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Abstract(s)
Introdução: Em Portugal, tem existido um crescimento da atividade na área da
Saúde Reprodutiva devido ao aumento do número de casais com indicação para as
técnicas de Procriação Medicamente Assistida (PMA). Existem várias hormonas
disponíveis para estimulação ovárica, o que demonstra que tem havido uma procura
contínua pelo protocolo que contenha a combinação hormonal que proporcione a melhor
resposta folicular, da forma mais segura e fisiológica possível. Contudo, ainda não foi
possível concluir qual o melhor protocolo.
Objetivo: Perceber qual dos protocolos de estimulação controlada ovárica (ECO),
utilizados em diferentes utentes, se relaciona com uma maior quantidade de oócitos
recuperados na punção folicular, além do número de dias necessários para o estímulo e o
doseamento total das hormonas administradas, e com qual estímulo final (trigger) se
obtém uma maior percentagem de oócitos maduros (estadio MII) para fertilização.
Materiais e Métodos: Estudo retrospetivo e observacional, realizado com base
na análise de processos clínicos de utentes submetidas a PMA (Fertilização In Vitro ou
Injeção Intracitoplasmática de Espermatozoides) na Unidade de Medicina Reprodutiva do
Centro Hospitalar e Universitário da Cova da Beira, entre 01 de janeiro de 2015 e 31 de
dezembro de 2019. Para o pareamento, procedeu-se à divisão da amostra em três grupos,
considerando-se a idade da utente, o doseamento da sua Hormona Anti-Mülleriana e a
contagem de folículos antrais para a obtenção do Ovarian Response Predictor Index
(ORPI) e consequente agrupamento em: G1-Baixa Reserva (ORPI<0,5), G2-Reserva
Normal (ORPI [0,5-0,9[) e G3-Alta Reserva (ORPI 0,9). Dos 317 ciclos analisados,
selecionaram-se 246 ciclos em que foram utilizados para ECO: FSH recombinante -
folitropina alfa ou beta (Protocolo 1) ou corifolitropina alfa (Protocolo 2), ambos
associados à HMG urinária e ao antagonista da GnRH, com o trigger realizado através da
hCG recombinante ou do agonista da GnRH.
Resultados: Nos 246 ciclos realizados, as mulheres foram distribuídas nos três
grupos através dos seus ORPIs: G1 (n=119), G2 (n=46) e G3 (n=81). O protocolo 1 foi
utilizado em 203 (82,5%) e o protocolo 2 em 43 (17,5%) ciclos. O trigger com hCG
recombinante foi realizado em 216 (88,9%) e o agonista da GnRH em 27 (11,1%) ciclos. O
número de oócitos obtidos foi superior no protocolo 1 em todos os grupos estudados,
sendo mais significativo no G1 (p<0,001) que nos G2 (p-0,579) e G3 (p-0,068).
Comparado com o protocolo padrão de dez dias de estímulo, o número de dias necessários na ECO para o protocolo 2 foi maior do que para o protocolo 1 em todos os grupos: um dia
a mais nos grupos G1 (p-0,011) e G3 (p-0,176) e dois dias a mais no G2 (p-0,039). A dose
total de FSH recombinante alfa ou beta / HMG urinária utilizada no protocolo 1 foi
inversamente proporcional à reserva ovárica. Quanto menor o ORPI, maior a quantidade
média de unidades internacionais (UI) administradas: respetivamente, 2120UI/935UI,
1778UI/856UI e 1441UI/652UI para os grupos G1, G2 e G3. No protocolo 2, com o uso
padrão de FSH recombinante de depósito (150μg) em todos os grupos, houve a
necessidade de complemento com maiores doses de HMG urinária quando comparado
com o protocolo 1. Utilizaram-se 1850UI, 2200UI e 1950UI respetivamente nos grupos G1,
G2 e G3. O doseamento do antagonista da GnRH ficou dependente do número de dias da
ECO até ao uso do trigger. Independentemente do protocolo ou do grupo, foi utilizada
uma média de cinco ampolas (entre quatro e sete), perfazendo 1,25mg de antagonista da
GnRH (entre 1,00 e 1,75mg) por ciclo. Na obtenção de oócitos maduros (MII), as
percentagens baseadas nos oócitos recolhidos foram semelhantes independentemente do
trigger utilizado (hCG recombinante / agonista da GnRH) com equivalência em todos os
grupos (G1- 78/89%, G2-79/80% e G3- 81/79%).
