目的: 探讨辅助生殖技术是否会增加胚胎染色体异常的风险。方法: 根据不同受孕方式,将2 318例早孕期流产的患者分成体外受精(in vitro fertilization, IVF)组(n=310)、卵细胞质内单精子显微注射 (intracytoplasmic sperminjection, ICSI) 组(n=86)、自然妊娠(natural conception, NC)组(n=1 922)3组,分析比较3组的异常核型发生率,分析患者年龄与非整倍体发生率间的关系,以及单核苷酸多态性微阵列芯片(single nucleotide polymorphism-based arrays,SNP-array)、下一代测序(next generation sequencing, NGS)、传统细胞培养结合G显带这3种不同检测方法的异常核型检出率。结果: 2 318例流产绒毛中,1 420例存在染色体异常,异常率为61.26%,其中异常核型以非整倍体占绝对多数,共发现1 040例,发生率为44.86%( 1 040/2 318),占异常核型的73.24%(1 040/1 420),涉及除1号染色体以外所有染色体,且以16-三体发生频率最高,其次为22-三体和45,X单体。IVF组、ICSI组及NC组间的流产物染色体总体异常率差异无统计学意义(57.74%、55.81%、 62.02%,P=0.207)。但ICSI组的三倍体发生率明显低于NC组及IVF组(0、7.23%、7.42%,P=0.035)。当根据流产患者年龄分组时,高龄组(≥35岁)的非整倍体发生率明显高于低龄组(<35岁)(60.25% 比40.07%,P<0.01)。SNP-array技术、NGS及核型分析对异常核型的总体检出存在差异(62.94%比53.13%、59.92%,P=0.035),SNP-array技术对非平衡性结构异常、三倍体、微重复和微缺失的检出率最高,还能检出单亲二倍体(uniparental disomy,UPD)和杂合性缺失(loss of heterozygosity,LOH),而核型分析对四倍体的检出率最高。结论: 胚胎染色体异常是自然流产的最重要原因;IVF不增加胚胎染色体异常的发生率,但ICSI有增加胚胎性染色体非整倍体风险的趋势。随着母亲年龄的增长,胚胎非整倍体的发生率显著升高。以SNP-array和NGS为代表的分子检测技术有望成为流产物染色体检测的一线方法。

Objective: To investigate whether assisted reproductive technology increases the risk of fetal chromosomal abnormalities. Methods: According to the way of pregnancy, 2 318 early abortion cases were divided into three groups, IVF (in vitro fertilization) group (310 cases), ICSI (intracytoplasmic sperm injection) group (86 cases), and NC(natural conception)group (1 922 cases). Frequency of abnormal karyotypes in the three groups were compared, and the correlation between age of pregnant woman and rate of aneuploidy as well as the performance of various methods for detecting abnormal karyotype were analyzed. Results: A total of 1 420 cases of chromosomal abnormality were detected in 2 318 aborted fetus, with an abnormal rate of 61.26% (1 420/2 318). In all abnormal karyotypes, aneuploidies accounted for 1 040 cases (73.24%, 1 040/1 420), which involved all chromosomes except chromosome 1. The frequency of trisomy 16 was the highest, followed by trisomy 22 and X monomer. Differences in the total chromosome abnormality rate between IVF group, ICSI group and NC group were not significant (57.74%, 55.81%, 62.02% respectively, P=0.207), but the incidence rate of triploid in ICSI group was significantly lower than those in NC group and IVF group (0 vs. 7.23% and 7.42%, P=0.035). The aneuploidy rate in pregnant women aged ≥35 years was significantly higher than that in younger women (<35 years old) (60.25% vs. 40.07%, P<0.01). Compared with other detectiontion rates of unbalanced structural chromosome abnormalities, triploid, and micro repeats and/deletions by SNP-array were different from NGS and cell karyotype analysis (62.94% vs. 53.13% and 59.92%, respectively, P=0.035), and SNP-array also could detecte UPD(uniparentaldisomy) and LOH(loss of heterozygosity). Karyotype analysis had the highest detection rate for tetraploid. Conclusions: The fetal chromosome abnormality is one of the most important causes of spontaneous abortion.and IVF as well as ICSIdo not increase the total incidence rate of fetal chromosomal abnormalities, but ICSI might increase the risk of fetal sex chromosome aneuploidy. Thepregnant women's age could be related to the increase of fetal aneuploidy. Molecular detection technologies, such as SNP-array and NGS are expected to replace karyotype analysis method as a first-line method for chromosome detection.