Abstract:Objective To investigate the clinical significance of whole exome sequencing (WES) in severe idiopathic oligoasthenoteratozoospermia(iOAT). Methods Fifty-four patients with severe iOAT treated from January to October 2019 were selected as the research subjects. After collecting the patients personal history, sex hormones and whole blood samples for WES detection, the patients were followed up for fertility outcomes. Results There were WES-positive Results in 8 of 54 patients （14.81%）and WES-negative in 46 of 54 patients (85.19%). In WES-positive group, 5 out of 9 gene variants (SLC26A8, SPO11, DPY19L2, DNAH1 and SUN5) were consistent with the clinical phenotype. There were no significant differences in hormone levels and personal history between WES-positive group and WES-negative group ( P >0.05). During the follow-up period, the overall successful fertility rate was 37.04% (20/54), in which the successful pregnancy rate through intracytoplasmic sperm injection (ICSI) accounted for 80.00% (16/20). The overall infertility rate was 62.96% (34/54), in which spontaneous abortion and in vitro fertilization(IVF) failure accounted for 38.24% (13/34), and the persons still preparing for pregnancy were 61.76% (21/34). The persons proposed for IVF accounted for 72.43%(15/21). Conclusions WES detection provides a basis for the genetic diagnosis of some severe iOAT patients. In clinical practice, IVF remains an effective option for successful pregnancy for the spouses of iOAT patients.