Reproductive carrier screening among Chinese couples experiencing unexplained recurrent pregnancy loss

To investigate the prevalence of pathogenic/likely pathogenic (P/LP) variants in 485 genes associated with autosomal recessive and X-linked disorders among Chinese couples experiencing unexplained recurrent pregnancy loss (RPL).

From March 2021 to December 2024, 48 couples with unexplained RPL and 100 control couples were recruited. A carrier screening panel covering 485 genes associated with 540 autosomal recessive and 84 X - linked hereditary diseases was used. Genomic DNA sequencing was performed, and variants were interpreted based on the American College of Medical Genetics and Genomics (ACMG) classification system.

Among the RPL couples, 93.8% (45/48) carried at least one P/LP variant, and 54.2% (26/48) carried three or more. High carrier rates were observed for GJB2 (1/12), DUOX2 (1/14), SRD5A2 (1/14), ABCA4 (1/16), and UGT1A1 (1/16). The carrier frequency of SRD5A2 variants was significantly higher in RPL females than in controls (P < 0.05). Two couples were identified as high-risk for offspring with phenylketonuria (PKU) or spinal muscular atrophy (SMA).

Chinese couples with unexplained RPL exhibit a high prevalence of P/LP variants, particularly in metabolic and developmental genes. These findings indicate potential genetic contributions to RPL pathogenesis and highlight the clinical utility of carrier screening for reproductive counseling. Future research should explore the roles of heterozygous variants in pregnancy loss and validate the associations in larger cohorts.