Conclusão: A utilização da folitropina alfa ou beta (Protocolo 1) leva à obtenção de
uma maior quantidade de oócitos recuperados do que a corifolitropina alfa (Protocolo 2)
em todos os ORPIs, especialmente no G1-baixa reserva (p<o,oo1). A dose utilizada de FSH
recombinante alfa ou beta em conjunto com a HMG urinária (Protocolo 1) aumenta de
modo inversamente proporcional com o valor do ORPI. Já a dose fixa de FSH
recombinante de depósito utilizada no protocolo 2 obriga a um aumento acentuado da
dose da HMG urinária, refletindo-se também no número de dias de ECO e
consequentemente no número de ampolas do antagonista da GnRH. A maturação final
(trigger) para obtenção de oócitos maduros (MII) mostra a mesma eficiência com o uso de
hCG recombinante ou com o uso de agonista da GnRH. Mais estudos são necessários com
outros protocolos estabelecidos.
Introduction: In Portugal, the activity in Reproductive Health has been increased, particularly to those couples who have indication for Assisted Reproductive Technology (ART) treatments. There are several hormones available for ovarian stimulation, which demonstrates that there has been a continuous search for the protocol that contains the hormonal combination that provides the best follicular response in the safest and most physiological way possible. However, it has not yet been possible to conclude which is the best protocol. Objective: To understand which of the controlled ovarian stimulation (COS) protocols, used in different patients are related to a greater amount of oocytes recovered by the Ovum Pick Up (OPU) technique, beyond the number of days required for the stimulus and the total dosage of the administrated hormones, and with which final stimulus (trigger) a higher percentage of mature oocytes (stage MII) is obtained for fertilization. Materials and Methods: Retrospective and observational study, carried out based on the analysis of clinical processes of patients submitted to ART (In Vitro Fertilization or Intracytoplasmic Sperm Injection) at the Reproductive Medicine Unit of the Hospital Center Cova da Beira Academic Medical Center, between 1st January 2015 and 31th December 2019. For matching, the sample was divided into three groups, considering the age of the patient, the measurement of her Anti-Müllerian Hormone (AMH) and the count of antral follicles to obtain the Ovarian Response Predictor Index (ORPI) and consequent grouping into: G1-Low Reserve (ORPI <0,5), G2-Normal Reserve (ORPI [0,5-0,9 [) and G3-High Reserve (ORPI0 ≥0,9). Of the 317 cycles analyzed, 246 cycles were selected in which COS was used: recombinant FSH - follitropin alfa or beta (Protocol 1) or corifollitropin alfa (Protocol 2), both associated with urinary HMG and the GnRH antagonist, with the trigger performed using recombinant hCG or GnRH agonist. Results: In the 246 cycles performed, women were distributed into the three groups through their ORPIs: G1 (n = 119), G2 (n = 46) and G3 (n = 81). Protocol 1 was used in 203 (82.5%) and protocol 2 in 43 (17.5%) cycles. The trigger with recombinant hCG was performed in 216 (88.9%) and the GnRH agonist in 27 (11.1%) cycles. The number of oocytes obtained was higher in protocol 1 in all groups studied, being more significant in G1 (p <0.001) than in G2 (p-0.579) and G3 (p-0.068). Compared with the standard tenday stimulation protocol, the number of days required in COS for protocol 2 was greater than for protocol 1 in all groups: one more day in groups G1 (p-0.011) and G3 (p-0.176) and two more days in G2 (p-0.039). The total dose of recombinant FSH alfa or beta / urinary HMG used in protocol 1 was inversely proportional to the ovarian reserve. The lower the ORPI, the greater the average number of international units (IU) administered: 2120IU/935IU, 1778IU/856IU and 1441IU/652IU for groups G1, G2 and G3, respectively. In protocol 2, with the standard use of recombinant FSH deposition (150μg) in all groups, there was a need to supplement with higher doses of urinary HMG when compared to protocol 1. There were 1850IU, 2200IU and 1950IU in groups G1, G2 and G3, respectively. The dosage of the GnRH antagonist was dependent on the number of COS days until the trigger was used. Regardless of the protocol or group, an average of five ampoules (between four and seven) was used, making up 1,25mg of GnRH antagonist (between 1,00 and 1,75mg) per cycle. In obtaining mature oocytes (MII), the percentages based on the collected oocytes were similar regardless of the trigger used (recombinant hCG/GnRH agonist) with equivalence in all groups (G1- 78/89%, G2-79/80% and G3- 81/79%). Conclusion: The use of follitropin alfa or beta (Protocol 1) leads to the obtaining of a greater amount of recovered oocytes than corifollitropin alfa (Protocol 2) in all ORPIs, especially in G1-low reserve (p <o, oo1). The dose of recombinant FSH alfa or beta used with urinary HMG (Protocol 1) increases inversely proportional to the ORPI value. The fixed dose of recombinant FSH deposit used in protocol 2 requires a sharp increase in the dose of urinary HMG, also reflected in the number of COS days and consequently in the number of ampoules of the GnRH antagonist. The final maturation (trigger) to obtain mature oocytes (MII) shows the same efficiency with the use of the recombinant hCG or with the use of the GnRH agonist. Further studies are needed with other established protocols.
