Pre-implantation genetic testing and fertility preservation

Kate’s experience with PGT-A was frustrating and made her wish there was more transparency about the evidence base behind such procedures.

So egg collection went really well. We managed to collect 22 eggs and we had about ten or 12 – I can’t remember the exact numbers now – that fertilised. And we had – it might have been about seven I think that made it to five-day old embryos. We sent a couple of those away for genetic testing. We sent three away. Two came back normal, one was abnormal so that was destroyed. And so far I’ve had three embryo transfers and all have been unsuccessful.

I’ve got one more frozen embryo to go and then that’s probably about it. Trying to figure out whether or not we would proceed with another stimulated cycle. Probably not, it’s getting very expensive. Very time-consuming and I’m starting to feel like – well I’m 39 now, we started this when I was 36. So three years we’ve been trying to conceive the third child.

The thing is I thought IVF would be the answer. Because I think that’s how people view IVF. But it’s really not. The success rates actually aren’t that great. And the older you are obviously even worse. But when we got so many eggs and when we got some good embryos I thought “Oh yeah, it’ll be all right. Yep”. So when the first two embryos that had been genetically tested and came back normal – and they say that increases your chances. They said to me if you genetically test them and they’re normal your chances go up to about 60 percent. So I thought “Oh yeah. Yeah we’ve got this. No problem.” But no. And it’s just more money. It’s just – you just keep throwing things at it. It’s ridiculous really.

I would love more transparency around outcomes and results, when the fertility specialist said that if we genetically test the embryos you’d have a 60 percent chance yet – I mean I’m not saying that that’s incorrect but I want more answers around why that hasn’t been the case but I don’t get many answers and maybe that’s because they don’t know. In which case I want them to say that. That they don’t know. I don’t want them to keep offering stuff unless they feel it’s really evidence based stuff. Yeah I want the honesty.

Kim was 41 when she started fertility treatment. She froze some of her eggs to avoid ‘wasting time’ while her known donor had his sperm donations checked, and in future hopes to bank some embryos.

I started looking into more about the donor process from the donor conceived child’s point of view and how they deal with things like growing up not knowing one of their parents and identity issues and things like that.

I guess looking at all that stuff also helped to make that decision to use a known donor because I think even if I’d used a clinic donor I would have tried to make contact with them early on.

So I’ve decided to use my friend as a donor as he’s quite happy to be around and to play some part in the child’s life as more of an uncle figure or something like that. So that’s why at the moment I’ve put him through the clinic process so he’s done all his tests. I also got him genetically screened and he came back with nothing, which is pretty unbelievable [laughter]. So at the moment he’s just doing his last donations before it gets puts into quarantine and then in the meantime I’ve been doing some rounds of egg freezing just so I’m not wasting that time.

Because it takes four or five months to get your donor through all the testing and the counselling and all the donations and everything and the quarantine.

So it’s quite a long time especially at my age so I didn’t want to waste that time just waiting. So I thought I’d do some egg freezing in the meantime.

So it’s exactly the same process as if you’re going through an IVF cycle. So I had the same drugs and the same quantities. So you’re basically stimulating your ovaries to mature the eggs that you would otherwise lose in a normal cycle so that you can collect them.

My first egg freeze round I actually developed a cyst on one of my ovaries which apparently is quite a normal thing to happen. So that prevented one of the ovaries from producing many eggs, so I only got two eggs from that cycle. Then the last cycle that I did I got nine eggs retrieved and then seven were actually mature enough to freeze.

So in an ideal world I would like to try and have two kids so that they’ve got siblings. So I’m going to try and embryo bank a little bit which is something that you can do with a known donor and this is something I found out through the process. You can’t do it with a clinic donor actually which was another reason that I wanted to use a known donor because with a clinic donor because they’ve got a limited amount of sperm you have to – any embryos that you make from one cycle you have to use those before you can go and do another cycle.

So I wanted to because of my age try and get as many embryos now as possible so that I can potentially have those in the freezer and try and have a second child at a later stage because my egg quality’s only going to decline further in the next few years and pretty drastically. So I wanted to try and make as many embryos as possible and freeze them so that I would have hopefully a good chance at having a second baby later on.

A BRCA 1 genetic mutation carrier, Elena had her uterine tubes removed to reduce her ovarian cancer risk. As she wanted to have a baby, she underwent IVF and PGT-M to detect any BRCA 1 mutations. Her clinic also performed PGT-A.

