
Una imagen de las actividades de reproducción médicamente asistida durante la pandemia de COVID-19 en Europa
Introducción
Después del brote local de la enfermedad por coronavirus 2019 (COVID-19) en Wuhan (China) en diciembre de 2019, no pasó mucho tiempo antes de que el virus llegara a Europa y luego al resto del mundo. Los primeros casos de infección por coronavirus 2 (SARS-CoV-2) del síndrome respiratorio agudo severo en Europa se notificaron en Francia el 24 de enero de 2020 y en Alemania el 28 de enero de 2020 ( Fig.1 ). El 30 de enero de 2020, la Organización Mundial de la Salud (OMS) declaró este primer brote del nuevo coronavirus una ’emergencia de salud pública de importancia internacional’ ( Organización Mundial de la Salud, 2020a). A finales de febrero, las autoridades italianas informaron sobre grupos de casos en Lombardía y casos adicionales en otras dos regiones, Piamonte y Véneto. Las medidas de salud pública se instalaron poco después. El 11 de marzo de 2020, el Director General de la OMS declaró al COVID-19 una pandemia mundial ( Organización Mundial de la Salud, 2020b ). Hasta el 25 de marzo de 2020, se han notificado casos en todos los países de la Unión Europea / Espacio Económico Europeo ( Centro Europeo para la Prevención y el Control de Enfermedades, 2020 ), con Montenegro como el último país europeo en informar sobre pacientes positivos al SARS-CoV-2.
¿QUÉ SIGNIFICA ESTO PARA LOS PACIENTES?
La pandemia de la enfermedad del coronavirus 2019 (COVID-19) tuvo un gran impacto en las parejas infértiles. Las clínicas de fertilidad cerraron sus puertas o redujeron sus servicios, ya sea voluntariamente o por recomendación de las autoridades nacionales. Este artículo proporciona una descripción general de cómo y cuándo COVID-19 afectó el acceso a los servicios de fertilidad en Europa, con el objetivo de proporcionar una base para futuras investigaciones, por ejemplo, sobre los efectos de suspender el tratamiento en parejas infértiles. Los datos de este artículo, combinados con investigaciones adicionales, ayudarán a las clínicas y autoridades de fertilidad a gestionar la atención de las parejas infértiles en una futura pandemia mundial.

