Girardi Laura, Patassini Cristina, Miravet Valenciano Jose, Sato Yoshimi, Fagundes Cagnin Natalia, Castellón Jose Antonio, Cogo Francesco, Zambon Paola, Blesa David, Jimenez Almazan Jorge, Akinwole Adedoyin, Coprerski Bruno, Rubio Carmen
Igenomix Italy, Reproductive Genetics, Marostica, Italy.
Igenomix Spain Lab S.L.U., Research and Development, Paterna, Spain.
J Assist Reprod Genet. 2024 Dec;41(12):3357-3370. doi: 10.1007/s10815-024-03278-4. Epub 2024 Oct 8.
We aimed to identify the correlation between morphological pronuclear (PN) status and the genetically determined ploidy configuration in preimplantation embryos.
A retrospective observational study was conducted on 1982 embryos displaying normal fertilization and 380 embryos showing an atypical PN pattern, tested for aneuploidies and ploidy status via preimplantation genetic testing (PGT) between May 2019 and May 2024. Ploidy prediction was performed using a validated targeted-NGS approach and a proprietary bioinformatic pipeline analyzing SNPs B-allele frequency information. Ploidy results were obtained in relation to the morphological PN pattern and further stratified by mode of PN observation, maternal age, and embryo quality parameters.
Abnormal ploidy results in 2PN-derived embryos were 1% (n = 20/1982): 0.8% showed triploidy and 0.2% haploidy. Ploidy results in relation to PN number in atypical fertilization were as follows: 0PN (n = 150/380) associated with 87.3% of diploidy, 8.7% of haploidy, and 4.0% of triploidy; 1PN-derived blastocysts (n = 73/153) were haploid in 47.7% of cases, 6.5% were triploid, and 45.7% diploid; 2.1PN (n = 23/280) and 3PN patterns (n = 54/280) predicted a triploid result in 34.8% and 74.1% of cases, respectively. PN observation with time-lapse increased ploidy status predictivity from 28.3% to 80.4% (p < 0.01) and reduced expected diploid rates to 19.6% (p < 0.01). Diploidy rate was higher for maternal age ≤ 35 years and for morphologically high-grade embryos.
Morphological PN check can be improved by incorporating ploidy analysis within the conventional PGT workflow. Euploid 2PN-derived embryos can be further selected removing haploids and triploids, and some atypical PN pattern can be better classified.
我们旨在确定植入前胚胎中形态学原核（PN）状态与基因测定的倍性构成之间的相关性。
对1982个显示正常受精的胚胎和380个显示非典型PN模式的胚胎进行了一项回顾性观察研究，这些胚胎在2019年5月至2024年5月期间通过植入前基因检测（PGT）检测了非整倍体和倍性状态。使用经过验证的靶向NGS方法和分析单核苷酸多态性B等位基因频率信息的专有生物信息学流程进行倍性预测。根据形态学PN模式获得倍性结果，并进一步按PN观察模式、产妇年龄和胚胎质量参数进行分层。
2PN来源胚胎的异常倍性结果为1%（n = 20/1982）：0.8%为三倍体，0.2%为单倍体。非典型受精中与PN数量相关的倍性结果如下：0PN（n = 150/380）中87.3%为二倍体，8.7%为单倍体，4.0%为三倍体；1PN来源的囊胚（n = 73/153）在47.7%的病例中为单倍体，6.5%为三倍体，45.7%为二倍体；2.1PN（n = 23/280）和3PN模式（n = 54/280）分别在34.8%和74.1%的病例中预测为三倍体结果。使用延时观察PN可将倍性状态预测性从28.3%提高到80.4%（p < 0.01），并将预期的二倍体率降低到19.6%（p < 0.01）。产妇年龄≤35岁和形态学上高级别的胚胎的二倍体率更高。
通过在传统PGT工作流程中纳入倍性分析，可以改进形态学PN检查。可以进一步筛选出整倍体2PN来源的胚胎，去除单倍体和三倍体，并且可以更好地分类一些非典型PN模式。
