Is it time to reconsider how to manage immature oocytes?

Immature oocytes obtained after ovarian stimulation can reach the metaphase II stage through in vitro maturation (IVM) and subsequently be microinjected, cleaved in vitro and give rise to a live birth. As some publications have suggested embryos derived from IVM oocytes lead to poor reproductive outcomes, immature oocytes are routinely discarded in most infertility centers. Since embryo culture conditions have improved in the last years, how to manage immature oocytes should be re-evaluated. Our study aimed to compare the outcomes of human embryos derived from IVM oocytes against those obtained by their IVO sibling oocytes. This retrospective study includes 63 cycles of patients who underwent an ICSI attempt at our center between May 2021 and December 2022. Following internal guidelines, when less than 6 oocytes were collected and/or less than 50% were mature, IVM was performed if immature oocytes were available. Overall, 489 oocytes were retrieved from 63 patients (38.7±3.3 years). After denudation, the maturity was classified as germinal vesicle (GV), metaphase I (MI), or metaphase II (MII). MII oocytes were considered in vivo mature oocytes (IVO) and were microinjected. The following day, the immature oocytes that reached the MII stage were microinjected. All embryos were cultured until day 5-6 of development. Fertilization, cleavage, blastulation and euploidy rates were compared between IVM and IVO. Initially, 171 oocytes (35.0%) were IVO, 51 (10.4%) were MI, 208 (42.5%) were GV, and the remaining 59 (12.2%) were atretic or empty zona pellucidas. After incubation, MI oocytes were more prone to reach the MII stage (n=35, 68.6%) than GV oocytes (n= 77, 37%), p<0.005. The fertilization rates for the MII coming from MI, GVs and IVO oocytes were 54.3%, 57.1% and 75.4%, respectively (p<0.05). The cleavage rates were similar in embryos coming from MI, GVs and IVO (100%, 95.4%, 99.2%, N.S.). Lower blastulation rates were observed in the embryos coming from MI and GVs vs. the rate obtained in the IVO group (15.8%, 27.3%, 59.7%, p<0.005). Overall, 14 patients (22.2%) obtained 1 additional blastocyst from IVM oocytes in their cohort, and in 3 of them (21.4%) the only usable blastocyst was generated by IVM. PGT was performed in 39 cycles due to Advanced Maternal Age. In these cycles, 2 blastocysts coming from MI were biopsied and both were chromosomally abnormal (100%). 8 blastocysts derived from GVs were biopsied, and 4 of them (50%) were aneuploid. A total of 10 blastocysts coming from IVO oocytes were analyzed, and 3 were chromosomally abnormal (30.0%). IVM oocytes lead to lower fertilization and blastulation rates, although they have similar cleavage and aneuploidy rates as their sibling embryos coming from IVO oocytes. Since there is a likelihood of obtaining euploid blastocysts from IVM oocytes, immature oocytes should not be discarded when the number of available oocytes is small.