Remixing reproduction and genetics

The European Society of Human Reproduction and Embryology (ESHRE) held their annual meeting in Tours last week. The European Society of Human Genetics (ESHG) held theirs in Geneva at the end of May. However, these two clinical and academic disciplines – until now rather separate – are becoming increasingly integrated. In the minds of the general public the two were never really separate, which means that we must be crystal clear about the aims of the different clinical interventions.

One ESHRE story picked up by British newspapers is the report from Dr Ferraretti's team in Bologna, Italy on the clinical outcome of 50 pregnancies obtained after preimplantation genetic diagnosis (PGD) for abnormal chromosome number (aneuploidy). These pregnancies represent a 40% success rate for women between 38 and 44 years compared with the expected 25% pregnancy rate for this age group. The claim made in The Guardian that 'women over 40 might now have the same chance of having a baby through IVF as women in their twenties' may be premature, but detection of chromosomal abnormalities should help avoid the transfer of embryos with poor viability and thereby improve the pregnancy rate.

This aim is NOT the same as that of prenatal screening for Down syndrome – an established clinical genetics service in mid-pregnancy. In the Italian pregnancies, one of the children born had Down syndrome, and the authors emphasised that women should be offered regular prenatal screening despite PGD for aneuploidy. Mosaicism may result in the cell biopsied for testing at the preimplantation stage having normal chromosomes, whilst some remaining embryonic cells do not. Much larger studies will be needed to establish how much, if at all, PGD reduces the chance of a child being born with aneuploidy. Medical geneticists have very good data on age-specific risks of Down syndrome at prenatal stage or at birth and so the expected figure can be estimated. But a series of a thousand or so older women will be needed to reach any statistically valid conclusions. Only then can one even begin to talk of women being able to make an informed decision on the use of PGD to avoid a child with aneuploidy.

There is clearly great room for confusion here. Currently PGD for aneuploidy in older women is an attempt to evaluate the viability of in vitro generated embryos and thereby improve the overall pregnancy rate. Increasing the success of IVF is a laudable and widely accepted aim, but quite distinct from Down syndrome screening on which there is no consensus and which must remain a very personal decision. To date this confusion only arises for chromosomal abnormalities, but relatively common genetic mutations impairing implantation and embryonic viability may well be discovered. A better understanding of these issues can be encouraged by clinical embryologists adopting less emotive terms – by discussing an embryo's 'viability' rather than 'quality'. 'Class I' and similar supermarket descriptions should be dumped just like the extraordinary phrase 'blighted ovum' beloved of obstetricians when I was a medical student in the '60s.