Assisted reproductive technologies (ART) have significantly impacted fertility treatment worldwide through innovations such as in vitro fertilization (IVF) and in vitro maturation (IVM). Currently, traditional controlled ovarian hyperstimulation combined with IVF or intracytoplasmic sperm injection (ICSI) is considered the most efficacious form of ART and, therefore, it is used far more frequently than abbreviated ovarian stimulation combined with IVM and subsequent IVF/ICSI as a treatment for infertility or genetic problems. During this process, oocyte maturation happens in the ovary, driven by a lengthy stimulation protocol of gonadotropin injections. Despite that, a significant number of the oocytes retrieved during typical IVF cycles can be immature and are therefore excluded from further treatments. In vitro maturation and fertilization appear as a solution to improve the outcome of mature oocytes for patients, however this is not yet routinely used in the clinic due to suboptimal maturation rates despite being highly utilized in animal models. We recently reported the development of human ovarian support cells (OSCs) generated from human induced pluripotent stem cells (hiPSCs) and demonstrated their ability to recapitulate dynamic ovarian function in vitro. Here we investigate the utilization of these OSCs in an in vitro co-culture system to mimic the ovarian environment and promote IVM to rescue denuded immature oocytes derived from conventional gonadotropin stimulated cycles. We find that OSC-IVM significantly improves oocyte maturation rates compared to spontaneous maturation in media matched controls. Additionally, oocytes matured in OSC-IVM are transcriptionally more similar to conventional IVF MII oocytes than those that spontaneously matured in media controls. Together, these findings demonstrate the efficacy of a novel approach to improve the outcome of matured MII oocytes in modern ART practice by leveraging an optimized IVM system that better mimics the ovarian environment in vitro.

Assisted reproductive technologies (ART) have significantly impacted fertility treatment worldwide through innovations such as in vitro fertilization (IVF) and in vitro maturation (IVM). IVM holds promise as a technology for fertility treatment in women who cannot or do not wish to undergo conventional controlled ovarian hyperstimulation (COH). However, IVM has historically shown highly variable performance in maturing oocytes and generating oocytes with strong developmental capacity. Furthermore, novel IVM approaches are usually highly limited to use in cycles lacking human chorionic gonadotropin (hCG) triggers, which is not standard practice in fertility treatment. We recently reported the development of ovarian support cells (OSCs) generated from human induced pluripotent stem cells (hiPSCs) that recapitulate dynamic ovarian function in vitro. Here we investigate the potential of these OSCs in an IVM co-culture system to improve the maturation of human cumulus-enclosed immature oocytes retrieved from abbreviated gonadotropin stimulated cycles. We reveal that OSC-IVM significantly improves maturation rates compared to existing IVM systems. Most importantly, we demonstrate that OSC-assisted IVM oocytes are capable of robust euploid blastocyst formation, a key marker of their clinical utility. Together, these findings demonstrate a novel approach to IVM with broad applicability to modern ART practice.