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Stating the obvious: discarding embryos does not increase your chance of having a baby

18 January 2016
By Heidi Mertes, Sjoerd Repping & Guido de Wert
Ghent University; Academic Medical Centre, Amsterdam; Maastricht University, the Netherlands
Appeared in BioNews 835

Under the auspices of the Virtual Academy of Genetics, COGEN (Controversies in Preconception, Preimplantation and Prenatal Genetic Diagnosis) recently issued a 'consensus statement' on preimplantation genetic screening (PGS), based on a scientific meeting held in Paris last September.

The goal of PGS is to screen out aneuploid embryos and only transfer those identified as chromosomally normal during IVF. Although the scientific rationale makes sense to a certain extent, previous versions of PGS were found to decrease pregnancy rates considerably following its use in clinics around the world for several years (1).

Nevertheless, many have high hopes for a PGS revival with new screening methods. As there was a lively debate on the merits of this 'new PGS' at the meeting (and a clearly divided opinion in the room at the end of the debate), one would expect the consensus statement to reflect this.

For example, the consensus might have been that PGS seems to be a promising technology for women who suffer psychologically from repeated miscarriages or for women who want to have the shortest time to pregnancy possible. But, with the caveat that more data are needed to confirm if, and for which patients, PGS might be useful (the three currently available RCTs, randomised controlled trials, have obvious shortcomings [2]). We must also bear in mind that some embryos that are reported as aneuploid do result in a healthy live birth (3).

Carefully informing the patient of those uncertainties is crucial. This is extremely important when it comes to PGS, as a meta-analysis of all trials conducted on the efficacy of the first versions of PGS demonstrated a decrease in live birth rate per cycle commenced (1). This fact might be too obvious to state for scientists in the field (how could success rates per started cycle ever increase by discarding embryos?), but it is far from clear in much of the information distributed to the lay public.

Alas, everything after the 'but' cannot be found in the 'consensus' statement – a missed opportunity, in our opinion. The statement reads more like a one-sided sales talk, boosting the (alleged) benefits of PGS and either downplaying or completely ignoring the concerns that were raised during the debate in Paris and in the literature (2,4,5). At the same time, issues that are not necessarily related to PGS, such as the benefits of single embryo transfer (which should be the norm in any case), and drop-out rates were included.

The 'consensus' statement reads: 'PGS should no longer to be considered an experimental procedure ... and, where possible, should be made available for routine practice.' They write: 'We therefore believe that PGS should be part of the discussion with all patients considering/undergoing IVF treatment' [our emphasis]. 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.

The irony of the matter is that, although the data are currently lacking, it might be that future data will show that PGS can reduce miscarriage rates and reduce time-to-pregnancy. Perhaps future data might even show that specific patient populations have a higher chance of having a baby thanks to PGS (namely, those who cannot afford to lose time on multiple transfer cycles that are bound to fail because their reproductive potential is decreasing fast).

So why is the offering company's focus on increasing IVF success rates (by which they really mean, but do not say, increased implantation rates per embryo transfer) and not on reducing miscarriage rates and time to pregnancy? Maybe they realise that, in the eyes of most patients, success really means going home with a baby. The truth about PGS is that it does not increase – but decreases – the chance of this happening and perhaps that reality doesn't sell quite so well.

1. Mastenbroek, S., Twisk, M., van der Veen, F., & Repping, S. (2011). Preimplantation genetic screening: a systematic review and meta-analysis of RCTs. Human reproduction update, 17(4), 454-466.
|  2011
2. Mastenbroek, S., & Repping, S. (2014). Preimplantation genetic screening: back to the future. Human Reproduction 2014; 29(9):1846-50.
|  2014
3.Gleicher, N., Kushnir, V. A., & Barad, D. H. (2014). Preimplantation genetic screening (PGS) still in search of a clinical application: a systematic review. Reprod Biol Endocrinol, 12(1), 22;
|  2014
4. Gleicher, N., Vidali, A., Braverman, J., Kushnir, V. A., Albertini, D. F., & Barad, D. H. (2015). Further evidence against use of PGS in poor prognosis patients: report of normal births after transfer of embryos reported as aneuploid. Fertility and Sterility, 104(3), e59.
|  2015
5. Franco Jr JG. Seven Reasons To Be Concerned About the Use of the New Preimplantation Genetic Screening (PGS). JBRA Assist. Reprod; 19: 189-191.
|  2015
2 July 2018 - by Shaoni Bhattacharya 
Scientists say they have developed the most robust model yet to estimate how likely a woman is to have a chromosomally normal embryo for IVF depending on her age...
25 September 2017 - by Chandni Patel 
Women who miscarry during their first IVF cycle still have a higher chance of a live birth with subsequent treatment, compared with women who do not get pregnant after their first round...
18 April 2016 - by Professor Caroline Ogilvie 
Press coverage of a recent study on mouse embryos speculates that termination of human pregnancies diagnosed with aneuploidy (a family of conditions including Down's syndrome) at prenatal diagnosis could be unnecessary, due to the ability of the fetus to 'heal itself'. In fact, the paper's findings are not relevant to aneuploidy detected at prenatal diagnosis...
4 April 2016 - by Dr Helen Robertson 
The presence of genetic abnormalities in cells taken from the placenta at the early stages of pregnancy does not necessarily mean that a baby will be born with a genetic disorder, a study in mice suggests....
21 March 2016 - by Heidi Mertes, Sjoerd Repping & Guido de Wert 
The cosignatories of the COGEN consensus statement attempt to refute our remarks and concerns about the increased use of preimplantation genetic screening by presenting the same low-level 'evidence' they continuously use to advocate the widespread adoption of PGS...
16 August 2010 - by Rosemary Paxman 
The successful use of PGS (preimplantation genetic screening) can be linked to access to appropriate technologies and the skill level and techniques used by embryologists, new research has found....
13 July 2009 - by Professor Joyce Harper 
Preimplantation genetic screening (PGS) for aneuploidy was first reported by Verlinsky et al (1995) and Munne et al (1995). Both of these initial studies analysed polar bodies. The aim of the technique is to help determine the best IVF embryo for transfer on the grounds of the polar body or embryo's chromosomes, by performing biopsy and analysis of the chromosomes using fluorescent in situ hybridisation (FISH). There have been hundreds of papers on the use of PGS. It is well known that for pa...
16 June 2008 - by Alison Cranage 
The British Fertility Society (BFS) has issued new guidelines for the use of pre-implantation genetic screening (PGS) in patients undergoing fertility treatment. The new guidelines, published in the journal Human Fertility, state that there is no evidence that PGS improves pregnancy rates or decreases miscarriage rates for...
17 July 2007 - by Dr Alan Thornhill 
Embryo selection following cleavage stage embryo biopsy and chromosome analysis to identify aneuploid embryos (those which have an abnormal number of chromosomes) in every couple having IVF/ICSI or all women of advanced maternal age is rightly considered by most clinics to be too invasive and potentially damaging for routine...
10 July 2007 - by Dr Jess Buxton 
A technique used to select IVF embryos most likely to implant and develop could actually reduce success rates, according to a study by Dutch researchers. Preimplantation genetic screening (PGS) involves removing a single cell from an IVF embryo and testing it for the presence of chromosome...
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