AVALIAÇÃO DE DESFECHOS DA APLICAÇÃO INTRAUTERINA DE PLASMA RICO EM PLAQUETAS (PRP) AUTÓLOGO PRÉVIA À TRANSFERÊNCIA DE EMBRIÕES EUPLOIDES EM MULHERES COM ESPESSURA ENDOMETRIAL NORMAL
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Data
2022-07
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Silva, André Anjos da
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Heidrich, Daiane
Muller, Gabriel Cardozo
Souza, Maria Do Carmo Borges De
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Múltiplos aprimoramentos permitiram que a técnica de fertilização in vitro (FIV) evoluísse ao longo das últimas décadas e se tornasse mais acessível, mais segura e mais efetiva. Na busca por um aumento nas taxas de sucesso, diferentes estratégias vêm sendo continuamente testadas, sendo uma das mais recentes, o uso de plasma rico em plaquetas (PRP) autólogo, já adotado em outras áreas da saúde, descrito pela primeira vez na medicina reprodutiva em 2015. Desde então, várias publicações vêm atribuindo potenciais benefícios do PRP aplicado na cavidade uterina previamente ao procedimento de transferência embrionária em casos desfavoráveis, como os de mulheres portadoras de endométrio fino e de repetidas falhas de implantação embrionária. Porém, ainda é exíguo o número de pesquisas com delineamento criterioso e os grupos de pacientes até então estudados correspondem a uma minoria dos ciclos. O presente estudo objetiva avaliar os desfechos reprodutivos do uso intrauterino do PRP autólogo, prévio à transferência embrionária, em casos com prognóstico mais favorável, grupo que corresponde à significativa parcela da população que se submete ao tratamento de FIV, porém ainda não estudado. Em ensaio clínico randomizado, 41 participantes foram alocadas em dois grupos: um submetido a duas aplicações intrauterinas de PRP (grupo da intervenção, n=21) e o outro não (grupo controle, n=20), em ciclos de transferência de embriões únicos, exclusivamente em estágio de blastocisto, cromossomicamente normais (euploides) em mulheres cuja espessura endometrial se encontra normal. A análise estatística foi realizada usando JAMOVI computer software (version 2.3 - 2022) e R Core Team (2021), sendo considerado estatisticamente significativo o valor de p<0,05. Verificou-se no grupo do PRP taxas de gravidez bioquímica, de gravidez clínica e de gravidez em evolução até as primeiras 8-9 semanas de 47.6%, 38.1% e 38.1%, respectivamente, enquanto no grupo controle tais resultados foram de 45%, 35% e 35%, não havendo entre os grupos diferenças estatisticamente significativas nos desfechos. Não foram observados casos de gestação gemelar. As pacientes que engravidaram foram monitoradas até 12 semanas, não sendo verificados episódios de abortamento espontâneo em nenhum dos grupos. O grau de qualidade da morfologia embrionária demonstrou correlação positiva, moderada, significativa com a idade feminina, i.e., conforme a idade aumenta, o grau de qualidade do embrião demonstra pior prognóstico (p<0.05). Mulheres que tinham diagnóstico de endometriose e adenomiose, bem como o fator idade, IMC, tempo de infertilidade, gestações prévias e fator masculino não apresentaram diferença entre os dois grupos avaliados. Diferentemente do que foi até estão descrito em alguns relatos de séries de casos, em poucos estudos de coorte e em raros ensaios clínicos, a presente pesquisa não observou resultados diferentes no grupo da intervenção em relação ao grupo controle, ao analisar população em que o endométrio apresentava espessura da mucosa uterina >7 mm. Ainda se faz necessário, contudo, um maior número de ensaios clínicos randomizados (ECRs), utilizando-se protocolos de preparo do PRP autólogo mais padronizados, aplicados a um maior número de sujeitos de pesquisa para que se obtenha conclusões mais confiáveis a respeito da utilização da aplicação intrauterina de PRP na área da reprodução humana.