Elena: I carry a BRCA1 genetic mutation and my mother passed away when she was quite young as have most of the women in my family that have this genetic mutation.   

I decided to have myself tested and wasn’t surprised to find out that I was also a carrier of the BRCA1 genetic mutation and made the decision to have a prophylactic mastectomy.  At the age of 38 I had my fallopian [uterine] tubes removed which significantly reduced my ovarian cancer risk and after giving birth to my son I had my ovaries removed. 

Interviewer: So when you first found out that you were a carrier of the gene, did they speak to you about fertility preservation or was it mostly on reducing cancer risk? 

Elena: I don’t recall any conversation around fertility preservation or using IVF to reduce, to select an embryo that didn’t carry my gene.  When I found out that I was a carrier for the BRCA1 genetic mutation, the science hadn’t developed far enough to be able to do pre-implantation genetic testing on embryos.  So it wasn’t a known opportunity at that time.  Fertility preservation also was in its infancy, and I think pre-2012 the success rate around frozen eggs was extremely poor.   

So it wasn’t ever a discussion that I had, the discussion was always, “You need to think about having kids sooner rather than later and you probably need to think about getting your ovaries removed when you’re 35 years old”.  So that was certainly the conversation at the time.  

I ended up going and working in cancer research in communications. Along the way I worked with a lot of medical researchers and they began talking about this amazing ability to stop cancer before it could even start.  The fact that you could select an embryo was possibly the closest thing to a cure for cancer that they had at the time.  So that really helped me make a decision that it was something that I wanted to do.   

So then I made the decision that I would be a solo mum by choice.   

That first round I ended up with seven embryos, but only one embryo came from an egg that had been frozen.  My frozen eggs performed very poorly, compared to the fresh eggs, so I guess that’s something to consider when you’re doing fertility preservation.  Of those seven embryos all were carriers for my BRCA1 genetic mutation.  I expected about half would be, which is what the odds were, but all were and that was pretty devastating. 

So I then went back for more rounds and even though I was getting embryos that were without my BRCA1 genetic mutation, the embryologists were saying, “Well there’s other chromosomes that aren’t right and you may be born with a baby with a disability, or it won’t work, it won’t take in the pregnancy,” and the fertility doctors refused to transfer them. 

I went away and did a lot of research around this, having a medical comms background and I was really quite uncomfortable with the science that apparently showed that these embryos were problematic.  Since then there’s been a lot of evidence that has come forward around mosaic embryos – embryos with some abnormal cells, with some healthy cells – actually having a very, very high success rate².  In the past these embryos were destroyed which I just find devastating, especially for women who maybe never achieved having a baby. 

 I was really quite frustrated with this because it really meant from the beginning my chance of success was extremely low, probably less than 5% but that wasn’t explained to me at the outset.  In the process, so as a 38, 39, 40-year-old woman I was actually getting a lot of embryos to day 5.  So my egg quality seemed okay but I decided I would swap sperm donors because I thought, ‘Well I can’t improve my egg quality any more than it is.  So how can I try and boost my chances of getting more embryos because I seem to need so many to try and get this one golden egg?’ 

I swapped sperm donors, and I got a lot more embryos.  I was back up around eight embryos for the round.  This time we got one that was free of my gene and also considered chromosomally normal.  We got a couple more that were free of my gene and considered mosaic and in my mind I considered them normal as well, based on all of the evidence that I’ve read around mosaic embryos.  So I transferred this one normal that was also free of my gene and yes and it worked.  So I’ve got a beautiful little boy and he is just delightful.   

So I started my first round just after I turned 38 and I gave birth to my son just before I turned 42.  In total I had around 80 to 100 eggs harvested.  I ended up with about 22 embryos that reached day 5 and I had one that was chromosomally normal and free of my BRCA 1 genetic mutation and another two that were free of my BRCA1 mutation and mosaic, across about eight rounds in total.

² Mosaic embryos can produce live births at around half the rate of ‘normal’ embryos (Zhang, L., Wei, D., Zhu, Y., Gao, Y., Yan, J. & Chen, Z. (2019). Rates of live birth after mosaic embryo transfer compared with euploid embryo transfer. Journal of Assisted Reproduction and Genetics, 36(1): 165-172. https://doi.org/10.1007/s10815-018-1322-2).