Progress in the Approach to In Vitro Maturation: Biphasic (Capacitation) In Vitro Maturation

Background: The clinical utility of early in vitro maturation (IVM) protocols was limited, largely due to asynchronous maturation of oocytes resulting in compromised cytoplasmic competence and lower rates of fertilisation, embryo development, and implantation. However, advances in understanding of oocyte biology and follicular physiology have contributed to the development of biphasic IVM systems, which include a pre-maturation (pre-IVM) phase designed to maintain meiotic arrest and preserve cumulus-oocyte communication, followed by the conventional IVM phase. In current research and practice, biphasic IVM is epitomised by capacitation (CAPA)-IVM. Objective: To provide an overview of the principles of biphasic IVM, present relevant data from preclinical and clinical studies, and examine the current and future clinical applications of biphasic CAPA-IVM. Results: The main indications for CAPA-IVM in current clinical practice are polycystic ovary syndrome and a high antral follicle count. In these populations, CAPA-IVM has been shown to result in acceptable fertility outcomes, does not cause ovarian hyperstimulation syndrome, and there appear to be no concerns about childhood development up to 24 months of age. Biphasic IVM also has a role in fertility preservation for women with cancer. Other possible clinical indications include gonadotropin-resistant ovary syndrome, normo-ovulatory women, general fertility preservation (“social egg freezing”), and delivery of assisted reproductive technology solutions in resource-limited or pandemic settings, where simple, safe, and predictable protocols are advantageous. Conclusions: Biphasic IVM has the potential to become an integral component of assisted reproductive technology (ART) offerings, with the potential to further refine and improve biphasic IVM protocols.