Igenomix, Reproductive Genetics, Marostica 36063, Italy.
Igenomix, Reproductive Genetics, Marostica 36063, Italy.
Am J Hum Genet. 2021 Dec 2;108(12):2238-2247. doi: 10.1016/j.ajhg.2021.11.002. Epub 2021 Nov 18.
Chromosome imbalance (aneuploidy) is the major cause of pregnancy loss and congenital disorders in humans. Analyses of small biopsies from human embryos suggest that aneuploidy commonly originates during early divisions, resulting in mosaicism. However, the developmental potential of mosaic embryos remains unclear. We followed the distribution of aneuploid chromosomes across 73 unselected preimplantation embryos and 365 biopsies, sampled from four multifocal trophectoderm (TE) samples and the inner cell mass (ICM). When mosaicism impacted fewer than 50% of cells in one TE biopsy (low-medium mosaicism), only 1% of aneuploidies affected other portions of the embryo. A double-blinded prospective non-selection trial (NCT03673592) showed equivalent live-birth rates and miscarriage rates across 484 euploid, 282 low-grade mosaic, and 131 medium-grade mosaic embryos. No instances of mosaicism or uniparental disomy were detected in the ensuing pregnancies or newborns, and obstetrical and neonatal outcomes were similar between the study groups. Thus, low-medium mosaicism in the trophectoderm mostly arises after TE and ICM differentiation, and such embryos have equivalent developmental potential as fully euploid ones.
染色体不平衡(非整倍体)是人类妊娠丢失和先天性疾病的主要原因。对人类胚胎的小活检分析表明,非整倍体通常起源于早期分裂,导致嵌合体。然而,嵌合体胚胎的发育潜力尚不清楚。我们对 73 个未经选择的植入前胚胎和 365 个活检进行了非整倍体染色体的分布分析,这些活检来自四个多灶滋养外胚层(TE)样本和内细胞团(ICM)。当一个 TE 活检中仅有少于 50%的细胞存在嵌合体(低-中等级嵌合体)时,只有 1%的非整倍体影响胚胎的其他部分。一项双盲前瞻性非选择试验(NCT03673592)显示,在 484 个整倍体、282 个低等级嵌合体和 131 个中等级嵌合体胚胎中,活产率和流产率相当。在随后的妊娠或新生儿中未发现嵌合体或单亲二倍体,研究组之间的产科和新生儿结局相似。因此,TE 和 ICM 分化后,滋养外胚层中的低-中等级嵌合体主要发生,并且此类胚胎与完全整倍体胚胎具有相当的发育潜力。