Mapping allele with resolved carrier status of Robertsonian and reciprocal translocation in human preimplantation embryos

Abstract

Reciprocal translocations (RecT) and Robertsonian translocations (RobT) are among the most common chromosomal abnormalities that cause infertility and birth defects. Preimplantation genetic testing for aneuploidy using comprehensive chromosome screening for in vitro fertilization enables embryo selection with balanced chromosomal ploidy; however, it is normally unable to determine whether an embryo is a translocation carrier. Here we report a method named "Mapping Allele with Resolved Carrier Status" (MaReCs), which enables chromosomal ploidy screening and resolution of the translocation carrier status of the same embryo. We performed MaReCs on 108 embryos, of which 96 were from 13 RecT carriers and 12 were from three RobT carriers. Thirteen of the sixteen patients had at least one diploid embryo. We have confirmed the accuracy of our carrier status determination in amniotic fluid karyotyping of seven cases as well as in the live birth we have thus far. Therefore, MaReCs accurately enables the selection of translocation-free embryos from patients carrying chromosomal translocations. We expect MaReCs will help reduce the propagation of RecT/RobT in the human population.

A systematic review on concurrent aneuploidy screening and preimplantation genetic testing for hereditary disorders: What is the prevalence of aneuploidy and is there a clinical effect from aneuploidy screening?

“…Title and abstract screening resulted in 73 papers. Full text screening resulted in 26 publications fulfilling the inclusion criteria . No randomized controlled trials were identified.…”

“…All but four studies reported a statistically significant reduction in the percentage of embryos suitable for transfer before and after PGT‐A. The remaining four studies most likely failed to reach statistically significant differences due to the small sample size . As a direct consequence of this, opting for PGT‐A will most likely increase the risk of experiencing a cycle with no transferable embryos and patients should therefore be informed about this risk during counseling on when to opt for PGT‐A or not, as well as about the ongoing discussion of a clinical effect.…”

Preimplantation genetic testing of Robertsonian translocation by SNP array‐based preimplantation genetic haplotyping

“…MaReCs could improve the accuracy of breakpoint determination to approximately 200 kbp, reducing the current range limitation of informative SNPs to approximately 1 Mbp flanking the breakpoint. Therefore, this improvement reduces risk of misdiagnosis caused by recombination of the analyzed embryo . However, this method also has some limitations.…”

“…The risk of misdiagnosis will increase if the proband embryos only have trisomic translocated chromosomes. In this instance, it may be necessary to analyze a second polar body or sperm cell in female or male carriers, respectively, to establish the haplotype phase …”

“…But, these methods cannot perform whole chromosome screening, at present; however, certain technologies have been introduced to solve this problem. Three research groups reported novel next‐generation sequencing (NGS) strategies to discriminate between noncarrier and carrier balanced/euploid embryos for chromosome translocation, respectively . However, these methods are complicated, costly, and time‐consuming.…”