Falla de implante ESTUDIO ENDOMIC

ESTUDIO ENDOMIC

ANÁLISIS INTEGRADO DE LA FALLA DE IMPLANTACIÓN EMBRIONARIA

En un ciclo de Fecundación In Vitro (FIV), la tasa de embarazo se sitúa en torno al 60%. Es ampliamente aceptado que esto depende de un adecuado intercambio de señales entre el embrión y el endometrio En ocasiones, aún contando con embriones de calidad óptima, no es posible lograr una implantación exitosa, debido a factores que impiden la nidación.

Se definen como fallos de implantación embrionaria a aquellos casos en los que se ha realizado una transferencia de 4 a 6 embriones de calidad adecuada, en 2 o 3 procedimientos de FIV, sin lograr embarazo.

El protocolo ENDOMIC es un estudio multifactorial que aborda las causas probables de la Falla de Implantación Embrionaria analizándolas con una visión integral que complementa la conducta clínica frente a la patología.

ENDOMIC 1 ESTUDIO DEL FACTOR INFECTOLÓGICO

Fundamentos del estudio

Actualmente, se estima que la infertilidad afecta aproximadamente a un 15% de las parejas de todo el mundo. En general, los problemas de fertilidad se deben a una causa relacionada con la salud reproductiva de la mujer o la calidad espermática del hombre, para las cuales existen diferentes tratamientos. Sin embargo, aunque los métodos de diagnóstico de infertilidad han mejorado notablemente en los últimos años, existe entre un 15-30% de parejas en todo el mundo que desconocen cuál es el origen de su infertilidad. Hablamos en este caso de infertilidad idiopática, inexplicada o sin causa aparente, debido a que no es posible determinar cuál es el origen de este problema reproductivo.

A pesar de que las causas de infertilidad idiopática se han relacionado con diversos problemas de carácter endocrino, genético o fisiológico, numerosos estudios sugieren que gran parte de estos problemas reproductivos se deben a un factor infectológico. De todas las causas de infertilidad, justamente las infecciones del tracto genital constituyen el 30-40% de los casos. Existen una gran variedad de microorganismos que pueden colonizar el tracto reproductivo femenino y masculino y desencadenar procesos infecciosos, acompañados muchas veces de respuestas inflamatorias con múltiples consecuencias adversas. Este tipo de infecciones se caracterizan por ser comunes y en la gran mayoría de los casos, asintomáticas, por lo que son imperceptibles por parte de los pacientes. Esta falta de sintomatología evita que las infecciones sean tratadas, y en consecuencia, puedan causar daños crónicos que conduzcan a problemas en la fertilidad. En este aspecto, es importante destacar también las enfermedades de transmisión sexual, provocadas también por la colonización de distintos tipos de microorganismos en el tracto reproductivo y que, si no reciben tratamiento, pueden provocar problemas a largo plazo, incluida la enfermedad inflamatoria pélvica e infertilidad.

Por todo ello, el estudio de la presencia de agentes infecciosos se ha convertido en una estrategia indispensable para determinar si, en casos complejos de infertilidad idiopática, existe un factor infectológico causante de los problemas de infertilidad que esté impidiendo la correcta consecución del embarazo. Con la realización de un estudio exhaustivo de nuestro panel de detección de microorganismos patógenos, se busca identificar estas infecciones y combatirlas previamente a los métodos de fertilidad a los que vayan a ser sometidos los pacientes, con el fin de que no puedan interferir de forma negativa al correcto desarrollo del embarazo.

Metodología

Partiendo de muestras de exudado endocervical, exudado uretral, semen o primera fracción miccional, y mediante el uso de técnicas de qPCR y PCR convencional, esta prueba nos permite detectar los agentes patógenos más comunes causantes de infecciones en el sistema reproductor femenino y masculino. Estos agentes son:

  • Chlamydia trachomatis
  • Mycoplasma hominis
  • Ureaplasma urealyticum
  • Virus Herpes simplex (HSV-1, HSV-2)
  • Virus del papiloma humano (HPV)
  • Herpesvirus 6 de tipo A (HHV-6A)

 

ENDOMIC 2 TRANSCRIPTÓMICA EN VENTANA DE IMPLANTE

Fundamentos del estudio

La implantación embrionaria es un fenómeno biológico único, mediante el cual el embrión, en estado de blastocisto, se adhiere e invade el endometrio materno para formar la placenta, que proporcionará una interfase entre el feto en crecimiento y la circulación materna. Este proceso ocurre durante la fase secretora del ciclo menstrual, en un periodo concreto de tiempo denominado ventana de implantación, donde la receptividad endometrial es óptima. Este estado de receptividad óptima tiene lugar entre los días 20 y 21 del ciclo, siete días después del pico de LH. El embrión es capaz de adherirse al endometrio únicamente durante este corto periodo de tiempo, por lo que el éxito de la implantación depende tanto de la calidad del embrión como de la receptividad del endometrio, afectando la variabilidad en cualquiera de estos dos factores a la correcta consecución del embarazo.

