After a decade in planning and delivery and at a cost of surely a few million euros, the results of the ESTEEM trial of aneuploidy testing with polar body analysis by array CGH were finally delivered today. Karen Sermon, co-ordinator of the trial following the retirement of its instigator Joep Geraedts, said that at the time of planning this approach made sense – polar body analysis would avoid the problem of mosaicism in the embryo, and most live births with chromosomal problems are anyway maternal in origin. A pilot study was launched to test feasibility and the RCT – ESTEEM – would eventually follow.
And so today, four years after recruitment began we had the initial results. The trial’s first primary outcome question was whether full chromosome analysis of both polar bodies would increase the likelihood of a live birth within one year – and the answer to that question is unequivocally ‘no’. Among the 205 patients allocated to aneuploidy testing there were 41 with at least one live birth; and among the 191 randomised to no intervention there were 42. A score draw.
It would be easy to describe the results as disappointing, but unlike history’s previous landmark PGS trial (from Amsterdam with FISH) delivery rates now were not adversely affected by screening. It was also clear from the smaller print details that that there were far fewer transfers in the screening group (178 vs 270), suggesting that aneuploidy testing did at least make for more efficient treatment. The bare details of the data – without additional calculation – also made a suggestion that the miscarriage rate in the PB group was substantially lower than in the no intervention group. These were important positive findings for trial participant Cristina Magli, but would they be enough in the patient’s view to compensate for no benefit in delivery rate?
Of course, other questions remain, and opinion was divided among those in the room listening to the results. There was debate on both their strict interpretation and on their wider implications. For example, can we consider this study a model for the whole broader concept of aneuploidy testing? Is it ever possible for screening to really increase live birth rate? Clearly, there’s much work yet to be done in the calculations and conclusions of ESTEEM, but there’s no doubt that the final published paper will attract a fair amount of comment. And no-one present today was in any doubt that this was a monumental work of diligence, determination and scientific discipline. So still in high esteem.
* The trial was funded by ESHRE and by Illumina, who freely provided the arrays for the CGH.
Simon Brown, Editor of Focus on Reproduction