The Role of Electroencephalography in Children with Acute Altered Mental Status of Unknown Etiology: A Prospective Study.

INTRODUCTION: Acute altered mental status (AAMS) is often a challenge for clinicians, since the underlying etiologies cannot always easily be inferred based on the patient's clinical presentation, medical history, or early examinations. The aim of this study is to evaluate the role of electroencephalogram (EEG) as a diagnostic tool in AAMS of unknown etiology in children. MATERIALS AND METHODS: We conducted a prospective study involving EEG assessments on children presenting with AAMS between May 2017 and October 2019. Inclusion criteria were age 1 month to 18 years and acute (<1 week) and persistent (>5 minutes) altered mental status. Patients with a known etiology of AAMS were excluded. A literature review was also performed. RESULTS: Twenty patients (median age: 7.7 years, range: 0.5-15.4) were enrolled. EEG contributed to the diagnosis in 14/20 cases, and was classified as diagnostic in 9/20 and informative in 5/20. Specifically, EEG was able to identify nonconvulsive status epilepticus (NCSE) in five children and psychogenic events in four. EEG proved to be a poorly informative diagnostic tool at AAMS onset in six children; however, in five of them, it proved useful during follow-up. CONCLUSIONS: Limited data exist regarding the role of EEG in children with AAMS of unknown etiology. In our population, EEG proved to be valuable tool, and was especially useful in the prompt identification of NCSE and psychogenic events.

Focal nonconvulsive status epilepticus in children: clinical and electroencephalographic features in 38 patients.

PURPOSE: The aim of this study was to characterize clinically, etiologically, and electroencephalographically focal Nonconvulsive Status Epilepticus (NCSE) in children. Moreover, we tried to identify focal NCSE features distinguishing between different ages, NCSE etiologies, and cases of de novo onset. METHODS: We retrospectively identified patients (aged 1 month to 18 years) who had EEG-documented focal NCSE between January 2001 and December 2019. We analyzed the clinical features, etiology, and EEG features of each event. RESULTS: Thirty-eight patients were included in this study. NCSE had a de novo onset in 26 patients and was the first manifestation of previously undiagnosed epilepsy in 12 patients. NCSE etiology was acute symptomatic in 13 patients. Acute symptomatic NCSE events were mainly observed in hospitalized children, were usually longer, and had a significantly higher frequency of repetitive EEG patterns than other etiologies. In patients with epilepsy, the etiology of NCSE was remote symptomatic in 14, progressive in 6, and cryptogenic in 5; a definite or suspected genetic disorder was observed in 11. EEG localization was frequent in posterior regions (18 children). Eleven patients had refractory NCSE and 4 required admission to the intensive care unit. CONCLUSION: Focal NCSE in children is more frequent in the first years of life, mainly involves posterior regions, and often has de novo onset. In the case of de novo focal NCSE both acute symptomatic NCSE and new-onset epilepsy must be considered and investigated. A higher frequency of repetitive EEG patterns and an inpatient setting are significantly associated with acute symptomatic NCSE.

Further delineation and long-term evolution of electroclinical phenotype in Mowat Wilson Syndrome. A longitudinal study in 40 individuals.

