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

Pituitary block with gonadotrophin-releasing hormone antagonist during intrauterine insemination cycles: a systematic review and meta-analysis of randomised controlled trials

BACKGROUND: Several randomised controlled trials (RCTs) have investigated the usefulness of pituitary block with gonadotrophin-releasing hormone (GnRH) antagonists during intrauterine insemination (IUI) cycles, with conflicting results. OBJECTIVE: The aim of the present systematic review and meta-analysis of RCTs was to evaluate the effectiveness of GnRH antagonist administration as an intervention to improve the success of IUI cycles. SEARCH STRATEGY: Electronic databases (MEDLINE, Scopus, EMBASE, Sciencedirect) and clinical registers were searched from their inception until October 2017. SELECTION CRITERIA: Randomised controlled trials of infertile women undergoing one or more IUI stimulated cycles with GnRH antagonists compared with a control group. DATA COLLECTION AND ANALYSIS: The primary outcomes were ongoing pregnancy/live birth rate (OPR/LBR) and clinical pregnancy rate (CPR). Pooled results were expressed as odds ratio (OR) or mean differences with 95% confidence interval (95% CI). Sources of heterogeneity were investigated through sensitivity and subgroups analysis. The body of evidence was rated using GRADE methodology. Publication bias was assessed with funnel plot, Begg's and Egger's tests. MAIN RESULTS: Fifteen RCTs were included (3253 IUI cycles, 2345 participants). No differences in OPR/LBR (OR 1.14, 95% CI 0.82-1.57, P = 0.44) and CPR (OR 1.28, 95% CI 0.97-1.69, P = 0.08) were found. Sensitivity and subgroup analyses did not provide statistical changes in pooled results. The body of evidence was rated as low (GRADE 2/4). No publication bias was detected. CONCLUSION: Pituitary block with GnRH antagonists does not improve OPR/LBR and CPR in women undergoing IUI cycles. TWEETABLE ABSTRACT: Pituitary block with GnRH antagonists does not improve the success of IUI cycles

Fertility-sparing approach in women affected by stage i and low-grade endometrial carcinoma: An updated overview

Endometrial cancer (EC) is a deleterious condition which strongly affects a woman’s quality of life. Although aggressive interventions should be considered to treat high-grade EC, a conservative approach should be taken into consideration for women wishing to conceive. In this scenario, we present an overview about the EC fertility-sparing approach state of art. Type I EC at low stage is the only histological type which can be addressed with a fertility-sparing approach. Moreover, no myometrium and/or adnexal invasion should be seen, and lymph-vascular space should not be involved. Regarding the pharmaceutical target, progestins, in particular medroxyprogesterone acetate (MPA) or megestrol acetate (MA), are the most employed agent in conservative treatment of early-stage EC. The metformin usage and hysteroscopic assessment is still under debate, despite promising results. Particularly strict and imperious attention should be given to the follow-up and psychological wellbeing of women, especially because of the double detrimental impairment: both EC and EC-related infertility consequences

Prediction of Ablation Volume in Percutaneous Lung Microwave Ablation: A Single Centre Retrospective Study

Background: Percutaneous Microwave Ablation (MWA) of lung malignancies is a procedure with many technical challenges, among them the risk of residual disease. Recently, dedicated software able to predict the volume of the ablated area was introduced. Cone-beam computed tomography (CBCT) is the imaging guidance of choice for pulmonary ablation in our institution. The volumetric prediction software (VPS) has been installed and used in combination with CBCT to check the correct position of the device. Our study aimed to compare the results of MWA of pulmonary tumours performed using CBCT with and without VPS. Methods: We retrospectively reviewed 1-month follow-up enhanced contrast-enhanced computed tomography (CECT) scans of 10 patients who underwent ablation with the assistance of VPS (group 1) and of 10 patients who were treated without the assistance of VPS (group 2). All patients were treated for curative purposes, the maximum axial diameter of lesions ranged between 5 and 22 mm in group 1 and between 5 and 25 mm in group 2. We compared the presence of residual disease between the two groups. Results: In group 1 residual disease was seen in only 1 patient (10%) in which VPS had ensured complete coverage of the tumour. In group 2 residual disease was found in 3 patients (30%). Conclusions: Using this software during MWA of lung malignancies could improve the efficacy of the treatment compared to the conventional only CBCT guidance

Fibrotic idiopathic interstitial lung disease: the molecular and cellular key players.

