Clinical outcomes and euploidy rates of embryos derived from zygotes with nonpronuclear (0PN) and monopronuclear (1PN) in IVF or ICSI cycles: a systematic review and meta-analysis

BACKGROUND: During routine fertilization checks, the presence of two pronuclei (2PN) with two polar bodies is generally regarded as normal fertilization. Nonpronuclear (0PN) zygotes often suggest failed fertilization, but some do cleave and develop into viable embryos due to delayed appearances of pronuclei that were originally missed. Monopronuclear (1PN) zygotes may result from a lack of maternal or paternal pronuclei, fusion of pronuclei, or asynchronous appearance of pronuclei. These embryos may sometimes be transferred when no others are available. OBJECTIVE AND RATIONALE: Current evidence on the euploidy rates (ER) and clinical outcomes of embryos derived from 0PN and 1PN zygotes is discordant across publications, resulting in conflicting conclusions regarding whether they are suitable for transfer. This review aims to present an updated synthesis of current knowledge regarding the potential adverse outcomes associated with 0PN and 1PN embryo transfers and to identify important gaps that should be addressed in future studies. SEARCH METHODS: CENTRAL, Embase, Fertility and Sterility, MEDLINE, and PubMed databases were searched on 10 November 2025 using the keywords '0PN embryo' and '1PN embryo'. All types of studies, except case reports and reviews, were included if they compared 0PN/1PN with 2PN zygotes in women of any age undergoing IVF/ICSI cycles, followed by single embryo transfer (SET) and/or preimplantation genetic testing for aneuploidy (PGT-A). Pronuclear status was assessed 16-18 h post insemination. Only data from SET cycles were included for embryo transfer outcomes. OUTCOMES: Eleven studies reporting on 37 240 SET cycles and 27 195 biopsied blastocysts were included. Compared to 2PN embryos, those derived from 0PN zygotes showed no significant differences in live birth rate (LBR) (OR = 0.94, 95% CI = 0.83-1.06, P = 0.33, I2 = 2%), clinical pregnancy rate (CPR) (OR = 0.96, 95% CI = 0.85-1.08, P = 0.48, I2 = 0%), miscarriage rate (MR) (OR = 1.04, 95% CI = 0.84-1.29, P = 0.70, I2 = 0%), malformation rate (OR = 1.05, 95% CI = 0.45-2.45, P = 0.91, I2 = 0%), and ER (OR = 0.86, 95% CI = 0.50-1.48, P = 0.59, I2=63%). However 0PN-derived embryos had a significantly lower blastulation rate (OR = 0.34, 95% CI = 0.17-0.68, P = 0.002; I2 = 99%). Compared to 2PN, 1PN embryos showed a significantly lower LBR (OR = 0.83, 95% CI = 0.70-0.98, P = 0.03, I2 = 12%), CPR (OR = 0.81, 95% CI = 0.68-0.96, P = 0.01, I2 = 22%), and blastulation rate (OR = 0.26, 95% CI = 0.14-0.48, P < 0.001; I2 = 96%), but a similar MR (OR = 1.34, 95% CI = 0.76-2.37, P = 0.31, I2 = 67%), malformation rate (OR = 0.46, 95% CI = 0.16-1.32, P = 0.15, I2 = 0%), and ER (OR = 1.05, 95% CI = 0.70-1.58, P = 0.80, I2 = 66%). WIDER IMPLICATIONS: In the meta-analysis, both 0PN- and 1PN-derived embryos showed no significant differences in rates of euploidy, miscarriage, and malformations compared to 2PN-derived embryos. However, clinical pregnancy and LBRs were significantly lower for 1PN, but not 0PN, embryos than for 2PN embryos. These findings suggest that 0PN-, and possibly even 1PN-, derived embryos, especially those that have undergone PGT-A, may represent a viable source for embryo transfer in certain clinical settings, particularly in cases where 2PN embryos are limited or unavailable. REGISTRATION NUMBER: CRD42024546685.