Infertility patients with chromosome inversions are not susceptible to an inter-chromosomal effect

Abstract

Purpose The aim of this study was to evaluate the incidence of an inter-chromosomal effect (ICE) in blastocyst-stage embryos from carriers of balanced chromosome inversions. Methods Infertility patients (n = 52) with balanced inversions (n = 66 cycles), and maternal age-matched controls that concurrently cycled (n = 66), consented to an IVF cycle with preimplantation genetic testing for aneuploidy (PGT-A). Blastocyst-stage embryos underwent trophectoderm biopsy for PGT-A with only euploid blastocysts transferred in a subsequent frozen embryo transfer. Subtypes of inversions were included in aggregate: paracentric/pericentric, polymorphic/non-polymorphic, male/female carriers, and varying inversion sizes. Results The incidence of aneuploidy was not significantly higher for the inversion patients compared to the controls (inversion = 48.8% vs. control = 47.2% ns). Following euploid blastocyst transfer, there were excellent live birth outcomes. Conclusions Carriers of balanced chromosome inversions did not exhibit higher aneuploidy rates for chromosomes that were not involved in the inversion compared to maternal age-matched controls, signifying the absence of an inter-chromosomal effect for this data set. These results provide the largest investigation of blastocyst embryos regarding the debated existence of an ICE resulting from the presence of an inversion during meiosis. However, further studies are warranted to investigate an ICE among inversions subtypes that were outside the scope of this study.

Clinical outcomes of Preimplantation genetic testing (PGT) application in couples with chromosomal inversion, a study in the Chinese Han population

“…Our observations showed that there were no statistically significantly differences in de novo aneuploid rates between pericentric and paracentric inversion carriers. As is well-known, the production of de novo aneuploids is closely related to maternal advanced age, and the interchromosomal effect is inconspicuous just as many studies indicated [7,21]. Therefore, paracentric inversion cannot be considered less pernicious than pericentric inversion in genetic counseling.…”

“…Inversion carriers with small distal segments of the inverted chromosome are more likely to give birth to chromosomally unbalanced or phenotypically abnormal offspring. Accordingly, inversion heterozygotes in which one or both distal segments are large have a risk for producing gametes and recombinants with considerable genetic imbalance, leading to implantation failure or pregnancy loss [7]. Besides, there are other factors such as the location of breakpoints that are likely to affect the chance of inversion loop formation as well [6].…”

Clinical Outcomes of Preimplantation Genetic Testing (PGT) Application in Couples with Chromosomal Inversion, a Study in the Chinese Han Population

“…Inversion carriers with small distal segments of the inverted chromosome are more likely to give birth to chromosomally unbalanced or phenotypically abnormal offspring. Accordingly, inversion heterozygotes in which one or both distal segments are large have a risk for producing gametes and recombinants with considerable genetic imbalance, leading to implantation failure or pregnancy loss [6].…”

Clinical Outcomes of Preimplantation Genetic Testing (PGT) Application in Couples with Chromosomal Inversion, a Study in the Chinese Han Population

“…The chromosomes of embryos fertilized by abnormal gametes can result in a partial monosomy or a trisomy represented as congenital defects [7]. The frequency of recombination within the gametes is related to parameters such as the involved chromosome, the location of breakages, the size of the inverted segment and its proportion in relation to the size of the whole chromosome [8].…”