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Spontaneous abortion is a pregnancy complication characterized by complex and multifactorial etiology. About 5% of childbearing women are globally affected by early pregnancy loss (EPL) and most of them experience recurrence (RPL). Epigenetic mechanisms and controlled inflammation are crucial for pregnancy maintenance and genetic predispositions may increase the risk affecting the maternal-fetal crosstalk. Combined analyses of global methylation, inflammation and inherited predispositions may contribute to define pregnancy loss etiopathogenesis. LINE-1 epigenetic regulation plays crucial roles during embryo implantation, and its hypomethylation has been associated with senescence and several complex diseases. By analysing a group of 230 women who have gone through pregnancy interruption and comparing those experiencing spontaneous EPL (n = 123; RPL, 54.5%) with a group of normal pregnant who underwent to voluntary interruption (VPI, n = 107), the single statistical analysis revealed significant lower (P < 0.00001) LINE-1 methylation and higher (P < 0.0001) mean cytokine levels (CKs: IL6, IL10, IL17A, IL23) in EPL. Genotyping of the following SNPs accounted for different EPL/RPL risk odds ratio: F13A1 rs5985 (OR = 0.24; 0.06-0.90); F13B rs6003 (OR = 0.23; 0.047-1.1); FGA rs6050 (OR = 0.58; 0.33-1.0); CRP rs2808635/rs876538 (OR = 0.15; 0.014-0.81); ABO rs657152 (OR = 0.48; 0.22-1.08); TP53 rs1042522 (OR = 0.54; 0.32-0.92); MTHFR rs1801133/rs1801131 (OR = 2.03; 1.2-3.47) and FGB rs1800790 (OR = 1.97; 1.01-3.87), although Bonferroni correction did not reach significant outputs. Principal Component Analysis (PCA) and logistic regression disclosed further SNPs positive/negative associations (e.g. APOE rs7412/rs429358; FGB rs1800790; CFH rs1061170) differently arranged and sorted in four significant PCs: PC1 (F13A, methylation, CKs); PC3 (CRP, MTHFR, age, methylation); PC4 (F13B, FGA, FGB, APOE, TP53, age, methylation); PC6 (F13A, CFH, ABO, MTHFR, TP53, age), yielding further statistical power to the association models. In detail, positive EPL risk association was with PC1 (OR = 1.81; 1.33-2.45; P < 0.0001) and negative associations with PC3 (OR = 0.489; 0.37-0.66; P < 0.0001); PC4 (OR = 0.72; 0.55-0.94; P = 0.018) and PC6 (OR = 0.61; 0.46-0.81; P = 0.001). Moreover, significant inverse associations were detected between methylation and CKs levels in the whole group (r IL10  = - 0.22; r IL17A  = - 0.25; r IL23  = - 0.19; r IL6  = - 0.22), and methylation with age in the whole group, EPL and RPL subgroups (r 2  = 0.147; r TOT  = 0.136; r 2  = 0.248), while VPI controls lost significance (r EPL  = 0.136; r 2 RPL  = 0.248), while VPI controls lost significance (r 2 VPI  = 0.011). This study provides a valuable multilayer approach for investigating epigenetic abnormalities in pregnancy loss suggesting genetic-driven dysregulations and anomalous epigenetic mechanisms potentially mediated by LINE-1 hypomethylation. Women with unexplained EPL might benefit of such investigations, providing new insights for predicting the pregnancy outcome and for treating at risk women with novel targeted epidrugs., (© 2024. The Author(s).)

Background: Percutaneous left atrial appendage occlusion (LAAO) is indicated in subjects with atrial fibrillation who cannot receive oral anticoagulants. This procedure requires transesophageal echocardiography guidance and is usually performed under general anesthesia. The Janus Mask is a new device designed to allow upper endoscopic procedures during noninvasive ventilation (NIV)., Aims: This study aims to assess the possibility of performing LAAO under sedation and NIV., Setting: Cardiac electrophysiology laboratory., Design: Case-control study., Materials and Methods: Data from 11 subjects undergoing LAAO under sedation and NIV with the Janus Mask were retrospectively collected. Procedure duration, outcomes, and physicians' satisfaction were compared with those of 11 subjects who underwent LAAO under general anesthesia in the same period., Statistical Analysis: Univariate analysis and analysis of variance for between-groups comparison., Results: The 11 subjects treated with sedation experienced a good outcome, with a high degree of satisfaction from the medical team. An increase in arterial partial pressure of carbon dioxide in the Janus group (45 [43-62] mmHg vs. 33 [30-35] mmHg in the general anesthesia group, P < 0.001) led to a transient pH decrease 45 min after the beginning of the procedure (7.30 [7.18-7.36] vs. 7.40 [7.39-7.46], P = 0.014). No differences in arterial partial pressure of oxygen, FiO 2 , and hemodynamic parameters were observed. The subjects' conditions at discharge from the recovery room were comparable. No difference in procedure duration was registered., Conclusions: LAAO procedure under sedation and NIV through the Janus Mask is safe and feasible. This strategy might represent a valuable alternative to manage such a compromised and fragile population.

Background: Infertility represents a major challenge to the emotional balance and sexual life of couples, with long-lasting and gender-specific effects. The objective of this study is to explore personality features of infertile patients and detect possible sexual disorders in couples undergoing infertility treatment., Materials and Methods: In this prospective study 60 infertile couples and 52 fertile control couples were asked to complete standardized and validated questionnaires: the Adjective Check List (ACL) to enquire about personality features and the Female Sexual Function Index (FSFI) or the International Index of Erectile Function (IIEF) to assess sexual functioning of female and male partners. The study population was divided into 3 groups: Group A (N = 30, recently diagnosed infertile couples) Group B (N = 30, infertile couples already undergoing Intrauterine Insemination) and Group C (N = 52, fertile control group)., Results: Infertile patients did not display any distinguishing personality features. Regarding sexual function, men of all the three groups scored higher in both questionnaires (sexual satisfaction, desire and orgasm) than their female partners. Comparing results between groups, Group A male partners obtained lower scores in all the subscales. Women belonging to Group A and Group B showed an impairment of sexual arousal, satisfaction, lubrification and orgasm when compared to fertile controls., Conclusions: Even if at the very first stages of infertility treatment no personality disturbances can be detected, the couples' sexual life is already impaired with different sexual disorders according to gender.

Objectives: To verify whether Doppler velocimetry on the uterine arteries can be used to single out abnormal hemodynamic adjustments in the uteroplacental district and to prognose adverse gestational outcomes in pregnant women with autoimmune and trombophilic disease., Methods: The study included 67 patients divided into 3 groups selected by a developed pathology. Attention was given to the performance of the Resistance Index (RI) in Doppler velocimetry checks at 10th, 16th-18th, 21st and 28th weeks of gestation., Results: A significant correlation between Doppler values at week 21st and development of preeclampsia was observed (p <0.05) in the three patient groups. High Doppler values at the 21st week were found to be strongly associated (p <0.01) with preterm delivery. We also observed a significant correlation (p <0.05) between high Doppler values at week 21st and low weight at birth. Doppler was found to have a predictive power for gestational adverse outcomes already at week 16th., Conclusion: RI values of more than 0.58 (taken as a cut-off) at 16/18th weeks allowed us to identify the category most at risk, if confirmed at 21 weeks.