Hatching a Plan

welcome to episode three of

hatching a plan my name's

simon i'm emma the embryologist's husband

i'm emma emma the

embryologist and this is

simon yeah i think that's

how we do our intro now

maybe we should do that

every time but thank you so

much folks um for joining

us today

right.

So just to clarify, I am the tech geek.

I am not a medical professional.

Emma is the expert here.

And today, this is all about PGT.

But before we dive into that,

we thought we'd get to know

the audience a little bit more.

So

We are based in Teddington

in Greater London.

So if you do want to share

where you're dialling in from today,

that'd be lovely.

Kind of get to know where the audience is,

whereabouts you're based.

If you don't want to share,

you don't have to,

but it's always nice to

hear from where folks are

dialling in from today.

So whilst those comments are coming in,

Emma,

why are we doing this podcast just

before we dive into this topic today?

Well,

you call it a podcast and I don't

think we've ever really

spoken about that.

We've turning this into a

podcast because this

started off as a live webinar,

educational thing.

And then we got talking and we were like,

actually,

it needs to go out in different

places so that people can

listen to it as well as

watch it live or watch it

on YouTube and all of that thing.

So yeah,

it is a podcast and we're doing it

because I don't think it

should be that difficult

for people to get information.

about all of this stuff i

don't think you're going

into a journey that is so

complex and complicated and

i just don't think you

should fight that hard to

find out what i believe are

quite basic facts yeah

absolutely and i've uh well

how long we lived together

about 18 years now 18 too

long too too long oh boy oh

that's awkward this is live

live couple uh

but but in those 18 18

wonderful years uh yeah

i've been listening to emma

and emma if you don't know

emma already says listening

drowning and training on no

emma has serious passion

about what she does um you

know like day in day out is

is there just to do amazing

things for people and to help people

um from all walks of life to

to move forward with

whatever treatment they're

going through so yeah she's

ace and if yeah if you're

not familiar with emma then

please do follow her on

instagram at emma the

embryologist we also have

as mentioned the podcast

which is available um if

you if you head over to

uh where have we got that

link now oh i haven't got

that link to hand we'll

talk about that a little

bit later but if you if you

look up hatching a plan on

various podcasting

platforms it will be

available so there's two

episodes so far we've got

choosing a fertility clinic

understanding the vienna

consensus and then our last

episode was everything you

need to know about donor

sperm loads of fascinating

information shared on there

So we've got some people

dialing in from all over the world.

This is wonderful.

Okay, let's go back to the top.

So we've got Ascot.

Hi there, Ewa or Ewa.

Apologies if I mispronounce your name.

Ewa.

Ewa.

Ah, okay.

Lauren from Vauxhall.

Just down the road.

Ah, there you go.

And Kelly Weybridge,

just down the road as well.

Laura from Luzerne in Switzerland.

Hannah from Gloucestershire.

Melissa from Costa Rica, CA.

Would that be California?

I don't know.

Oh, wow.

Amazing.

From Woking, Hertfordshire, Croydon,

London.

Oh, Yannica,

you're in Greece at the moment

for your IVF.

Oh, amazing.

Yeah, yeah.

And Sepi from Aberdeen.

Oh, and Kelly, very kind words.

She is great on Insta.

Yeah, she is indeed.

Emma really tries her best to just,

you know, schedule with, well,

we have a family and you're

very busy at your clinic or clinics,

I should say.

Clinics.

Yeah, both clinics.

And what's your official title?

It's got lots of words in it.

I am the Director of

Embryology and Genetics for

the Evewell Group.

So I've got a clinic in

Harley Street and a clinic

in Hammersmith.

And I divide my time between the two.

And I have a very lovely, wonderful,

big team of 15

embryologists and admin

assistants and stuff that

make it all work.

It's all about the team.

It's never about the eye.

I'm quite nervous about this one.

How come you're nervous?

What's up?

Because this is my area of expertise.

So really...

I want to get this right

because it's something I

genuinely believe people

should be aware exists.

I think people have gone

through IVF without even

knowing about PGT,

and I want to try and swing

it on its head about where

and how you use it.

So I'm quite nervous about

this one because it's

something that is... I'm a

genetic disease expert,

so I deal with genetic disease,

which we'll come on to.

So I'm really keen to get this right.

Yeah, I get it.

So, folks, please go easy on Emma.

But, well,

saying that... You haven't gone

easy on me, it's fine.

No, this is amazing, right?

So Emma asked,

put out like a Q&A thingy on Instagram,

and we have got a whole

load of questions to get through.

This is amazing.

So thank you so much to

those that are joining us

that have already asked

their questions on Insta.

We've got some brilliant

questions come through.

So we've got a copy of them.

We're going to whiz through.

But before we do that...

what is pgt like let's step

right back what does it

stand for you know why does

it matter where does it

come from like give us give

us a bit of history where

does the pgt come from yeah

yeah why why did what was

pre-pgt why did you say pgt

started in like probably in nine

the mid-90s,

Alien Handyside did the first one,

I think,

at the Bridge Clinic in London in 96.

Right.

And it was looking for, from memory,

it was trying to detect

Fragile X Syndrome,

which is a condition that

is inherited through families,

and they created...

a group of embryos,

and then they used the technology,

very basic technology back then.

I mean, it's not basic, but it is now,

according to where we are now.

And they managed to help

this family have a baby

that was unaffected from

Fragile X. So it started in disease.

It very much started in disease.

Cystic fibrosis came next.

Huntington's disease came

probably after that.

The cancer genes, the BRCA's,

trying to rid families of really,

really hideous genetic disease.

That probably happened in the late 90s.

And then in the early noughties,

we started developing a

process called fish

florescence in situ hybridization,

which allowed us to see

just five chromosomes.

It was all done by staining.

And that's when we used to

biopsy embryos at day three.

We now know that that

probably wasn't our

greatest idea because

embryos are only eight

cells at day three.

So by removing a cell,

you are removing an eighth

of its overall makeup.

And we then really don't know.

how many of those embryos

didn't grow because of that

biopsy and you're going

back to like like the

noughties so it's um and

you got into it in 2008

2008 i did my biopsy

training so i've been

biopsy trained for 16 years

i started in day three

embryos and then we moved

into blastocyst biopsy in

2000 and i want to say 11

or 12 when we started doing

that so that's been about

10 15 years ago amazing

okay so with a bit of

history let's dive into

some of the questions and

thank you folks i can see

on the comments there's

some questions coming in we

will do our very best to

get to them we're going to

start first with the

questions that we had via

instagram and then for

folks sharing in the

comments thank you so much

we will do our best to get

to them we have got another

50 or so minutes so we

might we might have to go

rapid fire i think you like

well do we want to do what it is first

Oh, okay.

So we've done the history.

So what is it?

Pre-GT stands for

pre-implantation genetic testing.

And that doesn't define what

we're testing for.

That is the process of us

removing cells from an

embryo at a certain stage

in its development to try

and diagnose it for what

we're looking for.

If that's disease, that's disease.

If it's what we call aneuploidies,

which is when the... So

most embryos are made...

All embryos are made up of chromosomes.

And those chromosomes,

half of them come from the

egg and half of them come from the sperm.

And as we age as women,

we make more mistakes when

we make our eggs because

we're born with all our eggs.

I think people are probably

quite familiar with this idea now.