Multiple improvements have allowed the technique of in vitro fertilization (IVF) to evolve over the last few decades and become more accessible, safer and more effective. In the search for an increase in success rates, different strategies have been continuously tested, being one the most recent, the use of autologous platelet- rich plasma (PRP), already adopted in other areas of health, firstly described in reproductive medicine in 2015. Since then, several publications have been attributing potential benefits of PRP applied to the uterine cavity prior to the embryo transfer procedure in unfavorable cases, such as women with thin endometrium and with repeated failures of embryo implantation. However, the number of studies with a careful design is still small and the groups of patients studied so far correspond to a minority of the cycles. The present study aims to evaluate the reproductive outcomes of the intrauterine use of autologous PRP, prior to embryo transfer, in cases with a more favorable prognosis, a group that corresponds to a significant portion of the population undergoing IVF treatment, but not yet studied. In a randomized clinical trial (RCT), 41 participants were assigned into two groups: one submitted to two intrauterine injections of PRP (intervention group n=21) and the other one not (control group, n=20), in single embryo transfer (SET) cycles, exclusively in the blastocyst stage, chromosomally normal (euploid) in women whose endometrial thickness is normal. Statistical analysis was performed using JAMOVI computer software (version 2.3 - 2022) and R Core Team (2021), with p<0.05 being considered statistically significant. In the PRP group, rates of biochemical pregnancy, clinical pregnancy and pregnancy in progress up to the first 8-9 weeks were 47.6%, 38.1% and 38.1%, respectively, while in the control group such results were 45%, 35% and 35%, with no statistically significant differences in outcomes between the groups. There were no cases of twin pregnancies. Patients who became pregnant were monitored up to 12 weeks, and there were no episodes of spontaneous abortion in any of the groups. The degree of embryonic morphological quality showed a positive, moderate, significant correlation with female age, i.e., as age increases, the degree of embryo quality shows a worse prognosis (p<0.05). Women who were diagnosed with endometriosis and adenomyosis, as well as the age factor, BMI, time of infertility, previous pregnancies and male factor, showed no difference between the two groups evaluated. Unlike what has been described in some case series reports, in a few cohort studies and in rare clinical trials, the present study did not observe different results in the intervention group in relation to the control group, when analyzing a population in which the endometrium had uterine mucosa thickness >7 mm. However, a greater number of randomized clinical trials is still necessary, using more standardized protocols for the preparation of autologous PRP, applied to a greater number of research subjects in order to obtain more reliable conclusions regarding the use of intrauterine application of PRP in the area of human reproduction.
Multiple improvements have allowed the technique of in vitro fertilization (IVF) to evolve over the last few decades and become more accessible, safer and more effective. In the search for an increase in success rates, different strategies have been continuously tested, being one the most recent, the use of autologous platelet- rich plasma (PRP), already adopted in other areas of health, firstly described in reproductive medicine in 2015. Since then, several publications have been attributing potential benefits of PRP applied to the uterine cavity prior to the embryo transfer procedure in unfavorable cases, such as women with thin endometrium and with repeated failures of embryo implantation. However, the number of studies with a careful design is still small and the groups of patients studied so far correspond to a minority of the cycles. The present study aims to evaluate the reproductive outcomes of the intrauterine use of autologous PRP, prior to embryo transfer, in cases with a more favorable prognosis, a group that corresponds to a significant portion of the population undergoing IVF treatment, but not yet studied. In a randomized clinical trial (RCT), 41 participants were assigned into two groups: one submitted to two intrauterine injections of PRP (intervention group n=21) and the other one not (control group, n=20), in single embryo transfer (SET) cycles, exclusively in the blastocyst stage, chromosomally normal (euploid) in women whose endometrial thickness is normal. Statistical analysis was performed using JAMOVI computer software (version 2.3 - 2022) and R Core Team (2021), with p<0.05 being considered statistically significant. In the PRP group, rates of biochemical pregnancy, clinical pregnancy and pregnancy in progress up to the first 8-9 weeks were 47.6%, 38.1% and 38.1%, respectively, while in the control group such results were 45%, 35% and 35%, with no statistically significant differences in outcomes between the groups. There were no cases of twin pregnancies. Patients who became pregnant were monitored up to 12 weeks, and there were no episodes of spontaneous abortion in any of the groups. The degree of embryonic morphological quality showed a positive, moderate, significant correlation with female age, i.e., as age increases, the degree of embryo quality shows a worse prognosis (p<0.05). Women who were diagnosed with endometriosis and adenomyosis, as well as the age factor, BMI, time of infertility, previous pregnancies and male factor, showed no difference between the two groups evaluated. Unlike what has been described in some case series reports, in a few cohort studies and in rare clinical trials, the present study did not observe different results in the intervention group in relation to the control group, when analyzing a population in which the endometrium had uterine mucosa thickness >7 mm. However, a greater number of randomized clinical trials is still necessary, using more standardized protocols for the preparation of autologous PRP, applied to a greater number of research subjects in order to obtain more reliable conclusions regarding the use of intrauterine application of PRP in the area of human reproduction.
Descrição
Palavras-chave
Plasma rico em plaquetas; Fertilização in vitro; Endométrio normal; Platelet-rich plasma; In vitro fertilization; Normal endometrium
Citação
HÖHER, Marcos Alexandre. AVALIAÇÃO DE DESFECHOS DA APLICAÇÃO INTRAUTERINA DE PLASMA RICO EM PLAQUETAS (PRP) AUTÓLOGO PRÉVIA À TRANSFERÊNCIA DE EMBRIÕES EUPLOIDES EM MULHERES COM ESPESSURA ENDOMETRIAL NORMAL. 2022. Dissertação (Mestrado) – Curso de Ciências Médicas, Universidade do Vale do Taquari - Univates, Lajeado, 21 jul. 2022. Disponível em: http://hdl.handle.net/10737/4369.