pathology of EPs remain uncertain; nevertheless, it has been suggested that persistent inflammation within the endometrium might lead to the development of EPs []. The prevalence of proliferative and anti-apoptotic activity in CE was observed through the upregulation of transforming growth factor-beta 1, vascular endothelial growth factor (VEGF), tumor protein P73, tumor protein P63, and BAX (BCL-2 associated X protein) transcript variant alpha. This has the potential to facilitate the advancement of Eps []. Consistent with our findings, Qu et al. [] conducted a retrospective cohort study involving 233 people who underwent hysteroscopic polypectomy as a therapeutic intervention for EPs. The objective of their study was to assess the influence of CE on the recurrence of EPs in premenopausal women who had undergone hysteroscopic polypectomy. CE has a prevalence rate of 27.5% in the population. Consistent with our findings, Kuroda et al. [] proposed a robust correlation between EPs and CE. Most infertile patients with EPs (92.6%) had CE. Nevertheless, Carvalho et al. [] and Volodarsky-Perel et al. [] reported a prevalence rate of 45.3% for CE in the polyp group of infertile women, which exceeded the rates reported in previous research. The presenting clinical characteristic emerged as the most significant factor influencing prevalence. The inconsistent data may be attributed to many factors, including a lack of agreement about the diagnosis of recurrent pregnancy loss (specifically, two or three successive losses) and the criteria used to diagnose CE. To address the dispute, it is necessary to do prospective cohort research using a fertile control group []. The stage of the menstrual cycle from which the endometrial sample was taken for diagnosis emerged as the second most significant determinant influencing the incidence of CE []. Also, four previous studies have investigated the potential correlation between the prevalence of CE and the stage of the menstrual cycle during which the specimen was collected. One of these studies did not find any significant difference in prevalence between the proliferative and luteal phases []. However, three other studies have reported a higher prevalence of CE during the proliferative phase compared with the secretory phase [,,]. A study by, Vitagliano et al. [] found a high prevalence of CE in premenopausal women with EPs (51.35%). The findings from this study agreed with the results of Cicinelli et al. [] showed an association between CE and EPs. In the present study, regarding ultrasound and hysteroscopic description, regarding patients with CE, polyp number was single in nine (60%) patients and multiple in six (40%) patients and polyp size ranged from 0.7–3.8*0.6–3.7 cm with a mean value (±SD) of 1.6 ± 0.77*1.33 ± 0.78 cm. Regarding patients without CE, polyp number was single in 33 (73.33%) patients and multiple in 12 (26.67%) patients and polyp size ranged from 0.6–4.7*0.5–2.7 cm with a mean value (±SD) of 1.51 ± 0.7*1.18 ± 0.43 cm. Polyp number and polyp size were insignificantly different between patients with CE and patients without CE with P value of polyp number =0.329, and P value of polyp size=0.641. Our results were not supported by the study of Qu et al. [] who revealed that regarding polyp numbers in EPs patients with CE, 26.6% of the patients had solitary and 73.4% had multiple polyp numbers and in EPs patients without CE, 29.0% of the patients had solitary and 71.0% had multiple polyp number. Polyp size (cm) less than or equal to 1,greater than 1, and less than or equal to 2 was found in 18.8, 76.6, and 4.7% of the patients with CE, and 11.8, 80.5, and 7.7% of the patients without CE. In the study of, Peng et al. [] found a significantly higher prevalence of CE in the single-polyp group and multiple-polyp group compared with the nonpolyp group. Also, they revealed that no significant difference regarding CE between the A1 group and A2 group. Additionally, EPs either single or multiple significantly correlated with CE. Our results were in contrary with the study of Guo et al. [] suggested that multiple ectopic pregnancy (EP) may represent a distinct subtype characterized by a distinct etiopathogenesis compared with the conventional single EP. Additionally, there is a potential latent association between chronic inflammation and the onset of multiple EP. Additionally, the researchers observed a statistically significant increase in the occurrence of CE in the multiple EP group compared with the single EP group (58.7% vs. 28.0%, P < 0.001). The frequency of CE did not change between the single EP and nonpolyp groups (28.0% vs. 29.1%, P=0.872). In our results, regarding the hysteroscopic description of the studied patients, the suspecious manifestation of CE as (hyperemia and stromal edema) was significantly higher in patients with CE than in patients without CE (P value <0.001). In the current study, regarding histopathology, simple EP was present in 33 (55%) patients, Adenomyomatous polyp was present in eight (13.33%) patients, angiofibromatous polyp was present in one (1.67%) patients and polypoid endometrial hyperplasia was present in 18 (30%) patients. In the present study, histopathology of the patients with CE was simple EP with CE in three (20%) patients, simple EP with CE and chronic cervicitis in two (13.33%), simple EPs and endocervical polyp with chronic cervicitis and CE in one (6.67%) patient, simple EP with disordered proliferative endometrium and CE in one (6.67%) patient, simple EP with disordered proliferative endometrium with CE and chronic cervicitis in one (6.67%) patient, polypoid endometrial hyperplasia with CE six (40%) patients and angiofibromatous polyp with CE in one (6.67%) patient. Histopathology of the patients without CE was simple EP with progestational effect in eight (17.78%) patients, simple EP with cystic changes in one (2.22%) patient, simple EP with proliferative endometrium in 16 (35.56%) patients, adenomyomatus polyp in eight (17.78%) patients, and polypoid endometrial hyperplasia in 12 (26.67%) patients. In a study by, Song et al. [] according to the analysis, the histological diagnosis of endometrial hyperplasia was identified as the third most significant factor. The occurrence of CE was shown to be as high as 50% in women diagnosed with endometrial hyperplasia. The correlation between hyperplasia and CE is a novel finding that has not been previously documented. Nevertheless, the researchers choose to omit instances of endometrial cancer in their investigation. The variation in histology may be related to the large differences in histologic criteria for CE, both in pathology practice and in the literature. A study conducted among general and gynecologic pathologists in academic and community practice settings revealed that a mere 19% of participants correctly diagnose CE upon identifying a solitary plasma cell in a sample. Additionally, 43% of the respondents did not distinguish between CE and secretory endometrium []. Nevertheless, there exists evidence supporting the pathological involvement of plasma cells in the endometrium of patients diagnosed with CE. This is evidenced by the observed variations in the expression levels of selectin E, CXCL13, and CXCL1 within the endometrium of CE patients. These findings indicate physiological alterations that promote the pathological migration of B cells into the endometrium during the CE state []. In our study we only used H and E stain for histopathological examination, and we did not use immunohistochemistry.

The investigation was conducted at a single center. Limited sample size. The recurrent rate of EP and the potential impact of antibiotic therapy on reducing this incidence in individuals with both EP and CE were not examined in our study. The research reveals significant variability in the incidence of CE, which may be attributed to factors such as the specific population under investigation, the pathologic criteria used for diagnosis, and the timing of biopsy within the menstrual cycle.

In pre-menopausal women identified with EP by 3D transvaginal ultrasonography, CE and EPs may be dependent and two phases of a same pathogenic process. Either single or many EPs positively correlate with CE. CE prevalence was comparable for single- and multiple-polyp individuals. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

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