Shi Panlai, Wang Conghui, Liang Hongbin, Zhu XiaoFan, Wang Xinyan, Ning Yanting, Leigh Don, Cram David S, Kong Xiangdong
Genetic and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Genetics and Precision Medicine Center, First People's Hospital of Kunming, Beijing Road 1228, Panlong, Kunming, China.
J Transl Med. 2025 Jun 15;23(1):656. doi: 10.1186/s12967-025-06678-x.
Unexpected pregnancy loss can be a traumatic experience for fertile couples. The aim of the study was to assess the nature and type of chromosomal variants involved in early and late pregnancy loss and provide couples an explanation on the cause of their pregnancy loss.
Investigations were conducted on 2928 pregnancy loss cases where products of conception (POC) samples could be retrieved for genetic analysis. Chromosomal variants were detected by low pass copy number variation sequencing (CNV-seq).
In first-trimester miscarriages, 1272 of POC (60.4%) samples had a chromosome abnormality. Autosomal aneuploidy and monosomy X were the predominate variants (73.2%), followed by autosomal and sex chromosome mosaicism (10.7%), triploidy (9.6%), pathogenic CNVs (6.2%) and haploidy (0.3%). The chromosomal variants were similar in type and frequency regardless of whether the fetus had normal or abnormal ultrasound findings. In second trimester pregnancy loss where there was either a structural or non-structural ultrasound anomaly, only 15.3% of POC samples had a chromosome abnormality, involving mainly the smaller autosomes and monosomy X (55.7%), autosomal and sex chromosomal mosaicism (11.5%), triploidy (4.1%) and pathogenic CNVs (28.7%).
Chromosomal variants contribute to fetal demise in almost two thirds of pregnancy losses.
意外流产对有生育能力的夫妇来说可能是一次痛苦的经历。本研究的目的是评估早期和晚期流产中涉及的染色体变异的性质和类型，并为夫妇提供流产原因的解释。
对2928例流产病例进行了调查，这些病例的妊娠产物（POC）样本可用于基因分析。通过低通量拷贝数变异测序（CNV-seq）检测染色体变异。
在孕早期流产中，1272例（60.4%）POC样本存在染色体异常。常染色体非整倍体和X单体是主要变异类型（73.2%），其次是常染色体和性染色体嵌合体（10.7%）、三倍体（9.6%）、致病性拷贝数变异（6.2%）和单倍体（0.3%）。无论胎儿超声检查结果正常与否，染色体变异的类型和频率相似。在孕中期流产且有结构或非结构超声异常的病例中，只有15.3%的POC样本存在染色体异常，主要涉及较小的常染色体和X单体（55.7%）、常染色体和性染色体嵌合体（11.5%）、三倍体（4.1%）和致病性拷贝数变异（28.7%）。
染色体变异导致了近三分之二流产病例中的胎儿死亡。
