Genetic Testing

[Mouseorchestra7]

If you were going for IVF at 36, would you get your embryos tested? I have no known fertility issues.

I did PGS aged 41/42, but wouldn't have at 36. I'd rather let nature take its course at your age, as around half of your embryos, or just under, should still be normal.

Plus, if this is your first round, you've no idea how you'll respond to the meds and how many eggs/embryos you're likely to get, so i think i'd just transfer without testing for this round at least.

I understand @IslandStars's point of view, but personally, I am going to test (40yo atm), and would test even if younger. In my mind, it's just like a check-up. But, maybe you could wait and start testing from the 2nd round and on, just to avoid adding to the stress.

Does anyone know what the chances are that the embryo doesn’t survive the thaw and or is damaged by the sampling process? I have one blastocyst that I am thinking of testing. Age 42.

I tested age 36 and didn't get any normals - it was devastating as abnormals have to be destroyed as not allowed to transfer them in the U.K.

I decided not to test again and put 2 back on my next transfer and had twins so very sceptical of it all now

We did it at 39 as my uterus needs 3+ months of preparation for each transfer.

I get hardly any blastocysts (6 in total from 4 collections, before testing) but we felt it worth it, as the preparation is emotionally very draining.

My clinic says with a euploid embryo you have 70% chance of pregnancy and 60% chance of live birth, and I have had so much treatment that I really couldn’t face more failed rounds.

Our clinic also recommends it from age 38 onwards.

My clinic is one of the top in the country for testing embryos for inherited genetic issues but interestingly they are completely against PGT-A.
My Dr said there is around a 30% margin of error with this test (so 30% of embryos that come back aneuploid could actually be normal and vice versa) which as far as she’s concerned is too high.

It’s also still red on the HFEA traffic light rating and costs like £500 per embryo or something so if you end up with a good number of embryos that racks up quite a bill on top of everything else.

I think as a test it adds more reassurance but it’s not a guarantee of success as euploid employs still sometimes fail to implant and can miscarry.

As others have said, personally at your age and for your first round of IVF, I wouldn’t bother but if I was older or had been through several rounds I’d consider it.

Good luck OP!

@Everhopeful41 Depending on the clinic, the chances of an embryo not surviving the thaw are usually somewhere around the 3-5% mark. However if you thaw, test and refreeze it goes up to about 8-10% (this is more to do with the double freezing/thawing than the test itself as far as I’m aware). You could ask your clinic what their rates are as it does vary marginally. Best of luck to you too.

Thank you all for your comments. I have actually had two rounds of mild IVF already (got five (not great quality) blasts from around 18 eggs). Two fresh transfers failed. I’m now contemplating doing ‘full-on’ IVF (225 menopur) in the new year, hence why I asked about genetic testing. Based on responses, I think I will not do genetic testing and just give this round (with different drugs, different lab) a go and hope for success. But any additional insights based on my circumstances would be much appreciated!

That's really interesting @RiverRiot

I wouldn't at 36 either. My history is that I had a baby at 36 through ivf without testing. I got 4 blasts and second transfer stuck.

2 years later I transferred the last two which didn't work. Then did a new round, got 6 blasts and decided not to test again. After the best 3 of those failed to implant I lost my nerve but rather than defrosting and testing the last 3 I decided to collect again and test prior freezing. Got 4 and sent for testing only to find they all had "complex abnormalities".

Feeling very much in despair I did a double transfer of my second worst and third worst embryo overall, out of all 3 rounds (based on grading and embryoscope score), and to my amazement one (or maybe both, don't know yet) seems to have stuck. I was not expecting that. It's early days and I mustn't get ahead of myself but I think the lesson is that nature knows things that we don't, that grading is meaningless and that you have to be patient (frustrating as it is when the first transfer fails). Ultimately I think you have to remember that testing them doesn't make them more likely to succeed, but it does risk discarding something that would otherwise work.

