Think differently


Published 07 August 2018

ESTEEM trial co-ordinating investigator Willem Verpoest believes there are important benefits - and messages - to be found in this ESHRE study of aneuploidy screening

"The surest way to corrupt a youth is to instruct him to hold in higher esteem those who think alike than those who think differently." Friedrich Nietzsche

As co-ordinating investigator of the ESTEEM trial, I often wondered whether it was justified to recruit patients for a study on polar body biopsy and array CGH while we at the VUB in Brussels were already using trophectoderm biopsy and gradually introducing SNP arrays and NGS for our routine PGT cases. This was one of the reasons why recruitment for this study was not an easy task.

Furthermore, the intention-to-treat design did not raise high expectations for a potential benefit in the trial's primary endpoint, cumulative live birth rate. The design was, however, a scientifically correct way to address an issue which in the past had been investigated under biased conditions. The results of the ESTEEM study show that cumulative live birth rate is not increased by applying genetic screening at the earliest stage of embryo development - and by extrapolation I dare say that no invasive genetic screening test will do so in this methodological design. Importantly, however, miscarriage rates and number of interventions were both lower in the PGT-A arm of the trial.

Many may criticise the design of the study, but from a clinical point of view the results allow surprisingly clear conclusions. As clinicians we simply cannot tell a couple at a first meeting that PGT-A will improve their cumulative live birth rate. However, by selecting out chromosomally abnormal embryos we can reduce the risk of miscarriage as well as the number of interventions. And bearing in mind that the publications of a decade ago showed a decrease in pregnancy rates following cleavage stage biopsy and PGT-A by FISH, a potentially even more important conclusion can be drawn. Pregnancy rates in the ESTEEM trial and other recently published trials on PGT-A, using WGA techniques, are not lower than in control groups when performed by experienced labs.

This latter finding may indeed be the principal clinical conclusion as a base for investigating the potential benefits of PGT-A in different age groups and phenotypes subject to ovarian response and embryo development. As far as future studies are concerned, only good research will tell us the truth. The ESTEEM trial shows us we should not be afraid to think differently: the truth is not necessarily unpleasant.

ESHRE deserves credit for supporting a study with investigators ranging from private to academic centres, from conservative to progressive countries, from experienced to very experienced laboratories. The ESTEEM trial was an example in diplomacy, reflecting selflessness of the investigators and their sheer determination to bring this trial to a fruitful end. None of them or their collaborators were funded for their efforts.

Finally, a plea for caution in the wider field of reproductive medicine and a demand for all possible effort to follow-up the children who are conceived with a range of techniques, including embryo biopsy, prolonged culture and cryopreservation techniques. As much as we cannot promise a guarantee of success to the patient, so we cannot guarantee the health of the child, nor can we say that the child may not have late-onset complications. IVF, ICSI and PGT-A are therefore useful for many of our esteemed patients, but not for all.

Willem Verpoest
Associate Medical Director
Centre for Reproductive Medicine, UZ Brussel