Polar body array CGH for prediction of the status of the corresponding oocyte. Part I: clinical results

Abstract

BACKGROUNDSeveral randomized controlled trials have not shown a benefit from preimplantation genetic screening (PGS) biopsy of cleavage-stage embryos and assessment of up to 10 chromosomes for aneuploidy. Therefore, a proof-of-principle study was planned to determine the reliability of alternative form of PGS, i.e. PGS by polar body (PB) biopsy, with whole genome amplification and microarray-based comparative genomic hybridization (array CGH) analysis.METHODSIn two centres, all mature metaphase II oocytes from patients who consented to the study were fertilized by ICSI. The first and second PBs (PB1and PB2) were biopsied and analysed separately for chromosome copy number by array CGH. If either or both of the PBs were found to be aneuploid, the corresponding zygote was then also processed by array CGH for concordance analysis.RESULTSBoth PBs were biopsied from a total of 226 zygotes from 42 cycles (average 5.5 per cycle; range 1–15) in 41 couples with an average maternal age of 40.0 years. Of these, the ploidy status of the zygote could be predicted in 195 (86%): 55 were euploid (28%) and 140 were aneuploid (72%). With only one exception, there was at least one predicted aneuploid zygote in each cycle and in 19 out of 42 cycles (45%), all zygotes were predicted to be aneuploid. Fresh embryos were transferred in the remaining 23 cycles (55%), and one frozen transfer was done. Eight patients had a clinical pregnancy of which seven were evolutive (ongoing pregnancy rates: 17% per cycle and 30% per transfer). The ploidy status of 156 zygotes was successfully analysed by array CGH: 38 (24%) were euploid and 118 (76%) were aneuploid. In 138 cases complete information was available on both PBs and the corresponding zygotes. In 130 (94%), the ploidy status of the zygote was concordant with the ploidy status of the PBs and in 8 (6%), the results were discordant.CONCLUSIONSThis proof-of-principle study indicates that the ploidy of the zygote can be predicted with acceptable accuracy by array CGH analysis of both PBs.

Effect of maternal age on the outcomes of in vitro fertilization and embryo transfer (IVF-ET)

“…Comparative genomic hybridization (CGH) and array-CGH were widely used now for PGS which could make the result more sensitive and exact [27][28][29][30].…”

Comparison of array comparative genomic hybridization and quantitative real-time PCR-based aneuploidy screening of blastocyst biopsies

“…Several other methods of chromosome screening have demonstrated poor predictive value of an aneuploidy diagnosis based on finding normalcy later in development. 7,8 However, a more relevant assessment of the negative predictive value of a screening method is the ultimate clinical outcome after transfer of an embryo that would have been predicted as aneuploidy.…”

SNP array-based copy number and genotype analyses for preimplantation genetic diagnosis of human unbalanced translocations

“…20 Polar bodies have the advantage that only meiotic errors are detected and would therefore be the ideal specimen for PGS. Prospective, randomized-controlled trials, currently ongoing, 44 will need to elucidate this. In PGD, a polar body approach would be applicable only to female carriers of a genetic condition.…”