Reply: Embryo selection and IVF

(i) We can all agree that chromosome aneuploidy is an important factor in the inefficiency of human reproduction, and that we want what is best for our patients and to improve the quality of assisted conception. However, it must also be highly desirable that any new genetic test should only have widespread implementation when it is safe and appropriate to do so. It might well be that there are patient groups who will benefit from PGS but the temptation to apply this testing indiscriminately has so far appeared to be difficult to resist. (ii) We agree that the psychological burden of repeated implantation failure and spontaneous abortion of a much-wanted clinically recognized pregnancy is severe. However, we are also aware that the financial costs of PGD are associated with increases in anxiety, and the expectancy of establishing a pregnancy may be unrealistically high (Karatas et al., 2010). (iii) In our opinion, PGS is not ethically preferable in all cases, for instance, for fertile couples with recurrent spontaneous abortions. Perhaps because it is counterintuitive, it is not well understood that the chance of a successful pregnancy is likely to be higher following a failed aneuploid pregnancy than following one where no chromosome abnormality was found (Carp et al., 2001). This is because most chromosome aneuploidy associated with pregnancy loss is sporadic; it explains the failed pregnancy and is unlikely to present next time. For couples with chromosomally normal recurrent spontaneous abortions, there are likely to be other factors causing the pregnancy losses, and ART with PGS will therefore be ineffective. Even after three spontaneous abortions, over two-thirds of patients achieve a successful natural pregnancy which is higher than that generally achieved by IVF, even if PGS is carried out. It therefore seems clear that for these couples, assisted conception with PGS is likely to reduce the chance of, and increase the time to, successful pregnancy. (iv) ‘The aim of testing is not only to establish a pregnancy but to select the best embryo to have a healthy child’. In our opinion, the primary objective of PGD should be to give disadvantaged couples with inherited genetic conditions the same chance of a healthy child as any couple in the general population. (v) Our article primarily focused on the accuracy of PGS using aCGH. However, we are pleased that Geraedts and Gianaroli have chosen to raise in their letter the cost-effectiveness of PGS using aCGH. Hirshfeld-Cytron et al. do not have anything specific to say on this topic but it is something that we have modelled in detail, although at present unpublished. However, it is perhaps worth noting here that a recent prospective blinded non-selection study (Scott et al., 2012), which included 146 couples, found that complete chromosome screening (CCS) could have prevented two first trimester spontaneous abortions (both non-viable trisomy 17) at a cost, we estimate, of around $500 000 (additional cost of CCS: http://wantedonegoodembryo.blogspot.co.uk/2010/ 07/cost-of-ccs.html, accessed 22 May 2012) for each spontaneous abortion. Interestingly, in the same study, 4 out of 55 healthy live births had an incorrect aneuploid biopsy result; these embryos would have been discarded if the CCS had been carried out as a diagnostic PGS test, leading to a reduction of 11% in the odds of a healthy live birth. These data suggest that both financially and in terms of pregnancy outcome, PGS has not yet been shown to offer overall benefit to patients.