MUM-1 immunohistochemistry has high accuracy and reliability in the diagnosis of chronic endometritis: a multi-centre comparative study with CD-138 immunostaining.

PURPOSE: The current gold standard for chronic endometritis (CE) diagnosis is immunohistochemistry (IHC) for CD-138. However, IHC for CD-138 is not exempt from diagnostic limitations. The aim of our study was to evaluate the reliability and accuracy of MUM-1 IHC, as compared with CD-138. METHODS: This is a multi-centre, retrospective, observational study, which included three tertiary hysteroscopic centres in university teaching hospitals. One hundred ninety-three consecutive women of reproductive age were referred to our hysteroscopy services due to infertility, recurrent miscarriage, abnormal uterine bleeding, endometrial polyps or myomas. All women underwent hysteroscopy plus endometrial biopsy. Endometrial samples were analysed through histology, CD138 and MUM-1 IHC. The primary outcome was to evaluate the diagnostic accuracy of MUM-1 IHC for CE, as compared with CD-138 IHC. RESULTS: Sensitivity and specificity of CD-138 and MUM-1 IHC were respectively 89.13%, 79.59% versus 93.48% and 85.03%. The overall diagnostic accuracy of MUM-1 and CD-138 IHC were similar (AUC = 0.893 vs AUC = 0.844). The intercorrelation coefficient for single measurements was high between the two techniques (ICC = 0.831, 0.761-0.881 95%CI). However, among CE positive women, MUM-1 allowed the identification of higher number of plasma cells/hpf than CD-138 (6.50 [SD 4.80] vs 5.05 [SD 3.37]; p = 0.017). Additionally, MUM-1 showed a higher inter-observer agreement as compared to CD-138. CONCLUSION: IHC for MUM-1 and CD-138 showed a similar accuracy for detecting endometrial stromal plasma cells. Notably, MUM-1 showed higher reliability in the paired comparison of the individual samples than CD-138. Thus, MUM-1 may represent a novel, promising add-on technique for the diagnosis of CE.

Chronic endometritis and altered embryo implantation: a unified pathophysiological theory from a literature systematic review.

PURPOSE: Chronic endometritis (CE) is a frequent hysteroscopic and histological finding which affects embryo transfer implantation during IVF-ICSI cycles. In particular, CE impairs proper decidualization and, subsequently, implantation. Although this correlation has been clearly clarified, a pathophysiological explanation assembling all the studies performed has not been elucidated yet. For this reason, we have structured a systematic review considering all the original articles that evaluated a pathological element involved in CE and implantation impairment. METHODS: The authors searched electronic databases and, after screening, collected 15 original articles. These were fully scanned and used to create a summary pathway. RESULTS: CE is primarily caused by infections, which lead to a specific cytokine and leukocyte pattern in order to prepare the uterus to fight the noxa. In particular, the immunosuppression requested for a proper semi-allogenic embryo transfer implantation is converted into an immunoreaction, which hampers correct embryo implantation. Moreover, endometrial vascularization is affected and both irregular vessel density and luminal thickening and thrombosis reduce what we have first identified as endometrial flow reserve. Finally, incorrect uterine wave propagation could affect embryo contact with decidua. CONCLUSION: This is the first summary of evidence on CE pathophysiology and its relationship with infertility. Understanding the CE pathophysiology could improve our knowledge in embryo transfer success.

Use of Sotrovimab in a cohort of pregnant women with a high risk of COVID 19 progression: a single-center experience.

Neutralizing monoclonal antibodies (mAbs) have been shown to reduce disease progression in patients with underlying predisposing conditions. Unfortunately, there is no evidence on the use of Sotrovimab in pregnant women. Herein we present a case series of pregnant women who received mAbs with Sotrovimab following the Italian Drug Agency (AIFA) indications. Since February 1, 2022 all pregnant women - regardless of gestational age - admitted to Obstetrics & Gynaecology of Policlinico University of Bari, with positive nasopharyngeal NAAT for SARS-CoV-2 were screened according to the AIFA indications for Sotrovimab and, if eligible, were proposed for treatment. Data on COVID-19, pregnancy, delivery, newborn outcomes, and adverse events were collected. From February 1 to May 15, 2022, 58 pregnant women were screened. Fifty (86%) patients were eligible, 19 of them (32.7%) denied their consent, in 18 cases (31%), the drug was temporarily unavailable, and the remaining 13 (22%) were treated with Sotrovimab. Out of these 13 patients, 6 (46%) were in the 3rd and 7 (54%) in the 2nd trimester of pregnancy. None of the 13 patients experienced adverse reactions due to Sotrovimab and all had a good clinical outcome. Furthermore, evaluating pre- and post-infusion clinical status and hematochemical profile, a reduction in D-dimers and an increase in SARS-CoV-2 antibodies (p < 0.01) during the 72 h following the infusion were observed. Our data, the first on the use of Sotrovimab in pregnant women, showed the safety and efficacy drug profile and its potential crucial role in preventing COVID-19 disease progression.