MAR, reproducción médicamente asistida;
SARS-CoV-2, síndrome respiratorio agudo severo coronavirus 2;
UE / EAA, Unión Europea / Espacio Económico Europeo;
OMS, Organización Mundial de la Salud.
En respuesta al brote del virus en Europa, ESHRE lanzó, el 27 de febrero de 2020, una primera declaración en la que aconseja un enfoque de precaución y recomienda evitar los embarazos con TAR en pacientes que cumplen los criterios de diagnóstico de COVID-19. A mediados de marzo, ESHRE recomendó ampliar este consejo a todos los pacientes, incluso si no cumplían con los criterios de diagnóstico de COVID-19. A principios de abril de 2020 se publicó una declaración más elaborada en la que se aconsejaba no iniciar un nuevo TAR por las siguientes razones: para evitar complicaciones por el TAR y el embarazo con TAR; para evitar posibles complicaciones relacionadas con el SARS-CoV-2 durante el embarazo; para mitigar el riesgo desconocido de transmisión vertical en pacientes con SRAS-CoV-2 positivo; apoyar la necesaria reasignación de recursos sanitarios; y observar las recomendaciones vigentes de distanciamiento social. Esta declaración también incluyó una excepción para los tratamientos urgentes de preservación de la fertilidad, indicando que la criopreservación de gametos, embriones y tejido germinal aún debe considerarse, siendo un procedimiento de emergencia para pacientes que de otra manera podrían potencialmente volverse estériles. Además, ESHRE tomó la iniciativa de medir el impacto de la pandemia de COVID-19 en la práctica de reproducción médicamente asistida (MAR) / ART en Europa mediante el uso de un cuestionario diseñado a propósito.
Materiales y métodos
Una encuesta de ocho preguntas (Datos Complementarios ) se distribuyó entre los miembros del Comité de Representantes Nacionales (CNR) de la ESHRE el 7 de abril de 2020. Se preguntó a los representantes nacionales sobre el estado de la actividad de TAR en sus respectivos países en ese momento. También se les pidió que detallaran los tratamientos que se estaban realizando y los que se detuvieron temporalmente. Después de la encuesta inicial, se contactó con el CNR para que brindara una actualización periódica sobre el estado de la actividad en su país. Si se reiniciaban los tratamientos, se les pedía más detalles sobre las restricciones o precauciones. Los datos fueron analizados y presentados en forma de tabla y formato visual, publicados en el sitio ESHRE en el momento de su creación y de manera progresiva en el tiempo ( www.eshre.eu/covidwg). Los datos discrepantes o poco claros se aclararon con el CNR a través del correo electrónico, y se pidió a los representantes del mismo país que confirmaran que la descripción general de la información sobre su país (Tabla complementaria SI ) era correcta.
Para investigar cualquier factor que pudiera estar relacionado con la fecha de interrupción de los tratamientos, la fecha de reinicio de los tratamientos y la duración del cese de la actividad, incluimos datos nacionales sobre casos y muertes de COVID-19 notificados diariamente, disponibles en el Centro Europeo para Control de enfermedades ( https://www.ecdc.europa.eu/en/publications-data/download-todays-data-geographic-distribution-covid-19-cases-worldwide ). Las fechas de parada y reinicio de los tratamientos MAR / ART se agregaron a las curvas y se evaluó la alineación con diferentes fases en las curvas.
Además, investigamos la posible correlación entre la duración del cese del tratamiento MAR / ART y los casos notificados de COVID-19 por 100 000 habitantes: este último se calculó a partir de los datos nacionales del Centro Europeo para el Control de Enfermedades.
Resultados
Se recopiló información de 41 de los 51 países europeos, y todos los resultados a continuación se basan en datos de los 41 países europeos, a menos que se especifique lo contrario.
Cronología de la interrupción / reinicio de los tratamientos MAR / ART
Los datos recopilados de la encuesta sobre la actividad MAR / ART permitieron la construcción de una línea de tiempo. En la figura 2 se representa una descripción general de la interrupción y reinicio de las actividades de MAR / ART en Europa a intervalos de 2 semanas entre el 1 de marzo y el 29 de mayo de 2020 .. Italia fue el primer país donde se detuvo la actividad de MAR / ART, a partir del 1 de marzo de 2020. Para el 15 de marzo, nueve países habían detenido toda la actividad de ART, y en cuatro países adicionales, algunos centros habían interrumpido su actividad. Para el 1 de abril, todos los países para los que se dispone de datos informaron de una interrupción (total o parcial) de la actividad MAR / ART. Para algunos países (Noruega, Suecia), los representantes informaron solo un impacto mínimo de la pandemia COVID-19 en la actividad MAR / ART, limitado a los centros públicos que redujeron las actividades principalmente debido a la reasignación de recursos o personal de salud.

Resumen del cese y reinicio de las actividades MAR / ART en Europa entre el 1 de marzo y el 30 de mayo de 2020 .
Los primeros países en reiniciar las actividades fueron República Checa, Dinamarca, Alemania, Luxemburgo y Noruega, durante la semana del 20 de abril de 2020. La mayoría de los países restantes esperaron el comienzo de mayo para reiniciar la actividad MAR / ART. Estos datos se centraron en los tratamientos MAR / ART que se estaban realizando, excluyendo los tratamientos de preservación de la fertilidad (ver más abajo) y las consultas de pacientes en línea o telefónicas, antes de la reapertura. En la mayoría de los países, el apoyo al paciente en línea y por teléfono estuvo disponible durante el período en que los centros MAR / ART estuvieron cerrados.
En el 57,5% (n = 23) de los 40 países para los que se disponía de información, las autoridades locales o nacionales recomendaron interrumpir las actividades de TAR y en el 27,5% (n = 11) de los países las autoridades locales hicieron cumplir la interrupción. Seis representantes informaron que las clínicas pararon voluntariamente sus actividades en su país y algunos indicaron que esto se basaba en recomendaciones internacionales como la declaración ESHRE ( Fig. 3 ).

