O-105 Reconsidering the clinical value of 1PN-derived embryos: a systematic review and meta-analysis

Abstract Study question Are monopronucleated (1PN)-derived embryos euploid and suitable for embryo transfer? Summary answer 1PN-derived embryos showed lower biological and clinical outcomes compared to 2PN-derived embryos, but similar euploidy, live-birth with euploid blastocyst transfer, and neonatal malformations. What is known already In assisted reproductive treatments (ARTs), normal fertilization typically results in zygotes displaying two pronuclei (2PN). However, some oocytes exhibit abnormal fertilization patterns, i.e. a single pronucleus “1PN”. The 1PN-derived embryos have often been used with caution due to concerns about their compromised developmental competence, as they are frequently associated with an increased risk of polyploidy. Currently, guidelines from the European Society of Human Reproduction and Embryology affirmed that 1PN-derived embryos should not be recommended for clinical use. Nonetheless, several studies have reported healthy live birth from 1PN embryos. Study design, size, duration This systematic review and meta-analysis was conducted according to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. A systematic literature search was performed up to 31 November 2024. PubMed, Embase, and SCOPUS were systematically searched for peer-reviewed original papers using relevant keywords and Medical Subject Heading (MeSH) terms: (“1PN” OR “monopronucleated”) AND (“pregnancy” OR “live birth” OR “euploidy” OR “clinical outcomes” OR “blastulation rate” OR “embryo quality” OR “embryo development”). Participants/materials, setting, methods Studies assessing developmental competence and clinical outcomes from 1PN-derived embryos were included. The risk of bias was evaluated using the Newcastle-Ottawa Scale. The primary outcome was live-birth. Secondary outcomes included, cleavage, blastulation, euploidy, clinical pregnancy, miscarriage, and malformation rates. Odds ratios (OR, 95%CI) were calculated by applying a random effects model. Sub-analyses were performed for: i) 1PN-derived embryos from a time-lapse system; ii) euploid blastocyst transfer; iii) 1PN-derived embryos from ICSI vs conventional IVF. Main results and the role of chance A total of 20 studies were included in the meta-analysis. 1PN-derived embryos showed significantly reduced cleavage [OR = 0.17 95%CI (0.12-0.24), p-value<0.00001], blastulation [OR = 0.25 95%IC (0.17-0.36, p-value<0.00001], clinical pregnancy [OR = 0.73 95%CI (0.62-0.87), p-value=0.0002], and live birth rates [OR = 0.76 95%CI (0.62-0.94), p-value= 0.01] compared to 2PN-derived embryos. No significant differences were observed in euploidy rate [OR = 0.98 95%CI (0.40-2.38),p-value=0.96], good quality embryos [OR = 0.86 95%CI (0.26-2.79),p-value=0.68], good quality blastocyst [OR = 0.44 95%CI (0.18-1.07),p-value=0.07], malformation rate [OR = 1.37 95%CI (0.57-3.31),p-value=0.48], miscarriage rate [OR = 1.00 95% CI (0.71-1.41), p-value=1.00], and low birthweight [OR = 0.90 95%IC (0.44-1.86), p-value=0.78]. A higher risk of polyploidy was found in 1PN-derived embryos [OR = 2.88 95%IC (0.87-9.48), p-value=0.08], although not statistically significant. No differences in clinical pregnancy and live birth rates were observed following euploid blastocyst transfer [OR = 0.71, 95% CI (0.36–1.43), p-value=0.34] and [OR = 0.65, 95% CI (0.41–1.02), p-value=0.06], respectively. A significant reduction in the blastulation rate was also observed in 1PN-derived embryos analyzed using time-lapse technology [OR = 0.16, 95% CI (0.09–0.26), p-value<0.00001]. Interestingly, we found a significant reduction in pregnancy and live birth rates for 1PN-derived embryos from ICSI compared to 1PN-derived embryos from cIVF [OR = 0.43 95%CI (0.23-0.80), p-value=0.007] and [OR = 0.47 95%CI (022-1.01), p-value=0.05]. Limitations, reasons for caution The major limitation of this analysis is represented by the observational nature of the studies (prospective or retrospective) included, but they are the only source of evidence available in the literature. Furthermore, we observed heterogeneity between studies; to compensate for this limitation, we adopted a conservative approach using random-effects models. Wider implications of the findings Although 1PN-derived embryos exhibited lower embryo development, they showed potential for healthy live births, particularly when euploid. Howewer, due to the risk of polyploidy, their use should be restricted to PGT-A cycles. These findings suggest the development of more inclusive and flexible guidelines, potentially improving cumulative success rates. Trial registration number No

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