Embryo selection in IVF: is polar body array comparative genomic hybridization accurate enough?

Abstract

The emergence of the array comparative genomic hybridization technique (aCGH) is considered an advance in preimplantation genetic testing. Analysis of the recently published pilot study using polar body aCGH indicates that the test accuracy compares favourably with the fluorescence in situ hybridization technique although a substantial number of euploid zygotes are still likely to be excluded incorrectly. A sound argument against selection in principle has recently been published, based on accumulating evidence that potentially all embryos can now be cryopreserved and transferred in subsequent frozen replacement cycles without impairing pregnancy rates. We suggest that vitrification and serial transfer without testing are likely to give patients the best chance for a successful pregnancy, and avoid the use of an expensive technology.Key words: PGS / PGD / aCGH / diagnostic accuracy Preimplantation genetic screening (PGS) for aneuploidy, using chromosome-specific fluorescence in situ hybridization (FISH) probes, has been offered extensively at many centres, with the aim of selecting euploid embryos for transfer and thus improving the efficiency of assisted conception. Randomized controlled trials of PGS using FISH have failed to demonstrate a beneficial effect on the live birth rate (Mastenbroek et al., 2011a), and the advent of new technology has led to the ESHRE-funded pilot study on PGS using the recently developed array comparative genomic hybridization (aCGH) technique to test polar bodies and hence to predict the chromosome status of the corresponding zygote (Geraedts et al., 2011). This pilot study has concluded that the ploidy of the zygote can be predicted with an acceptable accuracy using the new technology. We believe that this is worthy of further analysis. We have used the study results to estimate the measures of diagnostic accuracy and applied a theoretical model developed for preimplantation genetic testing for further sensitivity analysis and to provide a theoretical comparison using 23-chromosome FISH (Scriven and Bossuyt, 2010). In brief, the theoretical model calculates diagnostic accuracy measures uncomplicated by mosaicism for any number of chromosomes tested greater than two. The input values are the degree of aneuploidy per chromosome and the accuracy per chromosome, defined as the proportion of normal diploid nuclei with a normal signal pattern. In our analysis of the data from Geraedts et al. Table I shows the outcome

Polar body based aneuploidy screening is poorly predictive of embryo ploidy and reproductive potential

“…In fact, the European Society of Human Reproduction and Embryology (ESHRE) PGS Task Force has launched a multicenter randomized controlled trial to characterize the utility of polar body aCGH [12, 13]. However, owing to the indirect nature of polar body based aneuploidy screening, there is concern regarding its ability to accurately predict the chromosomal status of the embryo [14–16] and its reproductive potential. We sought to address these concerns by comparing sequential biopsies of polar bodies and ensuing embryos to determine the predictive value of polar body testing for embryo ploidy and to perform a prospective blinded nonselection analysis of the predictive value of polar body based screening for delivery after embryo transfer.…”

Array comparative genomic hybridization

“…]. For this reason, whether the accuracy achievable using aCGH for PGS is good enough to improve the patient outcome remains debatable and has still to be demonstrated by means of randomized trial [8,35].…”

“…However, regardless of the effectiveness of aneuploidy screening in delivering acceptable live birth rates over a shorter time period, the application of an expensive technology for embryo selection to improve IVF success rates may be unnecessary with the development of highly effective and efficient cryopreservation protocols such as vitrification [36]. Other authors [35] believe that in such a scenario, the use of a selection method cannot increase (but could decrease) the live birth rate per stimulated IVF cycle when all embryos are serially transferred (albeit potentially reducing the time to first delivery). Indeed, there may be an argument for vitrification of all embryos without fresh transfers, considering potentially superior perinatal outcome of births resulting from transfer of thawed blastocysts [37].…”

“…Indeed, there may be an argument for vitrification of all embryos without fresh transfers, considering potentially superior perinatal outcome of births resulting from transfer of thawed blastocysts [37]. Therefore, these authors [35,36] suggest that vitrification and serial transfer without testing are likely to give patients the best chance for a successful pregnancy, and avoid the use of an expensive technology.…”

Le screening des embryons par diagnostic préimplantatoire avant transfert intra-utérin a un intérêt

“…Ces techniques rendent aussi possible l'étude du comportement d'une anomalie d'un éjaculât à l'autre et/ou dans différents foyers de spermatogenèse dans les testicules [21][22][23].…”