The landscape of chromosomal aberrations in couples seeking assisted reproductive treatment

Abstract STUDY QUESTION What are the prevalence, type, and stratified risks (reproductive failure subtype, sex, age, semen quality, and prior adverse pregnancy events) of chromosomal aberrations in couples seeking ART treatment in a large-scale cohort study? SUMMARY ANSWER The prevalence of chromosomal aberrations in couples with reproductive failure was 3.42%, with a higher prevalence in younger individuals, men with poorer semen quality, and those experiencing multiple adverse pregnancy outcomes. WHAT IS KNOWN ALREADY Reproductive failure is a global health issue, with chromosomal aberrations playing an important role. ART is widely used for the treatment of reproductive failure; however, large-scale, comprehensive studies characterizing the stratified risks of chromosomal aberrations in couples seeking ART remain scarce. STUDY DESIGN, SIZE, DURATION This retrospective study analysed chromosomal data from 227 818 couples seeking ART at our hospital between January 1993 and March 2024. PARTICIPANTS/MATERIALS, SETTING, METHODS This study included 227 818 couples with reproductive failure, including 130 213 couples with primary infertility, 58 161 with secondary infertility, and 39 444 with adverse pregnancy outcomes. All participants underwent routine cytogenetic analysis using GTG-banding prior to ART. Statistical analysis was performed using R software (v4.4.0), with significance set at P < 0.05. MAIN RESULTS AND THE ROLE OF CHANCE Chromosomal aberrations were detected in 7785 couples (3.42%), with the highest prevalence in those with adverse pregnancy outcomes (4.83%), followed by those with primary infertility (3.54%) or secondary infertility (2.18%) (all P < 0.001). Significant sex differences were observed in infertile couples (men: 1.91% vs women: 1.52%) and couples with adverse pregnancy outcomes (men: 2.04% vs women: 2.81%), (P < 0.001). The prevalence of chromosomal aberrations was inversely correlated with age (2.36% in <25 years to 1.29% in ≥35 years) and increased significantly with poorer semen quality (0.89% in normozoospermia to 12.54% in azoospermia) and more adverse pregnancy events (3.07% in 1 event to 9.38% in ≥3 events, P < 0.001). Common structural aberrations included reciprocal and Robertsonian translocations and inversions, with frequent breakpoints at 11q23, 22q11, and 7q22. The percentage of haploid length of each autosome and the corresponding percentage of breakpoints showed a strong Pearson’s correlation (R = 0.933, P < 0.001, two-tailed test). Robertsonian translocations and t(11;22)(q23;q11) were recurrent. The most frequent aneuploidies identified were 47,XXY (Klinefelter) and 45, X (Turner) syndromes, in both mosaic and non-mosaic forms. LIMITATIONS, REASONS FOR CAUTION The lack of detailed clinical characteristics limited patient stratification and hindered the in-depth analysis of karyotype–phenotype relationships. The absence of a large fertile control group restricted comparative analysis. Conventional GTG-banding resolution may miss some cryptic chromosomal abnormalities. Single-centre data may limit the generalizability of our findings to more diverse populations. WIDER IMPLICATIONS OF THE FINDINGS Stratified risk data (such as the higher prevalence of chromosomal aberrations in younger populations, individuals with poor semen quality, or those with a history of multiple adverse pregnancies) provide crucial evidence for clinicians to assess reproductive risks associated with chromosomal aberrations and make karyotyping decisions prior to ART treatment. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Key Research and Development Program of China (2023YFC2705605). The authors declare that there are no competing interests. TRIAL REGISTRATION NUMBER N/A.