High normal CGG repeat number on the fragile x mental retardation 1 (FMR1) gene is not correlated with diminished ovarian reserve

Abstract

OBJECTIVE: Inversions are structural chromosome abnormalities that are associated with infertility due to the increased risk of producing unbalanced gametes from recombination events within the inverted chromosome segment. However, there is also evidence indicating the presence of an inter-chromosomal effect during chromosome segregation influencing the generation of other chromosome aneuploidies. The aim of this study was to evaluate the nature of chromosome errors in IVF blastocysts from carriers of balanced chromosome inversions. DESIGN: Research study. MATERIALS AND METHODS: Infertility patients with balanced chromosome inversions (n1⁄430; female carriers1⁄420, male carriers1⁄410) and maternal age-matched infertile controls with normal karyotypes that concurrently cycled (n1⁄430), consented with IRB approval to an IVF cycle with comprehensive chromosome screening (CCS). All embryos were cultured to the blastocyst stage with a trophectoderm biopsy performed for CCS using SNP microarray (RMA-NJ). Only euploid or balanced blastocysts were transferred in a subsequent frozen embryo transfer. Statistical analysis of aneuploidy and outcome data was performed using a two sided Fisher’s exact test with p value of 0.05 for significance. RESULTS: Maternal ovarian reserve, paternal age, oocytes retrieved, fertilization rate and the number of blastocysts biopsied were comparable between the two groups. The chromosomes that contained the balanced inversions varied but were mostly the larger chromosomes including 1, 2, 3, 5, 7, 9 and 17. The incidence of aneuploidy, excluding the chromosome with the inversion, was significantly higher for the inversion patients compared to the maternal age matched controls (Inversion1⁄459% vs. Control1⁄449%; P<0.001). However, following transfer of a euploid blastocyst there was an equivalent live birth rate (Inversion1⁄473.7% vs. Control1⁄478.3%; ns). CONCLUSION: Carriers of balanced chromosome inversions exhibited higher aneuploidy rates for chromosomes that were not involved in the inversion compared to maternal age-matched controls, signifying the occurrence of an inter-chromosomal effect. However, despite a higher aneuploidy rate, carriers of balanced inversions experienced excellent ART outcomes following the transfer of euploid blastocysts. These results provide valuable information for clinical management of infertility patients carrying balanced inversions prior to infertility treatment.