BACKGROUND: Epilepsy is a main feature of Mowat Wilson Syndrome (MWS), a congenital malformation syndrome caused by ZEB2 variants. The aim of this study was to investigate the long-term evolution of the electroclinical phenotype of MWS in a large population. METHODS: Forty-individuals with a genetically confirmed diagnosis were enrolled. Three age groups were identified (t1 = 0-4; t2 = 5-12; t3 = >13 years); clinical data and EEG records were collected, analyzed, and compared for age group. Video-EEG recorded seizures were reviewed. RESULTS: Thirty-six of 40 individuals had epilepsy, of whom 35/35 aged >5 years. Almost all (35/36) presented focal seizures at onset (mean age at onset 3.4 ±â€¯2.3 SD) that persisted, reduced in frequency, in 7/22 individuals after the age of 13. Absences occurred in 22/36 (mean age at onset 7.2 ±â€¯0.9 SD); no one had absences before 6 and over 16 years old. Paroxysmal interictal abnormalities in sleep also followed an age-dependent evolution with a significant increase in frequency at school age (p = 0.002) and a reduction during adolescence (p = 0.008). Electrical Status Epilepticus during Sleep occurred in 14/36 (13/14 aged 5-13 years old at onset). Seven focal seizure ictal video-EEGs were collected: all were long-lasting and more visible clinical signs were often preceded by prolonged electrical and/or subtle (erratic head and eye orientation) seizures. Valproic acid was confirmed as the most widely used and effective drug, followed by levetiracetam. CONCLUSIONS: Epilepsy is a major sign of MWS with a characteristic, age-dependent, electroclinical pattern. Improvement with adolescence/adulthood is usually observed. Our data strengthen the hypothesis of a GABAergic transmission imbalance underlying ZEB2-related epilepsy.

Training RAN or reading? A telerehabilitation study on developmental dyslexia.

Rehabilitation procedures recommended for developmental dyslexia (DD) are still not fully defined, and only few studies directly compare different types of training. This study compared a training (Reading Trainer) working on the reading impairment with one (Run the RAN) working on the rapid automatized naming (RAN) impairment, one of the main cognitive deficits associated with DD. Two groups of DD children (N = 45) equivalent for age, sex, full IQ, and reading speed were trained either by Reading Trainer (n = 21) or by Run the RAN (n = 24); both trainings required an intensive home exercise, lasting 3 months. Both trainings showed significant improvements in reading speed and accuracy of passages and words. Bypassing the use of alphanumeric stimuli, but empowering the cognitive processes underlying reading, training RAN may be a valid tool in children with reading difficulties opening new perspectives for children with severe impairments or, even, at risk of reading difficulties.

Telerehabilitation in developmental dyslexia: methods of implementation and expected results.

BACKGROUND: Developmental Dyslexia is a disorder, highly frequent in the school population, for which the recommended rehabilitation procedures are not well defined. This study aimed to automatize reading decoding skills by using an innovative system for rehabilitation, based on a telerehabilitation method. It requires an intensive home-exercise with the supervision, by web, of the clinician. The study had three main aims: to diffuse knowledge on new methods for rehabilitation of reading difficulties; to verify whether an intensive and simplified exercise, targeted to the automation of reading, is suitable for different subgroups of dyslexic children; to define the treatment effects on basic cognitive functions underlying reading. METHODS: Twenty-five children, grouped according to the neuropsychological and anamnestic profiles, took part to the treatment by the software Reading Trainer®. RESULTS: Both speed and accuracy of reading decoding increased significantly after treatment, independently from the functional neuropsychological profile or the history of oral language delay. These changes were specific to decoding and not associated with improvements in reading comprehension or spelling skills. However, there was a "cascade effect" of the treatment efficacy on those basic cognitive functions considered precursors of the ability to read, with significant improvements in rapid lexical access, phonological processing and visual attention. CONCLUSIONS: This study provides information on the efficacy of new tools for telerehabilitation of specific reading disorders.

First adaptation of coping power program as a classroom-based prevention intervention on aggressive behaviors among elementary school children.

Children with high levels of aggressive behavior create a major management problem in school settings and interfere with the learning environment of their classmates. We report results from a group-randomized trial of a program aimed at preventing aggressive behaviors. The purpose of the current study, therefore, was to determine the extent to which an indicated prevention program, Coping Power Program, is capable of reducing behavioral problems and improving pro-social behavior when delivered as a universal classroom-based prevention intervention. Nine classes (five first grade and four second grade) were randomly assigned to intervention or control conditions. Findings showed a significant reduction in overall problematic behaviors and in inattention-hyperactivity problems for the intervention classes compared to the control classes. Students who received Coping Power Program intervention also showed more pro-social behaviors at postintervention. The implications of these findings for the implementation of strategies aimed at preventing aggressive behavior in school settings are discussed.

