Abstract
Abstract Study question Are monopronuclear-originated blastocysts from ICSI prone to have uniparental genome and does it correlate with specific morphokinetic parameters? Summary answer Extended compaction was notably observed in parthenogenetic monopronuclear blastocysts, suggesting a potential correlation between morphokinetic traits and parental origin. What is known already Previous studies indicated monopronuclear embryos with larger pronucleus exhibit a propensity to develop into blastocysts as normal fertilized embryos, which was considered as evidence supporting the presence of a diploid genome enclosed within a singular pronucleus.However, diploid blastocysts may also arise from haploid spontaneous diploidization following parthenogenetic or androgenetic activation, particularly in ICSI-derived blastocysts. Although certain characteristics were discerned in prior morphokinetic studies on monopronuclear blastocysts, these embryos were not proceeded to comprehensive chromosomal analysis to authenticate the association with parental inheritance, which requires further clarification and investigation. Study design, size, duration This retrospective cohort study, conducted in a university-affiliated reproductive medical center, focused on ICSI-derived monopronuclear blastocysts (n = 151) obtained from 145 PGT cycles spanning January 2013 to December 2022. Among these, nineteen were subject to morphokinetic analysis within a time-lapse system, while 35 bipronuclear-originated sibling blastocysts from the same cycles comprised the control group. Notably, the morphokinetic analysis incorporated 10 uniparental monopronuclear blastocysts, with 7 originating from parthenogenesis and the remaining from androgenesis. Participants/materials, setting, methods The data was collected from patients who had at least one biopsied ICSI-derived monopronuclear blastocyst between 2013 and 2022 at the reproductive center. The genetic analysis of blastocysts were performed using SNP array or NGS. Morphokinetic recordings were obtained from blastocysts cultured in time-lapse system along with euploid bipronuclear sibling blastocysts in the same cycles. All annotations underwent manual scrutiny and standardization by the same embryologist to ensure consistency. Main results and the role of chance This study explored links between genetic origin and morphokinetics in ICSI-derived monopronuclear blastocyst through combine analysis. Among 151 blastocysts, 53 (35.1%) were biparental euploidies, while 20% demonstrated uniparental patterns, with 18 confirmed as parthenogenetic and 7 as androgenetic. The ratio of parthenogenesis to androgenesis was 2.6:1, aligning with reported figures. Pronuclear metrics revealed that pronuclei area of monopronuclear blastocysts were notably larger (91∼171 μm2) than that of maternal-origin pronuclei but equivalent to paternal-origin pronuclei from bipronuclear blastocysts.Kinetic analysis indicated that pronuclei of monopronuclear blastocysts vanished 1.9 hours earlier than those of bipronuclear blastocysts, and furtherly biparental monopronuclear blastocysts had a 2.74-hour shorter visible duration compared to bipronuclear blastocysts, whereas uniparental monopronulcei showed no significant difference. Following pronucleus disappearance, the compaction period of monopronuclear blastocysts lasted 2.85 hours longer than bipronuclear blastocysts. Notably, in parthenogenetic uniparental monopronuclear blastocysts, this gap expanded to 10.92 hours. Additionally, there was a significantly higher proportion of asymmetrical halo and dysmorphism in monopronuclear blastocysts (78.95%, 63.16%) compared to bipronuclear blastocysts (40.00%, 34.29%), but neither differences was related to parental origins. The study corroborated a high incidence of uniparental diploidy and identified the discrepancies in pronuclear parameters and compaction before blastulation of monopronuclear blastocysts with different parental origins. Limitations, reasons for caution The scarcity of ICSI-derived monopronuclear blastocysts undergoing PGT and time-lapse culture posed challenges in discerning additional morphokinetic distinctions related to parental inheritance and conducting in-depth analyses for androgenetic blastocysts. It is noted that parental ploidy results from NGS were deduced from targeted chromosome, which may not represent the whole genome. Wider implications of the findings Our results confirmed the high risk of uniparental diploidy in ICSI-derived monopronuclear blastocysts, suggesting the necessity of comprehensive screening. We pinpointed morphokinetic features in monopronuclear embryos associated with parental origin. While it remains unreliable to gauge parental compositions through morphokinetics, these distinctions could serve as supplementary indicators evaluating monopronuclear embryos. Trial registration number not applicable
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