Introduction: In Portugal, the activity in Reproductive Health has been increased, particularly to those couples who have indication for Assisted Reproductive Technology (ART) treatments. There are several hormones available for ovarian stimulation, which demonstrates that there has been a continuous search for the protocol that contains the hormonal combination that provides the best follicular response in the safest and most physiological way possible. However, it has not yet been possible to conclude which is the best protocol. Objective: To understand which of the controlled ovarian stimulation (COS) protocols, used in different patients are related to a greater amount of oocytes recovered by the Ovum Pick Up (OPU) technique, beyond the number of days required for the stimulus and the total dosage of the administrated hormones, and with which final stimulus (trigger) a higher percentage of mature oocytes (stage MII) is obtained for fertilization. Materials and Methods: Retrospective and observational study, carried out based on the analysis of clinical processes of patients submitted to ART (In Vitro Fertilization or Intracytoplasmic Sperm Injection) at the Reproductive Medicine Unit of the Hospital Center Cova da Beira Academic Medical Center, between 1st January 2015 and 31th December 2019. For matching, the sample was divided into three groups, considering the age of the patient, the measurement of her Anti-Müllerian Hormone (AMH) and the count of antral follicles to obtain the Ovarian Response Predictor Index (ORPI) and consequent grouping into: G1-Low Reserve (ORPI <0,5), G2-Normal Reserve (ORPI [0,5-0,9 [) and G3-High Reserve (ORPI0 ≥0,9). Of the 317 cycles analyzed, 246 cycles were selected in which COS was used: recombinant FSH - follitropin alfa or beta (Protocol 1) or corifollitropin alfa (Protocol 2), both associated with urinary HMG and the GnRH antagonist, with the trigger performed using recombinant hCG or GnRH agonist. Results: In the 246 cycles performed, women were distributed into the three groups through their ORPIs: G1 (n = 119), G2 (n = 46) and G3 (n = 81). Protocol 1 was used in 203 (82.5%) and protocol 2 in 43 (17.5%) cycles. The trigger with recombinant hCG was performed in 216 (88.9%) and the GnRH agonist in 27 (11.1%) cycles. The number of oocytes obtained was higher in protocol 1 in all groups studied, being more significant in G1 (p <0.001) than in G2 (p-0.579) and G3 (p-0.068). Compared with the standard tenday stimulation protocol, the number of days required in COS for protocol 2 was greater than for protocol 1 in all groups: one more day in groups G1 (p-0.011) and G3 (p-0.176) and two more days in G2 (p-0.039). The total dose of recombinant FSH alfa or beta / urinary HMG used in protocol 1 was inversely proportional to the ovarian reserve. The lower the ORPI, the greater the average number of international units (IU) administered: 2120IU/935IU, 1778IU/856IU and 1441IU/652IU for groups G1, G2 and G3, respectively. In protocol 2, with the standard use of recombinant FSH deposition (150μg) in all groups, there was a need to supplement with higher doses of urinary HMG when compared to protocol 1. There were 1850IU, 2200IU and 1950IU in groups G1, G2 and G3, respectively. The dosage of the GnRH antagonist was dependent on the number of COS days until the trigger was used. Regardless of the protocol or group, an average of five ampoules (between four and seven) was used, making up 1,25mg of GnRH antagonist (between 1,00 and 1,75mg) per cycle. In obtaining mature oocytes (MII), the percentages based on the collected oocytes were similar regardless of the trigger used (recombinant hCG/GnRH agonist) with equivalence in all groups (G1- 78/89%, G2-79/80% and G3- 81/79%). Conclusion: The use of follitropin alfa or beta (Protocol 1) leads to the obtaining of a greater amount of recovered oocytes than corifollitropin alfa (Protocol 2) in all ORPIs, especially in G1-low reserve (p <o, oo1). The dose of recombinant FSH alfa or beta used with urinary HMG (Protocol 1) increases inversely proportional to the ORPI value. The fixed dose of recombinant FSH deposit used in protocol 2 requires a sharp increase in the dose of urinary HMG, also reflected in the number of COS days and consequently in the number of ampoules of the GnRH antagonist. The final maturation (trigger) to obtain mature oocytes (MII) shows the same efficiency with the use of the recombinant hCG or with the use of the GnRH agonist. Further studies are needed with other established protocols.
Description
Keywords
Contagem de Folículos Antrais Estimulação Controlada Ovárica Hormona Anti-Mülleriana Infertilidade Procriação Medicamente Assistida