Chronic Endometritis in Infertile Women: Impact of Untreated Disease, Plasma Cell Count and Antibiotic Therapy on IVF Outcome-A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aims to evaluate the impact of chronic endometritis (CE) and its therapy on in vitro fertilization (IVF) outcome. Additionally, we aim to investigate whether various degrees of CE severity may exert a different effect on IVF outcome. Ongoing-pregnancy rate/live-birth-rate (OPR/LBR), clinical-pregnancy rate (CPR), and miscarriage rate (MR) were calculated. A total number of 4145 patients (from ten studies) were included. Women with CE had lower OPR/LBR (OR 1.97, p = 0.02) and CPR (OR 2.28, p = 0.002) compared to those without CE. CE cure increased OPR/LBR (OR 5.33, p < 0.0001) and CPR (OR 3.64, p = 0.0001). IVF outcome was comparable between women with cured CE and those without CE (OPR/LBR, CPR and MR: p = ns). Women with severe CE had lower OPR/LBR (OR 0.43, p = 0.003) and CPR (OR 0.40, p = 0.0007) compared to those mild CE. Mild CE showed no influence on the IVF outcome as compared to women without CE (OPR/LBR, CPR and MR: p = ns). Based on this data analysis, CE significantly reduces OPR/LBR and CPR in women undergoing IVF. Importantly, CE resolution after antibiotic therapy may improves IVF outcome, leading to similar OPR/LBR and CPR as compared to unaffected patients. The negative effects of CE on IVF outcome may be restricted to severe disease, whereas mild CE may have no influence on IVF success.

Association between Endometrial Polyps and Chronic Endometritis: Is It Time for a Paradigm Shift in the Pathophysiology of Endometrial Polyps in Pre-Menopausal Women? Results of a Systematic Review and Meta-Analysis.

BACKGROUND: Chronic endometritis (CE) and endometrial polyps (EPs) are common conditions in reproductive age women. CE is an infectious disorder of the endometrium characterized by signs of chronic inflammation at hysteroscopic and histological analyses. EPs are abnormal endometrial growths containing glands, stroma and blood vessels projecting from the lining of the uterus. During the last years, different authors have investigated the correlation between CE and EPs, with controversial results. The aim of this study was to summarize available evidence on the potential correlation between CE and EPs. DESIGN: Systematic literature review and meta-analysis. METHODS: Observational-studies were identified by searching electronic databases from their inception to September 2021. Only studies on pre-menopausal women were included. Statistical analysis was performed using MedCalc 16.4.3 (Ostend, Belgium) and Review Manager version 5.3 (Nordic Cochrane Centre, Cochrane Collaboration). The summary measures were reported as pooled proportion or odds ratio (OR) with 95% confidence interval (CI). The primary outcome was to evaluate the prevalence of CE in women with EPs. The secondary outcome was to determine the prevalence of CD-138-positive EPs among EPs. Tertiary outcomes were to compare the prevalence of CE in women with EPs versus women with a non-polypoid endometrium and to compare the prevalence of CE in women with a single EP versus women with multiple EPs. RESULTS: Eight observational studies (n = 3225 patients) were included in quantitative synthesis. Pooled prevalence of CE among women with EPs was 51.35% (95% CI, 27.24-75.13%). Pooled proportion of CD-138-positive EPs among EPs was 70.73% (95% CI, 55.73-83.68%). Women with EPs showed higher prevalence of CE compared to women without EPs (OR 3.07, 95% CI 1.59-5.95). Women with ≥3 EPs had higher prevalence of CE then women with a single EP (OR 3.43, 95% CI 1.83-6.46). CONCLUSIONS: In pre-menopausal women, CE and EPs may have a dependent relationship and may represent two consequent steps of a common pathological process.

Antibiotic therapy versus no treatment for chronic endometritis: a case-control study.

