Fertility preservation in cancer patients : from cryopreserved ovarian tissue to isolated follicles
(2014)
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- Ovarian tissue cryopreservation (OTC) and transplantation is a well established procedure to preserve fertility in young cancer patients. Although more than 30 live births have been achieved in adult patients so far, there are some concerns that need to be addressed when contemplating this approach: (i) Do ovarian follicles in cryopreserved ovarian tissue from prepubertal patients have the capacity to survive and develop properly after transplantation and exogenous stimulation? (ii) Is there a risk of reintroducing malignant cells after autotransplantation of cryopreserved ovarian tissue from patients with advanced-stage breast cancer? (iii) Would it be possible to offer an alternative option to patients who cannot undergo transplantation of frozen-thawed ovarian tissue? The aim of this thesis was to answer these specific questions. For this reason, it was divided into three parts: Transplantation of cryopreserved ovarian tissue from prepubertal patients After 21 weeks of transplantation to immunodeficient mice and exogenous hormonal stimulation, prepubertal ovarian follicles were able to survive and grow up to the antral stage, proving their sensitivity to gonadotropins. Follicular density was high in prepubertal ovarian tissue and remained so after transplantation, with a preserved primordial follicle pool, suggesting a longer lifespan of grafted ovarian tissue. Safety of ovarian tissue transplantation: the specific issue of breast cancer patients While transplantation of frozen-thawed ovarian tissue from early-stage breast cancer patients is reportedly to be safe, our study with advanced-stage breast cancer patients confirms that there is a potential risk of reimplanting metastatic cells in these subjects, as some cells expressing the MGB2 gene were detected after grafting. However, the real malignant potential of these cells is not known, as transplantation of frozen-thawed ovarian tissue from advanced-stage breast cancer patients to immunodeficient mice did not evidence tumor development after 6 months of grafting. Artificial ovary For patients running the potential risk of ovarian invasion by malignant cells, a safe alternative would be transplantation of isolated ovarian follicles, encapsulated in a biocompatible matrix. In order to develop a biodegradable ovary with a fibrin-based scaffold through establishment of a central composite design evaluating different formulations of fibrinogen and thrombin (F/T), two combinations (F12.5/T1 and F25/T4) were identified. These concentrations appear to promote survival and proliferation of isolated human ovarian cells (OCs), with high degradation of the fibrin network and positive evolution of stromal cell density. Isolated murine OCs and follicles in these two F/T combinations were able to successfully survive and develop up to the antral stage after one week of autografting. In conclusion, OTC is the only available option to preserve ovarian tissue in prepubertal girls and when gonadotoxic treatments cannot be delayed. When there is a risk of reimplanting malignant cells, a fibrin-based matrix appears to be a promising candidate for construction of a biodegradable scaffold to transplant isolated ovarian follicles and OCs (artificial ovary).
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Luyckx, V. (2014). Fertility preservation in cancer patients : from cryopreserved ovarian tissue to isolated follicles. https://hdl.handle.net/2078.5/197272