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Interview with Professor Simon Fishel by Dr Jacques Cohen at COGI Amsterdam 2016

Prof Simon Fishel-HD 1080p

Q. Hello, welcome to the COGI meeting. We are here in Amsterdam and it is in November 2016 and I am here with Dr Simon Fishel, whom I have worked with 35 years ago, for a number of years in Bourn Hall Clinic, where we worked with Drs Edwards and Steptoe. I have kept in touch and I have very similar interests; there are differences – I am wearing a tie and he is not.
A. It used to be the other way around!

Q. It used to be the other way around. Simon is the founder of CARE, one of the founders of CARE, which is the largest IVF clinic network in the United Kingdom and he is now the Chief of R&D – I hope I am saying it right – and the President of CARE. You gave two terrific talks yesterday; really good talks. One was on key performance indicators with is massively complicated, how complicated it is, and the second talk was on the fact that, if you do PGS and you transfer euploid embryos, there are still a considerable number that are not going to make it. You and others, but you are trying to find reasons why that is.
A. Yes.

Q. What are you looking at? What are your interests in that particular area?
A. That particular study is a fascinating one because it is about how the implanting embryo, whose trophectoderm becomes a placenta and then starts to intermingle with the spiral arteries of the mother’s endometrium, somehow may go wrong. For example, it may produce, in certain thrombophilic diseases little micro-clots, and we know that, in thrombophilic disease, those cause a failure of the placenta and also potential damage to the growing foetus and a whole raft or problems, including small for gestational age babies. How do you get round that problem? First of all, the one thing that we haven’t been able to do for years is have a precision medicine approach to those patients who may have that problem. What is important about this, it is not about the embryo per se, it is about the embryo-endometrial relationship, because even though it might be a euploid embryo, and we know the benefits of PGS, which are huge, the problem will be that, if you have another factor that is preventing that embryo implanting, it could be one of the reasons why the 25% euploid embryos don’t make babies. What we have found is that there is a significant population of people and the incidence varies according to the ethnic group, where they are carriers of a mutation, a four-base permutation, in what is known as the annexin V gene. The annexin are a group of proteins involved in the coagulability of the placenta. It is part of the thrombophilic disorders, but this particular annexin, there are loads of the, annexin V, and a mutation known as the N2 haplotype, this is unrelated to the known thrombophilic disorders, so it is separate to that. There have been a lot of studies originating out of the University of Münster, showing that in recurrent pregnancy loss, if this mutation is there, it is a high incidence in a recurrent pregnancy loss group. Our interest was to look at this in our IVF patients because, particularly in IVF, we can get in early. When you have a trial going on in the normal population, patients don’t come until they are well pregnant – four/five/six weeks pregnant and therefore it may be too late, if they are carrying this mutation, which causes early micro-clots in the early developing placenta and, indeed, that is what we found. By isolating this particular group of patients, doing a peripheral blood test, showing that they are a carrier, we can use low molecular weight heparin. What is fascinating about this though, carrier state is equal in men and women. The mutation gets into the embryo, the trophectoderm, from either the man or the woman, so the man causes a miscarriage in the woman if he is carrying the mutation, but if we treat the woman with low molecular weight heparin, we now know that she has the same chance of a live birth as our control when before these patients have a history of never having a live birth. Lots of miscarriages or failed IVF.

Q. Right, so how far are you able to now eliminate that gap that exists between the euploid embryo and full success? Is this 2% up, or 5%? What did you see, or are able to analyse that?
A. That is a brilliant question. Our next study is to work with, and we are working now with different colleagues in different parts of the world who are doing a lot of PGS to just do this in PGS issues, because we haven’t done that, so that is our next study.

Q. Right, okay; wonderful.
A. Yes; it is fascinating because there has to be other reasons; we have to work with biology and that is why the advent of precision medicine will help us do this and then we can make everything much more efficient, we hope.

Q. That’s great. You hope by doing the aneuploidy diagnosis that you eliminate that variable that, of course, is going to exist in a limited series of patients when you do your test.
A. Yes.

Q. That is an excellent plan. Thank you very much. It is great talking to you again. You always have original ideas and I hope we will meet at the next COGI meeting.
A. I certainly hope so. It is always good to see you.

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