If the embryo content of

chromosome copy number is incorrect,

it's called an aneuploidy.

So for example, a Down syndrome embryo,

I use that because

everybody knows what it is,

is an extra copy of chromosome 21.

So you are 46XY, I am 46XX,

and a Down syndrome embryo is 47XY or XX,

but it carries that extra copy.

You can have less copies or

more copies you can have.

And some of them are

compatible with life and

some of them aren't,

but ultimately the majority

of these embryos will

result in miscarriage, failure to implant,

or...

So the most common reason we

use PGT now is what we call PGT-A,

which is pre-implantation

genetic testing for aneuploidies.

I'm not going to keep saying

pre-implantation genetic

testing because it takes ages.

Just PGT-A.

PGT-A.

Got it.

And then you've got something called PGTM,

which is when we're looking

for a monogenic disease,

and that's when we're

looking for a specific genetic disease.

And actually the laboratory

process for us doing it is identical.

We are growing embryos.

We are taking a few cells

from a blastocyst on day

five or day six or day seven,

and we are then freezing the embryo.

and the tiny amount of cells

between five and eight

cells that we take from the

outer cell line of the

embryo gets sent to a

genetics testing lab the

testing they do determines

what they find out my

process is the same you

tell them what to test for

okay you say right this

specific type of test or

groups of tests i tell them

what i want yeah and what

the patient is after yeah

um if it's a genetic

disease it takes a little

bit longer to work up it we

have to go through the process of gaining

parental DNA to produce some

matching exercises.

But if it's PGTA,

which I would say 95% of

the work I do is PGTA,

then I send them the cells

and I tell them that we are

wanting a PGTA result for each embryo.

Got it.

Okay.

So that's what PGT is.

Yeah.

The process for me is a biopsy.

It's the growth of an embryo.

It's an embryo getting to

the right stage and it's

freezing those embryos down.

Embryos are always frozen

when you do

pre-implantation genetic

testing because it takes

between a week and two weeks

mainly towards the two week

mark to get the results.

So you can't then be

transferring embryos back

until you've got the

results because then they

would just be on screen.

So we call them screened

embryos or unscreened embryos.

I think that's the way it's

sort of spoken about in this in the UK.

Yeah.

Cool.

So just to clarify that you

mentioned about the UK, so your UK base,

obviously you're connected

to many clinics across the globe,

but when you talk about PGT,

is it specific to the UK or

could it be relevant to other parts?

PGT is done in the same,

it's probably done by the

same six or seven companies

all over the globe,

but it's what you're

allowed to know about the

embryos that changes from the country.

So like in the US,

you're allowed to know the

gender of the embryos.

In the UK,

you're not unless it's medically

relevant.

So there are circumstances.

Fragile X is a prime example

that it affects boys more

than it affects girls.

So you can do gender selection on embryos.

So you have to know.

You don't have to know,

but you can choose to know gender.

It's complicated.

But in this country,

you are not allowed to

gender identify an embryo

for anything other than medical reasons.

Cool.

Just verify this country, UK,

based in the UK,

because your clinic's UK based.

Cool.

still nervous are you all

right kind of yeah a little

bit okay okay let's get

stuck in folks okay here we

go so would you recommend

pgt after four early

miscarriages five six and a

half weeks losses yeah i

would and i think this is

one of the main players for

me early miscarriage um you

know the more like let's i

think i always say this

when i do any any sort of

talking topic i'm going to

take emotion out of this

because no one can

determine how long emotionally

anyone takes to get through a miscarriage.

It's a very personal journey,

but scientifically and

clinically and medically speaking,

an early miscarriage is

normally anything before we've seen

a heartbeat or anything

that's probably before

seven or eight weeks.

We call it early.

I think it's quite

derogatory to call it early.

A loss is a loss.

But clinically,

an early miscarriage before

eight weeks is medically

quite manageable and it

doesn't normally impact on

the time it takes for you to try again.

Emotionally is a different conversation.

If you are miscarrying,

that many times.

The most common reason for

early miscarriage,

unless you've got an

underlying disorder that

maybe the doctors haven't

checked or something,

there are things that cause miscarriages,

but it is mostly,

we know that 80 to 90% of

miscarriages are caused by

genetic aneuploidies,

so the wrong number of chromosomes.

It's actually nature's way

of being kind and I know

that sounds really awful.

A genetically aneuploid

embryo will either not make

you pregnant because nature

is actually good at quality

control or it will miscarry

because the body and the

embryo knows that the

information isn't correct.

Think of it like a blueprint

and the blueprint can't

make the building grow so

the embryo doesn't keep

growing so it miscarries.

However,

if you do continue to miscarry

like that and then you

require surgery for those miscarriages,

they can also lead to

long ongoing scarring

problems in the uterus,

which can stop you getting

pregnant full stop.

So yes, I do think PGT,

this is where I would use

it in the younger age group actually,

because it's not really

recommended in women under 35,

given that what we're trying to do is,

for me,

it's about reduction in time to

pregnancy and getting you there quicker.

so that you're not wasting

valuable time and

financials and resources

and emotional horrendousness.

But in women of under 35

with recurrent miscarriage,

I would use it.

I think it's incredibly powerful.

Okay, on to the next one.

Would you recommend it, being PGT,

for someone who has had

five failed cycles,

currently now aged 40?

Yeah, 100%, because again,

like I've just said,

the embryo either fails to implant.

But in some women,

there's definitely a difference in women.

Some women will grab onto

every embryo and miscarry them.

other women just won't get

pregnant with them you can

decide yourselves which is

kinder um i think that's a

very personal thought

process as well um at 40 we

know that only between 25

and 32 percent of our

embryos are going to be

genetically normal in a 40

year old maybe you might be

lucky and it could be as

high as 35 but overall we

know that we're on the flip

side of our early 40s so

given that you are if you

are able to create a group of embryos

and we know, say, for example,

five embryos,

only one of those is going to be normal,

why don't we just work that

out and only use that one embryo?

And then at least you know,

going into a cycle with a normal embryo,

that if that doesn't work,

we know that we've done

everything we can to make it work.

I would also be having a very,

very good look at before I

got to someone to put a new

ploid embryo back that had

had this many failed attempts,

I'd be looking at all the

other stuff as well just to

make sure it's not something else.

You often talk about like the holistic,

like not just,

it's not one specific thing.

You've got to look at history.

You've got to look at

everything that's happened in the past.

Okay.

On to the next one.

If no embryos are normal,

are you allowed to still

transfer as potential for

them to correct?

Now I'm,

I'm interested that we're getting

to this quite soon, actually.

Um, so under the UK law,

we are governed by UK law,

which is by the HFEA code of practice,

which I think anyone would know is,

is not my favorite place, but they do,

they are regulator and they

do the very best they can.

And they're chronically underfunded,

but in the code of practice,

we are bound by rules and regulation.

And one of the rules is the

actual wording of it is you

may not transfer

an abnormal embryo in the

presence of a normal.

So if someone has normal embryos,

you are not allowed to

prioritize abnormal embryos.

There is actually nothing in

the code of practice that

says you can't transfer an

abnormal embryo, but you will be very,

very pushed to find a

clinic that will do it.

And especially given the

evidence that has come out

in the last 18 months about

using abnormal embryos.