Epilepsy in Mowat-Wilson syndrome: delineation of the electroclinical phenotype.

Mowat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene and is characterized by distinctive facial features, epilepsy, moderate to severe intellectual disability, corpus callosum abnormalities and other congenital malformations. Epilepsy is considered a main manifestation of the syndrome, with a prevalence of about 70-75%. In order to delineate the electroclinical phenotype of epilepsy in MWS, we investigated epilepsy onset and evolution, including seizure types, EEG features, and response to anti-epileptic therapies in 22 patients with genetically confirmed MWS. Onset of seizures occurred at a median age of 14.5 months (range: 1-108 months). The main seizure types were focal and atypical absence seizures. In all patients the first seizure was a focal seizure, often precipitated by fever. The semiology was variable, including hypomotor, versive, or focal clonic manifestations; frequency ranged from daily to sporadic. Focal seizures were more frequent during drowsiness and sleep. In 13 patients, atypical absence seizures appeared later in the course of the disease, usually after the age of 4 years. Epilepsy was usually quite difficult to treat: seizure freedom was achieved in nine out of the 20 treated patients. At epilepsy onset, the EEGs were normal or showed only mild slowing of background activity. During follow-up, irregular, diffuse frontally dominant and occasionally asymmetric spike and waves discharges were seen in most patients. Sleep markedly activated these abnormalities, resulting in continuous or near-to-continuous spike and wave activity during slow wave sleep. Slowing of background activity and poverty of physiological sleep features were seen in most patients. Our data suggest that a distinct electroclinical phenotype, characterized by focal and atypical absence seizures, often preceded by febrile seizures, and age-dependent EEG changes, can be recognized in most patients with MWS.

Risk factors for multimorbidity in adulthood: A systematic review.

BACKGROUND: Multimorbidity, the coexistence of multiple chronic diseases in an individual, is highly prevalent and challenging for healthcare systems. However, its risk factors remain poorly understood. OBJECTIVE: To systematically review studies reporting multimorbidity risk factors. METHODS: A PRISMA-compliant systematic review was conducted, searching electronic databases (MEDLINE, EMBASE, Web of Science, Scopus). Inclusion criteria were studies addressing multimorbidity transitions, trajectories, continuous disease counts, and specific patterns. Non-human studies and participants under 18 were excluded. Associations between risk factors and multimorbidity onset were reported. RESULTS: Of 20,806 identified studies, 68 were included, with participants aged 18-105 from 23 countries. Nine risk factor categories were identified, including demographic, socioeconomic, and behavioral factors. Older age, low education, obesity, hypertension, depression, low pysical function were generally positively associated with multimorbidity. Results for factors like smoking, alcohol consumption, and dietary patterns were inconsistent. Study quality was moderate, with 16.2% having low risk of bias. CONCLUSIONS: Several risk factors seem to be consistently associated with an increased risk of accumulating chronic diseases over time. However, heterogeneity in settings, exposure and outcome, and baseline health of participants hampers robust conclusions.

Executive Functions and Rapid Automatized Naming: A New Tele-Rehabilitation Approach in Children with Language and Learning Disorders.

Executive function deficits are documented in many neurodevelopmental disorders and may contribute to clinical complexity or rehabilitation resilience. The present research was primarily aimed at presenting and evaluating the feasibility and effectiveness of a telerehabilitation program used during the pandemic period. MemoRAN (Anastasis), a computerised cognitive training to improve executive control during visual-verbal integration tasks was used in a sample of 42 children (5-11 years old) with specific learning or language disorders. The MemoRAN training was based on exercises of inhibition, cognitive flexibility and updating in working memory for three months, with a frequency of approximately three sessions per week. Afterwards, a comparison between a subgroup of children using Memo-RAN and an active control group, using a tele-rehabilitation program directed on reading was conducted. Effect size analysis in pre-post measurements suggests an average effect of MemoRAN in measurements that require control processes, such as accuracy in dictation, reading, inhibition and working memory testing. Comparison with the active control group and the clinical utility implications of these types of treatment will be discussed.

