P-560 Diagnostic value of whole exome sequencing (WES) in case of recurrent pregnancy losses

Abstract

Abstract Study question Is it justified during genetic counseling to inform families with recurrent pregnancy losses about the possibility of testing abortion material using the WES method? Summary answer Informed families have the opportunity to find the monogenic cause of recurrent pregnancy losses with subsequent PGT-M analysis of embryos to prevent it. What is known already Despite WES is not recommended for recurrent pregnancy losses as a routine procedure, there are more and more data in favor of the practice. Study design, size, duration This is a retrospective study from 2019 to 2021 including 21 cases that were negative in case of routine karyotyping or aCGH. Three of them (14,3%) were found the cause of diseases by using WES. The study is ongoing. Participants/materials, setting, methods Whole exome sequencing of abortion material, chorionic villi specimens. Main results and the role of chance Family 1 has a history of euploid fetuses losses during the pregnancy. An autosomal recessive disease, Smith-Lemli-Opitz syndrome type II with early lethality (MIM 270400) was revealed by WES Trio at the 6th pregnancy loss case (mutations detected: c.964-1G>C and c.651C>A in DHCR7 gene in compound heterozygote state). The parents are Ashkenazi Jews and heterozygous carriers of a mutation in the same gene. The risk of pregnancy loss or stillbirth is 25%, and pregnancy planning by IVF with PGT-M is recommended. Family 2 has recurrent pregnancy losses, happening up to 11 weeks. A child was born with cardioencephalomyopathy, fatal infantile, due to cytochrome C oxidase deficiency 1 (MIM 604377). Mutation: c.418G>A in SCO2 gene in a homozygous state. The mutation was previously described as the cause of missed abortion. For family 3 was performed WES of abortus with congenital pathology. Mutation c.8263delC in Ciliary dyskinesia, primary, 40 (MIM 618300) gene DNAH9 in homo/heterozygous state. The mutation can result in malformations and stops in pregnancy development. The family is suggested to perform IVF with PGT-M. Limitations, reasons for caution The low detection frequency of monogenic causes of pregnancy losses and the high cost of the testing does not allow the use of WES of abortion material as a screening method. Wider implications of the findings Performing the WES helps to identify the high risks of monogenic pathology in the families. Changing reproductive tactics and pregnancy planning by IVF with PGT-M is recommended for early prevention of severe congenital pathology, stillbirth, malformations during pregnancy, recurrent pregnancy losses and reduction of the time to achieve healthy childbearing. Trial registration number not applicable