So to give everyone some

context about abnormal embryos,

when we talk about abnormal

embryos from recent times,

so the technology that we use now,

we are 98 to 99% certain

now that the outcome of

what we call a uniform

chromosome aneuploidy,

so that's a whole gain or a

whole loss of an embryo.

So a downs is a whole gain.

And a loss is something like

Turner syndrome,

which is missing a sex chromosome.

There's not many losses

actually that will result

in live birth at all, even pregnancy.

We, over the last sort of so many years,

there's been studies done on this.

And all genetic testing

laboratories have their own methods,

but one in particular,

which I work with called Juno,

have actually done what was

called a blinded study.

So they transferred a load

of embryos into women.

They had about 400 women

that transferred embryos

based on morphology grade alone,

so grading of an embryo.

They had actually done a

biopsy on these embryos and

they didn't get the results

until two years later

because they held them in

freezers and they let the

pregnancies play out.

They then found that in the one arm,

there was 200 normal

embryos transferred and we

had about 60 to 62% live

birth rate in that group,

which is what you'd expect.

And they then looked and

they had about 102

uniformly aneuploid embryos

and it was 100% lethal.

There was no babies.

There was about 12

pregnancies but they all miscarried.

Other people have repeated

that study and overall we

now know that 353 embryos

have been transferred as

aneuploid embryos.

And there is reports of two

babies being born.

One of which everyone is

convinced is actually a

mosaic and not an aneuploid.

And the other embryo

unfortunately has come from

quite a significantly,

how do I word this without being rude?

controversial individual in

the US who has already had

five papers redacted.

So again, I'm not overly convinced,

but hey, do you know what?

If it's one out of 353, for me,

that is enough of a paper

to show me that all we're

getting here is

miscarriages and heartache.

So that's where the data

stands with abnormal embryos.

So in the UK,

you probably won't find a

clinic that will do it.

There are places in the US

that will transfer abnormal embryos,

but the literature doesn't

support correction.

it does it just doesn't show

it it shows that if you are

using the best technology

now that we've got now then

it does correlate to almost

100 what we call lethality

so no ongoing pregnancies

once we've done the

aneuploidies and stuff gosh

fascinating those studies

okay should we jump on some

questions coming in from

the audience yeah should we

do that so let's jump back

out um okay so i think we had

Um,

let's bring this one up on the screen

from Lauren.

So I'm 42.

So I think I understand the

benefits doing PGT from

your previous webinars,

but I believe there's a

high chance that I may not

find a euploid in two,

three or more cycles.

So should I not consider

giving those day three or

five embryos a chance untested?

Thank you for your question, Lauren.

I suppose it comes back to the stats again,

um, Lauren, and if you are, you know,

you can put those embryos back.

Ultimately, if those embryos are normal,

then they've got the chance

for pregnancy as a normal embryo,

the risk of doing an

untested embryo at the age of 42.

is that there is an excess

of an 80% chance that the

embryos are aneuploid.

And it's what comes with an

aneuploid conception.

Like I said earlier,

if it doesn't make you pregnant, then yes,

remove emotion.

Like I said, it's heartbreaking.

But if it does make you

pregnant and you deal with

an eight week miscarriage

that then needs surgery,

you're potentially three to

six months down the line

before you can try again.

And at the age of 42,

we don't have that sort of

time before we can go and

collect more eggs.

So I get the argument.

But the realistic outcome of

what happens in aneuploid

conceptions needs to be discussed.

Yeah.

Yeah.

Thank you for your question, Lauren.

Lauren,

appreciate you being so open with

us and the audience today.

A question here from Janica.

So I have transferred a PGT

euploid embryo and still miscarriage.

Two of my non-tested embryos

came back genetically

normal with 46 chromosomes

when the issue was also tested.

And this might be the follow-on.

What could be the reasons

for miscarrying genetically

normal embryos?

I mean,

if you think that miscarriage is

one in four pregnancies and

even higher than that, I think,

because now we all test so early.

I don't know about,

I do know about everyone on here actually,

but I was testing from like, for our kids,

from day nine, day 10,

after I knew I could pick

up a positive pregnancy test.

Yeah, yeah, yeah.

And you've got to remember

back when our parents had us,

those pregnancy tests didn't exist.

So what we now know to be one in three,

one in four miscarriages,

people were just thinking

their period was late 20 years ago.

So we now know that

miscarriage is incredibly common,

especially the really early

ones that sometimes go as a

missed period.

And then you're just a few

days late and you have a bleed.

You were actually in a

biochemical pregnancy situation.

So we know that miscarriage

is something that happens

regardless of genetics.

It's definitely less with PGTA embryos.

I think overall we'd say in

any embryo going back that's unscreened,

you've got about a 24%

chance of a miscarriage, unfortunately.

And that gets higher with age.

As you get into your early to mid-40s,

it can be as high as 50%

miscarriage if you get pregnant with a...

an unscreened embryo.

We know that in PGTA tested embryos,

there's about 13 or 14% miscarriage rate.

And that comes down to why.

And so then you would really,

really need to be getting

into the elements of what

else causes miscarriage.

Immunes,

which I'm not a massive believer on,

but there's definitely

something in the body

rejecting something.

Lining, implantation factors.

microbiome of the uterus.

That's why we've got a lot

of other tests now that we would do.

So if a woman's only got one

newborn embryo in my clinic, for example,

they will do a full

diagnostic cycle to check

that everything's perfect

as it can be on paper

before you put that embryo back.

Because you might not get another one.

Yeah, yeah, I see.

So a bit like I don't

believe that you should be

using IVF as a diagnostic

tool when you can do ICSI.

Yeah,

I don't believe you should be using

an euploid embryo until

you're absolutely sure it's

going to have the opportunity to take.

Yeah, yeah.

So there are other tests

that need to be done.

There's things called ERAs

and EMAs and ALASs and...

There's so many things out there now.

And I think they've all got a place.

I don't think they're for everyone.

I don't think anything,

I don't think it's right for everyone.

But I think if you are

recurrently miscarrying or

losing euploid normal embryos, then yeah,

we need to start looking at something.

And I guess taking a step back,

a lot of why we're doing

these webinars and this is

a podcast and all the

educational stuff you share

on Instagram is...

Just so people have

questions to ask their

clinics and know what questions to ask,

not just kind of just sit there thinking,

oh, my goodness,

this is really overwhelming,

which clearly it is.

But just having a set and

series of questions.

So I think over time,

we're slowly going to build

out a set of questions,

a good crib sheet per kind

of area just to help people just to give,

you know,

your belief in education is just

so important.

Absolutely.

Thank you for that, Janneke.

We're going to jump on to

this one from Kirsten.

Kirsten,

is there a timeframe you can PGTA test in,

or could you test embryos

at a later date once they've been frozen?

So you can, you can do what we call,

we do quite a lot of them now, actually.

They're called thaw biopsy refreezes.

And what you have to do is

thaw the embryos out,

which if they're blastocysts,

you are thawing out the embryo.

you allow the embryo to

recover as if you were

going to transfer it.

So the aim is that it recovers,

it re-expands,

which is what we would aim for it to do,

and then we would do the

biopsy and re-freeze it.

Now,

the misconception here is that it is

harmful to freeze an embryo twice.

From my data, it's not.

I've got the same clinical

pregnancy rates from doing it twice.