Comparison of the characteristics, morbidity and mortality of COVID-19 between first and second/third wave in a hospital setting in Lombardy: a retrospective cohort study.

Coronavirus disease 2019 (COVID-19) represents a major health problem in terms of deaths and long-term sequelae. We conducted a retrospective cohort study at Montichiari Hospital (Brescia, Italy) to better understand the determinants of outcome in two different COVID-19 outbreaks. A total of 634 unvaccinated patients admitted from local emergency room to the Internal Medicine ward with a confirmed diagnosis of SARS-CoV-2 infection and a moderate-to-severe COVID-19 were included in the study. A group of 260 consecutive patients during SARS-CoV-2 first wave (from February to May 2020) and 374 consecutive patients during SARS-CoV-2 2nd/3rd wave (from October 2020 to May 2021) were considered. Demographic data were not significantly different between waves, except a lower prevalence of female sex during first wave. Mortality was significantly higher during the 1st wave than in the following periods (24.2% vs. 11%; p < 0.001). Time from symptoms onset to hospital admission was longer during first wave (8 ± 6 vs. 6 ± 4 days; p < 0.001), while in-hospital staying was significantly shorter (10 ± 14 vs. 15 ± 11 days; p < 0.001). Other significant differences were a larger use of corticosteroids and low-molecular weight heparin as well less antibiotic prescription during the second wave. Respiratory, bio-humoral and X-ray scores were significantly poorer at the time of admission in first-wave patients. After a multivariate regression analysis, C-reactive protein and procalcitonin values, % fraction of inspired oxygen on admission to the Internal Medicine ward and length of hospital stay and duration of symptoms were the strongest predictors of outcome. Concomitant anti-hypertensive treatment (including ACE-inhibitors and angiotensin-receptor blockers) did not affect the outcome. In conclusion, our data suggest that earlier diagnosis, timely hospital admission and rational use of the therapeutic options reduced the systemic inflammatory response and were associated to a better outcome during the 2nd/3rd wave.

Dialogic Reading to Empower Executive Functions in Preschoolers.

Among the interventions recently developed to enhance Executive Functions (EFs) in preschoolers, Quincey Quokka's Quest (QQQ) is an illustrated book proposing EF activities embedded within a shared reading framework (Howard et al., 2017). In the present study, the Italian version of QQQ (QQQIT) was tested in 20 typical developing 4-5 year old children. Standardized tests were used to assess EFs pre- and post- intervention. QQQIT was conducted once a week for 8 weeks in small groups. A positive trend was registered in QQQIT performances from the first to the last sessions and a significant improvement, in comparison to the control condition, was obtained in the Color and Form Game test. These results, supporting the feasibility of the QQQIT intervention and its efficacy in increasing shifting abilities, confirm the usefulness of ecological interventions to empower specific EF components in preschool contexts.

Short-Term Consequences of SARS-CoV-2-Related Pneumonia: A Follow Up Study.

