Chuang Tzu-Hsuan, Chang Ya-Ping, Lee Meng-Ju, Wang Huai-Ling, Lai Hsing-Hua, Chen Shee-Uan
Stork Fertility Center, Stork Ladies Clinic, Hsinchu City, Taiwan.
Department of Obstetrics and Gynecology, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan.
Front Genet. 2021 Jan 6;11:565348. doi: 10.3389/fgene.2020.565348. eCollection 2020.
Mosaicism, known as partial aneuploidies, mostly originates from mitotic errors during the post-zygotic stage; it consists of different cell lineages within a human embryo. The incidence of mosaicism has not been shown to correlate with maternal age, and its correlation with individual chromosome characteristics has not been well investigated. In this study, the results of preimplantation genetic testing for aneuploidy (PGT-A) derived from 4,036 blastocysts (930 IVF couples) were collected from 2015 to 2017. Via next-generation sequencing for comprehensive chromosome screening, embryo ploidy was identified as aneuploid, mosaic, and euploid. Total mosaicism was classified into two categories: "mosaic euploid/aneuploidy" (with mosaic aneuploidy between 20 and 80%) and "mosaic and aneuploidy" (a uniformly abnormal embryo superimposed with mosaic aneuploidies). Frequency of mosaicism was analyzed according to the function of chromosomal lengths, which divides involved chromosomes into three groups: group A (156-249 Mb), group B (102-145 Mb), and group C (51-90 Mb). The results show that the aneuploidy was more frequent in group C than in group A and group B (A: 23.7%, B: 35.1, 41.2%, < 0.0001), while the mosaicism was more frequent in group A and group B than in group C [(Mosaic euploid/aneuploid) A: 14.6%, B: 12.4%, C: 9.9%, < 0.0001; (mosaic and aneuploid) A: 21.3%, B: 22.9%, C: 18.9%, < 0.0001; (Total mosaicism) A: 35.9%, B: 35.3%, C: 28.8%, < 0.0001]. The significantly higher frequency of aneuploidy was on the shorter chromosome (< 90 Mb), and that of mosaicism was on the longer chromosomes (> 100 Mb). The length association did not reach significance in the patients with advanced age (≥ 36 years), and of the chromosome-specific mosaicism rate, the highest prevalence was on chromosome 14 (5.8%), 1 (5.7%), and 9 (5.6%). Although the length association was observed via group comparison, there may be affecting mechanisms other than chromosomes length. Eventually, twenty patients with mosaic embryo cryotransfers resulted in six live births. No significant correlation was observed between the transfer outcomes and chromosome length; however, the analysis was limited by small sample size.
嵌合体，也称为部分非整倍体，主要源于合子后阶段的有丝分裂错误；它由人类胚胎内不同的细胞谱系组成。嵌合体的发生率与母亲年龄无关，其与个体染色体特征的相关性也尚未得到充分研究。在本研究中，收集了2015年至2017年来自4036个囊胚（930对体外受精夫妇）的非整倍体植入前基因检测（PGT-A）结果。通过下一代测序进行全面的染色体筛查，将胚胎的倍性鉴定为非整倍体、嵌合体和整倍体。总嵌合体分为两类：“嵌合整倍体/非整倍体”（嵌合非整倍体比例在20%至80%之间）和“嵌合与非整倍体”（一个均匀异常的胚胎叠加嵌合非整倍体）。根据染色体长度功能分析嵌合体的频率，将涉及的染色体分为三组：A组（156 - 249 Mb）、B组（102 - 145 Mb）和C组（51 - 90 Mb）。结果显示，C组的非整倍体比A组和B组更常见（A组：23.7%，B组：35.1%，C组：41.2%，<0.0001），而A组和B组的嵌合体比C组更常见[（嵌合整倍体/非整倍体）A组：14.6%，B组：12.4%，C组：9.9%，<0.0001；（嵌合与非整倍体）A组：21.3%，B组：22.9%，C组：18.9%，<0.0001；（总嵌合体）A组：35.9%，B组：35.3%，C组：28.8%，<0.0001]。非整倍体在较短染色体（<90 Mb）上的频率显著更高，而嵌合体在较长染色体（>100 Mb）上的频率更高。在高龄（≥36岁）患者中，长度关联未达到显著水平，在特定染色体的嵌合体发生率中，最高患病率出现在14号染色体（5.8%）、1号染色体（5.7%）和9号染色体（5.6%）上。尽管通过组间比较观察到了长度关联，但可能存在除染色体长度之外的影响机制。最终，20例进行嵌合胚胎冷冻移植的患者中有6例活产。移植结果与染色体长度之间未观察到显著相关性；然而，分析受样本量小的限制。
