Author:
Giovannini Alexa,Piechota Sabrina,Marchante Maria,Potts Kathryn S,Rockwell Graham,Paulsen Bruna,Noblett Alexander D,Estevez Samantha L,Figueroa Alexandra B,Aschenberger Caroline,Kelk Dawn A,Forti Marcy,Marcinyshyn Shelby,Barrachina Ferran,Wiemer Klaus,Sanchez Marta,Belchin Pedro,Smela Merrick Pierson,Fortuna Patrick R.J.,Chatterjee Pranam,McCulloh David H,Copperman Alan,Ordonez-Perez Daniel,Klein Joshua U,Kramme Christian C
Abstract
Structured AbstractPurposeTo determine if rescuein vitromaturation (IVM) of human oocytes can be improved by co-culture with ovarian support cells (OSCs) derived from human induced pluripotent stem cells (hiPSCs).MethodsFertility patients undergoing conventional ovarian stimulation for oocyte cryopreservation or IVF donated denuded immature germinal vesicle (GV) and metaphase I (MI) oocytes for research, which were allocated between either the control or intervention cultures. Fertility patients aged 25 to 45 years old donated immature oocytes under informed consent, with no additional inclusion criteria. The 24-28 hour OSC-IVM culture condition was composed of 100,000 OSCs in suspension culture with human chorionic gonadotropin (hCG), recombinant follicle stimulating hormone (rFSH), androstenedione and doxycycline supplementation. The Media-IVM control lacked OSCs and contained the same supplementation. Primary endpoints consisted of MII formation rate and morphological quality assessment. Additionally, metaphase spindle assembly location and oocyte transcriptomic profiles were assessed compared toin vivomatured MII oocyte controls.ResultsWe observed significant improvement in maturation outcome rates (∼1.7X) for oocytes that underwent IVM with OSCs. Specifically, the OSC-IVM group yielded a maturation rate of 62% ± 5.57% SEM versus 37% ± 8.96% SEM in the Media-IVM (p=0.0138, unpairedt-test). Oocyte morphological quality between OSC-IVM and the Media-IVM control did not significantly differ. OSC-IVM resulted in MII oocytes with no instances of spindle absence and no significant difference in position compared toin vivomatured IVF-MII controls. OSC-IVM treated MII oocytes display a transcriptomic signature significantly more similar to IVF-MII controls than the Media-IVM control MII oocytes did.ConclusionThe novel OSC-IVM platform is an effective tool for rescue maturation of human oocytes obtained from conventional stimulation cycles, yielding oocytes with improved nuclear and cytoplasmic maturation. OSC-IVM shows broad utility for application in modern fertility treatment to improve the total number of available mature oocytes for fertility treatment.
Publisher
Cold Spring Harbor Laboratory