Numerosos estudios han demostrado que la incapacidad del endometrio para establecer un fenotipo receptivo es una causa muy común de infertilidad idiopática, incluso cuando se utilizan técnicas de reproducción asistida donde los embriones seleccionados son de alta calidad. Por todo ello, contar con una herramienta que permita identificar cuándo se encuentra abierta la ventana de implantación en una mujer, supone una estrategia esencial para aumentar las posibilidades de conseguir un embarazo exitoso.

Metodología

Gracias a la extracción de ARN procedente de una biopsia endometrial, y mediante el empleo de la tecnología de PCR a tiempo real, esta herramienta es capaz de analizar el perfil de expresión génica de 48 genes vinculados con aspectos como la receptividad endometrial y la respuesta inmunológica para detectar de manera precisa cuál es el estado de receptividad de la muestra analizada. En la mayoría de los casos, el momento de mayor receptividad del tejido endometrial ocurre 5 días y medio (P+5.5) después de la primera toma de progesterona en un ciclo sustituido, por lo que se recomienda tomar la biopsia en esta fecha.

Interpretación de los resultados

El análisis del perfil de expresión génica endometrial devolverá 3 posibles resultados:

  • Endometrio receptivo: se corresponde con un endometrio que ha alcanzado la ventana de implantación, por lo que se recomienda realizar la transferencia embrionaria en un ciclo de similares características al desarrollado para la toma de la biopsia endometrial.

  • Endometrio pre-receptivo: se corresponde con un endometrio que aún no ha alcanzado la ventana de implantación, por lo que se recomienda una segunda toma de biopsia o transferencia personalizada realizada con 24 horas más de impregnación con progesterona en un ciclo de similares características al desarrollado en el ciclo evaluado.

  • Endometrio post-receptivo: se corresponde con un endometrio que ha cerrado la ventana de implantación, por lo que se recomienda una segunda toma de biopsia o transferencia personalizada realizada con 24 horas más de impregnación con progesterona en un ciclo de similares características al desarrollado en el ciclo evaluado.

 

ENDOMIC 3. ESTUDIO DE FACTORES INMUNOLÓGICOS ENDOMETRIALES Y SISTÉMICOS

Fundamentos del estudio

A pesar de que la infertilidad se considera un desorden reproductivo de carácter multifactorial, actualmente, gran parte de los problemas reproductivos que se presentan en las consultas ginecológicas se deben a un desequilibrio a nivel inmunológico. El sistema inmune es un factor clave en la consecución y el mantenimiento del embarazo, por lo que cualquier alteración en el estado inmunológico puede conducir a problemas de infertilidad de diversa índole en distintas etapas del embarazo, como fallos de implantación o abortos de repetición.

En este contexto inmunológico cobra gran relevancia el endometrio, siendo uno de los tejidos maternos más importantes durante el proceso reproductivo. Para que el embarazo se produzca y se lleve a término de manera correcta, es necesario que el endometrio sufra numerosos cambios, tanto a nivel morfológico como en su composición celular. En este último aspecto, es de gran importancia el cambio que experimenta este tejido en la composición de sus células inmunológicas para, en primer lugar, permitir la correcta implantación del embrión en el útero materno, y posteriormente, asegurar el correcto desarrollo y crecimiento del feto.

Durante la ventana de implantación embrionaria, existe en el endometrio un flujo constante de células inmunes, donde el 70% está formado por células Natural Killer (NK), un 20% por macrófagos y células dendríticas, y un 10% por linfocitos T, siendo los linfocitos B más minoritarios. El tipo celular más abundante durante el proceso de implantación es el formado por las células NK, siendo denominadas células NK uterinas o deciduales (dNK). Durante la preparación del endometrio a lo largo del ciclo menstrual, las células NK deciduales viran su función a fin de preparar el tejido para una probable implantación. En lugar de actuar como citotóxicas y proinflamatorias, las células dNK contribuyen a la construcción y remodelación de tejido y formación de nuevos vasos con el objeto de revascularizar el endometrio, creando un ambiente adecuado en el endometrio para el logro de un embarazo exitoso.

