O-304 Whole-exome sequencing in women with reproductive failure is a potentially useful diagnostic test in clinical practice

Abstract Study question Could whole-exome sequencing (WES) be useful in clinical practice for primary infertile female involving oocyte or embryo defects and unexplained recurrent miscarriage (RM) patients? Summary answer Identifying key genes involved development helps explain approximately 17% cases of reproductive failure. WES results will help optimize therapeutic treatment. What is known already Dozens have been reported to the genetic causes human infertility. Variants these specific effects on certain processes early reproduction result a spectrum phenotypes, such as maturation arrest, fertilization defects, cleavage failure, embryonic lethality, miscarriage. design, size, duration This retrospective cohort study was conducted from July 2020 August 2022. A total 129 affected females were enrolled. Most them women who suffered repeated failure vitro (≥2 cycles) due abnormal oocytes embryos (PI group, n = 125). Our also comprised small number RM subjects without offspring (RM 4). All patients their spouses had normal karyotype. Participants/materials, setting, methods The peripheral blood samples all participants available family members obtained DNA extraction. Genomic probands subjected identify candidate variants. Subsequently, variants validated by Sanger qPCR. Familial co-segregation analyses then carried out within members. relationship between phenotype genotype tests records studied. Main role chance Firstly, that are potentially relevant phenotypes infertility identified 17.05% (n 22), including TUBB8 14 cases, PATL2 2 ZP2, ZP3, PANX1, TLE6, NLRP2 NLRP7 1 case each. breakdown revealed we 16.00% 20) PI group 50% 2) group. Secondly, 16 which 8 novel, 3 previously reported, 5 novel amino acid change occurring at same position another change. We found (p.C211R, p.T232I, p.A342T) arrest families mutation (p.A102V) family, maternally inherited. Thirdly, 75 phenotypic variant underwent ≥1 cycles ovulation and/or frozen transfer after WES, 49.33% achieved pregnancy 37). Limitations, reasons caution genomic parents not 22 families, so cannot determine whether de novo inherited some cases. Additionally, further functional studies should performed prove mutations affect protein function. Wider implications findings present expands kinds gene with regard Genetic causative recommended conditions patients. Trial registration applicable