The aim of the study was to assess the short-term consequences of SARS-CoV-2-related pneumonia, also in relation to radiologic/laboratory/clinical indices of risk at baseline. This prospective follow-up cohort study included 94 patients with confirmed COVID-19 admitted to a medical ward at the Montichiari Hospital, Brescia, Italy from February 28th to April 30th, 2020. Patients had COVID-19 related pneumonia with respiratory failure. Ninety-four patients out of 193 survivors accepted to be re-evaluated after discharge, on average after 4 months. In » of the patients an evidence of pulmonary fibrosis was detected, as indicated by an altered diffusing capacity of the lung for carbon monoxide (DLCO); in 6-7% of patients the alteration was classified as of moderate/severe degree. We also evaluated quality of life thorough a structured questionnaire: 52% of the patients still lamented fatigue, 36% effort dyspnea, 10% anorexia, 14% dysgeusia or anosmia, 31% insomnia and 21% anxiety. Finally, we evaluated three prognostic indices (the Brixia radiologic score, the Charlson Comorbidity Index and the 4C mortality score) in terms of prediction of the clinical consequences of the disease. All of them significantly predicted the extent of short-term lung involvement. In conclusion, our study demonstrated that SARS-CoV-2-related pneumonia is associated to relevant short-term clinical consequences, both in terms of persistence of symptoms and in terms of impairment of DLCO (indicator of a possible development of pulmonary fibrosis); some severity indices of the disease may predict short-term clinical outcome. Further studies are needed to ascertain whether such manifestations may persist long-term.

A web-based versus paper questionnaire on alcohol and tobacco in adolescents.

OBJECTIVE: Our study was aimed at comparing health behavior data collected from a Web-based self-administered questionnaire (Web SAQ) versus a paper-and-pencil self-administered questionnaire and assessing the feasibility of the application. MATERIALS AND METHODS: One hundred and ninety (n = 190) pupils (ages 14-16 years) of senior high schools anonymously completed a questionnaire, with demographics and queries about lifestyle, alcohol, and tobacco use. For each class, the adolescents were randomly assigned to complete either the paper version of the questionnaire or the equivalent Web-based one, which used a customized platform developed for the purposes of this survey. RESULTS: Females who filled out the Web SAQ required significantly less time and completed a significantly higher percentage of its items. Although the majority of questions on tobacco and alcohol did not differ significantly across the two administration modes, there were gender-related differences in some sensitive information. Male adolescents on the Web SAQ accounted higher per hour drink consumption (r = 0.27, p = 0.015) and more numerous episodes of inebriety (r = 0.26, p = 0.010), whereas females seemed to state a younger age of alcohol onset (r = 0.33, p = 0.002). Females were more likely to report being monthly smokers on the Web SAQ (odds ratio = 0.37). Adolescents felt significantly less observed and females referred being more independent while compiling the Web SAQ. CONCLUSIONS: The findings of the study suggest that differences in reporting of some behavior of adolescents when using a Web SAQ do exist, despite the small-to-medium effect sizes. Exploiting the Web requires further investigation for extensive comprehension of the reasons for such differences.

Prognostic factors and predictors of outcome in patients with COVID-19 and related pneumonia: a retrospective cohort study.

The aim of the present study was to simultaneously assess several potential predictors of outcome (co-morbidity, previous and in-hospital treatment, radiologic Brixia score) in patients with COVID-19. This retrospective cohort study included 258 consecutive patients with confirmed COVID-19 admitted to a medical ward at Montichiari Hospital, Brescia, Italy from February 28th to April 30rd, 2020. Patients had SARS-CoV-2 related pneumonia with respiratory failure, and were treated with hydroxychloroquine and lopinavir plus ritonavir. In some patients, additional treatment with tocilizumab, dexamethasone and enoxaparin was adopted. Outcomes (death or recovery) were assessed at the end of the discharge period or at the end of the follow-up (August 2020). During hospitalization, 59 patients died, while 6 died after discharge. The following variables were demonstrated to be associated with a worse prognosis: Radiologic Brixia score higher than 8, presence at baseline of hypertension, diabetes, chronic obstructive pulmonary disease, heart disease, cancer, previous treatment with ACE-inhibitors or anti-platelet drugs. Anticoagulant treatment during hospital admission with enoxaparin at a dose higher than 4000 U once daily was associated with a better prognosis. In conclusion, our study demonstrates that some co-morbidities and cardiovascular risk factors may affect prognosis. The radiologic Brixia score may be a useful tool to stratify the risk of death at baseline. Anticoagulant treatment with enoxaparin might be associated to a clinical benefit in terms of survival in patients with COVID-19.

