Is the pre-antral ovarian follicle the 'holy grail' for female fertility preservation?

Fertility preservation is not only a concern for humans with compromised fertility after cancer treatment. The preservation of genetic material from endangered animal species or animals with important genetic traits will also greatly benefit from the development of alternative fertility preservation strategies. In humans, embryo cryopreservation and mature-oocyte cryopreservation are currently the only approved methods for fertility preservation. Ovarian tissue cryopreservation is specifically indicated for prepubertal girls and women whose cancer treatment cannot be postponed. The cryopreservation of pre-antral follicles (PAFs) is a safer alternative for cancer patients who are at risk of the reintroduction of malignant cells. As PAFs account for the vast majority of follicles in the ovarian cortex, they represent an untapped potential, which could be cultivated for reproduction, preservation, or research purposes. Vitrification is being used more and more as it seems to yield better results compared to slow freezing, although protocols still need to be optimized for each specific cell type and species. Several methods can be used to assess follicle quality, ranging from simple viability stains to more complex xenografting procedures. In vitro development of PAFs to the pre-ovulatory stage has not yet been achieved in humans and larger animals. However, in vitro culture systems for PAFs are under development and are expected to become available in the near future. This review will focus on recent developments in (human) fertility preservation strategies, which are often accomplished by the use of in vitro animal models due to ethical considerations and the scarcity of human research material.