Clinical application of next-generation sequencing in preimplantation genetic diagnosis cycles for Robertsonian and reciprocal translocations

Abstract

Purpose The purpose of this study was to apply nextgeneration sequencing (NGS) technology to identify chromosomally normal embryos for transfer in preimplantation genetic diagnosis (PGD) cycles for translocations. Methods A total of 21 translocation couples with a history of infertility and repeated miscarriage presented at our PGD clinic for 24-chromosome embryo testing using copy number variation sequencing (CNV-Seq).Results Testing of 98 embryo samples identified 68 aneuploid (69.4 %) and 30 (30.6 %) euploid embryos. Among the aneuploid embryos, the most common abnormalities were segmental translocation imbalances, followed by whole autosomal trisomies and monosomies, segmental imbalances of nontranslocation chromosomes, and mosaicism. In all unbalanced embryos resulting from reciprocal translocations, CNV-Seq precisely identified both segmental imbalances, extending from the predicted breakpoints to the chromosome termini. From the 21 PGD cycles, eight patients had all abnormal embryos and 13 patients had at least one normal/balanced and euploid embryo available for transfer. In nine intrauterine transfer cycles, seven healthy babies have been born. In four of the seven children tested at 18 weeks gestation, the karyotypes matched with the original PGD results. Conclusion In clinical PGD translocation cycles, CNV-Seq displayed the hallmarks of a comprehensive diagnostic technology for high-resolution 24-chromosome testing of embryos, capable of identifying true euploid embryos for transfer.

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.…”

“…Of the 26 publications, six studies reported on the prevalence of mosaicism. One publication reported mosaicism on a per chromosome level only . The remaining five publications reported on mosaicism ranging from 0% (0/175 and 0/18 embryos) to 10.8% (11/102 embryos), with the two largest studies reporting 3.7 (42/1122 embryos) and 6.8% (44/646) .…”

“…The remaining five publications reported on mosaicism ranging from 0% (0/175 and 0/18 embryos) to 10.8% (11/102 embryos), with the two largest studies reporting 3.7 (42/1122 embryos) and 6.8% (44/646) . Three of the six studies detail their classification and transfer policy with respect to mosaic embryos, with two never transferring mosaic embryos, and one considering mosaic embryos for transfer if there were no euploid embryos available and the level of mosaicism was 40% or less . The remaining three studies do not detail their classification of or transfer policy with respect to mosaic embryos …”

Preimplantation genetic haplotyping for six Chinese pedigrees with thalassemia using a single nucleotide polymorphism microarray

“…Next‐generation sequencing is a rapidly developed technology and has a great potential on the areas of PGD/preimplantation genetic screening. Recent studies utilizing this technique show promising results in the application on IVF …”

“…Recent studies utilizing this technique show promising results in the application on IVF. [24][25][26][27]…”