I think what you need to make sure of,

if you are going to do a

Thor biopsy refreeze on embryos,

that you're working with a

clinic that will get your

embryos out and allow them

to do a full recovery

before they attempt to biopsy them.

I could biopsy an embryo

straight out of the freezer.

It's not challenging,

but is it the right thing to do?

Because if that embryo is

never going to recover,

it's not going to make a pregnancy anyway.

And you are then biopsying

something that was never

going to come out of that

first thought anyway.

So much like we do when

we're doing embryo

transfers from a frozen embryo,

we leave them for two to

three hours to make sure

they are fully recovered

before we do the transfer.

If they don't do well and a

patient's got more embryos,

we will then phone the

patient and talk to them

about thawing another

embryo to make sure they've

given it the best shot.

An embryo that doesn't re-expand,

which is when it gets

bigger after it's been thawed,

so it thaws out and it

takes on fluid again,

it gets bigger and starts to make itself

we freeze them down and

shrink them into balls by

taking the water out.

The water has to go back in

and then they get bigger again.

An embryo that doesn't do

that has got a really,

really low pregnancy potential.

So the question then is why

would you put it back in the freezer?

So we would leave our embryos,

we would thaw them out in the morning.

We would leave them all day,

probably till two,

three o'clock in the afternoon,

sometimes even overnight if

they're still not ready.

And then we would do the

biopsy and refreeze them.

And by doing that,

I've got almost identical

survival rates on the flip

side of the second thaw and

identical clinical pregnancy rates.

I think it can be done safely,

but it has to be done safely.

I think there's ways that

you can do it wrong.

So question the question to

ask your clinic.

Yeah.

How long are you going to

leave them after you've

thawed them before we do

the biopsy on them?

Are we going to make sure

they're absolutely intact?

Because you really don't,

there's no point in you

paying all that money to

have them biopsied and put

them back in the freezer if

they're not going to, you know,

regardless of genetics,

whether they were just not

going to survive that

freezing process anyway.

Yeah, that's fascinating.

And that's a great question to ask.

That's like the nitty gritty

detail that I think is

going to help people out there.

Okay, Kirsten, thank you for that.

Let's jump onto this one from Laura.

Would you recommend any

other type of genetic

testing before getting to PGT?

We've been recommended PGTA

testing after five failed transfers.

My husband already has two children,

so if there would be a genetic disorder,

could we assume this is coming from me,

age 37, fit and healthy?

So genetic disorder,

when you use that phrase,

means a genetic disease,

which is at the gene level.

What we're talking about

when we're talking about

PGTA is at the chromosome level.

So your genes are carried on chromosomes.

So let's do a quick science

lesson because I think this will help.

Here we go.

This will help.

Here it comes.

So on my Insta,

there's a thing called the

library analogy,

and I think it helps just

having a visual.

So in each of your cells is your library.

Your library is what makes

up all your information,

what makes you you.

It's your blueprint.

Half of your library came

from your mum and half of

your library came from your

dad to make a unique brand new library,

which is you.

In your library,

you have 23 bookshelves on

the right and 23 bookshelves on the left.

They represent your chromosomes.

On the chromosomes,

there are a load of books,

different amount of books

depending on the number

that the bookshelf is.

Bookshelf number one,

which is chromosome one,

has something ridiculous

like 6,000 books on it

because it's a big beast.

It's an important one.

It's a really important one.

Yeah, yeah.

You go down the library and

as you go through the library,

the bookshelves get smaller

because the chromosomes get

smaller and they have less books on them.

In this library, in your library,

you have identical books on each side.

So you have books...

Jane Austen there and you

have Jane Austen here.

They're identical copies.

When we talk about genetic disease,

what we're looking for is a

problem in a page on a book,

on a bookshelf.

because it's when it doesn't

tell the story right.

So there's an error or

there's a page missing or

there's some letters missing.

And then therefore that book

doesn't read right anymore.

So the book doesn't tell the

story properly,

so it can't function properly.

Now in some genetic disease cases,

you need both books to be

wrong to cause the disease.

That's called a recessive disorder,

so cystic fibrosis.

And in some books,

they're so important that

even if one of the books on

the bookshelves doesn't

tell the story correctly,

you end up with a genetic

disease such as Huntington's,

which is what we call dominant disease.

So when we talk about PGTM,

we're talking about the

letters in the books on the bookshelves.

Yeah.

And that's why we have to

know where we're looking,

because we can't just look

at all 23,000 books in your library.

When we're talking about PGTA,

we're talking about the bookshelves.

There are the correct number

of bookshelves there.

And if you've obviously got

an extra bookshelf,

you've also got all the

extra books that comes on that bookshelf.

So the embryo has either too

much information or too little.

With me?

100%, that's great.

Right,

so what you're asking is a genetic

disorder

can actually come from

either of you but we know

that because women are

destined just to take the

rough side of life let's

face it yeah um as we age

our we're trying to make

when we when we create

gametes so eggs and sperm

we're actually creating a

whole new library you're

you're half in your library

to give to your egg and

your partner is half in his

library to give it to his sperm

And what we know is that in females,

that halving process

doesn't go very well and

the bookshelves don't go in

the right way.

So you end up with too many

bookshelves in the egg or too little.

So you would definitely be

looking at testing if you

were having recurrent miscarriage.

There are certain genetic

tests that we look at for that,

but failed transfers,

I think that that could be genetics,

but you're only 37.

So I think I would be

wanting my clinic to be looking at,

A lot more.

I would want them to be

looking at the environment.

And like I said earlier, the Emma,

the Alice's, the DNA frags in the man.

Have we actually looked at him properly?

Because although your embryo

can be genetically normal,

if the sperm isn't functioning properly,

it may stop the embryo

growing at a later stage.

I'm not going to go into DNA

frag tonight because that's

a whole other webinar.

But it's bigger than that.

So I would be looking at everything else,

but I do think that with

failed transfers at the age of 37,

the fact that you've had

five failed transfer tells

me that you've made at

least five embryos.

So let's test them if you do

another cycle.

And let's find out if

they're normal first.

Because I imagine if, you know,

and it's also about,

I'm going to come on to this in a minute,

about family building.

So you can carry on asking me questions.

I'll just keep talking.

I'm going to keep going.

Thank you, Laura,

for sharing your question.

The next one's perfect

because it then keeps me going.

This one here?

No, this one here.

Yeah, the PGTSR.

Oh, wrong one.

Let's bring this up from Sepi.

Can you explain a bit about PGTSR?

So PGTSR is pre-implantation

genetic testing.

I said it again.

Yeah.

for structural rearrangements.

So what happens here is in

certain individuals,

the bookshelves are all

present and the books are all there,

but they're in the wrong place.

So bookshelf one might be

stuck onto bookshelf eight

and it's called a translocation.

So you are normal, you are healthy,

there is nothing wrong with you at all.

But when you try and make gametes,

eggs and spam the

bookshelves were all in the

wrong places so you make

more errors and you make

quite specific errors so

you would make so there's

different types of

translocations they're

normally called reciprocal

or robertsonians can you

give me one an example um

so a really really common

example of a robertsonian

translocation affects

people between chromosome

13 and chromosome 21.

