Dear Professor Winston
I am hoping you can help me with a question.
I have had 1 unsuccessful and 1 successful round of IVF.
Recently we found out our son is likely to have ARPKD (Autosomal Recessive Polycystic Kidney Disease) and therefore we are currently having genetic testing on him. On the assumption his form of the disease can be genetically identified, we can then test my husband and I and the ultimately test the embryos we have left (8). Is there any research on the viability of embryos that have been defrosted, tested, refrozen and implanted?
I’m not sure whether we should simply go for a fresh cycle. I was 34 when the embryos were created and will be 36/37 when we next try.
Any thoughts would be gratefully received.
Thanks,
N.
Dear N,
A perfectly simple question but difficult to answer. As you possibly may know, we at Genesis in Imperial College invented preimplantation genetic diagnosis. When we launched the treatment we generally tried to avoid freezing embryos as we felt the added procedure of also taking cells away from an embryo after thawing was possibly going to give less good results.
I still think that this just might be true but I was unaware of any recent evidence which suggests it definitely make a difference to the chances of pregnancy. Consequently I have run a literature search on your behalf to see what the latest evidence shows. I was aware of the results of the Kings College Hospital group many years ago, run by Professor Braude (a very good programme) but your question does give me opportunity to look at more recent data. Prof Braude’s group was interested in biopsy of the embryo both at the early stage of development and at the time of blastocyst development. In a nutshell, show evidence which suggested that cryopreservation did not reduce the chance of pregnancy after embryo freezing. But that was over ten years ago and more cycles using these techniques in many more countries have now been assessed.
An important review of world experience was published in the reputable journal Reproduction last year, warned that there might be risks in all these techniques irrespective of what stage the embryo was biopsied to have a cell or cells taken away. Though not precisely relevant to your question, the survey by Zacchini (from Poland) and her colleagues argues that any of these techniques might cause some risk to a foetus after cells are removed, with or without freezing being part of the process. They quoted Chinese experience in mouse research which suggested that biopsy of the embryo at any stage might modify adult development, and reviewed the evidence of harm to human adults. Of course the oldest child born after embryo biopsy is still not yet 30 years old, but there is some evidence that some pregnancies grew slower (we found that in our embryo research too) that miscarriage might be a bit more common and that babies tended to be smaller at birth. In mice, studies have shown that embryo biopsy, (with or without freezing) resulted in some animals having increased body weight, impaired memory, increased anxiety traits and an altered responses to stress, some hormonal changes and reduced fertility bin older age. Now, of course, these are only mice studies and might not apply to humans at all. But it implies a justified criticism of us, as professionals, that there are not better follow-up studies in children born after any of these interventions. Moreover, it is massively disappointing that our own regulatory authority, the HFEA, has not managed to collect better statistics so such studies could be accomplished. Unfortunately, the Data Protection Act (a typical unintended consequence) makes these studies more difficult in one of the countries most set up to undertake such work.
Quite recently a study in Israel (which has great expertise in IVF) by Shinar, Komecki, Schwartz and colleagues, in the Journal Gynecological Endocrinology suggests that survival of embryos and pregnancy rates may be better if biopsy is done after freezing, rather than before it. They had access to data from over 60 of their patients (which a large number in a specialised area like this). The difference in survival was not great, but their results were statistically significant. But the bigger question, which is implied to some extent in your question, is what are the risks of all the biopsy techniques which we pioneered. Probably not that great, but more research is really needed. But to my mind biopsy in a family like yours, where the alternatives are so problematic make the decision definitely justified. But I seriously wonder about the ethical issues raised when so many women are being sold costly embryo biopsy simply in the hope of increasing their chance of a pregnancy a bit (preimplantation genetic screening). Is the risk to any fetus justified when the procedure is not done for a serious genetic disease?
I hope this is helpful
Best wishes
Robert Winston