Invited Talk ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Development of a new form of IVM and path to clinical application (#161)

Robert Gilchrist 1
  1. Fertility & Research Centre, Discipline of Women’s Health, School of Clinical Medicine, University of New South Wales, Sydney, NSW, AUS

Oocyte in vitro maturation (IVM) is a technique that generates embryos using oocytes from patients that have received minimal or no gonadotrophin stimulation. Whilst this brings many advantages to patients, this typically means oocytes are collected from small – medium sized (4- 12 mm) antral follicles. These oocytes are under-developed, and yet removal of these from the follicle and culture in vitro leads to spontaneous oocyte meiotic maturation, without the benefit of the physiological signals that naturally induce oocyte maturation at ovulation. Using animal models, over the past decade seminal advances have been made in our understanding of the fundamental mechanisms regulating oocyte maturation in vivo. Most IVM systems, as practised clinically today, typically do not recapitulate these key cellular processes, possibly accounting for the lower efficiency of IVM compared to IVF. A key objective of modern approaches to IVM is to restore in vitro, as far as possible, the natural processes that occur during oocyte maturation in vivo. One strategy to achieve this in IVM is to: 1) prevent spontaneous meiotic resumption at oocyte collection using phosphodiesterase inhibitors, then 2) artificially maintain or elevate cumulus-oocyte complex (COC) cAMP levels, and finally to 3) induce oocyte meiotic resumption using EGF-like peptides. This typically requires the use of biphasic or 2-step IVM systems. One such biphasic IVM system is called capacitation-IVM (CAPA-IVM), as the oocyte is “capacitated” for development in vitro. CAPA-IVM uses the follicle’s natural oocyte meiotic inhibitor, c-type natriuretic peptide (CNP), in the pre-IVM phase, and amphiregulin as the oocyte meiotic inducer in the second IVM phase. Such biphasic-IVM systems typically lead to subsequent improvements in embryo yield compared to standard IVM, and indeed this is the case for CAPA-IVM. Several pilot RCTs and a large RCT of CAPA-IVM vs conventional IVF have been completed, and CAPA-IVM is now practiced in a few centres globally, including in our own centre in Sydney. The development and clinical application of modern IVM systems, built on decades of animal discovery research, is an example of successful bench-to-bedside translational research. IVM is now classified as a routine (non-experimental), safe, minimally invasive procedure for the treatment of infertility in specific patient groups and for fertility preservation in female cancer patients.