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O risco de pré-eclâmpsia em gravidezes resultantes de doação de oócitos
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A pré-eclâmpsia é uma doença hipertensiva da gravidez, que complica cerca de 2-8% das gestações e constitui uma das principais causas de morbilidade e mortalidade materno-fetal. Ainda são amplamente desconhecidos os mecanismos que culminam no estado inflamatório, anti-angiogénico e de hipercoagulação que a caracterizam. Contudo, a literatura parece deixar bem estabelecida uma associação entre as gravidezes resultantes de doação de oócitos e um risco de desenvolver pré-eclâmpsia maior do que o existente em casos de concepção espontânea, ou com técnicas que recorram a oócitos autólogos. A teoria fisiopatológica mais aceite atualmente postula que a utilização de oócitos doados, por resultar num embrião que é totalmente alogénico à mãe e, consequentemente, com maior dissemelhança antigénica, induz alterações imunológicas sistémicas e placentárias semelhantes às que ocorrem na pré-eclâmpsia, provavelmente aumentando precocemente a susceptibilidade materna para que esta seja despoletada mais tarde na gravidez. Todavia, ainda não estão bem estabelecidas as características que determinam o desenvolvimento ou não de complicações nesta população obstétrica. À partida, revela-se difícil individualizar o papel do oócito doado perante a presença de outras variáveis, potencialmente de risco, intrínsecas a esta técnica, como a manipulação dos gâmetas em laboratório e o controlo hormonal exógeno do ambiente uterino. Também se argumenta que as características basais da população que lhe recorre, como a idade materna avançada, a maior frequência de comorbilidades, a existência de uma causa de infertilidade de base e o número elevado de gestações múltiplas possam traduzir-se neste incremento do risco. Sendo a doação de oócitos uma realidade crescente, destaca-se a importância de aperfeiçoar a investigação nesta área, para que melhor sejam esclarecidos os factores com impacto no risco de pré-eclâmpsia. Isto permitirá não só a definição e implementação de medidas redutoras de risco dirigidas às mulheres que recorrem a oócitos doados, mas também uma melhor compreensão da fisiopatologia da pré-eclâmpsia.
Preeclampsia is a hypertensive disorder of pregnancy, which develops in 2-8% of all pregnancies and is a major contributor to maternal and fetal morbility and mortality. The mechanisms that lead to the inflammatory, anti-angiogenic and hipercoagulable state that characterizes this disorder are still largely unknown. However, the literature portrays a wellestablished relationship between oocyte donation pregnancies and a risk of developing preeclampsia greater than the one associated with spontaneous conception or even techniques that use autologous oocytes. The most accepted pathophysiological theory postulates that the fully allogeneic embryo that results from the use of a donated oocyte, due to the naturally greater antigenic dissimilarity present, induces placental and systemic immunological changes similar to those found in preeclampsia. It is hypothesized that this increases the maternal susceptibility to this pathology on early stages of gestation, contributing to its occurrence later on. Notwithstanding, the variables that determine the manifestation of complications on these pregnancies are still unascertained. For example, it is challenging to individualize the role of the donated oocyte from other risk factors inherent to this technique, such as the manipulation of gametes in a laboratory environment and the exogenous hormonal stimulation of the endometrial cavity. Additionally, some characteristics, common in this population, such as the advanced maternal age, the high incidence of multiple gestations, the presence of comorbilities, or even infertility itself hold a risk of their own. The steep increase in the number of women resorting to oocyte donation in the last few years emphasizes the urgency of perfecting the research conducted on this area, so as to better elucidate the risk factors for developing preeclampsia during these pregnancies. This would allow not only a better definition and implementation of risk reducing measures in this population, but also a possibly better insight into the pathophysiology of preeclampsia.
Preeclampsia is a hypertensive disorder of pregnancy, which develops in 2-8% of all pregnancies and is a major contributor to maternal and fetal morbility and mortality. The mechanisms that lead to the inflammatory, anti-angiogenic and hipercoagulable state that characterizes this disorder are still largely unknown. However, the literature portrays a wellestablished relationship between oocyte donation pregnancies and a risk of developing preeclampsia greater than the one associated with spontaneous conception or even techniques that use autologous oocytes. The most accepted pathophysiological theory postulates that the fully allogeneic embryo that results from the use of a donated oocyte, due to the naturally greater antigenic dissimilarity present, induces placental and systemic immunological changes similar to those found in preeclampsia. It is hypothesized that this increases the maternal susceptibility to this pathology on early stages of gestation, contributing to its occurrence later on. Notwithstanding, the variables that determine the manifestation of complications on these pregnancies are still unascertained. For example, it is challenging to individualize the role of the donated oocyte from other risk factors inherent to this technique, such as the manipulation of gametes in a laboratory environment and the exogenous hormonal stimulation of the endometrial cavity. Additionally, some characteristics, common in this population, such as the advanced maternal age, the high incidence of multiple gestations, the presence of comorbilities, or even infertility itself hold a risk of their own. The steep increase in the number of women resorting to oocyte donation in the last few years emphasizes the urgency of perfecting the research conducted on this area, so as to better elucidate the risk factors for developing preeclampsia during these pregnancies. This would allow not only a better definition and implementation of risk reducing measures in this population, but also a possibly better insight into the pathophysiology of preeclampsia.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2019
Palavras-chave
Gravidez Pré-eclâmpsia Doação de oócitos Risco Resposta imunológica Obstetrícia Ginecologia