The egg donation fertilisation process in the UK

7th October 2014

An Altrui egg donor questions Dr Virginia Bolton, Consultant Embryologist, about the egg donation fertilisation process. Egg donors go through the donation process with many aspects fully explained at all stages. However what happens with the eggs after they have been removed and what happens in the laboratory and with the fertilisation process is explained once the donated eggs have been removed. This conversation held at the Assisted Conception Unit, Guys and St Thomas’ NHS Trust, London.


Egg Donor: What happens when you’ve collected the eggs? How soon are they met with the sperm?Dr Bolton: Well what happens is, it, it depends on the quality of the sperm from the partner of the recipient. So if it’s just going to be straightforward IVF, which is the sort of classic ‘test tube baby’ treatment that was developed for Louise Brown’s birth, then all that has to be done is the sperm has to be prepared erm, and have been mixed with the eggs at about – well, if the egg collection’s at say half past eight, we’ll mix the eggs and the sperm at half past three in the afternoon.
And so the eggs will sit in the lab in an incubator; we’ve got a lot of incubators, obviously, so each, each donor’s eggs will be put into a dish allocated to the recipient, and will sit in a nourishing, warm environment of moist warm air, until they’re ready to be inseminated.So with IVF we just concentrate the vigorous, moving, healthy sperm into a really concentrated suspension and add a tiny droplet of that to each drop of fluid containing the eggs, and the sperm will swim around overnight. One of them will penetrate each egg, hopefully, and fertilise it.Egg Donor: What do they grow into, before they’re put into the recipient? Do they call it a blastocyst?

Dr Bolton: No, no – what happens is the egg, the embryo doesn’t actually grow at all, it stays the same size for the first five days of development, and in those five days – well we can put the embryo back into the womb of the recipient any point between fertilisation and the end of those first five days, because there’s something very special about mammalian embryos, but the egg itself is coated with a sort of gelatinous coating and it’s – we think that that is there as part of this very special thing about the human embryo, which is that it’s a free-floating entity – or the mammalian embryo, I should say – it’s a free-floating entity for those first five days.

And that’s the time that it’s, it’s released from the ovaries, an egg, and becomes fertilised, and it trundles down the fallopian tubes – you know you’ve got your two fallopian tubes. It trundles down the fallopian tubes, stays the same size, still coated in this outer coating, protected, and the cells divide during that process of its little journey down to the, into the womb. And each division, the cells halve in size. So the embryo is called a cleavage stage embryo, because those divisions are called cleavage divisions, rather than the divisions of the cells, the rest of the cells in your body, where you end up with – a cell sort of grows, and then divides, and you end up with two cells the same size as the original cell. With your embryo it’s the same size for five days; the cells get smaller and smaller and smaller and smaller, until a little ball of cells arrives in the womb, and that’s the blastocyst, at five days.

But we can put the embryo back into the, into the womb with IVF treatment at any point during those first five days. After five days, between six and seven days, the embryo is called a ‘hatching blastocyst; it bursts out of that outer coating, and that’s the point at which a pregnancy really can begin, because you’ve got the cells of the embryo emerging from this protective coating, and they’re literally naked cells against the naked cells of the uterus, and you get that burrowing into the lining of the womb in the beginning of a pregnancy, and that’s called implantation.

Egg Donor: And when, when and where – ‘cause the eggs get graded as well.

Dr Bolton: The eggs don’t – tend not to get graded. Certainly here we don’t grade them –

Egg Donor: Right.

Dr Bolton: Because – you remember I mentioned this blob of jelly like cells that, you can’t really see the egg unless you can strip away those cells. So if you’re doing ICSI –

Egg Donor: Yeah.

Dr Bolton: – you do strip those cells away and you can look very closely at the naked egg, but with IVF you leave the cells around the egg, so you can’t really tell what it looks like. The following day, when you come in to look for fertilisation – so you can see whether the egg’s fertilised the day after the egg collection. The DNA, the genetic material, from the sperm, mixes with the genetic material from the egg, and at – initially it, it literally looks like two craters in the middle of the egg. That’s on day one. And then, later on on day one, those two sets of genetic material fuse to form one unique set of genes that’s the new genetic material of a new individual, and erm, then later on, on that same day, the first cleavage division will happen, and erm, and then the, over the next few days it goes from two cells to four cells to eight cells and so on.

Egg Donor: Do you know the moment the person who’s retrieving the eggs does the collection? Are you ready thereon waiting to – ?

