Efecto de la vitrificación en la incidencia de aneuploidías en los resultados clínicos del programa de Diagnóstico Genético Preimplantacional

En pacientes definidas como pobres respondedoras el limitado número de ovocitos obtenidos supone el principal problema para optimizar las tasas de recién nacido vivo. El resultado de recuperar menos óvulos es obtener menos embriones para seleccionar y transferir y, por ello, estas pacientes tienen tasas más bajas de gestación por transfer y menor tasa acumulada de embarazo por ciclo de fecundación in vitro iniciado en comparación con pacientes con respuesta adecuada a la estimulación. Los resultados de un ciclo de Diagnóstico Genético Preimplantacional (PGD) también van a estar influidos por el número de embriones que se puedan analizar en cada caso. Las pacientes bajo respondedoras tienen por tanto un menor número de ovocitos y embriones, hecho que reduce significativamente sus posibilidades de éxito en un ciclo de PGD. En estas pacientes existe además una alta tasa de abandono del tratamiento. Teniendo en cuenta estos dos aspectos, en los últimos años se han llevado a cabo una serie de estrategias en el laboratorio a fin de aumentar el rendimiento del ciclo y disminuir en lo posible la tasa de cancelación. Este trabajo de tesis doctoral pretende evaluar mediante un estudio retrospectivo la eficacia del programa de PGD en sus diferentes estrategias y en pacientes bajo respondedoras después de varios ciclos de estimulación ovárica y acumulación de ovocitos previos al análisis genético, en combinación o no de embriones obtenidos de ovocitos frescos de un ciclo de ICSI.In patients identified as poor responders limited number of oocytes is the main problem to optimize live birth rates. The result is get back less egg fewer embryos to select and transfer and, therefore, these patients have lower pregnancy rates per transfer and lowest cumulative pregnancy rate per IVF cycle started compared with patients with adequate response to stimulation. The results of a series of pre-implantation genetic diagnosis (PGD) will also be influenced by the number of embryos that can be analyzed in each case. Low responder patients therefore have fewer oocytes and embryos, a fact that significantly reduces their chances of success in a cycle of PGD. In these patients there is also a high rate of treatment discontinuation. Considering these aspects, in recent years they have carried out a number of strategies in the laboratory to increase the cycle efficiency and reduce as far as possible the cancellation fee. This doctoral thesis aims through a retrospective study evaluating the efficacy of PGD program in its various strategies and low responder patients after several cycles of ovarian stimulation and oocyte prior accumulation of genetic analysis, in combination or not embryos of fresh oocytes ICSI cycle

False positive rate of an arrayCGH platform for single-cell preimplantation genetic screening and subsequent clinical application on day-3

In this work, false positive rate of an arrayCGH platform for its use in day-3 single-blastomere analysis was calculated. For this purpose, 38 embryos diagnosed as abnormal on day-3 by FISH were re-biopsied on day-4. Single-cell day-4 arrayCGH diagnosis was then performed. A successful amplification was obtained in 97.4 % (37/38) of the day-4 cells analysed by arrayCGH. Day-3 FISH and day-4 arrayCGH diagnosis were concordant in 35/37 cases. The two discordant embryos were spread and all the cells from each embryo were re-analysed by FISH on day 5. The same error rate (2.7 %) for day-3 FISH and day-4 arrayCGH was obtained when comparing day-5 FISH re-analysis. After this pre-clinical phase, the platform was used for day-3 arrayCGH clinical application in 320 patients (1,760 embryos). Day-3 amplification rate was 98.6 %. An optimal reproductive outcome was obtained when applying arrayCGH to a clinical program: clinical pregnancy rate per cycle of 38.4 % and 60.3 % per transference were obtained, with an implantation rate of 53.5 %. Overall miscarriage rate was 10.6 %. Additionally, day-5 FISH re-analysis was performed in 42 of the embryos from the clinical phase, obtaining a concordance rate of 97.6 % with day-3 arrayCGH.Electronic supplementary materialThe online version of this article (doi:10.1007/s10815-012-9918-4) contains supplementary material, which is available to authorized users

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective