Publicação
Fertility preservation: potential ovarian protective effect of GnRH analogues during chemotherapy
| Resumo: | Recent advances in cancer treatment field allowed significant increase in the survival rate of patients. However, the patients have commonly faced long-term adverse effects that severly affected the quality of life, specially concerning their fertility. It is established that radio- and chemotherapy treatments can cause a reduction of the ovarian reserve, resulting in a 40-60% rate of premature ovarian failure (POF) in women exposed to these treatments. In order to decrease POF risks, several fertility preservation options were developed: reduction of the exposure to gonadotoxic agents, gametes or embryos cryopreservation, oocyte donation, ovarian tissue cryopreservation and transplant, or a pharmacological protection of the ovaries during chemotherapy. While the last one appears as a less invasive and promising procedure, the studies and clinical trials continue to show inconsistent results, raising an almost 30-year discussion and controversy. The gonadotropin-releasing hormone (GnRH) is a hypothalamic hormone responsible for the releasing of gonadotropins. Due to its pulsatile fashion to induce FSH secretion, it was proposed that a continuous saturation of the receptor by synthetic GnRH analogues (GnRHa) could decrease the gonadotropins release and, therefore, could maintain the ovarian follicular pool at immature stages. Once it was suggested that initial stage follicles were less affected by alkylating agents, the women capacity to conceive could then be preserved. By a multiple approach study design, including histological, immunohistochemical, in vitro and in vivo assays in a mouse model, our group intended to better understand the potential preventive effect of GnRHa on the ovaries exposed to chemotherapy and to evaluate the efficiency of GnRH agonists (AGOs) and antagonists (ANTs) in this indication. Our results suggest, so far, that AGOs (triptorelin) and ANTs (cetrorelix) are not efficient to prevent the follicular depletion induced by a cyclophosphamide (Cy) treatment. Nevertheless, the fertility follow-up, until now, seems to show that the birth rate is not affected by neither Cy nor combined Cy-GnRHa treatment, suggesting that the mouse experimental model is not yet optimal. |
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| Autores principais: | Madureira, Márcio André Gonçalves, 1988- |
| Assunto: | Quimioterapia Fertilidade Ovários Teses de mestrado - 2012 |
| Ano: | 2012 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Recent advances in cancer treatment field allowed significant increase in the survival rate of patients. However, the patients have commonly faced long-term adverse effects that severly affected the quality of life, specially concerning their fertility. It is established that radio- and chemotherapy treatments can cause a reduction of the ovarian reserve, resulting in a 40-60% rate of premature ovarian failure (POF) in women exposed to these treatments. In order to decrease POF risks, several fertility preservation options were developed: reduction of the exposure to gonadotoxic agents, gametes or embryos cryopreservation, oocyte donation, ovarian tissue cryopreservation and transplant, or a pharmacological protection of the ovaries during chemotherapy. While the last one appears as a less invasive and promising procedure, the studies and clinical trials continue to show inconsistent results, raising an almost 30-year discussion and controversy. The gonadotropin-releasing hormone (GnRH) is a hypothalamic hormone responsible for the releasing of gonadotropins. Due to its pulsatile fashion to induce FSH secretion, it was proposed that a continuous saturation of the receptor by synthetic GnRH analogues (GnRHa) could decrease the gonadotropins release and, therefore, could maintain the ovarian follicular pool at immature stages. Once it was suggested that initial stage follicles were less affected by alkylating agents, the women capacity to conceive could then be preserved. By a multiple approach study design, including histological, immunohistochemical, in vitro and in vivo assays in a mouse model, our group intended to better understand the potential preventive effect of GnRHa on the ovaries exposed to chemotherapy and to evaluate the efficiency of GnRH agonists (AGOs) and antagonists (ANTs) in this indication. Our results suggest, so far, that AGOs (triptorelin) and ANTs (cetrorelix) are not efficient to prevent the follicular depletion induced by a cyclophosphamide (Cy) treatment. Nevertheless, the fertility follow-up, until now, seems to show that the birth rate is not affected by neither Cy nor combined Cy-GnRHa treatment, suggesting that the mouse experimental model is not yet optimal. |
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