Psychological status of infertile patients who had in vitro fertilization treatment interrupted or postponed due to COVID-19 pandemic: a cross-sectional study

Purpose: To explore the psychological status of infertile women and men who had in-vitro fertilization (IVF) treatment interrupted or postponed because of the COVID-19 emergency. Materials and methods: An electronic survey (NCT04395755) was e-mailed between April and June 2020 to couples whose IVF treatments have been interrupted or postponed due to the COVID-19 pandemic. The presence and severity of symptoms suggestive of anxiety and/or depression were assessed using the Generalized Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9). Subjects with preexisting psychiatric disorders were excluded. Results: Overall, 524 out of 646 patients completed the survey. The prevalence of anxiety and/or depression feelings was significantly higher in women, mainly if aged more than 35 years and with a previous IVF attempt. The occurrence of these psychological symptoms was significantly associated with the time spent on COVID-19 related news per day and partner with evidence of psychological disorder and, in females, with a diagnosis of poor ovarian reserve, diagnosis of endometriosis or uterine fibroids. Conclusions: The psychological impact of the COVID-19 pandemic on the infertile couples who should have undergone IVF treatment has been significant. IVF centers should systematically offer these couples adequate psychological counseling to improve mental health

Evolving trend in the management of heterozygous familial hypercholesterolemia in Italy: a retrospective, single center, observational study

Background and aims: The effective reduction of LDL-C in patients with heterozygous familial hypercholesterolemia (HeFH) is crucial to reduce their increased cardiovascular risk. Diagnostic and therapeutic (PCSK9 inhibitors) tools to manage HeFH improved in recent years. However, the impact of these progresses in ameliorating the contemporary real-world care of these patients remains to be determined. Aim of this study was to assess the evolution of treatments and LDL-C control in a cohort of HeFH patients in Italy. Methods and results: Four hundred six clinically diagnosed HeFH followed in a single, tertiary lipid centre were included in this survey. Data on lipid levels and medications were collected at baseline and during a median 3-year follow-up. At baseline, 19.8% of patients were receiving conventional high-potency lipid lowering therapies (LLT) and this percentage increased up to 50.8% at last visit. The knowledge of results of molecular diagnosis was associated with a significant increase in treatment intensity and LDL-C lowering. Nevertheless, the new LDL-C target (<70 mg/dl) was achieved only in 3.6% of HeFH patients under conventional LLTs and this proportion remained low (2.9%) also in those exposed to maximal conventional LLT. In 51 patients prescribed with PCSK9 inhibitors, 64.6% and 62.1% reached LDL-C<70 mg/dl at 3- and 12-month follow-up, respectively. Conclusions: Although treatments of HeFH improved over time, LDL-C target achievement with conventional LLT remains poor, mainly among women. The use of molecular diagnosis and even more the prescription of PCSK9i may improve LDL-C control in these patients

Clinical implications of monogenic versus polygenic hypercholesterolemia: Long-term response to treatment, coronary atherosclerosis burden, and cardiovascular events

BACKGROUND: Familial hypercholesterolemia (FH) may arise from deleterious monogenic variants in FH-causing genes as well as from a polygenic cause. We evaluated the relationships between monogenic FH and polygenic hypercholesterolemia in influencing the long-term response to therapy and the risk of atherosclerosis. METHODS AND RESULTS: A cohort of 370 patients with clinically diagnosed FH were screened for monogenic mutations and a low-density lipoprotein-rising genetic risk score >0.69 to identify polygenic cause. Medical records were reviewed to estimate the response to lipid-lowering therapies and the occurrence of major atherosclerotic cardiovascular events during a median follow-up of 31.0 months. A subgroup of patients (n=119) also underwent coronary computed tomographic angiography for the evaluation of coronary artery calcium score and severity of coronary stenosis as compared with 135 controls. Two hun-dred nine (56.5%) patients with hypercholesterolemia were classified as monogenic (FH/M+), 89 (24.1%) as polygenic, and 72 (19.5%) genetically undefined (FH/M−). The response to lipid-lowering therapy was poorest in monogenic, whereas it was comparable in patients with polygenic hypercholesterolemia and genetically undetermined. Mean coronary artery calcium score and the prevalence of coronary artery calcium >100 units were significantly higher in FH/M+ as compared with both FH/ M− and controls. Finally, after adjustments for confounders, we observed a 5-fold higher risk of incident major atherosclerotic cardiovascular events in FH/M+ (hazard ratio, 4.8; 95% CI, 1.06–21.36; Padj =0.041). CONCLUSIONS: Monogenic cause of FH is associated with lower response to conventional cholesterol-lowering therapies as well as with increased burden of coronary atherosclerosis and risk of atherosclerotic-related events. Genetic testing for hyper-cholesterolemia is helpful in providing important prognostic information

Refinement of pathogenicity classification of variants associated with familial hypercholesterolemia: implications for clinical diagnosis

Background: The lack of functional evidence for most variants detected during the molecular screening of patients with clinical familial hypercholesterolemia (FH) makes the definitive diagnosis difficult. Methods: A total of 552 variants in LDLR, APOB, PCSK9 and LDLRAP1 genes found in 449 mutation-positive FH (FH/M+) patients were considered. Pathogenicity update was performed following the American College of Medical Genetics and Genomics (ACMG) guidelines with additional specifications on copy number variants, functional studies, in silico prediction and co-segregation criteria for LDLR, APOB and PCSK9 genes. Pathogenicity of LDLRAP1 variants was updated by using ACMG criteria with no change to original scoring. Results: After reclassification, the proportion of FH/M+ carriers of pathogenic (P) or likely pathogenic (LP) variants, and FH/M+ carriers of likely benign (LB) or benign (B) variants, was higher than that defined by standard criteria (81.5% vs. 79.7% and 7.1% vs. 2.7%). The refinement of pathogenicity classification also reduced the percentage of FH with variants of uncertain significance (VUS) (17.7% vs. 11.4%). After adjustment, the FH diagnosis by refined criteria best predicted LDL-C levels (Padj <0.001). Notably, FH with VUS variants had higher LDL-C than those with LB (all Padj ≤ 0.033), but similar to those with LP variants. Conclusion: Accurate variant interpretation best predicts the increase of LDL-C levels and shows its clinical utility in the molecular diagnosis of FH

Prevalence and associated psychological risk factors of postpartum depression: a cross-sectional study

This cross-sectional study aimed to evaluate the prevalence of postpartum depression and the associated risk factors in a sample of Italian women at three months after delivery. Eighty women were screened by completing the Edinburgh Postnatal Depression Scale (EPDS). Women with a score ≥10 were evaluated as positive and other variables were detected through the administration of the Postpartum Depression Predictors Inventory. The prevalence of postpartum depression in the sample was 11.25% (EPDS score >10). A statistically significant relationship was found between the predisposition to postnatal depression and various risk factors such as prenatal depression, stressful life experiences marital problems. Furthermore, strong emotional and instrumental support from the partner and a good economic status can represent protective factors. It is essential to promote an integrated approach to postpartum affective disorders in which psychosocial risk factors are taken into account, and adequate screening programs are implemented.Impact StatementWhat is already known on this subject? Pregnancy can cause emotional stress for women with consequent development, in some cases, of mood disorders such as postpartum depression. What do the results of this study add? According to this study, women suffering from postpartum depression showed a significant tendency to anxiety and depression, low perceived support from the partner, and low socio-economic status. What are the implications of these findings for clinical practice and/or further research? It would be desirable to promote an integrated approach to postpartum affective disorders in which psychosocial risk factors are taken into account and adequate screening programs are implemented