The long pentraxin 3 is a soluble and cell-associated component of the human semen.

The long pentraxin 3 (PTX3) is a multifunctional soluble pattern recognition receptor, involved in several processes ranging from innate resistance and inflammation to clearance of apoptotic cells and organization of hyaluronic acid-rich extracellular matrices. PTX3 is also a novel marker in several pathological conditions of infectious, inflammatory, or autoimmune origin. This study was designed to assess whether PTX3 is expressed in the male reproductive tract and whether PTX3 interacts with human spermatozoa influencing their function. Here we show for the first time by immunohistochemistry that PTX3 is expressed in the male genital tract in perivascular connective tissue, in endothelial cells, in the interstitium, and in the cytoplasm of prostatic epithelial glandular cells; PTX3 was detectable in seminal plasma in variable levels, which correlated with the percentage of normal spermatozoa. Moreover, PTX3 binds to spermatozoa, in particular with immotile cells, localizing in the neck and in the subacrosomial region. Finally, recombinant PTX3 did not interfere with sperm motility.

Sleep in Mowat-Wilson Syndrome: a clinical and video-polysomnographic study.

OBJECTIVE: Sleep disturbances are frequently reported in Mowat-Wilson Syndrome (MWS). The current study aimed to evaluate clinical and video-polysomnographic (VPSG) characteristics of the sleep architecture and abnormal electroencephalogram (EEG) patterns during sleep in MWS. METHODS: Sixteen individuals with MWS (range 16 months-25 years), attending the Department of Child Neurology and Psychiatry of the University of Bologna, were included. The "Sleep Disturbances Scale for Children (SDSC)" questionnaire was administered to all parents of MWS patients, and all patients underwent a VPSG recording. RESULTS: The analysis of the SDSC questionnaire revealed disturbances mainly at the sleep-wake transition and in initiating and maintaining sleep. Evaluation of sleep structure in MWS patients showed a significant reduction of total sleep time, an increase of wake after sleep onset and arousal index as compared to normal controls. An EEG pattern characterized by slowing of background activity and poverty of physiological sleep characterisitcs was observed in all patients. Moreover, in patients aged >7 years, anteriorly predominant spike and waves were observed, markedly activated by sleep configuring a sub-continuous or continuous activity. CONCLUSION: Our data (both clinical and VPSG) documented the presence of significant and clinically relevant sleep disturbances in MWS patients. Moreover, we identified a characteristic age-dependent sleep EEG pattern that could provide a new element to assist in the management of MWS.

The clomiphene citrate challenge test (CCCT) in women with elevated basal FSH: biological significance and predictive value.

OBJECTIVE: The rationale of the clomiphene citrate challenge test (CCCT) is that day 10 serum FSH is influenced by the quality of the recruited oocytes. Biological evidence supporting this assumption is, however, lacking. The aim of this study is to investigate the relationship between results from the CCCT and the quantity and the quality of the recruited oocytes. STUDY DESIGN: Patients selected for in vitro fertilization (IVF) and who were found to have elevated basal FSH (n=114) underwent an IVF cycle using follicles developing during CCCT. Subsequently, a subgroup of patients (n=89) underwent a second cycle receiving high doses of gonadotropins. The main outcome considered was the transfer of viable embryos. RESULTS: During the CCCT cycle, the area under the receiver operating characteristics (ROC) curves for day 3 and day 10 serum FSH to predict embryo-transfer was 0.48 (95% CI, 0.37-0.60) and 0.74 (95% CI, 0.63-0.82), respectively. In the subsequent cycle, the area under the ROC curves for the two variables was 0.58 (0.43-0.72) and 0.58 (0.43-0.72), respectively. CONCLUSIONS: CCCT effectively mirrors the quantity and the quality of the recruited oocytes but its predictive value is low.

