Importance of embryo aneuploidy screening in preimplantation genetic diagnosis for monogenic diseases using the karyomap gene chip

Abstract

We investigated the incidence of aneuploidy in embryos from couples carrying monogenic diseases and the effect of embryo aneuploidy screening on the monogenic disease preimplantation genetic diagnosis (PGD). From November 2014 to April 2017, 36 couples carrying monogenic diseases were enrolled. The karyomap gene chip technique was used to analyze the blastocysts from the subjects and select normal embryos for transfer. A total of 43 single-gene PGD cycles were performed. A total of 687 eggs were obtained and 186 blastocysts were biopsed. After analysis via karyomap chip, 175 blastocysts received diagnostic results. In our monogenic disease PGD, 66.8% (117/175) of the embryos were diagnosed as normal or non-pathogenic (silent carriers), and 33.2% (58/175) of the embryos were diagnosed as abnormal or pathogenic. For preimplantation genetic screening (PGS), the aneuploidy rate of embryos was 22.9% (40/175). Among embryos diagnosed as normal for monogenic diseases, 26.5% (31/117) of the embryos were aneuploid and could not be transferred. Thus, approximately 1/4 of normal or non-pathogenic blastocysts diagnosed based on monogenic disease PGD were aneuploid, indicating the necessity and importance of embryo aneuploidy screening during PGD for monogenic diseases.

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.…”

“…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) . 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 .…”

“…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 …”

Successful Pregnancy Following Preimplantation Genetic Diagnosis of Adrenoleukodystrophy by Detection of Mutation on the ABCD1 Gene

“…The majority of the patient population (53.2%) had at least one blastocyst with unaffected single gene defect were aneuploid, approximately 26.5% of normal or nonpathogenic blastocysts diagnosed based on monogenic disease PGD were aneuploid which would have been transferred, resulting in negative impacts in pregnancy outcome unless PGS had performed. 40 Conversely, concurrent screening demonstrably aided in embryo selection, as evidenced by the significant improvement in single embryo transfer rates, so 24-chromosome aneuploidies screening became more and more popular to apply in embryos biopsied for PGD to reduce the risk of miscarriage in the gestational period. [41][42][43] Indeed, PGD combined with PGS allowed opting for an embryo that did not carry the mutated allele and euploid embryos to transfer into the mother's uterus then, fortunately, achieved pregnancy with a baby girl.…”

A High-Density Genetic Linkage Map of SLAFs and QTL Analysis of Grain Size and Weight in Barley (Hordeum vulgare L.)

“…With the development of high-throughput genotyping and sequencing technology, the massive single nucleotide polymorphisms (SNPs) were extensively identified in different species, which usually used for high-density map construction, genome-wide association analysis, gene mapping, gene chip, MAS, etc. (Wang et al, 1998;Slate et al, 2009;Huang et al, 2010;Shao et al, 2015;Li et al, 2018). However, whole genome deep re-sequencing is still costly and not necessary for most studies.…”