Interchromosomal effect in carriers of translocations and inversions assessed by preimplantation genetic testing for structural rearrangements (PGT-SR).

PURPOSE: Balanced carriers of structural rearrangements have an increased risk of unbalanced embryos mainly due to the production of unbalanced gametes during meiosis. Aneuploidy for other chromosomes not involved in the rearrangements has also been described. The purpose of this work is to know if the incidence of unbalanced embryos, interchromosomal effect (ICE) and clinical outcomes differ in carriers of different structural rearrangements. METHODS: Cohort retrospective study including 359 preimplantation genetic testing cycles for structural rearrangements from 304 couples was performed. Comparative genomic hybridisation arrays were used for chromosomal analysis. The results were stratified and compared according to female age and carrier sex. The impact of different cytogenetic features of chromosomal rearrangements was evaluated. RESULTS: In carriers of translocations, we observed a higher percentage of abnormal embryos from day 3 biopsies compared with day 5/6 biopsies and for reciprocal translocations compared with other rearrangements. We observed a high percentage of embryos with aneuploidies for chromosomes not involved in the rearrangement that could be attributed to total ICE (aneuploid balanced and unbalanced embryos). No significant differences were observed in these percentages between types of rearrangements. Pure ICE (aneuploid balanced embyos) was independent of female age only for Robertsonian translocations, and significantly increased in day 3 biopsies for all types of abnormalities. Furthermore, total ICE for carriers of Robertsonian translocations and biopsy on day 3 was independent of female age too. High ongoing pregnancy rates were observed for all studied groups, with higher pregnancy rate for male carriers. CONCLUSION: We observed a higher percentage of abnormal embryos for reciprocal translocations. No significant differences for total ICE was found among the different types of rearrangements, with higher pure ICE only for Robertsonian translocations. There was a sex effect for clinical outcome for carriers of translocations, with higher pregnancy rate for male carriers. The higher incidence of unbalanced and aneuploid embryos should be considered for reproductive counselling in carriers of structural rearrangements.

Confirmation rates of array-CGH in day-3 embryo and blastocyst biopsies for preimplantation genetic screening.

PURPOSE: The purpose of this study was to compare the confirmation rate of day-3 embryo biopsy (blastomere) and trophectoderm biopsy using array-comparative genomic hybridization (array-CGH) technology. METHODS: A blinded study was conducted to re-analyse 109 embryos previously diagnosed as chromosomally abnormal by array-CGH. Preimplantation genetic screening (PGS) was performed using array-CGH on day 3 (n = 50) or day 5 (n = 59). Partial chromosome gains or losses were excluded (n=6), and only whole chromosome aneuploidies were considered. Re-analysis of whole blastocysts was carried out following the same array-CGH protocol used for PGS. RESULTS: The PGS result was confirmed in the whole blastocyst in (a) 49/50 (98 %) abnormal embryos after day-3 biopsy and (b) 57/59 (96.6 %) abnormal embryos after trophectoderm biopsy. One embryo (1/50; 2 %) was diagnosed as abnormal, with monosomy 18, on day 3, and software analysis of the whole blastocyst gave a euploid result; however, a mosaic pattern was observed for monosomy 18 in the whole blastocyst. Two trophectoderm biopsy cases (3.4 %) did not have the abnormalities (trisomy 7, and trisomy 1 and 4, respectively) verified in the whole embryo. Concordance rates for both biopsy strategies and for individual chromosomes were evaluated by Fisher's exact test and showed no significant differences. CONCLUSIONS: Both types of biopsies showed similar high concordance rates with whole blastocyst results. Therefore, regarding the confirmation rates shown in this work, day-3 embryo biopsies can be representative of the whole embryo and both types of biopsy can be used for clinical analysis in PGS following the described array-CGH protocol.

Y chromosome microdeletions, sperm DNA fragmentation and sperm oxidative stress as causes of recurrent spontaneous abortion of unknown etiology.

BACKGROUND: The aim of the present study was to evaluate the implication of male factor, in terms of sperm DNA oxidation and fragmentation, and Y chromosome microdeletions in recurrent spontaneous abortion (RSA) of unknown origin in a strictly selected cohort. METHODS: A prospective cohort study was carried out in a private university-affiliated setting. Three groups, each comprised of 30 males, were compared. The first was formed by healthy and fertile sperm donors (SD) with normal sperm parameters (control group), the second by men presenting severe oligozoospermia (SO) without RSA history, and the third by men from couples who had experienced idiopathic RSA. Frequency of Y chromosome microdeletions and mean sperm DNA fragmentation and oxidation were determined. RESULTS: Y chromosome microdeletions were not detected in any of the males enrolled in the study. Moreover, sperm DNA oxidation measurements were not demonstrated to be relevant to RSA. Interestingly, sperm DNA fragmentation was higher in the SO group than in the RSA and the SD groups, and also higher in the RSA group compared with the SD group, but lacked an adequate predictive power to be employed as a discriminative test of RSA condition. CONCLUSIONS: Sperm DNA features and Y chromosome microdeletions do not seem to be related to RSA of unknown origin. Other molecular features of sperm should be studied to determine their possible influence on RSA. Clinicaltrials.gov reference: NCT00447395.

