Artificial ovary: where are we?

In recent years, advanced chemo/radiotherapeutic treatments have led to high survival rates in cancer patients, giving rise to new issues for cancer survivors. Indeed, one major concern is future fertility in these women, since they may face premature ovarian failure. For this reason, different strategies have been proposed to preserve their fertility. When gonadotoxic treatment cannot be delayed, ovarian tissue cryobanking appears to be the most promising way of preserving a patient’s fertility. Moreover, this is the sole means of safeguarding fertility in prepubertal girls. Autotransplantation is the only option able to reestablish ovarian function from cryopreserved ovarian tissue in cancer survivors at present. So far, this technique has led to successful ovarian function restoration and up to 40 pregnancies in a number of centers around the world. However, there is a legitimate concern regarding the possible presence of malignant cells in frozen-thawed fragments, which could provoke a recurrence of the primary disease after reimplantation. Although many types of cancer never metastasise to the ovaries, leukaemia is systemic in nature and poses a greater threat to the patient, while breast cancer and some types of lymphoma are classed as moderate risk. For these patients, a safer alternative could be grafting of isolated preantral follicles, as these structures are enclosed in a basement membrane that prevents direct contact between follicular cells and capillaries, white blood cells, and nerve processes. Since ovarian cells (OCs) are essential for follicle development and neovascularization, autologous OCs should be grafted together with isolated follicles. To replace the original ovarian structure, a transplantable artificial ovary (TAO) should be created in order to encapsulate and protect the isolated follicles and OCs. As in case of a natural ovary, the main goal of the TAO is to offer an environment that allows follicle survival and development. Therefore, a TAO should maintain the original structure of follicles, ensure proper communication between follicles and OCs, preserve their interaction with the extracellular matrix and supply factors involved in follicular survival and development. In other words, the TAO should spatially and temporally mimic the ECM. In order to do so, it should include some design parameters, such as physical support of follicles, porosity, bioactivity, vascularization, interaction with cells, and biodegradability, which are all interconnected and influence each other