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Since the first publications on the artificial ovary, many advances have been made. At that time, no studies had yet proved the feasibility of the concept, so it might have appeared provocative to unable to propose this option as a future fertility restoration approach for women unable to undergo ovarian tissue transplantation. Today, different artificial ovary prototypes demonstrate that this technique is able to restore both endocrine and reproductive functions in a murine model, producing healthy pups. However, with a view to future clinical application, further studies with human ovarian tissue and human follicles are essential. The aim of this chapter is to highlight the latest developments and advances in the field, as well as future directions for prompt translation to a clinical setting.
According to the European Society of Human Reproduction and Embryology (ESHRE) Working Group on Oocyte Cryopreservation , between 2010 and 2014, cancer patients in Europe underwent similar numbers of ovarian tissue cryopreservation procedures (~4,400) and oocyte cryopreservation procedures (~3,800). This milestone in the field of ovarian tissue cryopreservation is responsible for a new surge of interest in primordial follicles and their requirements for survival and development, as they represent more than 90% of the follicle population to be cryopreserved. When patients cannot have their frozen-thawed ovarian tissue reimplanted due to the risk of transmission of malignant cells, these follicles can be isolated and grafted inside a bioengineered ovary (see Chapter 36) or grown in vitro (see Chapter 31). We will focus on the latter strategy, more specifically on the main elements that primordial follicles need to survive in vitro.
Detection of minimal residual disease in ovarian tissue was carried out by histology, real-time quantitative polymerase chain reaction (RT-qPCR) and long-term xenografting. To avoid transferring malignant cells together with grafted ovarian tissue, ovarian follicles may be isolated from the surrounding tissue and then either cultured for in vitro follicle maturation or transplanted directly into the recipient. Transplantation of frozen-thawed isolated primordial follicles has been successfully carried out in mice, yielding normal offspring. After isolation and recovery of human follicles, the developmental capacity and viability of these isolated human follicles are evaluated after transplantation. New matrices have been developed based on hydrogels, foams or natural polymers which could be suitable to nestle the isolated follicles and form a kind of artificial ovary before grafting to the patient. This would allow patients at risk of ovarian metastasis to benefit also from ovarian tissue cryopreservation and transplantation.