Abstract Study question Are neonatal outcomes normal up to 3 years of ages from the transfer of blastocysts derived from mono-pronuclear(1PN) zygotes? Summary answer There was no effect on growth up to 3 years of ages in babies born from 1PN-implanted blastocysts. What is known already In human ART, 1PN zygotes are observed at low rates. We have previously reported that 80.7% of 1PN zygotes had a biparental chromosome using a Live-Cell imaging technique, and some of these developed to the blastocyst stage (Tokoro et al. ASRM 2013). Furthermore, we have reported that these blastocysts can result in a viable pregnancy and healthy live birth (Tsuji et al. ASRM 2020), and there was no effect on growth up to 18-months (Tsuji et al. ESHRE 2021). However, there is no information on the long-term prognosis of babies derived from1PN-zygotes. Study design, size, duration This was a retrospective study which included 86 cases where there was a live birth after single embryo transfer of a blastocyst derived from 1PN zygote. The incidence of birth defects, birth weight were recorded as well as a physical development survey of 19 children who responded to a 3-years follow-up survey. The time period was 108 months (January 2013 to December 2021). Participants/materials, setting, methods Patients seeking fertility treatment at an established private IVF clinic. We compared the birth weight, 3-years old height and weight of children born from 1PN zygotes with data from a control, 2PN group. Statistical significance was determined using the t-test (level of P < 0.05). Main results and the role of chance The incidence of birth defects in 1PN embryo-derived infants was 1.2% (1/86). The average birth weight of boys in the 1PN group was 3147.6+/-408.7 g, which was not significantly different from 3070.5+/-479.5 g in the 2PN group. In girls, the average birth weight was 3048.1+/-510.7 g in the 1PN group, which was not significantly different from the 2PN group (2966.2+/-462.7 g). The average height at 18-months, was 81.3+/-2.5 cm vs 80.9+/-3.4 cm for boys; 79.5+/-2.2 cm vs 79.5+/-3.0 cm for girls in the 1PN and 2PN groups, respectively. The average body weights of the 1PN and 2PN groups were 11.0+/-1.2 kg vs 10.8+/-1.1 kg for boys; 9.8+/-1.0 kg vs 10.2+/-1.1 kg for girls, respectively. The average height at 3-years, was 95.2+/-3.1 cm vs 93.8+/-4.5 cm for boys; 91.5+/-2.9 cm vs 92.5+/-4.9 cm for girls in the 1PN and 2PN groups, respectively. The average body weights of the 1PN and 2PN groups were 14.7+/-1.2 kg vs 14.1+/-1.5 kg for boys; 13.2+/-1.9 kg vs 13.6+/-1.5 kg for girls, respectively. There was no significant difference in average height and weight up-to the 3-years follow-up survey. Limitations, reasons for caution The incidence of 1PN- zygotes that develop to blastocysts resulting in births is low and the study was limited to cases of single blastocyst embryo transfer. Wider implications of the findings The incidence of congenital anomalies in Japan is around 1.7 to 2%, and the incidence was similar in the 1PN group. Also, there was no difference in 3-years follow-up survey of the 1PN compared with the 2PN. These data are reassuring for the clinical utility of 1PN derived embryos. Trial registration number not applicable
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