Human induced pluripotent stem cell-derived ovarian support cell co-culture improves oocyte maturation in vitro after abbreviated gonadotropin stimulation

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. ### Competing Interest Statement The majority of this work was performed by employees and shareholders of the for-profit biotechnology company Gameto Inc. C.C.K., S.P., M.M., A.G., B.P., K.S.P., G.R., A.D.N., are listed on a patent covering the use of OSCs for in vitro maturation, Non-provisional Patent Application No. 63/492,210. Additionally, C.C.K. and K.W. are listed on two patents covering the use of OSCs for in vitro maturation: Non-provisional Patent Application No. 17/846,845 and U.S. Non-provisional Patent Application No. 17/846,725. C.C.K., M.P.S. and P.C. additionally are listed on a patent for the TF-directed production of granulosa-like cells from stem cells: U.S. Provisional Application No. 63/326,640.