Embryo development and evaluation - a look back over time with Professor David Gardner.

Reflecting on progress in the IVF lab. 

So many things have happened in the IVF lab over the last 25-30 years. Back in 1995, in the US, the average number of embryos transferred was four. That was done because we really couldn’t grow the embryos in the laboratory very well; we couldn’t get them past the eight cell stage so we were condemned to put cleavage stage embryos back in the uterus, which meant they were going back too early, and we know from research in animal models that if you do that, you get compromised outcomes. So, while transferring multiple embryos was a necessary means to an end, it meant we were getting low pregnancy rates and a lot of multiple pregnancies. It wasn’t satisfactory for anybody, least of all the patients. 

One of the biggest things from my perspective was in the 90s, when a lot of basic research in animal models, and also the analysis of human oviduct and uterine fluids, led us to develop sequential media, and then we were able to grow the human embryo to the blastocyst stage so that we could do what we call synchronous transfer, and of course, that led to an almost doubling of implantation rates. Ultimately by 2004, we were doing single blastocyst transfer in the US. To go from four embryos in 1995 to single embryo transfer in 2004, was a huge breakthrough and attaining higher pregnancy rates with just one embryo was a fantastic turning point for IVF. 

Breakthroughs only occur through research

I can’t undersell the significance of doing the basic research to understand the physiology of the tissues that we work with. We have to remind ourselves that the human embryo is smaller than a full stop on a printed page, and you need to develop specialised skills to work with that. Prior to the clinical translation of blastocyst transfer, it took us about 10 years to work out the full system - people used to say we were an overnight success, except that we were an overnight success 10 years in the making! It took all that backlog of research to get to the clinical translation.

For me, 1999 was a real purple patch, the trifecta of successes. We developed a transfer medium called Embryo Glue, which is proven to be successful in improving implantation rates, we were the first to vitrify the human blastocyst and we published the Gardner Grading System which went on to be used worldwide. That was 20 years ago, at the turn of the century, and now as I look at where we are going with technology and AI, I think we’re entering another purple patch. I’m tremendously excited by the research that we are now starting to translate into the clinical arena which I think will show that 2020, and moving forward, will be incredibly exciting period in IVF.

The future: it’s how big dare you dream. 

I smile when I hear people say everything has been done and it’s been optimised. I always think we are optimising – we are always in the process of making it better or always in-between paradigms.
There’s two things that we are all working on as a group, the doctors and the scientists together. The first is the time to pregnancy; a lot of what we talk about is getting our patients pregnant sooner, on their first or second cycle. The second one is getting more patients pregnant. Time to pregnancy is really dependent on having superior embryo selection technologies and this is where AI and the initiatives driven by Virtus have been highly significant. Our RCT (the VISA Study) is investigating the next generation of Artificial Intelligence in embryology, helping us to select and identify those embryos with the greatest possibility of giving us a healthy pregnancy. Getting more patients pregnant will result from improvements in the culture environment itself.

There is a whole range of things to come; we are going to be busy for the next decade or so, that’s for sure.