S. McCormick

Chromosome errors involving large metacentric and submetacentric chromosomes are more common in young infertility patients

OBJECTIVE: Advanced maternal age (AMA) is the most significant risk factor associated with oocyte aneuploidy. Women at 40 years of age have a 50% reduction in fecundity compared to women a decade younger, including a significant increase in pregnancy loss. Chromosome analysis of pre-implantation embryos has revealed that all 23 pairs of chromosomes are involved in both chromosome gains and losses. The aim of this study was to evaluate the classification of blastocyst chromosome errors in association with maternal age at the time of infertility treatment. DESIGN: Research study. MATERIALS AND METHODS: Infertility patients consented, with IRB approval, to an IVF cyclewith comprehensive chromosome screening (CCS). All embryos were cultured to the blastocyst stage with a trophectoderm biopsy performed for CCS using either SNP microarray or quantitative PCR (RMA-NJ). Aneuploid blastocysts from infertility patients were divided among two groups: Group A1⁄4maternal age<35 years (n1⁄41,091 aneuploid blastocysts) and Group B 1⁄4 maternal age R40 years (n1⁄43,624 aneuploid blastocysts). Chromosome aneuploidy results were analyzed using Chi square test with p value of 0.05 for significance. RESULTS: Predictably, a significant difference was observed for the incidence of aneuploidy relative to AMA (Group A 1⁄4 33% vs. Group B 1⁄473%; P<0.0001). Interestingly, the classification of these chromosome errors was significantly different between the two maternal age groups. AMA infertility patients (Group B) displayed a significant increase in errors (71.2% vs. 63.3% in Group A; p<0.0001) involving small metacentric and acrocentric chromosomes (13-22) that are observed in clinical pregnancy losses. Conversely, younger infertility patients (Group A) showed a significant increase in errors (16.5% vs. 13.5% in Group B; p1⁄40.01) involving the large metacentric and submetacentric chromosomes (1-5), which are not typically observed in miscarriages but predominantly result in implantation failure. CONCLUSION: The frequency and classification of chromosome errors in human blastocysts were significantly different between AMA (R40 years) and younger infertility patients (<35 years), reflecting potential alternative mechanisms associated with aneuploidy generation. These results indicate a clinical advantage of blastocyst aneuploidy screening for younger infertility patients with a history of recurrent implantation failure.