I mean a bit of chromosome

13 is stuck on the top of

chromosome 21 or vice versa

and the reason that one's

really important is because

when you actually make eggs

and sperm when you carry

this translocation you're

basically making embryos

with partial extra copies

of 21 so you're actually

making partial Down's

embryos and they are

incredibly compatible with

pregnancy and life they

aren't as severely affected

as Down's individuals but they are

affected so that's the one I

see a lot of how they come

about they're normally in

families they're a bit like

genetic disorders they are

a genetic disorder but they are so

In essence, you should,

if the maths was to play out,

you should make one in four

of your eggs or sperm

should be unaffected by the imbalance.

Two in four will be affected

and unbalanced.

So have the wrong amount, either side,

less or too much.

And one in four will be like you,

have it but balanced so

that you can make healthy

embryos that way.

So when we do genetic testing for PGTSR,

the finale,

is i actually don't know yet

that's the testing can't do

that yet it can't tell me

whether the embryo is

balanced or unaffected it

just tells me that

everything's got the right

copy number and that's

really frustrating for

patients who don't want to

pass this on yeah i think

it's coming i think that

technology is coming and i

think it'll be with us in

the next 12 months that we

will be able to tell the

difference between an

embryo that has a

translocation like yourself

and is normal or doesn't have it at all

Fascinating.

Because we'd rather get rid

of it if we can,

because any children born

with the same as their

parents is going to have

the same fertility problems

in 30 years' time.

It causes lots of miscarriages,

so anyone with a structural

rearrangement generally has

quite a lot of miscarriages

because of the unbalance.

Thank you for asking that question, Sepi.

That was, yeah, good timing.

We got into the nitty gritty science then,

so this is good stuff.

So hopefully you're still with us, folks.

My brain is like going, whew, there's that,

there's that, there's that.

This is why I need to get this right,

because it's really complicated.

Yeah, no, like, you know, take your time,

right?

And if we have to go over the hour,

so be it,

if folks do want to stick around,

we might break the rules and go,

we'll see how it goes, right?

We'll see how it goes.

Okay,

so Mel would like to know a little

bit about the process and

timeline for PGTM.

This is a great question.

So PGTM is when we're

looking for a monogenic disorder.

Now this is incredibly sad

because normally this comes

because either

you have a family member

that has been diagnosed

with a genetic disease,

like an older relative.

So breast cancer is a really,

really obvious example for this.

So someone in your family

will have breast cancer.

They will then get tested

for the BRCA gene.

Say, for example, it's your mum,

you then have a 50% chance

of also having that gene.

And it's so different to 30 years ago.

We've now got massively good

prophylactic treatment,

which means you can have

your breasts removed and

you can have your ovaries done.

There is things we can do to

prevent the cancer,

but ultimately you're still

in a position where you're

passing that gene on to

future generations.

So that is an error in a

book on bookshelf number 17.

That's where the BRCA gene lives.

Now,

I think the misconception about

monogenic disorders is that

the page that's missing in

the book causes the problem.

It doesn't because the BRCA

gene is a tumor suppressing gene.

And when there is an error,

it stops the gene working.

So it can't suppress tumors anymore.

So the error isn't causing the problem.

The error switches the gene off.

I see.

So BRCA is an example of a

dominant disease.

And if you were working up a BRCA case,

I would need...

blood from the person who carries it.

So let's say it's the woman.

I then need blood from the partner.

So where are we at at this point?

So they've just walked into

your clinic and they've

come to you for diagnosis

of embryos for PGTM.

Okay,

so we're on day one of... They would

come and they would meet me.

We'd do an inquiry.

We'd go through the whole process.

I would look for genetic reports.

You have to have a genetic

report to say what the mutation is.

I would do a full

consultation on these and

then make sure I've got all

the background I need.

Now, the more family members you can get,

and I talk about this as direct relatives,

not cousins,

it has to be a direct relative, either a,

actually offspring is really good,

daughters, sons, embryos, they're all,

because they're the puzzle, right?

They are you and your

partner together is your reference.

But you would take DNA, so blood from mum,

DNA, blood from dad,

And then you would send that

to the genetics lab with

all the information.

If you have got a mum with it,

you would then see if we

can get DNA from her.

If you've got any embryos,

we can use them.

And basically you're

creating a puzzle so that

when we do create embryos

and we try and overlay the embryos DNA,

it's where do they fit?

have they got it have they

not got it are they

carriers and all of those

things and that sort of

thing about timeline how

long would that all take so

about four to six weeks

okay okay so four to six

weeks what i will say about

genetic disease is you

absolutely have to have

genetic counseling that is

mandated in the code of

practice and that and

actually what i will say

about genetic disease some

people choose not to test

When no one's mandating you test,

you can't force someone to test.

We will have to have like MDTs about it.

MDT?

Like a management discussion,

full profile of senior people in the team,

clinical team,

to make sure that we're

happy to proceed and that

we feel the patient's been informed.

But we have to make sure we've covered,

like got all the

documentation to support

treatment without testing.

But yeah,

so the timeline from probably

walking into a clinic to

being able to start an IVF

cycle is probably,

I would gear yourself up

for two to three months.

because of all the

counselling and all the bits,

but the actual PGTM bit,

once I've sent everything

to the genetics lab,

they come back to me about

six weeks later and say, we're good to go,

we're ready.

And, you know, the importance about,

you've touched on, you know,

you're being very

scientific and very much,

this is what happens,

this is what happens.

You briefly mentioned the

emotional side of things.

So, because that's important, right?

The mental wellbeing of

anyone who's going through

this experience,

what does the genetic counselling offer?

So genetic counsellors are

amazing because they will

talk you through the risk

of inheritance patterns,

what the risk of the disease is,

if it's something that's in your family,

like BRCA.

That has massive

implications to you and

your health and your future.

And some people don't want to know.

They don't want to know.

And that's OK.

That's like no one gets to

have a say on that.

That is your journey.

But the genetic counsellors

will help you work out that bit.

Because it's so personal,

like wanting to know that information.

Yeah.

So some people don't want to know.

Yeah.

And there is something

called blinded PGTM.

So we can do it without finding out.

But that is an incredibly

complicated thing to bring up.

And without I could draw it for you,

but I can't talk about it.

There are options.

So there's so PGTM.

Yeah.

I would always say if you've

just found out there's

something in your family,

make sure you've got as

many much information as you can.

The genetic reports are key.

We have to know where we're looking.

And also one bracket.

patient is completely

different to another BRCA

patient because actually

the problem in the book is

different every time, most times.

Does that make sense?

Yeah, it's so complex.

I think the way you're describing this,

and this is what I find fascinating,

is how your patients and

patients across the globe

in various other clinics

how they can wrap their head

around some of the science

and how much they need to

know about the science and

how much you need to kind of

handhold them and say, look, you know,

as much as it can be hard

not to have all the information,

there's an element of trust

and an element of like,

we are going to work with you,

present you information to

help you make decisions.

Is that really what it comes down to?

Yeah.

And I think actually it

depends on how much you want to know.

I mean,

I always ask patients when I'm

doing these calls because I

do a full hour consultation

with PGTM patients because

that's like I said,

that's what my expertise is.

I always ask them how much

they want me to go into it.

Yeah.

Because that's quite personal as well.

Yeah.

They want me to just take it off them.

I will.

Yeah.

But you have to have counselling.

It's a legal requirement.

And I can't do it,

because I'm not a genetic counsellor.