Psychosocial and Ergonomic Conditions at Work: Influence on the Probability of a Workplace Accident.

Today, the economic and social importance of occupational accidents is undeniable worldwide. Hence, research aimed at reducing this type of accident is considered a discipline of great interest for society in general. In this environment, working conditions play a fundamental role in the occurrence of accidents, and from their study, results can be obtained that provide information for decision-making that guarantee optimum conditions for the development of the employees' tasks. Organizing the conditions of work execution is also a task that constitutes an essential aspect for a firm's productivity, therefore, affecting their viability and results. In this work, a model is proposed for the study of different groups of working conditions and their influence on the probability of occupational accidents, in accordance with the data provided by the 7th National Survey of Working Conditions (VII NSWC). The survey sampled 8892 workers active in all sectors of national production and is the last nation-wide survey administered in Spain. Bayesian networks (BNs) are used to generate a network that analyzes working conditions in all areas (27 variables have been included in addition to those corresponding to the sector and accident), and then, more specifically, the relationship that is established between ergonomic factors in the workplace, psychosocial factors of the worker, and the probability of an accident. The results are achieved through the network obtained by highlighting some of the proposed variables. The dependencies generated by the chosen variables are analyzed, and subsequently, the probability of accident for each of the productive sectors is determined. It is concluded that the ergonomic risks associated with physical strains in the workplace, together with the lack of job satisfaction on the employer's behalf, both pose a very significant increase in the probability of being involved in an occupational accident, above the other variables of study.

Data on the main working conditions with influence on the development of hearing loss amongst the occupational population in Spain.

Obtaining reliable and objective data on certain working conditions is necessary to analyse the causes and variables that can influence the development of hearing loss amongst the working population. Objective occupational data have been collected from a heterogeneous sample of 1418 workers in Spain, see "How activity type, time on the job and noise level on the job affect the hearing of the working population. Using Bayesian networks to predict the development of hipoacusia" (Barrero et al., 2018) [1]. Among the main factors analysed are the noise levels to which these workers are exposed, measured at their respective workstations, and the assessment of their hearing status, evaluated by audiometric medical tests. These factors provide information to predict the development of hypoacusia.

Data on the working population in Spain related to training, workplace conditions and accident rates.

Obtaining data on worker accident rates is necessary in order to analyze the causes and variables involved in the occurrence of said accidents. The majority of these data, collected after the accident occurs, do not consider the employee׳s working conditions. Here are presented the data on workplace accidents and the conditions of the workers by analyzing the generic data supplied as part of the 7th National Survey of Workplace Conditions (EWCS) in Spain, conducted in 2011. These data will yield the variables needed to determine if the information on workplace risks provided by the survey respondents has an appreciable effect on the occurrence of occupational accidents in the working population, and will also be used to explore other variables.

Genetic Analysis of Human Preimplantation Embryos.

Preimplantation development comprises the initial stages of mammalian development, before the embryo implants into the mother's uterus. In normal conditions, after fertilization the embryo grows until reaching blastocyst stage. The blastocyst grows as the cells divide and the cavity expands, until it arrives at the uterus, where it "hatches" from the zona pellucida to implant into the uterine wall. Nevertheless, embryo quality and viability can be affected by chromosomal abnormalities, most of which occur during gametogenesis and early embryo development; human embryos produced in vitro are especially vulnerable. Therefore, the selection of chromosomally normal embryos for transfer in assisted reproduction can improve outcomes in poor-prognosis patients. Additionally, in couples with an inherited disorder, early diagnosis could prevent pregnancy with an affected child and would, thereby, avoid the therapeutic interruption of pregnancy. These concerns have prompted advancements in the use of preimplantation genetic diagnosis (PGD). Genetic testing is applied in two different scenarios: in couples with an inherited genetic disorder or carriers of a structural chromosomal abnormality, it is termed PGD; in infertile couples with increased risk of generating embryos with de novo chromosome abnormalities, it is termed preimplantation genetic screening, or PGS.