Challenging Boundaries in Ovarian Tissue Cryopreservation and Transplantation: From Experimental Insight to Clinical Impact

Abstract

Ovarian tissue cryopreservation (OTC) followed by transplantation (OTT) represents an effective technique for preserving fertility for women undergoing gonadotoxic chemotherapy. With survival rates among cancer patients continuously improving, the demand for reliable fertility preservation options is higher than ever. Although OTC/OTT has resulted in more than 200 reported live births worldwide, several steps still require optimization to maximize graft longevity and functionality. Current cryopreservation protocols vary widely between centres, complicating cross-study comparisons and emphasizing the need for standardized procedures. Besides, OTT carries the potential risk of reintroducing malignant cells. Therefore, it is important to assess this risk for each cancer type and explore ways to limit the number of malignant cells in the graft. Furthermore, the greatest challenge remains the post-transplantation phase, where ischemia-induced follicle loss significantly compromises graft longevity. Numerous experimental interventions have been explored to improve and accelerate vascularization of the graft, including pharmacological interventions and the use of artificial ovaries. While many of these approaches show promising improvements in vascularization, most remain in experimental stages. Future progress will rely on the transition from experimental findings to translational and clinical applications. A multidisciplinary approach combining safe cryopreservation, malignant-cell removal, and advanced transplantation strategies will be key to achieving not only survival but also quality of life for cancer survivors wishing to restore fertility.