P-509 Genomic characterization of couples and their embryos/fetuses with idiopathic recurrent pregnancy loss

Abstract

Abstract Study question To what extent do genomic variants contribute to idiopathic recurrent pregnancy loss (RPL)? Summary answer Pathogenic uniparental disomy, copy number variations, and single nucleotide variants were identified in 18 of 83 couples and their embryos/fetuses with idiopathic RPL. What is known already RPL is defined as the loss of two or more pregnancies before 24 weeks gestation. The etiologies of RPL include antiphospholipid antibody syndrome, and anatomic, endocrinological and chromosomal abnormalities. About 50% of RPL is unexplained and is termed as idiopathic RPL. Chromosomal aberrations and genetic variants have been identified to be associated with idiopathic RPL, demonstrating that genomic factors underlie idiopathic RPL. Study design, size, duration We applied genome sequencing to study genomic variations that causing idiopathic RPL. Couples and their embryos/fetuses were collected and sequenced. Genomic variations from women and men experiencing RPL and their embryos/fetuses were analyzed to fully characterize the genomic contribution to idiopathic RPL. Participants/materials, setting, methods We recruited 83 Chinese couples with idiopathic RPL and collected 249 samples from their embryos/fetuses and peripheral blood. Genomic DNA of those samples were sequenced, and pathogenic chromosomal abnormalities and genetic variants were identified. Main results and the role of chance Generally, pathogenic variants were identified in RPL females, males and embryos/fetuses. One uniparental disomy, 9 copy number variations, and 1 homozygous and 1 de novo single nucleotide variants (SNVs) were identified pathogenic in 12 RPL embryos/fetuses. Five and three pathogenic SNVs were identified in 4 RPL females and 2 RPL males respectively. Many SNVs affect the genes involved in sexual development. In total, 18 of 83 (21.69%) couples with idiopathic RPL could be explained by genomic variation, providing information for clinical treatments. Limitations, reasons for caution The sample size is relatively small, and they are from one medical center. Wider implications of the findings Genomic variations in females, males and their embryos/fetuses can cause RPL, and identification of genetic causes will facilitate further precision intervention. Trial registration number not applicable