OBJECTIVE: To demonstrate the infectious nature of chronic endometritis (CE) in an inductive way by comparing the results of germ-oriented antibiotic therapy vs. no treatment in women with CE. DESIGN: Retrospective, nonconcurrent case-control study. SETTING: Tertiary hysteroscopic center in a university teaching hospital. PATIENT(S): Sixty-four consecutive women with CE who received antibiotic therapy (Group A) compared with a historical group of 64 patients with CE who refused antibiotic therapy (Group B). INTERVENTIONS(S): CE was diagnosed through hysteroscopy, histology, and immunohistochemistry for CD138. Patients in both groups were tested for CE twice to evaluate the cure rate after antibiotic therapy (Group A) or no treatment (Group B). For patients with persistent disease, antibiotic therapy was repeated up to 3 times. Antibiotics were chosen based on endometrial culture (with antibiogram). MAIN OUTCOME MEASURE(S): The primary outcome was to compare the cumulative cure rate of CE (defined as the percentage of patients without CE at the test of cure) between groups. RESULT(S): Among Group A, 20 patients (31.25%) experienced CE resolution after 1 antibiotic cycle, an additional 20 patients (31.25%) after 2 antibiotic cycles, and 12 patients (19.35%) after 3 antibiotic cycles. In 12 cases (18.75%), CE was persistent after 3 cycles of antibiotics. The cure rate of CE in Group A after 1 cycle of antibiotics was significantly higher than that of Group B (32.25% vs. 6%). Similarly, the cumulative cure rate was considerably higher in Group A vs. Group B (81.3% vs. 6%). Notably, the number of positive cases decreased significantly with all techniques between the first and second evaluation, whereas at the third evaluation, there was a statistical decrease only with hysteroscopy and CD138+ cell count but not with histology. The cumulative number of cases of CE diagnosed at hysteroscopy was significantly higher than histology and immunohistochemistry. CONCLUSION(S): Our study demonstrated the superiority of antibiotic therapy compared with no treatment for CE cure. Accordingly, the infectious nature of CE is inferred.

Altered Gene Expression Encoding Cytochines, Grow Factors and Cell Cycle Regulators in the Endometrium of Women with Chronic Endometritis.

To evaluate the expression of genes encoding cytokines, grow factors and cell cycle regulators in the proliferative endometrium of women with chronic endometritis (CE) compared to controls. We performed a case-control study on seven women with CE as diagnosed by hysteroscopy and histology (Cases) compared to six women without CE (Controls). All women underwent diagnostic hysteroscopy plus endometrial biopsy during the mid-proliferative phase of the menstrual cycle. Endometrial samples were divided into two different aliquots for histological and molecular analyses. The endometrial expression profile of 16 genes encoding proteins involved in the inflammatory process, proliferation and cell cycle regulation/apoptosis was assessed by using high-throughput qPCR. Study endpoints were between-group differences in the expression of VEGF A, VEGF B, VEGF C, EGF, TNF, TGF B1, IFNG, TP73, TP73L, BAXva, CDC2, CDC2va, CCND3, CCNB1, BAX and IL12. RESULTS: VEGF A, VEGF B, VEGF C, EGF, TNF, TGF B1, IFNG, TP73, TP73L, BAXva, CDC2, CDC2va, CCND3, CCNB1 were significantly overexpressed in women with CE compared to controls, while BAX and IL12 had similar expression between groups. In women with CE, we found an altered endometrial expression of genes involved in inflammatory, cell proliferation, and apoptosis processes. The dominance of proliferative and anti-apoptotic activity in CE may potentially promote the development of polyps and hyperplastic lesions.

Pregnancy related cancer in Apulia. A population based linkage study.

OBJECTIVE: Despite a quite large number of papers in literature, the current incidence of pregnancy associated cancer still remains uncertain. Moreover, different inclusion criteria and time intervals considered after delivery make these data poorly comparable. The aim of this study was to investigate the incidence of PACs in Apulia, an Italian region, while stressing differences or similarities with other populations. STUDY DESIGN: We collected 682,173 pregnancies from national discharge forms, regarding hospitals in Apulia from January 2003 to December 2015. Our aim was not only to obtain the raw incidence of PACs but also to estimate the odds ratio (OR) for some potential risk predictors such as calendar year, age, nationality and pregnancy outcome using a logistic model. Women were sorted into different groups by age (<30, 30-34, 35-39, >=40) and by nationality (Italian or foreign nationals). Each pregnancy had two possible outcomes: delivery or abortion. RESULTS: We achieved a final cohort of 867 PACs: therefore, the raw incidence is 127.1 per 100,000 pregnancies. Breast cancer was the most common cancer (37.7 cases per 100,000 pregnancies) and as a typical feature in our population thyroid cancers followed it by incidence (22.3 per 100,000 pregnancies). Cervical cancer is, as expected, the first gynaecological cancer by incidence(3.8 per 100,000). Younger women have the lowest risk for PACs (64.5 per 100,000, OR = 1) while the highest risk for PACs was for women aged >=40 years (OR = 4.29, p < 0.05). Considering calendar years, we observed an increased OR from 2006 to 2009 (OR = 1.39 and OR = 1.41 respectively) without spotting a trend throughout the whole decade. CONCLUSIONS: The ranking of each tumour by incidence more or less reflects its demographics in reproductive age females in western countries and the incidence for any cancer is expected to grow as the rate of first deliveries in older women continues to rise. We reported noticeable differences regarding the incidence of some cancers (such as thyroid cancer) with previous literature, reflecting an epidemiologic feature of our cohort. Women older than 40 years have a more than fourfold risk for oncologic diagnosis during pregnancy, and this finding is of pivotal clinical and social importance because of the tendency of women living in developed countries to postpone childbearing.