Systematic analysis and evaluation of chromosome aberrations in major birth defects associated with infertility

Previous studies have indicated an elevated risk of infertility in certain birth defects, including congenital heart disease (CHD), hypospadias, cryptorchidism, and disorders of sexual development (DSD). Although the identification of chromosomal abnormalities or chromosomal aberrations (CAs) is crucial for the diagnosis of these conditions, the assessment of CAs in these disorders remains unclear, and few large-scale studies have been conducted at multiple centers. The aim of the current study was to systematically evaluate the prevalence of CAs in CHD, hypospadias, cryptorchidism, and DSD. Studies reporting CAs in these birth defects were retrospectively analyzed from 1991- 2023, using online databases such as PubMed and Google scholar as well as preprints and references from related literature. Comprehensive screening, data acquisition, and systematic assessments of the identified literature were performed. Ultimately, searches yielded a total of 7,356 samples from 14 published articles on CHD, 298 hypospadias cases from 4 published articles, 1,681 cryptorchidism cases from 4 published articles, and 2,876 DSD cases from 7 published articles. Carrier rates of CAs varied widely among these studies and conditions. A retrospective analysis revealed that CHD was associated with the highest carrier rate (26%) for CAs, followed by DSD (21%), hypospadias (9%), and cryptorchidism (5%). A subtype analysis of CAs indicated a higher prevalence of numerical abnormalities among the reported cases. Therefore, considering CAs in birth defects associated with infertility is imperative. This provides a foundation for the further clinical implementation of chromosomal screening and enhancing high-risk screening for individuals in the real world.