Genetic etiology of spontaneous abortion in the first trimester: analysis of 815 cases
10.3760/cma.j.cn113903-20230905-00185
- VernacularTitle:早孕期自然流产的遗传学病因：815例分析
- Author:
Nan JIANG
1
;
Meiqin YU
;
Wei ZHAO
;
Shuo LI
Author Information
1. 青岛大学附属妇女儿童医院基因检测中心，青岛 266034
- Keywords:
Abortion;
Chromosome aberrations;
Uniparental disomy;
Whole genome sequencing;
Retrospective studies
- From:
Chinese Journal of Perinatal Medicine
2024;27(9):762-767
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the genetic etiology of spontaneous abortion in the first trimester.Methods:This study was a retrospective analysis. The subjects were 815 pregnant women who voluntarily underwent genetic testing of pregnancy miscarriage embryos due to spontaneous abortion or embryonic development arrest in six to thirteen gestational weeks from January 2021 to December 2022. High-throughput sequencing technology was used to detect the abortion tissue, and the results were analyzed by bioinformatics method. Statistical analysis was conducted using the Chi-square test. Results:(1) Chromosomal abnormalities were detected in 525 out of 815 cases (64.4%), including 479 cases (91.2%) of numerical abnormalities (421 cases of aneuploidy and 58 cases of triploidy), 44 cases (8.4%) of structural abnormalities (copy number variation, CNV), and two cases (0.4%) of uniparental disomy. (2) Among the numerical abnormalities, aneuploidy was the most common (87.9%, 421/479), involving all chromosomes except chromosome 1. Trisomy 16 had the highest frequency (17.5%, 84/479), followed by monosomy X (13.4%, 64/479) and trisomy 22 (11.3%, 54/479). Multiple chromosomal abnormalities were present in 27 cases (5.6%). Among the nine cases of autosomal monosomy, there were seven cases of monosomy 21, and one case each of monosomy 18 and monosomy 4. (3) Among the 44 cases of structural abnormalities, 62 pathogenic or possible pathogenic CNVs were identified, with fragment lengths ranging from 1.08 Mb to 103.81 Mb, averaging 19.58 Mb.Chromosome 8 was the most involved in CNV, with 16 cases (25.8%, 16/62), followed by chromosome 4 and 18 with six cases each (9.7%,6/62).Of the 62 CNVs, ten (16.1%) were ≤5 Mb in size, including three cases of microdeletion syndromes.(4) For embryos without autosomal numerical abnormalities indicated by low-depth copy number variation sequencing (CNV-seq) results, quantitative fluorescence polymerase chain reaction verification was performed, detecting two cases of complete uniparental disomy, both of which were paternal uniparental disomy and identified as complete hydatidiform moles. (5) Among the 44 cases where CNV-seq results indicated the presence of CNV in the embryos, 32 cases opted for peripheral blood karyotype analysis, with nine cases (28.1%) identified as carriers of balanced chromosomal translocations in one of the parents. These nine samples all involved variations in two chromosomes, both located at the chromosome ends. For CNV with fragment sizes≤5 Mb, two cases underwent CytoScan 750K array testing, and the chip results were consistent with the CNV-seq sequencing results. (6) Among the 32 couples who underwent peripheral blood karyotype analysis, nine underwent fluorescence in situ hybridization (FISH) testing for chromosomal regions, with six cases showing normal results and three showing abnormalities. The FISH abnormal regions were consistent with the karyotype results. (7) The rate of chromosomal abnormalities in embryos from pregnant women aged≥35 years, as well as the rate of numerical chromosomal abnormalities, were significantly higher than in those aged <35 years [75.8% (182/240) vs. 59.6% (343/575), χ2=23.37; 73.3% (176/240) vs. 53.2% (306/575), χ2=19.34; both P<0.001]. There was no statistically significant difference in the rate of structural chromosomal abnormalities between the two groups. Conclusion:Abnormal chromosome number is the main cause of spontaneous abortion in the first trimester, which is more obvious in pregnant women with abortion age≥35 years. CNV-seq may be more suitable for the detection of spontaneously aborted embryos in the first trimester.