Debido al importante papel que las células inmunológicas juegan durante el embarazo, cualquier desbalance en estas subpoblaciones celulares puede llevar a numerosos problemas reproductivos, siendo cada vez más los estudios que relacionan los cambios en los niveles de estas células con casos de infertilidad idiopática, fallos de implantación embrionaria, abortos recurrentes y otras patologías durante el embarazo. Por todo ello, estudiar el estado inmunológico de la mujer, es una herramienta indispensable para averiguar si sus problemas de infertilidad se deben a alguna alteración en su sistema inmune que esté impidiendo la consecución y el correcto desarrollo del embarazo, y en ese caso, ayudar a corregirla.

Metodología

Para realizar este estudio, es necesario contar con una muestra de sangre y una biopsia endometrial, en las que, mediante citometría de flujo, se realizará la inmunofenotipificación de distintas poblaciones celulares utilizando un panel de anticuerpos monoclonales conjugados en forma directa con diversos flurocromos.

Interpretación de los resultados

Tras la inmunofenotipificación de los distintos tipos celulares mencionados anteriormente, se proporcionará a la paciente un resultado detallado del recuento de cada una de estas poblaciones celulares inmunológicas, así como de la presencia de autoanticuerpos que puedan estar provocando algún desorden de carácter autoinmune, informando de si existe algún desequilibrio a este nivel que cree un ambiente inmunológico desfavorable para la correcta implantación del embrión y por tanto, la consecución del embarazo.

ENDOMIC 5. ESTUDIO DE FACTORES NUTRIGENETICOS ASOCIADOS A FERTILIDAD

Fundamentos del estudio

 Uno de los principales factores ambientales que modifican e influyen sobre nuestros genes es la nutrición. La nutrigenética estudia la relación entre los genes y la alimentación, con el objetivo de conseguir un estado óptimo de salud a través de la dieta. La nutrición y el estilo de vida son factores desencadenantes de problemas en la fertilidad. Así, estudios en el campo de la epigenética concluyen que bebés de padres obesos pueden heredar la predisposición a tener sobrepeso, así como la tendencia a padecer enfermedades y desórdenes metabólicos.

No solo es importante ese efecto ambiental en la genética del bebé, sino que también la calidad de los gametos se ve afectada, como se observa en casos en los que un consumo excesivo de productos grasos provoca un efecto negativo en la cantidad y la movilidad del esperma. El sobrepeso en la mujer también supone un riesgo, ya que dificulta el embarazo debido a que el tejido adiposo tiene una función endocrina que interfiere negativamente en ciertos procesos del organismo provocando una inflamación crónica que afecta a la coagulación y al sistema cardiovascular, indispensable en el útero de la mujer para el desarrollo del embrión.

Por todo ello, llevar una dieta adecuada se convierte en un factor clave para lograr un embarazo con éxito, por lo que las recomendaciones nutricionales son esenciales tanto para parejas que busquen concebir de manera natural como para aquellas que se sometan a tratamientos de fertilidad.

Metodología

Este análisis nutrigenético permite estudiar las variantes genéticas de cada paciente con el fin de determinar qué plan nutricional es el más apropiado para conseguir un estado de fertilidad óptimo. Las variantes que incluye el estudio se han asociado con requerimientos nutricionales específicos y sensibilidad a ciertos componentes de la dieta.

En esta prueba genética, se analiza el ADN extraído de muestras de sangre o saliva, con el fin de estudiar la variación genética individual en 107 variantes genéticas de 75 loci mediante genotipificación. Esta genotipificación se realiza utilizando un Microchip de ADN en una plataforma que permite el análisis genético óptimo mediante la combinación de las ventajas de una química exacta de los cebadores de extensión con la espectrometría de masas MALDI-TOF. Las diferentes masas de cada uno de los productos de PCR generados se convierte en información del genotipo, proporcionando un alto rendimiento de muestras y un análisis de alta precisión.

Interpretación de los resultados

Tras el resultado de la genotipificación, se elaborará un plan de acción de acuerdo con las variantes detectadas, estableciendo una pauta nutricional personalizada para cada paciente que consiga mejorar sus problemas de fertilidad y en consecuencia, aumentar las posibilidades de conseguir un embarazo.

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