To discard or not to discard 1PNs? A systematic review and meta-analysis on 291,474 embryos

Unlike embryos that display two pronuclei (2PN), monopronucleated (1PN) embryos are assumed to be haploid and can be routinely discarded. Although there are reports of live births after 1PN embryo transfer, the developmental and clinical prognosis of 1PN embryos has not been systematically evaluated. The aim of this review was to elucidate the developmental, clinical and neonatal outcomes of 1PN embryos compared with 2PN embryos. Twenty-four studies met the inclusion criteria. The blastulation rate was lower in 1PN embryos compared with 2PN embryos [risk ratio (RR) 0.50, 95% CI 0.48-0.51]. The live birth rate was lower in 1PN blastocysts when untested (RR 0.81, 95% CI 0.72-0.90), but was similar after euploidy confirmation by preimplantation genetic testing for aneuploidy (RR 0.85, 95% CI 0.59-1.23). The euploidy rate was comparable in 1PN and 2PN embryos (RR 0.91, 95% CI 0.81-1.02). In a subgroup analysis of untested embryos, 1PN-intracytoplasmic sperm injection (ICSI) blastocysts had a lower live birth rate compared with 2PN-ICSI blastocysts (RR 0.26, 95% CI 0.13-0.50), while no difference was observed with IVF (RR 0.93, 95% CI 0.82-1.06). These results are particularly important for patients with a poor prognosis and limited 2PN embryos, and can aid reproductive professionals to counsel patients on the clinical use of 1PN embryos. Future studies should utilise time-lapse and preimplantation genetic testing technologies for confirmation of diploidy and biparental inheritance. Monopronucleated embryos can be viable, expanding options beyond 2PN embryos.