Abnormally fertilized oocytes can result in healthy live births: improved genetic technologies for preimplantation genetic testing can be used to rescue viable embryos in in vitro fertilization cycles

Objective: To test whether abnormally fertilized oocyte (AFO)-derived blastocysts are diploid and can be rescued for clinical use.Design: Longitudinal-cohort study from January 2015 to September 2016 involving IVF cycles with preimplantation genetic testing for aneuploidy (PGT-A). Ploidy assessment was incorporated whenever a blastocyst from a monopronuclear (1PN) or tripronuclear zygote (2PN + 1 smaller PN; 2.1 PN) was obtained.Setting: Private IVF clinics and genetics laboratories.Patient(s): A total of 556 women undergoing 719 PGT-A cycles.Intervention(s): Conventional chromosome analysis was performed on trophectoderm biopsies by quantitative polymerase chain reaction. For AFO-derived blastocysts, ploidy assessment was performed on the same biopsy with the use of allele ratios for hetorozygous SNPs analyzed by means of next-generation sequencing (1: 1 = diploid; 2: 1 = triploid; loss of heterozygosity = haploid). Balanceddiploid 1PN-and 2.1PN-derived blastocysts were transferred in the absence of normally fertilized transferable embryos.Main Outcome Measure(s): Ploidy constitution and clinical value of AFO-derived blastocysts in IVF PGT-A cycles.Result(s): Of the 5,026 metaphase II oocytes injected, 5.2% and 0.7% showed 1PN and 2.1PN, respectively. AFOs showed compromised embryo development (P<. 01). Twenty-seven AFO-derived blastocysts were analyzed for ploidy constitution. The 1PN-derived blastocysts were mostly diploid (n = 9/ 13; 69.2%), a few were haploid (n = 3/ 13; 23.1%), and one was triploid (n = 1/ 13; 7.7%). The 2.1PN-derived blastocysts were also mostly diploid (n = 12/ 14; 85.7%), and the remainder were triploid. Twenty-six PGT-A cycles resulted in one or more AFO-derived blastocysts (n = 26/ 719; 3.6%). Overall, eight additional balanced-diploid transferable embryos were obtained from AFOs. In three cycles, the only balanced-diploid blastocyst produced was from an AFO (n = 3/ 719; 0.4%). Three AFO-derived live births were achieved: one from a 1PN zygote and two from 2.1PN zygotes.Conclusion(s): Enhanced PGT-A technologies incorporating reliable ploidy assessment provide an effective tool to rescue AFO-derived blastocysts for clinical use. ((C) 2017 by American Society for Reproductive Medicine.)