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PURPOSE: To estimate the probability of high-risk genetic matching when assisted reproductive techniques (ART) are applied with double gamete donation, following an NGS carrier test based on a complete study of the genes concerned. We then determine the results that would have been obtained if the genotyping tests most widely used in Spanish gamete banks had been applied. METHODS: In this descriptive observational study, 1818 gamete donors were characterised by NGS. The pathogenic variants detected were analysed to estimate the probability of high-risk genetic matching and to determine the results that would have been obtained if the three most commonly used genotyping tests in ART had been applied. RESULTS: The probability of high-risk genetic matching with gamete donation, screened by NGS and complete gene analysis, was 5.5%, versus the 0.6–2.7% that would have been obtained with the genotyping test. A total of 1741 variants were detected, including 607 different variants, of which only 22.6% would have been detected by all three genotyping tests considered and 44.7% of which would not have been detected by any of these tests. CONCLUSION: Our study highlights the considerable heterogeneity of the genotyping tests, which present significant differences in their ability to detect pathogenic variants. The complete study of the genes by NGS considerably reduces reproductive risks when genetic matching is performed with gamete donors. Accordingly, we recommend that carrier screening in gamete donors be carried out using NGS and a complete study with nontargeted analysis of the variants of the screened genes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-021-02381-0.

Resumen En las ultimas decadas ha habido grandes avances en los tratamientos personalizados en pacientes oncologicos gracias a un importante desarrollo cientifico. El analisis genomico ha mostrado que tumores que parecian tener un origen comun, en realidad constituyen un grupo de diversas entidades moleculares. Por otro lado, ha sido muy importante el desarrollo de farmacos dirigidos que actuan de forma especifica en las rutas bioquimicas involucradas en el proceso oncologico. El conocimiento de la biologia celular y molecular del cancer ha hecho posible identificar los mecanismos responsables de la transformacion maligna y esta permitiendo utilizar nuevos marcadores de especial utilidad para definir el pronostico y determinar el tratamiento de las enfermedades oncologicas.

Resumen La medicina personalizada, medicina de precision o medicina individualizada ha sido definida como una manera de abordar el tratamiento y la prevencion de las enfermedades en base a la variabilidad genetica, ambiental y al estilo de vida de cada persona. Clasifica a los individuos en subpoblaciones que difieren en la susceptibilidad a desarrollar una enfermedad determinada o en la respuesta a un tratamiento especifico, con el fin de aplicar el seguimiento y tratamiento mas adecuado a cada paciente. La implementacion de los procesos asociados a la Medicina Personalizada implica que los profesionales de laboratorio se enfrenten a una tecnologia muy avanzada y poco conocida y a la dificultad de interpretacion de los hallazgos, especialmente la valoracion de su significacion clinica. En este articulo se revisa la situacion actual de la Medicina Personalizada, la funcion del laboratorio dentro de la misma y los retos que se deben afrontar.

EnglishIntroduction: precision medicine (PM) has become a reality in clinical practice, however implementation of this approach is challenging due to their novelty and the highly-specialized knowledge required. Our aim is to describe the situation of PM in clinical laboratories in Spain by reporting the results of a survey addressed to Laboratory Medicine specialists. Materials and methods: the survey was created by the PM Committee of the Spanish Association of Medical Biopathology-Laboratory Medicine (AEBM-ML). The questionnaire was designed to assess several aspects of PM, mainly: knowledge, specific training, implementation in clinical practice and role of the clinical laboratory. Some survey results were analysed statistically employing Chi-square and Fisher’s exact tests. Results: a total of 113 responses were received from 68 different hospitals/clinics, 77.9 % from staff and 22.1 % from residents in training. Among those who had ever heard of PM, 84.9 % knew the concept of PM, but almost half of them did not know whether PM tests were incorporated into clinical guidelines in their centres and had never received any PM training. In 23 centres (33.8 %), an own PM portfolio was developed. In them, almost 40 % of the respondents stated that laboratory specialists have no role in management of PM tests, and that they do not participate or know about their participation in PM research projects. Conclusions: although PM is a well-known concept among laboratory professionals, our survey shows that they have a limited role in implementing PM tests. EnglishIntroduccion: la medicina de precision (MP) es una realidad en la practica clinica, aunque su implementacion supone un reto pues requiere un conocimiento altamente especializado. Nuestro objetivo es describir la situacion de la MP en los laboratorios clinicos espanoles mediante la descripcion de los resultados de una encuesta dirigida a especialistas en Medicina de Laboratorio. Material y metodos: la encuesta fue creada por el Comite de MP de la Asociacion Espanola de Biopatologia Medica - Medicina de Laboratorio (AEBM-ML) y disenada para evaluar varios aspectos de la MP: conocimiento, formacion, implementacion en practica clinica y papel del laboratorio clinico. Algunos resultados fueron analizados estadisticamente con los test chi-cuadrado y exacto de Fisher. Resultados: se recibieron 113 respuestas de 68 hospitales/clinicas diferentes, un 77,9 % de especialistas y un 22,1 % de residentes. Entre los que senalaron haber oido sobre MP, un 84,9 % conocia el concepto. No obstante, casi un 50 % desconocian si las pruebas de MP estaban incorporadas en guias clinicas y un porcentaje similar no habian recibido nunca formacion en MP. En 23 centros (33,8 %), existe una cartera propia de MP. En ellos, en torno a un 40 % de los participantes afirmo que los especialistas del laboratorio clinico no tienen un papel en la supervision de pruebas de MP ni tampoco participan (o desconocen su participacion) en proyectos de investigacion en MP. Conclusiones: aunque el concepto de MP es ampliamente conocido entre los profesionales del laboratorio clinico, nuestra encuesta muestra que su papel es limitado en la implementacion de pruebas de MP.