Do you recommend chromosome screening?

Dear Professor Winston
I am looking to find out what your views are on chromosome screening as this has been an option provided to me at a recent private IVF consultation. My partner and I have been diagnosed as having unexplained infertility. I have had one round of IUI and one round of NHS funded IVF (as this was all that was available to me under my postal code area). The IVF treatment resulted in nine eggs which produced seven embryos of which three of these went to 5 day blastocyst. The fresh cycle failed and the other two were frozen, the first one failed after FET and the third did not survive the thawing process. Due to my present age which is 40 years old and no pregnancies arising from any treatment, is chromosone screening something that you would recommend to think about? This treatment has added another £2500 on top of the costs that we’ve already been given for private IVF treatment!! I would greatly appreciate your views on this.
Thank you, J.

Dear J.,

All humans frequently produce chromosomally abnormal embryos and this seems to get more common as we age. Presumably the reason why they are suggesting chromosome screening is because the clinic is assuming that, because of your age, you may be producing more embryos with genetic defects which show up in the chromosomes. The technique involves taking one or two cells from a 3-day old embryo during development (biopsy) and staining for abnormalities in the chromosomes or taking a clump of cells (usually from the tissue which will become the placenta) from a blastocyst when rather more cells – perhaps a dozen or so can be extracted. The technique is referred to as preimplantation genetic screening and was first done (financed by the Genesis Research Trust to which I hope I can encourage donations) about 22 years ago in our unit at Imperial College in collaboration with Dr Delhanty at University College London.

Since that time, the identification of defects in chromosomes has been more and more refined and it is now possible, in a few clinics, to look at all the chromosomes and even major sequences of DNA in the cells. But the problems with the standard technique are rather understated by many clinics. Firstly, removing cells is possibly not ideal for the embryo (it is after all an injury) and its subsequent development which may be why pregnancy rates have sometimes tended to be lower than in unbiopsied embryos. Secondly, the cells removed may not representative of the cells left behind as human embryos are frequently ‘mosaic’ – that is to say that some cells may have normal chromosomes and other cells in the embryo may have abnormalities. So a normal biopsy does not necessarily the embryo is normal and an abnormal biopsy does not necessarily mean that the embryo is abnormal. So you can get a result which suggests the embryos are abnormal when they are not, and these embryos end up being discarded. At the present time, randomised trials do not show any advantage by undertaking preimplantation genetic screening – indeed, the reports suggest that this reduces the overall chance of pregnancy, in some cases by as much as 50% of the time. Most recently, new techniques for more accurate screening have been published and with the techniques a few clinics claim that there is a significant advantage. Until adequate trials are published I remain somewhat sceptical. In a heavily commercialised market I sometimes wonder whether there may be a conflict of interests when offering these tests.

I think that if I were you, I would want to ask what success rate the clinic you are attending is obtaining, and most important, what method of chromosome screening they are using and how many chromosomes in each cell are being examined. If they are using what are called ‘next generation sequencing’ techniques there may just be some merit in spending the money – but even then I urge caution because I have not seen enough really convincing evidence that this truly improves your chance of having a healthy baby if you and your husband both have normal chromosomes and are free of diagnosed genetic defects yourselves. Incidentally, one of the problems is that the drugs given to induce ovulation during an IVF cycle undoubtedly increase the number of chromosomal defects seen in embryos – Genesis Research Trust published that information around thirty years ago. This is one reason why I sometimes feel that that older women have more chance of successful pregnancy by just having natural sex than by going through IVF. Unfortunately, natural cycle IVF – without drugs – has not been at all successful except in a very few women in your age group.

I hope this is helpful,
My best wishes
Robert Winston