Avaliação da qualidade embrionária, potencial de implantação e perfil lipídico do fluido uterino, Quando transferidos embriões frescos, provenientes de oócitos frescos ou criopreservados e embriões criopreservados.
Data
2018-05-23
Autores
Mattar, Daniela Paes de Almeida Braga 
Orientadores
Turco, Edson Guimaraes Lo
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Objetivo: Identificar biomarcadores lipídicos da receptividade endometrial, em ciclos de descongelamento de embriões. Método: Amostras de fluido endometrial foram obtidas, imediatamente antes da transferência embrionária, a partir de 41 pacientes submetidas a ciclos de descongelamento de embriões. As amostras foram e divididas em dois grupos dependendo do diagnóstico de gestação: Gestação Positiva (n=24) e Grupo Gestação Negativa (n=17). Os dados foram adquiridos no modo positivo de um espectrômetro de massas do tipo MALDI-TOF e posteriormente analisados por métodos uni e multivariados. Resultados: Os dados brutos foram processados e 265 íons foram utilizados para a análise estatística. A análise de correlação entre os íons estabeleceu vinte razões, as quais foram utilizadas para as etapas seguintes. A análise de Componentes Principais mostrou uma tendência de separação entre os grupos estudados, enquanto a Análise Discriminatória do Método dos Quadrados Mínimos foi capaz de distinguir claramente o Grupo Positivo do Grupo Negativo. Quinze razões (13 hiper-representadas no Grupo Negativo e duas hiperrepresentadas no Grupo Positivo) foram selecionadas considerando sua importância para a predição do modelo. Essas razões foram utilizadas para construir a curva ROC, que apresentou área sob a curva e 81,8% (IC 95%: 62,7 - 94,7%, p = 0,009), e foram consideradas possíveis biomarcadoras de receptividade ao endométrio. Os íons atribuídos pelo programa foram: fosfoetanolamina, ácido fosfatídico, diacilglicerol, triacilglicerol, glicosildiacilglicerol, fosfatidilcolina, esfingolipidium neutro, lisofosfatidilglicerol. A análise de enriquecimento funcional revelou que o aumento na razão de triacilglicerol e fosfolípides leva à remodelação de lipoproteínas de baixa densidade, o que pode estar associado a alteração na síntese e liberação de esteróides e possivelmente à alteração na janela de implantação. Conclusão: A análise lipidômica do fluído uterino pode ser uma ferramenta clínica para a identificação da receptividade endometrial, em ciclos de descongelamento de embriões.
Objective: To identify lipid biomarkers able to differ receptive from non-receptive endometrium. Method: Endometrial fluid samples, were collected immediately before embryo transfer, from 41 patients undergoing thaw embryo transfers. Samples were split into two groups depending on the pregnancy outcome: Positive-Group (n=24) and Negative-Group (n=17). Data were acquired in the positive mode by MALDI-TOF mass spectrometry method. Uni and multivariate analyses were applied to the dataset. Results: Ions ratios were established according with their correlations and those variables were used for the analysis. The Principal Component Analysis showed a tendency of separation between the studied groups, while the Partial Least Square Discriminant Analysis was able to clearly distinguish Positive-Group from Negative- Group. Fifteen ratios (13 hyper-represented in the Negative-Group and two hyperrepresented in the Positive-Group) were selected considering their importance for the model prediction. These ratios were used to build the ROC curve, which presented an area under the curve (AUC) of 81.8% (CI 95%: 62.7 – 94.7%, p=0.009), and were considered possible biomarkers of endometrium receptivity. Ions identified by the lipidmaps database were: phosphoethanolamine, phosphatidic acid, diacylglycerol, triacylglycerol, glycosyl diacylglycerol, phosphatidylcholin, neutral sphingolipidium, Lysophosphatidylglycerol. Functional enrichment analysis was performed using the Cytoscape Software, which revealed that increase in the triacylglycerol and phospholipids ratio leads to the remodeling of low density lipoproteins, which may be associated with decreased steroid syntheses and production, and therefore, displacement in the window of implantation. Conclusion: Endometrial fluid lipidomics may be a powerful approach to define the exact time of the window of implantation in frozen/thaw embryo transfers.
Objective: To identify lipid biomarkers able to differ receptive from non-receptive endometrium. Method: Endometrial fluid samples, were collected immediately before embryo transfer, from 41 patients undergoing thaw embryo transfers. Samples were split into two groups depending on the pregnancy outcome: Positive-Group (n=24) and Negative-Group (n=17). Data were acquired in the positive mode by MALDI-TOF mass spectrometry method. Uni and multivariate analyses were applied to the dataset. Results: Ions ratios were established according with their correlations and those variables were used for the analysis. The Principal Component Analysis showed a tendency of separation between the studied groups, while the Partial Least Square Discriminant Analysis was able to clearly distinguish Positive-Group from Negative- Group. Fifteen ratios (13 hyper-represented in the Negative-Group and two hyperrepresented in the Positive-Group) were selected considering their importance for the model prediction. These ratios were used to build the ROC curve, which presented an area under the curve (AUC) of 81.8% (CI 95%: 62.7 – 94.7%, p=0.009), and were considered possible biomarkers of endometrium receptivity. Ions identified by the lipidmaps database were: phosphoethanolamine, phosphatidic acid, diacylglycerol, triacylglycerol, glycosyl diacylglycerol, phosphatidylcholin, neutral sphingolipidium, Lysophosphatidylglycerol. Functional enrichment analysis was performed using the Cytoscape Software, which revealed that increase in the triacylglycerol and phospholipids ratio leads to the remodeling of low density lipoproteins, which may be associated with decreased steroid syntheses and production, and therefore, displacement in the window of implantation. Conclusion: Endometrial fluid lipidomics may be a powerful approach to define the exact time of the window of implantation in frozen/thaw embryo transfers.
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Citação
MATTAR, Daniela Paes de Almeida Braga. Avaliação da qualidade embrionária, potencial de implantação e perfil lipídico do fluido uterino, quando transferidos embriões frescos, provenientes de oócitos frescos ou criopreservados e embriões criopreservados. 2018. 98 f. Tese (Doutorado em Medicina: urologia) - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2018