Estimulação ovariana controlada para criopreservação de oócitos em pacientes com câncer de mama
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Data
2017-04-07
Autores
Cavagna, Felipe Andreotta [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
O câncer de mama é uma doença maligna relativamente comum em mulheres adultas jovens, justificando a preocupação com a potencial toxicidade gonadal relacionada à quimioterapia. É importante considerar o encaminhamento precoce de pacientes jovens com câncer de mama que tenham desejos reprodutivos para especialistas, a fim de discutir sobre a preservação da fertilidade. A criopreservação de embriões ou de oócitos estão entre os principais métodos à disposição, e para conseguir isso, estimulação ovariana controlada (EOC) é o primeiro passo a ser considerado. O presente estudo tem como objetivo apresentar protocolo de estimulação ovariana em para preservação da fertilidade em pacientes com câncer de mama. De novembro de 2014 a dezembro de 2016, 109 pacientes com câncer de mama com menos de 40 anos de idade foram selecionadas para preservar seu potencial reprodutivo. Elas foram divididas de acordo com a fase do ciclo menstrual em que o estímulo ovariano foi iniciado: fase folicular inicial, fase folicular tardia e fase lútea. Para reduzir o tempo necessário da obtenção dos oócitos, este estudo utilizou o princípio do início aleatório, no qual a EOC pode ser iniciada durante qualquer período do ciclo menstrual sem consequências negativas. O letrozol foi utilizado durante toda a estimulação para diminuir as concentrações de estradiol, independentemente da imunohistoquímica tumoral. Na presença de tumores positivos ao estradiol, e indicação de quimioterapia neoadjuvante, o tamoxifeno foi utilizado como uma medida de proteção adicional. Um agonista do GnRH foi utilizado para desencadear a maturação folicular final, diminuindo o risco de síndrome de hiperestimulação ovariana. Foram analisados os seguintes parâmetros: idade das pacientes, dia de início da EOC, número de dias de EOC, dose total de FSH, níveis de estradiol no dia de maturação folicular final, número de oócitos coletados e número de oócitos vitrificados. A idade média dos pacientes foi de 31,27 ± 4,22 anos. A duração média da EOC foi de 10,0 ± 1,39 dias. O número médio de oócitos coletados foi de 11,62 ± 7,96 e o número médio de oócitos vitrificados foi de 9,60 ± 6,87. A concentração média de estradiol no dia do desencadeamento da ovulação foi de 706,30 ± 450,48 pg / mL, e a dose média de FSH administrada foi 2610,00 ± 716,51 UI. Ao comparar os resultados de acordo com a fase do ciclo no qual a EOC foi iniciada, não houve diferenças significativas no número de oócitos colhidos e vitrificados, duração da estimulação ovariana e dos níveis de estradiol no dia do desencadeamento da ovulação. Observou-se uma diminuição estatisticamente significativa da dose total de FSH administrada nos grupos que iniciaram a EOC na fase folicular tardia e na fase lútea, quando comparada com a fase folicular inicial. Esses resultados sugerem que a criopreservação de oócitos ou embriões com um protocolo específico para pacientes com câncer de mama, é eficaz e pode ser oferecida a mulheres jovens submetidas a tratamento citotóxico que têm preocupações relacionadas ao seu futuro reprodutivo.
Breast cancer is a relatively common malignancy in young adult women, justifying the concern about the potential gonadal toxicity related to chemotherapy. It is important to consider early referral of young breast cancer patients with reproductive desires to fertility specialists, in order to discuss the fertility preservation. Embryos or oocytes cryopreservation are among the main methods available, and to achieve that, controlled ovarian stimulation (COS) is the first step to be considered. From November 2014 to December 2016, 109 breast cancers patients under 40 years were enrolled to preserve their reproductive potential. They were divided according to the menstrual cycle status in: initial follicular phase, late follicular phase and luteal phase. In order to reduce the time necessary to obtain the oocytes, this study used the principle of random start, in which the COS can be initiated during any period of the menstrual cycle without negative consequences. Letrozole was used during all stimulation to reduce estradiol concentrations, regardless of tumor immunohistochemistry. In the presence of estradiol positive tumors, and indication of neoadjuvant chemotherapy, tamoxifen was administerd as an additional protective measure. A GnRH agonist was used to trigger ovulation, in order to mitigate the risk of ovarian hyperstimulation syndrome. The following parameters were analyzed: age, day of COS start, number of days required to COS, total FSH dosage, estradiol levels at final follicular maturation day, number of collected oocytes and number of vitrified oocytes. The mean age of patients was 31.27±4.22 years. The average duration of COS was 10.0±1.39 days. The mean number of collected oocytes was 11.62±7.96 and the mean number of vitrified oocytes was 9.60±6.87. The mean estradiol concentration on the day of the trigger was 706.30±450.48 pg/mL, and the mean dose of FSH administered was 2610.00±716.51 IU. When comparing the outcomes according to the phase of the cycle in which COS was commenced, there were no significant differences in the number of oocytes collected and vitrified, ovarian stimulation length and estradiol levels on the day of the trigger. It was observed a statistically decrease of the total FSH dose administered in the groups starting COS in the late follicular phase and in the luteal phase, when compared to the initial follicular phase These results suggest that oocyte or embryos cryopreservation with a specific protocol for breast cancer patients, is effective, safe, and may be offered to young women undergoing cytotoxic treatment who have concerns related to their reproductive future.
Breast cancer is a relatively common malignancy in young adult women, justifying the concern about the potential gonadal toxicity related to chemotherapy. It is important to consider early referral of young breast cancer patients with reproductive desires to fertility specialists, in order to discuss the fertility preservation. Embryos or oocytes cryopreservation are among the main methods available, and to achieve that, controlled ovarian stimulation (COS) is the first step to be considered. From November 2014 to December 2016, 109 breast cancers patients under 40 years were enrolled to preserve their reproductive potential. They were divided according to the menstrual cycle status in: initial follicular phase, late follicular phase and luteal phase. In order to reduce the time necessary to obtain the oocytes, this study used the principle of random start, in which the COS can be initiated during any period of the menstrual cycle without negative consequences. Letrozole was used during all stimulation to reduce estradiol concentrations, regardless of tumor immunohistochemistry. In the presence of estradiol positive tumors, and indication of neoadjuvant chemotherapy, tamoxifen was administerd as an additional protective measure. A GnRH agonist was used to trigger ovulation, in order to mitigate the risk of ovarian hyperstimulation syndrome. The following parameters were analyzed: age, day of COS start, number of days required to COS, total FSH dosage, estradiol levels at final follicular maturation day, number of collected oocytes and number of vitrified oocytes. The mean age of patients was 31.27±4.22 years. The average duration of COS was 10.0±1.39 days. The mean number of collected oocytes was 11.62±7.96 and the mean number of vitrified oocytes was 9.60±6.87. The mean estradiol concentration on the day of the trigger was 706.30±450.48 pg/mL, and the mean dose of FSH administered was 2610.00±716.51 IU. When comparing the outcomes according to the phase of the cycle in which COS was commenced, there were no significant differences in the number of oocytes collected and vitrified, ovarian stimulation length and estradiol levels on the day of the trigger. It was observed a statistically decrease of the total FSH dose administered in the groups starting COS in the late follicular phase and in the luteal phase, when compared to the initial follicular phase These results suggest that oocyte or embryos cryopreservation with a specific protocol for breast cancer patients, is effective, safe, and may be offered to young women undergoing cytotoxic treatment who have concerns related to their reproductive future.
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Palavras-chave
Fertility preservation, Breast neoplasms, Drug therapy, Ovulation induction, Cryopreservation