Implications of Nonphysiological Ovarian Primordial Follicle Activation for Fertility Preservation

In recent years, ovarian tissue cryopreservation has rapidly developed as a successful method for preserving the fertility of girls and young women with cancer or benign conditions requiring gonadotoxic therapy, and is now becoming widely recognized as an effective alternative to oocyte and embryo freezing when not feasible. Primordial follicles are the most abundant population of follicles in the ovary, and their relatively quiescent metabolism makes them more resistant to cryoinjury. This dormant pool represents a key target for fertility preservation strategies as a resource for generating high-quality oocytes. However, development of mature, competent oocytes derived from primordial follicles is challenging, particularly in larger mammals. One of the main barriers is the substantial knowledge gap regarding the regulation of the balance between dormancy and activation of primordial follicles to initiate their growing phase. In addition, experimental and clinical factors also affect dormant follicle demise, while the mechanisms involved remain largely to be elucidated. Moreover, most of our basic knowledge of these processes comes from rodent studies and should be extrapolated to humans with caution, considering the differences between species in the reproductive field. Overcoming these obstacles is essential to improving both the quantity and the quality of mature oocytes available for further fertilization, and may have valuable biological and clinical applications, especially in fertility preservation procedures. This review provides an update on current knowledge of mammalian primordial follicle activation under both physiological and nonphysiological conditions, and discusses implications for fertility preservation and priorities for future research.