关键词: 流产, 自然；, 妊娠初期；, 绒毛膜绒毛；, 染色体畸变；, 高通量测序；, 原位杂交, 荧光；, 核型分析；, 遗传咨询

Abstract: Objective: To investigate the application value of high-throughput sequencing, fluorescence in situ hybridization (FISH) and karyotype analysis in the detection of villi chromosome abnormality in spontaneous abortion of early pregnancy. Methods：100 patients with spontaneous abortion of early pregnancy in The First Hospital of Shijiazhuang from January 2017 to January 2019 were selected as the research objects. In 100 villus samples, 17 samples were detected by karyotype analysis, 11 samples by FISH, and 72 samples by high-throughput sequencing. Those patients with the successful karyotype detection in villus samples were followed up and provided genetic counseling. The pregnancy outcomes were then analyzed. Results：Finally, 88 cases were successfully detected, and 45 cases with chromosomal abnormalities were detected. There were no significant differences in the success rate of detection and the positive rate of abnormal karyotypes among three detection technologies (P＞0.05). In all 88 cases of successful detection, the follow up visiting was finished in 51 cases, including 32 cases with abnormal villous chromosomes and 19 cases with normal villous chromosomes. The proportion of chromosomal abnormalities in the patients aged ≥35 years was higher than that in the patients aged ＜35 years (75.00% vs. 47.83%, χ2=3.898, P=0.044)， while the proportion of villous chromosomal abnormalities in the patients with the gestation of between 8 and 12 weeks was higher than that in patients with gestational week ＜8 weeks (74.19% vs. 45.00%, χ2=4.432, P=0.035). As for genetic counseling and re-pregnancy outcomes, 32 patients with villous chromosomal abnormalities were followed up, 22 had genetic counseling, 16 had normal re-pregnancy, 4 had miscarriages, and 2 were not pregnant. In 10 patients without genetic counseling, 2 patients had normal pregnancy, 7 were aborted again, and 1 was not pregnant. The outcome of re-pregnancy in the patients with genetic counseling was better than that in the patients without genetic counseling (P＜0.05). Conclusions：The three detection techniques have their own advantages in detecting the villous chromosomes of spontaneous abortion in early pregnancy, which can be selected according to the actual clinical situation. The combined use can improve the detection rate of abnormal karyotypes. Villous chromosome examination should be recommended for the patients aged over 35 years, or the patients with spontaneous abortion within the gestational weeks of 8 to 12. The genetic counseling should be provided for those patients with abnormal villous chromosomes before their re-pregnancy.

Key words: Abortion, spontaneous；Early pregnancy trimester；Chorionic villi；Chromosome aberration；High-throughput sequencing；In situ hybridization, fluorescence；, Karyotype analysis；Genetic counseling