Learning disabilities in neuromuscular disorders: a springboard for adult life.

Although the presence of cognitive deficits in Duchenne muscular dystrophy or myotonic dystrophy DM1 is well established in view of brain-specific expression of affected muscle proteins, in other neuromuscular disorders, such as congenital myopathies and limb-girdle muscular dystrophies, cognitive profiles are poorly defined. Also, there are limited characterization of the cognitive profile of children with congenital muscular dystrophies, notwithstanding the presence of cerebral abnormality in some forms, and in spinal muscular atrophies, with the exception of distal spinal muscular atrophy (such as the DYN1CH1- associated form). Starting from the Duchenne muscular dystrophy, which may be considered a kind of paradigm for the co-occurrence of learning disabilities in the contest of a progressive muscular involvement, the findings of neuropsychological (or cognitive) dysfunctions in several forms of neuromuscular diseases will be examined and reviewed.

Blood cell mitochondrial DNA content and premature ovarian aging.

Primary ovarian insufficiency (POI) is a critical fertility defect characterized by an anticipated and silent impairment of the follicular reserve, but its pathogenesis is largely unexplained. The frequent maternal inheritance of POI together with a remarkable dependence of ovarian folliculogenesis upon mitochondrial biogenesis and bioenergetics suggested the possible involvement of a generalized mitochondrial defect. Here, we verified the existence of a significant correlation between blood and ovarian mitochondrial DNA (mtDNA) content in a group of women undergoing ovarian hyperstimulation (OH), and then aimed to verify whether mtDNA content was significantly altered in the blood cells of POI women. We recruited 101 women with an impaired ovarian reserve: 59 women with premature ovarian failure (POF) and 42 poor responders (PR) to OH. A Taqman copy number assay revealed a significant mtDNA depletion (P<0.001) in both POF and PR women in comparison with 43 women of similar age and intact ovarian reserve, or 53 very old women with a previous physiological menopause. No pathogenic variations in the mitochondrial DNA polymerase γ (POLG) gene were detected in 57 POF or PR women with low blood mtDNA content. In conclusion, blood cell mtDNA depletion is a frequent finding among women with premature ovarian aging, suggesting that a still undetermined but generalized mitochondrial defect may frequently predispose to POI which could then be considered a form of anticipated aging in which the ovarian defect may represent the first manifestation. The determination of mtDNA content in blood may become an useful tool for the POI risk prediction.

Genetic screening in 2,710 infertile candidate couples for assisted reproductive techniques: results of application of Italian guidelines for the appropriate use of genetic tests.

OBJECTIVE: To report the results of the routine application of Italian guidelines that apply to infertile patient candidates for any assisted reproduction technique (ART). The guidelines recommend performing a karyotype analysis in each couple and the screening test for mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) in one of the two partners. DESIGN: Case series. SETTING: Infertility unit. PATIENT(S): Two thousand seven hundred ten consecutive infertile couple candidates for ART. INTERVENTION(S): Peripheral blood evaluation of karyotype and CFTR gene. MAIN OUTCOME MEASURE(S): Frequency of aberrant karyotype and mutated CFTR gene. RESULT(S): A total of 74 aberrant karyotypes were diagnosed, corresponding to 1.3% (95% confidence interval [CI], 0.9%-1.7%) in women and to 1.5% (95% CI, 1.0%-2.0%) in men. In men, the frequency of chromosomal abnormalities differed according to the treatment group (0.3%, 1.1%, and 2.2% in IUI, IVF, and ICSI, respectively). The same was not observed in women. Excluding the 5T variant, 3.8% of the screened patients showed a mutated CFTR gene (95% CI, 3.1%-4.5%), and the mutation was found in both partners in 0.2% of the couples (95% CI, 0.0-0.4%). CONCLUSION(S): The frequency of aberrant karyotypes is higher in infertile couples than in the general population, whereas the frequency of a mutation of the CFTR gene is similar.