Whole-exome sequencing-based carrier screening in Chinese Han infertile couples attempting assisted reproductive technology: an exploratory, single-center retrospective descriptive study

Background This study aimed to describe carrier findings, genetic counseling recommendations, and subsequent ART plan choices observed after untargeted whole-exome sequencing (WES)-based carrier screening in infertile Chinese Han couples attempting assisted reproductive technology (ART). Methods This retrospective, exploratory, single-center descriptive study included infertile couples who had undergone genetic counseling and WES for carrier screening in an in vitro fertilization (IVF) clinic affiliated with a university in Central China. Genetic findings, counseling recommendations, and ART plans documented after WES were summarized descriptively. No comparator group, validated decision-making survey instrument, or pre-specified before-after decision outcome was available. Results A total of 130 infertile or subfertile couples were enrolled. Overall, 82.7% (215/260; 95% CI 77.6-86.8%) of individuals carried at least one P/LP variant, including 77.7% (101/130; 95% CI 69.8-84.0%) of males and 87.7% (114/130; 95% CI 80.9-92.3%) of females. The carrier burden was 1.6038 variants per person. GJB2-associated deafness was the most prevalent finding, occurring in 13.8% (36/260) of individuals. After excluding somatic and autosomal-dominant secondary findings from the reproductive carrier-risk denominator, 7.7% (10/130; 95% CI 4.2-13.6%) of couples met the strict AR/XL at-risk-couple definition. Among these 10 couples, PGT-M was recorded as the post-WES ART plan for three couples (30.0%; 95% CI 10.8-60.3%). Conclusion In this retrospective descriptive cohort, WES-based carrier screening identified a high carrier burden and generated counseling recommendations that were followed by different ART plan choices among AR/XL at-risk couples. Genetic counseling before and after WES remains important for couples receiving positive carrier-screening results.