Reply to Mertes, Repping and de Wert 'Stating the obvious: discarding embryos does not increase your chance of having a baby'
22 February 2016
The COGEN consensus statement 'On the use of Preimplanation Genetic Screening (PGS) of the chromosomes for IVF patients' was produced following a meeting entitled 'Controversies in Preconception, Preimplantation and Prenatal Genetic Diagnosis'. It is clear from the reply of Mertes et al in BioNews 835 that some controversy still remains regarding the benefits of PGS.
The reply of Mertes et al and the COGEN consensus statement both clearly state that that there is as yet an imperfect level of data to support PGS. Yet given that Mertes et al and COGEN are both supporters of evidence-based medicine, the quoted papers and evidence that Mertes et al use to support their reply is surprising.
FISH was the technology widely used in the last decade for PGS. Mastenbroek et al and other studies have showed that this application of PGS had no benefit to patients (1). The meta-analysis of Mastenbroek et al (2011) and the reviews (Mastenbroek et al 2014, Gleicher et al 2014, Franco 2015) noted in Mertes reply all focus largely or exclusively on FISH technology. However, since 2008-2009 PGS has been almost exclusively undertaken using technologies that determine aneuploidy in all 24 chromosomes. These technologies, as described in the COGEN Consensus Statement, of arrayCGH, qPCR and next-generation sequencing, have shown high degrees of accuracy, sensitivity and specificity for PGS in multiple publications, in multiple laboratories.
Twenty-four chromosome PGS technologies have been used in multiple randomised clinical trials (although limited in size, as mentioned in the consensus statement) and observational studies. It is odd that Mertes et al do not mention the meta-analysis papers (2, 3, 4) or the very large recent US Centres for Disease Control observational study of the SART data (5), which look at this newer technology and the positive outcomes of using this newer PGS technology for IVF.
PGS is named 'screening' since it is now well known that the biology of embryo biopsies are such that in very few circumstances the biopsy may not be representative of the remaining embryo. However, this is rare. Particularly with trophectoderm biopsy, very few PGS false negatives have been reported, and embryo follow-up studies have shown a low false-positive rate for PGS. It is odd, therefore, that as proponents of evidence-based medicine Mertes et al quote an extremely small uncontrolled observational study (Gleicher et al 2015) of PGS false positives as evidence for its lack of effectiveness, when a far larger body of data exists to show the low false-positive rates for PGS (6).
Mertes et al also make some very disappointing comments suggesting that the consensus statement could be a conflict of interest: 'Several of the eminent scientists who signed the statement disclose ties to commercial companies and at least six openly promote PGS on the Illumina website (the company selling PGS), which at least hints at possible conflicts of interest.' Some of the people on the consensus statement do have commercial links to Illumina and other companies (one is an employee of Illumina, and numerous other companies provide PGS technologies), all of which was openly stated at the meeting. However, this is not a commercially sponsored statement and many of signatories have no links to PGS companies.
It is now clear that PGS has many benefits, as stated in the consensus statement. What is odd is Mertes et al's reply title. In most countries, couples have limited financial and emotional ability to go through numerous IVF cycles to screen out aneuploid embryos, as Mertes et al seem to be proposing. Hence live birth per transfer and reduced miscarriage rates become paramount, and PGS has been shown to have benefits in these areas. Perhaps this reply could be alternatively titled, 'Stating the obvious: most IVF embryos are aneuploid and unless you use PGS you are more likely to implant aneuploid embryos and implanting aneuploid embryos severely increases your chance of a miscarriage and reduces your chances of having a baby'.