Oocyte in vitro maturation (IVM) makes use of oocytes from patients and animals that have received minimal gonadotrophin stimulation. Whilst this brings many advantages to patients, this typically means oocytes are collected from small – medium sized (4- 12 mm) antral follicles, and these oocytes are still in the process of acquiring the capacity to support subsequent embryo development. Oocyte developmental competence is established during the course of folliculogenesis. This process is at least partially regulated by the somatic compartment of the follicle. However, an essential somatic signalling network required for natural oocyte maturation and ovulation, the epidermal growth factor (EGF) signalling cascade, is grossly underdeveloped in cumulus-oocyte complexes (COCs) from small antral follicles. A broader objective of my research program is to restore in vitro, as far as possible, the natural processes that occur during oocyte maturation in vivo.
Using unstimulated animal models, we have discovered that cumulus cells from small antral follicles are EGF-peptide unresponsive (1). EGF signalling can be promoted in cumulus cells of COCs from small antral follicles by in vitro exposure to specific forms of the oocyte-secreted factors; BMP15, GDF9 or cumulin, in combination with careful management of oocyte cAMP levels (1-3). Enabling the EGF receptor signalling network using this approach leads to improvements in oocyte quality and hence blastocyst yield (1, 2), particularly with the use of cumulin (3). We propose that development of a functional EGF receptor signalling network in cumulus cells constitutes a key developmental milestone for the oocyte (1, 2). Translating these animal findings into improvements in human reproductive medicine is a major challenge. By partnering with research intensive IVF clinics we have been able to use this knowledge to gradually improve human IVM outcomes. This research has implications for improving the efficacy and clinical uptake of clinical IVM and fertility preservation.