I could do it,

but I'm not clinically

evaluated and licensed to do it.

Yeah, yeah.

I mean,

you're just... Because I know what

you're like as a person.

You do counselling anyway as

part of the service that you offer,

but not officially,

because it goes down the official route.

Okay, thank you, Mel, for that.

Let's take this one from Kath.

If you have never had a positive test,

so never miscarried and

under 35 years of age,

I've heard that testing is

not recommended.

But what if fertilisation is

happening and they are just

failing to implant due to abnormalities?

Thank you, Kath.

It's true.

So under 35.

So let's talk about what

recommendation means,

because my idea of

recommendation and the

HFVA's idea of

recommendation are two very

different things.

The HFVA stance on PGTA is

that by doing testing,

you will not give anyone more.

healthy babies in a cycle of treatment.

100% agree.

I can't change the embryos.

Your embryos are what you have created.

And I can't make them genetically normal.

So if you create eight and there is two,

I'm not going to make more

by testing them.

It's about information.

It's about information.

So the reason the HFA don't

recommend it for under 35

is it hasn't been shown to

be of a benefit when

getting to a live birth.

Now what and who gets to

define what a benefit is?

So I touched on it earlier

and I always talk about family, not baby.

So you walk in your clinic

at 35 and you turn around

to me or a member of the team and say,

I had always dreamed about

having two or three children.

I now feel like that's not

going to happen and I'm

desperate and I just want to have a baby.

I'm going to turn around and say, well,

hold on a minute.

You can still talk about that dream.

And I know you want to be pregnant now,

But if we start creating

embryos now and at 35,

you have about a 50 to 60%

chance of each embryo being

genetically normal.

And for example,

say you create four and I

come back to you and I say

two of them are normal.

You are still only 35 that month later.

Now I can put one of those

embryos back and make

hopefully with 60% certainty,

give you a baby.

But you will walk back in

potentially into the clinic at 37.

And your chance of now

making a normal embryo is 40%.

So shouldn't we have had

that conversation where we pause,

maybe create some more

embryos at 35 so that

you've got your future

family planned out.

So for me, that is a benefit.

Equally, you are 40 years old.

You're sat in the clinic.

you're lucky enough that

you've made six blastocysts

and only two of them are

normal as well and actually

it's the not the nicest two

it's not the ones we choose

in order because we would

choose them normally from

grade yeah yeah so you go

through four go through

transfer number one and

it's not pregnant and we

move on you're 40 you then

go through transfer number two and

and it miscarries you you

lose three months six

months yeah you then go

through transfer number

three and it's another

miscarriage which takes you back

emotionally really hard.

It hits you really hard.

So by transfer number four,

you're actually a bit broken.

And I've actually seen

people walk away from

treatment because it's

called infertility fatigue,

as I think we've all lived through.

So you might get to the

point where you're now 41.

You've got these two embryos

that are normal.

each frozen transfer is

costing the best part of

two and a half thousand

pounds and you're 10 like

there's a point here where

people give up so you may

never use them okay then

flip the argument around

and all six were abnormal

to use all six embryos by

the time you sit back in

front of a consultant

having used them all you're

41 and a half and now i've

got really really difficult

time to find an embryo so

Isn't that beneficial?

Yeah.

So the argument I have for

women at 35 is talked like

I say this so much,

but context is everything.

No,

I will not create any more babies by

doing testing,

but I might give you the

opportunity to create your family.

Yeah.

So I think we need to think

really realistically about

what we just we determine

is a benefit because their

argument is it's not beneficial.

My argument is.

That's not your right to say

what everyone's context is.

It is beneficial for certain

people to know what they've

got before they move on into pregnancy,

which takes nine months to

have a pregnancy.

And unfortunately, we still get older.

Our ovaries still get older

even if we're pregnant.

And then we might feed or we might,

you know, have a newborn.

And then before you even know it,

your baby's a year old and

you're thinking, oh.

Yeah.

Anyway.

yeah no so i mean i could

ask lots of questions about

that but i am conscious

we've got a heck of a lot

of more questions to get

through so so thank you for

that one kath we're going

to jump back to some of the

questions that we had via

instagram um so let's go

for um here we go oh this

is an interesting one uh

testing our two embryos

couldn't occur due to lab error

at the amplification stage?

Is that uncommon?

Oh, we're combining two topics here.

So what did I talk about in

the Vienna consensus?

KPIs.

Oh, yeah.

So one of the KPIs that we

have to adhere to is what

we call our no result rate.

Now, no results will happen.

They happen.

They should happen less than

5% of the time.

Now, a no result is when you do the biopsy,

you send the cells and the lab

send you the results and

they can't detect a result

for that embryo.

That embryo is just as

likely to be normal as it is abnormal.

Depending on your age group,

it doesn't mean there's anything wrong.

Sometimes poor quality

embryos are harder to get

viable cells from,

but we would normally warn

patients about that.

So my no result rate

personally in the Evewell

clinic group is under,

I think it's 1.6% because

Again,

this is down to the fact that I'm really,

really anal about when

embryos are tested and how

we test them and we leave

them to grow quite a long

time and we have lots of cells and hey,

that's what I do, right?

It's the biopsy.

But again, that's a KPI.

So you will see a varying

level of no results clinic

to clinic and it's

something we should ask.

What is your no result rate?

It's a great question.

It does happen,

but actually you can thaw

those embryos out and

biopsy them like we were

talking about earlier.

You can go back to them.

Now,

most genomics labs that I've ever

worked with will not charge

you for a retest.

So you get charged for the initial.

But a lab like Juno, who I work with,

if they give me a no result,

then I can go back to them

for free and do it again

without charge to the patient.

Interesting.

I didn't know that was the case.

I feel like we really are

building a crib sheet of

questions that you can go

in when it comes to PGT.

These are the top 10

questions you should be

asking your clinic when it comes to this.

The top 150.

Well, the top 150, yeah, exactly.

I mean, it's not just 10, right?

There'd be 15 parts to it.

So where do you want to go?

Do you want to take some questions?

There's a couple in here

that are really similar,

and I wanted to touch on them.

No, that one at the bottom is one of them.

Okay, let's go for that one then.

So, Lisa,

thoughts on lack of NHS funding

for PGTA for people with a

history of recurrent miscarriage.

Or advanced maternal age.

Again, yeah, I agree with you.

I think it's a really, really...

tragic sad state that we're

in but the nhs is

underfunded um and these

are expensive processes i i

find it incredibly

frustrating that people

even have to have a fight

to have miscarriage bloods

done i mean i've had women

sit in front of me with

five miscarriages and no

one's actually done any

bloods on them or anything

and it's like it's tough

you know um yeah but yes i

agree with you now i think

there's another question in

here that talks about pgtm now

Well, we touched on PGTM.

I probably forgot to mention

that when you do a PGTM

test with a private

external genomics company,

The technology actually

allows you to see both.

So you not only find out

whether the embryo is

affected or unaffected or a carrier,

depending on what disease

you're looking for,

you also find out the PGTA status.

So you would end up with

like a double result for a PGTM embryo.

So it would come back as,

so let's for argument's sake,

do the BRCA gene again,

just because it's dominant

and it's 50% of your embryos.

So the BRCA gene would be

like affected or unaffected

in the first column.