Dr Bolton: The most important thing, or one of the most important things throughout the whole process is making sure that we minimise any damage that we might cause to the eggs, because they’re precious, precious eggs, and each one is the potential contribution to a new family for the recipient. So what we must do is maintain the environment around the eggs as close to what’s inside your body as possible. And the way we do that is we keep everything at body temperature, we minimise the exposure time to air, to the environment, to the temperature, of room temperature. So yes, it’s really important that any embryologist is on standby to collect the tubes of fluid that hopefully contain eggs from the donors, and quickly examine them as fast as possible to get those eggs into the incubator where they can be kept warm.

But every step of the way we’ve got everything kept warm; so the surfaces of the microscope stages that we look down are kept at body temperature, there are hot – test tube blocks are heated to keep the tubes of fluid that come out of your ovaries at room temperature. So, everywhere that does any kind of assisting conception treatment would absolutely have to make sure that these sort of processes are possible with the minimum damage caused by fluctuations in temperature, which can be very harmful.

Egg Donor: I suppose if you get into the role quite, you know, seriously, it could be qui- it can be quite reassuring and quite exciting to come in the next day and see that, you know, the sperm has fertilised, and it…

Dr Bolton: It’s – yes, I mean, on a daily basis it’s, it’s something that we come in – I mean, it’s one of the wonderful things about biology, but also it’s one of the tragedies, in some cases, that you can’t predict. Even when you think everything is perfect, there might be something that you haven’t – you don’t even know about, that could contribute.

Egg Donor: I mean, have you physically watched it, step by step, and not –

Dr Bolton: You can’t, you can’t actually see that – the act of fertilisation.

Egg Donor: Can’t you?

Dr Bolton: Even, even with the time lapse imaging that we have now, which takes photographs of the embryo that’s developing, so you can play a video of the embryo dividing, erm, but to actually see the process of fertilisation… It’s such a long, drawn-out process; it takes about 18 hours for the sperm to penetrate the egg.

Egg Donor: So you’ve never physically sort of…

Dr Bolton: So even when you, even when you carry out ICSI so you inject the sperm in, you pull your injection needle out and you see the little sperm head sitting in the egg. But you could sit and watch it for hours and nothing would seem to happen. So it all happens very, very slowly.

With time lapse imaging you can see the, the genetic material forming the little crater like structures I told you about. You can see that forming, but you can’t physically sit and watch it happen yourself, it’s just too, too slow. And also we want to keep everything out of the incubator for as short a time as possible because any, anything that’s different from the environment of the body is potentially damaging, and there’s an awful lot we don’t understand, so we try and minimise any, any changes that we subject the eggs and embryos to.

Egg Donor: Do you also look after the frozen embryos as well, when recipients choo – er, choose to freeze? And, how often are they checked? Or are they just kept…?

Dr Bolton: No, no, no. Once, once frozen – once an embryo’s frozen, it will sit in liquid nitrogen, undisturbed, until it’s needed. There is no point in checking them, because literally the whole process of freezing is about putting them in a state of suspended animation, so provided you keep the liquid of, the liquid nitrogen topped up – they’re in these big tanks – erm, provided they’re submerged in liquid nitrogen nothing is going to change, ‘cause it’s – absolute zero, noth- no molecules are doing anything, they’re just sitting still.

So the act of removing them has to be the act of actively wanting to [form them 0:08:51] and use them, yes.

Egg Donor: In IVF, is it more common as, as a mum of multiples myself, how, how more common is it for multiples to be the res- as a result of IVF treatment?

Dr Bolton: Well that’s one of the concerns that are being addressed by responsible practitioners and actually the human fertilisation and embryology authority, because they recognise that it was one in five, even more, pregnancies resulting from IVF were twin pregnancies. But this is a few years ago now, but the simple reason is because to maximise the chances of a pregnancy, people were putting back two, possibly three embryos. I mean, in the old, old days, people would out back eight, nine embryos, and you’d have these high order multiple pregnancies. So, as everybody got better at doing IVF, we started to put back fewer and fewer embryos, and so it became common to put back two embryos and no more. Erm, except in possibly much older ladies, but even that carried with it this high, high chance of twin pregnancies, so that’s where the twin pregnancies come from, because you put two embryos back, if both take you have a twin pregnancy. So you put back one embryo you’re going to reduce the chances of that happening, and that’s what more and more centres are beginning to do.

Egg Donor: What determines a good embryo?

Dr Bolton: Very good question. This is actual the multi-million dollar question, because nobody knows. We think we’ve got little signals and signs which draw us towards the better embryos, but they confound us all the time, because we’ll have people where we think, “These embryos are rather poor quality, so to maximise the chances of pregnancy we’d better put two of those back in this lady,” and lo and behold she surprises us all and turns out with twins.
Equally, we might put back what we consider to be the best embryo you could hope to see, textbook beautiful, and – so we say we only put back one embryo, and the lady doesn’t get pregnant.