O-146 Extended carrier testing of inherited disorders for reproductive risk assessment in preconception care

Abstract

Abstract Study question What are the clinical implications of extended carrier screening including genetic risk factors linked to infertility and pregnancy? Summary answer The preconception care is simplified by combining the carrier screening for autosomal recessive and X-linked disorders with examination of other risk factors in one test. What is known already Preconception care includes screening for autosomal recessive and X-linked disorders, usually based on family history or ethnicity. Current molecular genetic methods allow simultaneous detection of mutations in a large number of genes and thus developing a unified test for all couples. Study design, size, duration Retrospective analysis of results from 19944 individuals (9972 couples) examined between March 2017 and July 2021. Participants/materials, setting, methods Massively parallel sequencing panel CarrierTest screens for mutations in 80 genes associated with severe inherited diseases along with common risk factors for infertility, pregnancy loss and IVF-related treatment complications. Main results and the role of chance The risk of disorders with autosomal recessive inheritance was found in 1.59 % of couples and risk of X- linked disorders in 1.56 % of couples. Risk of pregnancy complications due to inherited thrombophilia (Factor 5 Leiden mutation and Factor 2 Prothrombin mutation) in the woman was detected in 10.4 % couples and due to the M2 haplotype of ANXA5 gene in 3.53 % couples. Increased sensitivity for FSH due to the FSHR gene Ser680Asn variant in homozygous state was found in 30.7 % of women and microdeletions of chromosome Y associated with male infertility were detected in 0.72 % of men. Limitations, reasons for caution The findings in most genes for autosomal recessive genes are likely to represent the real population frequency of carriers, but in other categories the data are influenced by selection of patients and couples for testing due the reproductive problems or family history. Wider implications of the findings Implementation of CarrierTest allowed us to considerably extend the breadth of tested severe diseases and risk factors and thus to offer the examined couples the opportunity of primary prevention of the consequences of their carrier status. Trial registration number Not applicable