And on my second column,

it would say normal or

abnormal for chromosomes.

So you get both elements.

So you're not only just

transferring an unaffected embryo,

you know that it's

chromosomally healthy as well.

And one of the questions we

had was why don't the NHS,

the big NHS player that

does all the PGTM funding,

not perform PGTA alongside its PGTM?

So what this particular

clinic is actually doing is

giving you an unaffected

embryo that you're then

going on to miscarry

because of the chromosomes.

And the answer is, I don't know.

It's something that has

frustrated me for many, many years.

I'm sure it's to do with funding and

They actually do their own

in-house testing,

whereas I send mine off to

a diagnostic lab.

It feels like such a missed opportunity,

though.

Yeah.

Who could we lobby, or who could we...

Oh, I need to get on the HFEA board,

which is something I've

been putting off for years.

So, folks,

if you want to advocate for Emma

to get on the HFEA board,

it's just it's a lot of work.

Yeah, it's more it is more work,

but it's important work.

But yes,

we've got nine minutes of a quick

fire round, I reckon.

OK, here we go.

What morphological grading

means if chromosomally normal?

So we still use the grading.

So when I talk about grading,

as you all know,

I bang on about this enough.

So actually,

when you get a chromosomally

normal embryo,

if you're lucky enough to

have more than one and

we've got a selection,

then we go back to the grading, the day,

the development,

and we still priority score them.

So a day six normal embryo

will still not make you

pregnant as much as a day five,

because although it's

chromosomally normal,

It's to do with the

development process and the

speed of the embryo that

also correlates to pregnancy rates.

So we would always get

better pregnancy rates from

day five euploid embryos

than day six and then day seven.

Yep.

Okay.

That's not what drives that.

That is just standard.

You find that more embryos are...

abnormal as the embryo takes

longer to grow.

So 90% or if I think it's

88% of day seven embryos

are unemployed because

they've taken so long to get there.

It's because the machinery is not right.

But we still use the grade and the day,

even when we know the genetic status,

because it helps us have a ranking score.

Yeah.

okay let's jump on into the

next one um what insight do

you get from testing when

all embryos are abnormal

can it help the next cycle

yes if the abnormality is a

pattern then that might

have picked up something we

talked about earlier which

is called the translocation

um pgtsr is then needed so

you can certainly i have in

the last couple of years

picked up three patients with

unknown translocations

because i saw the pattern

in their embryos from what

they were all identical

patterns so it's unusual so

normally you get random

stuff with that with pgta i

don't normally see like you

do see a lot of plus 21s

because it's compatible

with embryo development we

know that downs embryos in plants

reasonably well you see a

lot of plus 18s a lot of

plus 15s they're just

really compatible things it

doesn't mean that they're

the other ones don't happen

they're the ones where the

embryos don't grow I don't

see a lot of like trisomy 2

so three copies of

chromosome 2 because that's

your bookshelf with about 5

000 books on it so it's not

compatible with embryo

development so we don't

tend to see them as much as

we see some of the other

ones like if that makes

sense and chromosome 21 is

quite small it's only got

about 600 books on it it's

not it's it's not a big gene

which would then make sense

so you can get some insight

equally there was a really

nice paper that came out a

couple years ago and it

said that the impact of one

cycle of all abnormal

embryos does not change

your potential for the second however

If you have two full cycles of over,

and I think the number was eight,

don't quote me on this

because I can't remember,

of all abnormal embryos in two cycles,

it can be very predictive

that this is going to be an

ongoing problem.

But your one cycle of all

abnormal embryos does not

correlate to your second.

Fascinating.

You normally get the same

percentages in the second

cycle of normality based on your age.

Yeah, yeah.

I got it.

Okay,

some of the nitty gritty question on

Insta.

Why is it so expensive with

set up fees and a cost per embryo?

So I think this is really different.

And I find this really

interesting because I know

for a fact that we get

charged a per embryo fee, which...

The patients pay per embryo.

Some clinics do a package

fee of up to eight or nine.

I don't know is the answer

because I'm pretty sure all

the genetics lab charge a per embryo fee.

Now,

PGTM is expensive because it's bespoke

and it has to be worked up for you.

So that isn't and it takes

the six weeks and it is expensive.

unfortunately incredibly

challenging so pgtm is a

very expensive process i

think one round of

treatment with pgtm so

looking for genetic disease

with all the workup fees

and all the costs and the

counseling and everything

can be upwards of 12 000

pounds yeah it's it's it is

tough um but i think most

clinics should be charging

a per embryo fee because

that is how we are billed

by the labs yeah i see

Good stuff there.

So now we do have some more

coming through on the chat.

Should we jump back on the comments?

Let's do it.

I'm pretty sure that's my sister.

Oh, yeah.

Yeah,

I just spotted someone in the crowd

called Kelly Phillips.

It might be another Kelly Phillips,

but yeah, this is a really good analogy.

Thank you.

Nice one, Kelly.

Thanks for joining us.

Oh, Laura, thank you so much.

Yeah, for saying thank you so much.

Oh,

thank you so much for saying thank you.

This is so helpful.

That's very kind.

Okay, Danny, a question here.

Should we bring this one up?

Yeah.

So I'm 37.

I have had two failed

natural transfers from two

previous cycles.

My third round has led to

three frozen euploids and

just at the start of the meds for an FET.

What is the four ring survival rate?

Does it differ if they're euploid or not?

um no so there was a theory

a while back that aneuploid

embryos genuinely didn't

survive the thawing process

as well and i think there's

something in that because i

think aneuploid embryos

tend to be poorer quality

sometimes sometimes not all

the time um so they won't

survive because of the

quality not because i don't

think of the aneuploidy um

euploid embryos that have been vitrified

Again, this is a KPI, right?

So this is one of those

things that you'd have to ask your clinic,

their survival rates.

Mine is 98% of our vitrified

embryos at the blastocyst

stage survive and get transferred.

So they do very well.

Vitrified embryos,

which is what all clinics are doing now.

I don't know any clinics

that are doing slow freezing anymore.

They should survive really well.

OK, thank you for that question, Danny.

We've got time for a few more,

so let's go for it.

Oh, this one.

either let's jump here and

then we jump back to

jessica sorry that did

flash up on screen there so

this one from emma can you

explain more about mosaic

embryos please so mosaic

embryos are those that are

determined on the testing

to be mosaic and they are

how do you word it it's

like there's a bit of good

and there's a bit of bad

and we can't be sure of

which is it inherently bad

so has it come from the

eggs and sperm and if that

is the case the embryo

is actually aneuploid and

the mosaic result is

potentially a wrong call,

but it's very unusual.

Or it can,

if you can imagine an embryo

goes single cell, right?

One to two, two to four, four to eight,

eight to 16.

Then let's just for argument's sake,

say one of those 16 cells

makes a mistake.

Yes.

That is called a mitotic error.

And why, let's just for argument's sake,

say you pick up some of those cells,

right?

But the other 15 are fine.

Yeah.

So the embryo itself as a

whole has come from a good

egg and a good sperm.

Yeah.

But an error has been made.

So we believe most mosaic embryos,

that's why they've got

really good potential,

is it's just a mitotic

error that's happened

during the process of embryo development.

We know that embryos are very,

very mosaic.

That's just what they are.

And we know that that is the

only place that the good

cells will then tell the

bad cells to die.

