Chromosome abnormalities identified by comparative genomic hybridization in embryos from women with repeated implantation failure

Abstract

Using comparative genomic hybridization, we have detected chromosome abnormality in 76/126 (60%) single blastomeres biopsied prior to implantation from embryos from 20 women with repeated implantation failure following IVF. The abnormalities detected included aneuploidy for one or two chromosomes [32/126 (25%)] and complex chromosomal abnormality [37/126 (29%)]. Most of the chromosomes involved in single aneuploidy were those commonly found in live births or spontaneously aborted fetuses, whereas a greater range of chromosomes were involved in double aneuploidy. In blastomeres with complex abnormality, random and extensive loss and gain of all the chromosomes was observed. Further blastomeres from 25 embryos with single or double aneuploidy and 11 embryos with complex abnormality were analysed following embryo disaggregation. The specific abnormality was confirmed in the majority of cases and in some cases could be assigned as errors in meiotic or mitotic segregation. Complex abnormalities, suggestive of errors in cell cycle regulation, were present in a slightly higher proportion of these embryos than were seen in our previously studied cohort of surplus embryos. The disruption of the normal sequence of chromosome replication and segregation in early human embryos, caused either by maternal cytoplasmic factors or mutations in cell cycle control genes, may be a common cause of repeated implantation failure.

Whole genome amplification in preimplantation genetic diagnosis

“…Voullaire et al (1999) reported that it was possible to use CGH with DOP-PCR amplified DNA for the diagnosis of chromosomal aneuploidy in single cells. And later, the same research group successfully detected chromosome abnormality by using CGH in embryos in women with repeated implantation failure following IVF (Voullaire et al, 2002). However, the nonrandom DOP-PCR amplification had greatly influenced the accuracy of CGH, and we found that this phenomenon could be corrected by selecting the normal single cell DOP-PCR product as a reference (Jin et al, 2000).…”

Preimplantation Genetic Screening (PGS) with Comparative Genomic Hybridization (CGH) following day 3 single cell blastomere biopsy markedly improves IVF outcomes while lowering multiple pregnancies and miscarriages

“…More than 50 % of euploid embryos would not have been able to be biopsed at day 5 (unpublished data). Most current data on day three blastomere biopsy with CCS is derived from retrospective case-control trials [14,28,[37][38][39]. A large randomized controlled trial comparing cleavage-stage and blastocyst stage biopsy utilizing CGH would be helpful to determine the best timing for biopsy.…”

Predictive value of preimplantation genetic diagnosis for aneuploidy screening in repeated IVF-ET cycles among women with recurrent implantation failure

“…The ovarian stimulation protocols used consisted of either a standard GnRH antagonist or GnRH agonist longprotocol with gonadotropins as determined by the managing physician [5]. No difference was noted in terms of embryonic aneuploidy between agonist and antagonist cycles.…”