Centros de TAR públicos versus privados
En la mayoría de los países europeos, el TAR se realiza en centros públicos y privados. Se pidió a los representantes que indicaran si había una diferencia en la actividad MAR / ART con respecto al estado de los servicios públicos o privados en el período de suspensión del tratamiento. El análisis excluyó los países en los que solo hay centros de TAR privados o públicos (n = 5) o para los que no se disponía de información (n = 7). De los 29 países restantes, 18 (62,1%) informaron que no había diferencia entre los centros públicos y privados, 11 (37,9%) informaron que hubo menos impacto en los centros privados, indicando que o bien cerraron menos centros privados o esa actividad en los centros privados no se interrumpió. Ninguno de los representantes de los países informó más actividad en los centros públicos en comparación con los centros privados.
Tratamientos urgentes de preservación de la fertilidad
Aunque no se incluyó en la encuesta inicial, varios CNR comentaron que no se interrumpieron las intervenciones para la preservación urgente de la fertilidad. Después de más preguntas, representantes de 38 países pudieron proporcionar información sobre la disponibilidad de tratamientos médicos para la preservación de la fertilidad. En 32 países (84,2%) se realizaron tratamientos de preservación urgente de la fertilidad durante todo el período y en seis países (15,7%) se cerraron centros de TAR para todas las pacientes, incluidas las pacientes de preservación de la fertilidad.
Factores relacionados con la fecha de parada y reinicio de actividades
Para dilucidar si la decisión de reiniciar el tratamiento con TAR se basó en el número informado de casos de COVID-19 recién diagnosticados en un país, superpusimos la fecha de ‘suspensión’ y ‘reinicio’ del TAR en la línea de tiempo del número de casos de COVID diagnosticados diariamente -19 casos, según lo publicado por el Centro Europeo para el Control de Enfermedades ( https://www.ecdc.europa.eu/en/publications-data/download-todays-data-geographic-distribution-covid-19-cases-worldwide ) . Cabe señalar que la cantidad de casos diarios de COVID-19 depende de la disponibilidad y los métodos de notificación y prueba del país, que variaron durante la duración de la pandemia.
En los gráficos respectivos, se indica la fecha en que se detuvo la actividad de ART (parcial o completa) y la fecha de reinicio ( Fig.4 yFig. Suplementaria S1 ).
Figure 4

Ejemplos del número informado de casos nuevos y muertes diarias asociados con COVID-19, con una indicación de la fecha en que se detuvo la actividad MAR / ART (rojo) y se reinició (verde) para cuatro países. Los gráficos de todos los países se incluyen enFigura complementaria S1 .

De los gráficos se puede concluir que existe una gran variación en el tiempo en que se suspendieron los tratamientos MAR / ART y cuando se reiniciaron. De manera similar, se encontró una gran variación en el número de casos / muertes por COVID-19 en la fecha de interrupción de los tratamientos MAR / ART, con un número medio de casos acumulados de COVID-19 de 3568,82 (que van de 3 a 111680 casos) y un número acumulado medio de muertes por COVID-19 de 222,03 (que van de 0 a 8189). El cálculo de los casos acumulados por 100000 habitantes no redujo la variación, con una media de 16,39 casos por 100000 (rango de 0,01 a 239,02) y 0,50 muertes (rango de 0 a 17,53) por 100000 habitantes en la fecha en que se interrumpieron los tratamientos. .
En promedio, la actividad de TAR se pausó durante 48,76 días, con un rango de 23 a 92 días, según los datos de 37 países para los que se disponía de la fecha exacta de interrupción e inicio de la actividad. Se analizó la posible correlación entre la duración de la interrupción de la actividad de TAR y el impacto de la pandemia de COVID-19 en el país respectivo: este último cuantificado por el número de casos / defunciones de COVID-19 notificados por 100 000 habitantes. No se detectó correlación entre la duración de la interrupción de la actividad de TAR y el impacto de la pandemia COVID-19 en el país respectivo (Fig. Suplementaria S2 )
En los gráficos de los diferentes países, podríamos dividir las curvas en cuatro fases de la epidemia, comenzando con una fase lineal (‘fase de rezago’), una fase de aumento exponencial en los casos de COVID-19 reportados diariamente (‘fase exponencial ‘), una meseta (‘ fase estacionaria ‘) y una fase de disminución en los casos notificados (‘ fase de disminución ‘) ( Fig. 5A). Para cada país, la etapa de la curva se estimó para el día en que se produjo la parada y el reinicio de la actividad. En la mayoría de los países (77,5%, 31/40), la actividad MAR / ART se detuvo durante la fase exponencial, principalmente al comienzo de la fase. Algunos países (n = 6, 15.0%) ya habían suspendido el TAR en la fase de rezago, mientras que otros (n = 3, 7.5%) pospusieron cualquier acción hasta que la curva epidemiológica alcanzó la fase estacionaria. De manera similar, para reiniciar la actividad, la mayoría de los países (n = 30; 75.0%) reiniciaron durante la fase de declive inicial, aunque en 10 (25.0%) países la actividad ya se reinició en la fase estacionaria antes de que comenzara la fase de declive ( Figura 5B ).
Figura 5
El tratamiento se detiene y se reinicia según las fases de la epidemia. ( A ) Resumen de los diferentes gráficos para un solo país, incluida una división en cuatro fases de la curva epidemiológica, incluida la fase de rezago, estacionaria exponencial y de declive. ( B ) Los porcentajes de países que pararon y reiniciaron sus actividades por fase de la curva epidemiológica.
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