Interstitial lung disease (ILDs) that are known as diffuse parenchymal lung diseases (DPLDs) lead to the damage of alveolar epithelium and lung parenchyma culminating into inflammation and widespread fibrosis. ILDs that account for more than 200 different pathologies, can be di-vided into two groups: ILDs that have a known cause and those where the cause is unknown clas-sified as Idiopathic Interstitial Pneumonia (IIPs). IIPs include idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP) known also as bronchiolitis obliterans organizing pneumonia (BOOP), Acute interstitial pneumonia (AIP), Desquamative Interstitial Pneumonia (DIP), Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), and lymphocytic interstitial pneumonia (LIP). In this review our aim is to de-scribe the pathogenic mechanisms that lead to the onset and progression of the different IIPs, starting from IPF as the most studied, in order to find both common and standalone molecular and cellular key players among them. Finally, a deeper molecular and cellular characterization of different interstitial lung disease without known cause, would contribute to give a more accurate diagnosis to the patients, that would translate in a more effective treatment decision

Stenting versus balloon dilatation in patients with tracheal benign stenosis: The STROBE trial

Background: It is well known that benign tracheal stenosis represents an obstacle to open surgery, and that its treatment could be challenging. Two endoscopic techniques have so far been adopted to restore tracheal patency: balloon dilatation (BA) through laryngoscopy, and tracheal stenting (ST) with rigid bronchoscopy. The main objective of this study was to compare the efficacy of BA and ST to treat benign tracheal stenosis not eligible for surgery. We also compared the rate of adverse events in the two treatment groups. Methods: A retrospective, observational cohort study was carried out at the University Hospital of Modena (Italy) from November 2012 to November 2017 in two separate departments. Patients were considered to be “stabilized” (primary outcome) if they did not report significant respiratory symptoms, or restenosis in the long-term (2 years) following the endoscopic procedure. Results: Sixty-six patients were included in the study (33 in the BA and 33 in the ST group, respectively). Unadjusted Kaplan–Meier estimates showed a greater therapeutic effect of ST compared to BA at 2 years (hazard ratio = 3.9 95%CI [1.5–9.8], p =.01). After adjusting for confounders, stratified analyses showed that this effect was significant in patients with complex stenosis, idiopathic etiology, and degree of stenosis >70%. Compared with BA, ST showed a higher rate of adverse events (p =.01). Conclusions: Compared to BA, ST seems to be more effective in achieving stabilization of tracheal patency in complex benign tracheal stenosis, although burdened with a significantly higher number of adverse effects. These findings warrant future prospective study for confirmation. Level of evidence: 3

Fertility Counseling Pattern over Time in Young Patients with Breast Cancer: A Retrospective Analysis at a Large Comprehensive Cancer Center

Background: One main issue to be considered in young patients diagnosed with early breast cancer (BC) is the impact of oncological treatments on fertility and future chances of conception. Current guidelines recommend a comprehensive addressing of oncofertility as part of the management of premenopausal BC patients, including counselling on available assisted reproduction technologies and fertility preservation (FP) strategies. The COVID-19 pandemic represented a potential hurdle to the integration of these procedures into clinical practice. This study aims to describe the time-related evolution in addressing oncofertility issues. Methods: This retrospective mono-institutional observational study considered 206 patients who received neoadjuvant chemotherapy, adjuvant chemotherapy (CT) or adjuvant endocrine therapy (ET), diagnosed with breast cancer at the age of 40 or younger in the years 2014-2015 and 2020-2021. Timerelated evolution in addressing oncofertility during oncological consultations and adoption of a fertility or ovarian function preservation (OFP) method were analyzed comparing the two different timeframes. Results: Comparing the two cohorts 2014-2015 and 2020-2021, we found a significant difference in the presence of fertility discussion records (37.4% vs 57.9%, p < 0.01), and in the application of OFP/FP techniques (54.5 vs 78.5%, p < 0.01). In the two cohorts there was a significant difference in OFP (57.6% vs 70%, p = 0.03) and FP techniques application rates (5.1% vs 19.6%, p < 0.01). In the study population, age at diagnosis resulted to influence clinicians' approach towards counseling and/or OFP/FP strategies (87.3% in patients <35 years old (yo) vs 56.7% in older patients, p < 0.01). In the 2020-2021 cohort, age resulted less influential in the choice of using an OFP/FP strategy (87% vs 72.1%, p = 0.18). A higher rate of documented fertility discussion and/or OFP/FP techniques application was recorder in patients who had not had children before BC diagnosis (80.6% vs 64.5%, p = 0.02). When considering only the 2020-2021 timeframe, parity no longer significantly affected the prescription of an OFP/FP strategy (80.4% vs 78.3%, p = 0.93). Conclusions: This study on real world data demonstrates the progressive evolution in the way clinicians approach oncofertility issues, showing a greater attention across years, with more BC patients receiving a dedicated counseling, despite the COVID-19 pandemic

Molecular Mechanisms and Physiological Changes behind Benign Tracheal and Subglottic Stenosis in Adults

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS