Variables modificadoras de la asociación expresividad emocional familiar-recidivas en pacientes esquizofrénicos.

RESUMEN Se trata de un estudio de intervención que analiza las variaciones en los perfiles de la Expresividad Emocional familiar y en la tasa de recidivas de una cohorte de pacientes esquizofrénicos y sus cuidadores principales a los que se han administrado, en el marco de la asistencia sanitaria pública, dos formatos terapéuticos distintos de intervención psicoeducativa de 12 meses de duración. Como objetivo general se analiza si los cambios en los niveles de la Expresividad Emocional y sus subescalas asociados a la realización de una intervención familiar reducen el riesgo de recaídas a corto y medio plazo. Como objetivos específicos determinar qué subescalas de la Expresividad Emocional son más sensibles al cambio y si la realización de formatos terapéuticos distintos de intervención familiar (formato grupal o formato centrado en la unidad familiar) se asocian a perfiles diferentes de Expresividad Emocional o distintas tasa de recaída. Como objetivos secundarios, describir el perfil de la Expresividad Emocional de los familiares remitidos a un programa de intervención familiar y analizar si estos perfiles se asocian a variables clínicas o sociodemográficas. Se realizan 3 evaluaciones. Una basal, previa a la intervención, otra inmediatamente tras concluir ésta y una última evaluación tras 5 años de la finalización de la intervención. No se encontró asociación de la Expresividad Emocional ni de sus subescalas con ninguna variable clínica o sociodemográfica en la evaluación basal, si bien se encontró un perfil de Expresividad Emocional similar al de otros países de base cultural latina y distinto al encontrado habitualmente en los estudios anglosajones, revelando la importancia de las diferencias transculturales. Tras la realización de la intervención, se redujeron significativamente los niveles de la Expresividad Emocional y sus subescalas, siendo la subescala más susceptible de cambio la sobreimplicación emocional y la más resistente la hostilidad. La tasa de recaídas también se redujo significativamente durante el período de intervención. Aunque ambos formatos de intervención se mostraron eficaces en la reducción de la Expresividad Emocional y las recidivas, produjeron diferentes perfiles de resultados. A los 5 años de la finalización de la intervención, los niveles de la Expresividad Emocional y sus subescalas se mantuvieron mayoritariamente estables en los alcanzados tras la intervención. Las variaciones en los perfiles de la Expresividad Emocional no se asociaron ya a las recaídas sino al funcionamiento social y la gravedad de la clínica productiva del paciente. Las recidivas volvieron a aumentar progresivamente una vez concluida la intervención, a pesar de la reducción de la Expresividad Emocional. Una intervención psicoeducativa de 12 meses de duración no es suficiente para mantener en el tiempo los beneficios obtenidos durante su realización sobre la tasa de recaídas. Los datos de esta tesis orientan a un modelo interactivo complejo de la asociación Expresividad Emocional y recidivas en las que la Expresividad Emocional tendría tanto atributos de rasgo como de estado. Los atributos de rasgo habrían sido modificados de forma duradera por la intervención, emergiendo entonces la asociación de los atributos de estado con la gravedad de la clínica psicótica o de ajuste social. __________________________________________________________________________________________________This is an study about intervention which analyzes the variations in familiar Expressed Emotion (EE from now) profiles, and in the relapse rate in a cohort of schizophrenic patients and their main carers, who have been given, in the frame of public health system, two different 12-month therapeutical programs of psychoevolutive intervention. The main objective is to analyse whether the changes in EE levels and its subscales, associated to the family intervention reduce the risk of relapses in a short and middle term. As specific objectives, to determine which Expressed Emotion subscales are more sensitive to change, and whether the application of different therapeutical programs of family intervention (groupal format or that centred in family unit) are associated to different levels of EE or to different relapse rates. As secondary objectives, to describe the profile in EE of the relatives sent to a family intervention program, and to analyse whether these profiles are associated to clinical or demographical variables. Three interventions take place: at baseline, previous to intervention, another one, straight after this, and a final assessment after 5 years of finishing the intervention. No association was found between EE -nor any of its sub-scales- and any clinical or socio-demographic variable in baseline assessment, although it was found a similar level of EE in countries of latin roots, different to that found in anglo-saxon studies, revealing the importance of trans-cultural differences. After the assessment, levels of EE and its subscales were reduced significantly, being emotional overinvolvement the subscale more prone to change, and hostility the more resistant. The relapse rate was also significantly reduced during the intervention period. Although both intervention formats proved efficient in reducing EE and relapses, they produced different levels of results. Five years after the finishing of the intervention, EE levels and its subscales were kept mainly stable in those reached after intervention. Variations in EE levels were then not associated to relapses, but to social behaviour and severity of the patients productive clinic. Relapses turned to progressively increase once the intervention finished, despite the lowering of EE. A 12-month psycho-educative intervention is not enough to keep in time the benefits obtained during its realization over the relapse rate. This thesis data lead to a complex interactive model of the association between EE and relapses, in which EE would have attributes of trait as much of state. Trait attributes would have been modificated in a long-lasting way by intervention, then emerging the association of state attributes with the severity of the psycotic clinic or of social adjustment

Deciphering the proteomic signature of human endometrial receptivity

STUDY QUESTION: Are there any proteomic differences between receptive (R) and non-receptive (NR) endometrial receptivity array (ERA)-diagnosed endometria obtained on the same day of a hormonal replacement therapy (HRT) treatment cycle? SUMMARY ANSWER: There is a different proteomic signature between R and NR ERA-diagnosed endometrium obtained on the same day of HRT cycles. WHAT IS KNOWN ALREADY: The human endometrial transcriptome has been extensively investigated in the last decade resulting in the development of a new diagnostic test based on the transcriptomic signature of the window of implantation (WOI). Much less is known about the proteomics derived from the transcripts present during the WOI. STUDY DESIGN, SIZE, AND DURATION: This study was a basic proteomic analysis of human endometrial biopsies taken from twelve IVF patients. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: Human endometrial biopsies were collected during HRT cycles after 5 days of progesterone (P) administration, and diagnosed as receptive (R; n = 6) or non-receptive (NR; n = 6) by the ERA test. Endometrial proteins were extracted, labelled and separated using differential in-gel electrophoresis (DIGE). Proteins were identified using mass spectrometry, followed up by in silico analysis. Validation studies using western blots and immunolocalization were performed for the progesterone receptor membrane component 1 (PGRMC1) and annexin A6 (ANXA6) proteins. MAIN RESULTS AND THE ROLE OF CHANCE: DIGE analysis followed by protein identification by MALDI-MS and database searches revealed 24 differentially expressed proteins in R versus NR samples. In silico analysis showed two pathways which were significantly different between R and NR samples. Expression of PGRMC1 and ANXA6 was validated and localized by western blots and immunohistochemistry. These results highlight these proteins as key targets likely to be important in the comprehension of human endometrial receptivity. LIMITATIONS, REASONS FOR CAUTION: This was mainly a descriptive study with no functional studies on the proteins found. We also used a low number of human endometrial samples for the DIGE analysis. WIDER IMPLICATIONS OF THE FINDINGS: This study identified the proteomic profile associated with receptive or non-receptive human endometria. Our findings suggest that although histological dating indicates a putative 'receptive' status within the WOI, a different transcriptomic and proteomic profile is observed in these samples. We should move towards using more personalized WOIs, where identification of the correct endometrial receptivity status, and consequently the success of IVF, relies on individual molecular signatures rather than traditional endometrial dating

iTRAQ comparison of proteomic profiles of endometrial receptivity

Endometrial receptivity is a limiting step in human reproduction. A disruption in the development of endometrial receptivity is responsible for recurrent implantation failures (RIF) of endometrial origin. To understand the molecular mechanisms behind the endometrial receptivity process, we used the isobaric tag for relative and absolute quantitation (iTRAQ) method to compare three different endometrial statuses: fertile women, intrauterine device (IUD) carriers, and RIF patients. Overall, iTRAQ allowed identified 1889 non-redundant proteins. Of these, 188 were differentially expressed proteins (DEP) (p-value < .05). Pairwise comparisons revealed 133 significant DEP in fertile vs. IUD carriers and 158 DEP in RIF vs. IUD carriers. However, no DEP were identified between fertile and RIF patients. Western blot validation of three DEP involved in endometrial receptivity (plastin 2, lactotransferrin, and lysozyme) confirmed our iTRAQ results. Moreover, functional KEGG enrichment revealed that complement and coagulation cascades and peroxisome were the two most significant pathways for the RIF vs. IUD comparison and ribosome and spliceosome for the fertile vs. IUD comparison, as possible important pathways involved in the endometrial receptivity acquisition. The lack of DEP between fertile and RIF patient endometria suggest that idiopathic RIF may not have an endometrial origin, with other as-yet-unknown factors involved

The role of thrombophilias in reproduction: A swot analysis.

Thrombophilia is a group of inherited or acquired coagulation disorders that have been associated with reproductive failure. However, there are still no clear recommendations on whether its inclusion in the initial study of the infertile couple or patients with recurrent implantation failure is necessary. In this discussion paper, based on a SWOT (strengths, weaknesses, opportunities, threats) analysis, the different aspects of the repercussions of thrombophilia screening and treatment in reproduction are evaluated. To avoid possible subjectivity in the analysis and results of this study, researchers followed Oxford criteria for the evaluation of evidence. The results from the evaluation of the reviewed bibliography seem to indicate that, pending new evidence, it would be advisable not to include thrombophilia screening in the initial baseline study of the infertile couple. There is no evidence to support a clear association between thrombophilia and implantation failure or infertility. Thrombophilia testing in this setting may increase cost, with minimal potential benefit and lead to inappropriate use of anticoagulants with possible deleterious adverse effects. Future well-designed studies are needed to assess the possible benefit of anticoagulant therapy in infertile thrombophilic patients with implantation failure

Impact of chronic endometritis in infertility: a SWOT analysis

Chronic endometritis is a pathology often associated with reproductive failure, but there are still no clear recommendations on whether its inclusion in the initial study of infertile couples is necessary. In this discussion paper, based on a SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis, the different aspects of the repercussions of chronic endometritis in fertility are evaluated. To avoid possible subjectivity in the analysis and results of this study, the researchers followed the Oxford criteria for the evaluation of evidence. The results from the evaluation of the reviewed literature seem to indicate that, pending new evidence, it would be advisable not to include chronic endometritis in the initial baseline study before assisted reproduction in order not to delay other assisted reproduction treatments. However, it would be advisable in cases of repetitive implantation failure and pregnancy loss after having undergone IVF with viable embryos and before continuing with costly reproductive processes, since results could be improved. The development of randomized studies assessing the impact of antibiotic treatment as a possible therapeutic option in infertile women with chronic endometritis, as well as the possible impact on endometrial microbiota and receptivity/implantation, would allow for the establishment of more precise clinical guidelines in this regard

Hysteroscopic septum resection and reproductive medicine: A SWOT analysis.

Hysteroscopic septum resection in women with unfavourable reproductive and clinical outcomes has become common practice worldwide to improve reproductive results. No clear evidence on the possible advantages and drawbacks of this procedure has been published. In this opinion paper, based on a SWOT (strengths, weaknesses, opportunities, threats) analysis, the different aspects of this strategy are evaluated. Currently, no level 1 published evidence supports uterine resection in women with septate uterus. Clinical evidence from the studies analysed matches the more recent guidelines and suggests an improvement in reproductive outcomes after hysteroscopic resection of the septum, particularly in infertile women and women who have experienced recurrent miscarriages. In a patient with no history of infertility or prior pregnancy loss, it may be reasonable to consider septum incision after counselling about the potential risks and benefits of the procedure. Published clinical data in favour of the intervention, however, are based on studies with important methodological limitations. In this situation, the clinician and patient should reach an agreement together, based on the pros and cons of this intervention. Well-designed randomized controlled trials are required to confirm the clinical benefits and cost-effectiveness of this procedure

Second-generation preimplantation genetic testing for aneuploidy in assisted reproduction: a SWOT analysis

Second-generation preimplantation genetic testing for aneuploidy (PGT-A 2.0) in patients with an unfavourable reproductive and IVF prognosis is becoming common practice, with the aim of improving reproductive outcomes. However, there is still no clear evidence on the possible advantages and drawbacks with regard to this procedure. In this discussion paper, based on a SWOT (strengths, weaknesses, opportunities, threats) analysis, the different aspects of this strategy are evaluated. Current evidence suggests that PGT-A 2.0 should not at present have an indiscriminate application, but it might be indicated in cases in which the risk of aneuploidy is increased

ALWAYS ICSI? A SWOT analysis

Purpose: Intracytroplasmatic sperm injection (ICSI) is a common procedure used to improve reproductive results, even among couples without male factor infertility. However, the evidence available is still uncertain on the possible advantages and deficiencies that this procedure may have in patients with no formal indication for ICSI. Methods: A SWOT (strengths, weaknesses, opportunities, threats) analysis examines the possible advantages and deficiencies of performing ICSI in these patients with no formal indication. Results: The evidence suggests that ICSI is not justified for non-male factor infertile couples requiring in vitro conception. One of the major strengths associated to the procedure is the virtual elimination of cases further complicated by total fertilization failure and a combination between IVF and ICSI on sibling oocytes has been advised in the literature. Greater technical difficulties, higher costs and performing an unnecessary invasive technique in some cases represent some of the weaknesses of the procedure, and questions regarding safety issues should not be ruled out. Conclusion: Despite the widespread use of ICSI in patients without a formal diagnosis of male factor infertility, evidence demonstrating its effectiveness in this population is still lacking. Additional large and well-designed randomized controlled trials are needed to clarify definitive indications for ICSI in non-male factor infertility

Day-3 embryo metabolomics in the spent culture media is altered in obese women undergoing in vitro fertilization

Objective: To determine whether the global metabolomic profile of the spent culture media (SCM) of day-3 embryos is different in obese and normoweight women undergoing in vitro fertilization (IVF). Design: Prospective cohort analysis. Setting: IVF clinic. Patient(s): Twenty-eight young, nonsmoking women with normoweight, nonsmoking male partners with mild/normal sperm factors undergoing a first IVF attempt for idiopathic infertility, tubal factor infertility, or failed ovulation induction: obese ovulatory women (n = 12); obese women with polycystic ovary syndrome (PCOS; n = 4); normoweight ovulatory women (n = 12). Intervention(s): Fifty μl of SCM collected from two day-3 embryos of each cohort. Main Outcome Measure(s): Metabolomic profiling via ultrahigh performance liquid chromatography coupled to mass spectrometry of SCM from a total of 56 embryos. Result(s): The untargeted metabolomic profile was different in obese and normoweight women. Partial least squares discriminant analysis resulted in a clear separation of samples when a total of 551 differential metabolites were considered. A prediction model was generated using the most consistent metabolites. Most of the metabolites identified were saturated fatty acids, which were detected in lower concentrations in the SCM of embryos from obese women. The metabolomic profile was similar in obese women with or without PCOS. Conclusion(s): The metabolomic profile in the SCM of day-3 embryos is different in normoweight and obese women. Saturated fatty acids seem to be reduced when embryos from obese patients are present

Endometrial receptivity tests in reproduction: a SWOT analysis.

Endometrial receptivity and its management in assisted reproduction is now a significant focus of research interest. Endometrial receptivity tests, which analyze different panels of gene expression, are usually offered in fertility clinics to determine the women's individual 'window of implantation', providing a personalized timing for embryo transfer. However, there are still no definite indications on whether its inclusion in the study of the infertile couple or the study of patients with repeated implantation failure is essential