Effect of cumulin and super-GDF9 in standard and biphasic mouse IVM

Purpose In vitro maturation (IVM) is a technology that generates mature oocytes following culture of immature cumulus-oocyte complexes (COC) in vitro. IVM is characterized by minimal patient stimulation, making it attractive for certain patient groups. Recently, a biphasic IVM system, capacitation (CAPA)-IVM, has shown improved clinical outcomes relative to standard IVM; however, it remains less efficient than IVF. This study assessed whether supplementation of CAPA-IVM culture media with the novel TGFβ superfamily proteins cumulin and super-GDF9 improves subsequent mouse embryo development. Methods Immature mouse COCs were cultured by standard IVM or biphasic IVM ± cumulin or super-GDF9. Results Both cumulin and super-GDF9 in standard IVM significantly improved day-6 blastocyst rate (53.9% control, 73.6% cumulin, 70.4% super-GDF9; p = 0.006; n = 382–406 oocytes). Cumulin or super-GDF9 in CAPA-IVM did not alter embryo yield or blastocyst cell allocation in an unstimulated model. Moreover, cumulin did not alter these outcomes in a mild PMSG stimulation model. Cumulin in CAPA-IVM significantly increased cumulus cell expression of cumulus expansion genes ( Ptgs2 , Ptx3 , Adamts1 , Gfat2 ) and decreased Lhr expression relative to control. However, cumulin-induced mRNA expression of cumulus cell ( Ptgs2 , Ptx3 ) and oocyte genes ( Gdf9 , Bmp15 , Oct4 , Stella ) in CAPA-IVM remained significantly lower than that of in vivo matured cells. Conclusion Cumulin did not provide an additional beneficial effect in biphasic IVM in terms of blastocyst yield and cell allocation; however in standard IVM, cumulin and super-GDF9 significantly improve oocyte developmental competence.