It's called apoptosis.

So that is a mosaic embryos

when we've got a bit of

good and a bit of bad.

However, saying all of that, thankfully,

we're in such a good place

now with mosaic embryos

that we can not only do...

Some genetics labs now offer

an extra layer of testing

to see if it's good in or good out,

if that makes sense.

And we're getting really

good pregnancy rates with them.

So again,

genetic counselling is key

because I wouldn't

personally be comfortable

transferring a Mosaic 21.

because of the impact of

having a mosaic downed individual.

But most of them are, we are now,

I think they have

transferred 2,000 mosaic

embryos with about a 36% live birth rate,

which is good.

And the mosaicism doesn't

seem to be following

through to the babies.

There have been a couple affected,

but no more than a normal,

if you were conceiving naturally.

Got it.

Okay.

Thank you, Emma.

Right.

We're going to jump onto

this one from Jessica.

So would frozen embryos that

were fertilized with sperm

with a DNA FRAG score of

54% still be worthwhile to

subject to PGT testing?

Or does the FRAG score act

as enough of a red flag already?

I'm 32, husband is 41.

So the FRAG, the DNA FRAG, like I said,

I need to do something on

this because it's really interesting.

I might try and get Jonathan

Ramsey to do something like

this with me because he's

really good at all the DNA FRAG.

He's a urologist,

so he does a lot on DNA FRAG in the men.

And I'm an embryologist,

so it would make sense to

bring on an expert in that one.

Maybe that's series two.

Because obviously we're

going to have a series two.

um so yeah the frag um is is

a red flag but it normally

stops embryos developing

rather than causing

aneuploidy it's not the

same it's it's the

aneuploidy's whole

chromosome gains and losses

genuinely come from the egg

um i hate it i hate that as

women we're always this you

are young you are 32 so

there is every possibility

that your your embryos are

going to be genetically

normal but the frag itself

can cause the embryos to miscarry um

That needs looking into.

A 54% DNA frag needs looking into.

A urologist should be

checking your partner out.

That's the right people to

go and see for that.

See if we can change it.

Get it down.

Great.

Hope that helps, Jessica.

I will do something on frag

because it's a massive topic,

but I could be here all

night talking about DNA frag.

I could be here all night

talking about anything.

Exactly.

Okay.

Just doing a quick time check, folks.

It looks like...

Is there one you want to take there, Em?

I think we've got time just for one more.

And just before we do that,

apologies if we weren't

able to get to your

question this evening.

Those that have come through

on Instagram and also those

that have come through via

the chat today.

I think, Em,

you'll try your best to reply

to some of the Q&A.

I might just put some of

them back on the gram and

then answer them one by one.

Because a lot of them I

think we've covered.

Damage rate.

Let's talk about damage.

So.

Yep.

Again, this is a KPI.

All of these things,

coming back to our first podcast.

Yeah, so that was the Vienna consensus.

So we have to talk about damage rates.

I have, touch wood,

I've not damaged an embryo

yet doing biopsy because of

the way we leave them to grow so much.

They are,

I think people think about them

as being really fragile.

If you think about what

they've actually got to do

to make people pregnant,

how any of us are here,

they're actually really, really robust.

They really don't mind what

we do to them too much.

It comes from training and

skill and technique and all

of those things.

And in the right setting,

embryos do not get damaged

through biopsy if it is done properly.

And that is all I'm going to

say on the subject because

I believe that there is a

way to do it and a way not to do it.

And I do quite a lot of

biopsy workshops and I have

done them all over Europe

because it's about making

sure people are doing it safely.

But embryos also are not fragile.

By the blastocyst stage they

are incredibly robust.

I will say that.

So we also know that

biopsying an embryo doesn't

change its outcome because

there was a paper on that as well.

So embryos that had been

biopsied and not biopsied,

same pregnancy rates.

So studies have been on it.

That's been done.

We're happy with that.

Let's pull one in because I

think this is a really good

question that has come in from Lauren.

Thank you, Lauren, for asking this.

What sort of questions

should we be asking a

chosen clinic before we

allow them to biopsy one precious embryo?

Those questions.

So you've got a four or five

layer approach there.

When do they biopsy them?

How big are they?

Are they letting them get to

the point where they're

really advanced embryos so

that you're fundamentally

only biopsying viable embryos?

Blastocysts can be early

blastocysts and still fail.

That's why I leave them to

be fours and fives,

which is the grading system

we will talk about.

What's their no result rate?

What's their freezing survival rates?

Because ultimately these

embryos have to be frozen.

So the most important KPI to

your outcome is,

are they going to come out

of the freezer okay?

Yeah, I mean,

I do biopsy a lot of single embryos,

I must admit.

And they go as well as doing

a group of embryos.

But those would be my

questions is mainly around the freezing.

Yeah.

Yeah.

Great.

Wow.

There we go, folks.

I think we're going to have to stop there.

Goodness me, this topic's huge.

It is a huge topic and it

realises we could probably

go a bit more niche on a few.

What we will say is do come back to this.

You know, as someone who's hosting this,

my mind is melting with all

the information that Emma has shared.

And I mean that in a positive way.

We do hope that it has been

helpful for you today.

Do come back to it.

So follow Emma on Instagram

at Emma the Embryologist,

where she'll link you to

all of the places.

You can find Emma the

Embryologist now on YouTube.

So we've got two previous

podcasts and this one will

be available soon.

As well,

coming soon in about a week or so.

We are also syndicating to

all the podcast platforms, so Spotify,

Apple Podcasts.

If you want to go and find

all the links to the podcast,

it's hatchingaplan.transistor.fm.

So do go check that out.

you can come back to this um

please do share it with

other folks who are out

there who you feel would

need some support do spread

the word uh emma really is

i mean as you can tell an

absolute expert and super

passionate about what she

does she really is here to

help so yeah keep on keep

on uh checking in and yeah

i will get some of these

put on actually because some of them um

I mean,

I think we've covered most of them.

I'm just looking through them.

So I hope it's been really helpful.

And then just feel free to

DM me if I haven't answered

a question that you wanted me to.

I can probably put it into 18 paragraphs.

Yeah, that's it.

I mean, it's...

yeah it is a skill in of

itself i think to taste

something so scientific and

turn it into something it's

hard it's hard to get your

head around this yeah it's

really hard yeah i think we

we can do more and maybe

the practical crib sheet

stuff we could start

focusing on yeah definitely

Any suggestions, throw them our way.

Absolutely.

Because we need a whole load

of content for series two.

We do.

So just some lovely messages coming in.

Yeah, thank you, Lauren, for that.

And very kind, Hector, Kelly, Hannah,

Danny.

Oh, wow.

Some very, very kind messages coming in.

So thanks so much for sticking with us,

folks.

And from Emma here,

thank you so much for

sharing all your knowledge.

We've chosen the Evewell, West London,

and we'll be starting our

journey there soon.

Thank you.

Oh, that's nice.

I'll see you there.

Wonderful, Emma.

Thanks for sharing, folks.

Really do appreciate all the

questions and everything

that you've asked today.

Please do come back to this

and do check out the other

episodes of Hatching a Plan.

I'm Simon signing off.

And I'm Emma,

off to bed before work tomorrow.

Indeed.

Take care, folks,

and we will speak with you soon.

Bye for now.