Restoring Ovarian Fertility and Hormone Function: Recent Advancements, Ongoing Efforts and Future Applications

Abstract

The last 20 years have seen substantial improvements in fertility and hormone preservation and restoration technologies for a growing number of cancer survivors. However, further advancements are required to fill the gaps for those who cannot use current technologies or to improve the efficacy and longevity of current fertility and hormone restoration technologies. Ovarian tissue cryopreservation (OTC) followed by ovarian tissue transplantation (OTT) offers those unable to undergo ovarian stimulation for egg retrieval and cryopreservation an option that restores both fertility and hormone function. However, those with metastatic disease in their ovaries are unable to transplant this tissue. Therefore, new technologies to produce good-quality eggs and restore long-term cyclic ovarian function are being investigated and developed to expand options for a variety of patients. This mini-review describes current and near future technologies including in vitro maturation, in vitro follicle growth and maturation, bioprosthetic ovaries, and stem cell applications in fertility restoration research by their proximity to clinical application.

Keywords: assisted reproduction technologies; bioprosthetic ovary; fertility preservation; oncofertility; ovarian tissue cryopreservation.

Figure 1.

Fertility preservation and restoration advancements, from the bench to the clinic. Graphical representation of the advancements in fertility restoration from methodologies used currently in the clinic to early preclinical studies. (1) In the clinic: (egg retrieval and freezing; embryo preservation; OTC, ovarian tissue cryopreservation; and IVM, in vitro maturation of cumulus-oocyte-complexes [COCs] collected during OTC). (2) Rounding the mark: optimizing the culture and growth of immature eggs (IVGM, in vitro follicle growth with isolated follicles or in situ within tissue). (3) Ongoing preclinical work: defining the necessary microenvironment needed to engineer a bioprosthetic ovary for humans (ECM, extracellular matrix; soluble factors, paracrine signaling, physical cues, and vascularization).