As you get older the balance shifts as you have to consider that other issues become more likely and if you already have children you have to consider the impact on them of adding a baby with additional needs to the family. That is the reason I might test if we were going to go again at 40+.

@Everhopeful41 there's no way I would test one embryo on its own either from a financial perspective or from point of view of risking your final embryo. I'd be transferring that and crossing my fingers.

I personally do not think I would do IVF at any age without testing- well, maybe under 27? But nothing past that for sure!

Based on a literature review, everything pointed to the fact that PGT-A leads to faster pregnancy in many cases, this very fact also means in SOME cases it can lead to a better clinical outcome. Transferring only euploid dramatically reduces chance of miscarriage, which can impact clinical outcome by a) avoided miscarriage will simply shorten time to pregnancy, which means lessen likelihood of some other health condition or issue developing in meantime b) avoiding miscarriage can mean avoiding D&C procedures or other procedures that leave scar tissue that would effect future ability o get pregnant c) avoiding miscarriage can mean avoiding a drop in mental health, which can affect someone's general fertility and implantation ability.

10 years ago, things were a bit different, but in the very recent years, due to advancements in assisted hatching and the biopsy process, as long as the lab is good there is almost no chance of damage to embryo, and very nearly no chance of a euploid embryo being misidentified as aneuploid. To me, those very tiny risks were totally worth the not-as-tiny, risks of having even one failed implantation or any type of miscarriage from transferring even one aneuploid. Given I think I may fall apart emotionally with even one chemical or heaven forbid late-term miscarriage, let alone a later one that could actually deeply effect my mental health and add on another 6 months - a year of the entire process, I'd do just about anything to reduce the likelihood of going through that. Plus, from a cost perspective, at my age about 50% chance of embryos being aneuploid, so about a 50% chance that my first FET costs (2.2kis) would be wasted- which is more than the cost of the genetic testing. So, the PGT-A testing as a 50%ish chance of at least paying for itself just by preventing one failed transfer, just purely looking at finances.

I completely agree with you in theory @tulipsandsnow but the trouble is, as both @tiggerwhocamefortea and me have found, testing can leave you with nothing at all to transfer and therefore definitely no baby, whilst taking your chances can weirdly mean you fall pregnant with an untested embryo that the doctor weren't giving much love to in the grading etc. My feelings on it have swung back over the last month. If I do now have a mc, perhaps they'll swing back to testing again. At 39 if doing a new collection I think I would, but op is only 36. However the later post detailing a few failed rounds maybe changes the analysis.

Forgot to add, on top of what I mentioned, in some cases PGT-A can actually end up being a diagnostic tool. You don't know ahead of time if you will be someone who has failed rounds, but if you do, it can quickly narrow down the most likely culprits if things aren't sticking, if the transfers that are failing are euploid or not. If you had three failed transfers out of 5 embryos for example, maybe 2-3 of those 5 are simply aneuploid and that's why, and you simply got unlucky and transferred the 'bad' ones first but you have no way of knowing that without testing. You might go down a different rabbit hole versus if you know that actually the embryos themselves are all genetically normal so three failed ones would point hugely to receptivity window or other environmental issue.

Some people argue that picking the best morphology should counterbalance this happening, but there's a lot of research showing that the relationship between morphology and ploidy isn't THAT strong. Tons of people have had a 5AA fail only to have a 3BC work, etc. It's pretty common to have someone's lower graded embryo(s) be the only euploid ones out of a given batch and the higher graded ones from that batch were the non- genetically normal ones.

@whatcangowrong I know what you mean- but for me I'd a 1000% more have nothign to transfer than to go on a several-month-longer £2k farce (for a FET) and the pain (trauma even) of another BFN. I'd much rather have put that money and time immediately more into another EC round, or just simply saving myself from the further stress and pain. I'd rather take the

It'd be different if there was like a 5% chance it could be misidentified or damaged, but it appears to be more like

Hi all,

Just to add to all this that when I had the consultation at my new clinic (LWC) after the failed transfers, the consultant said he only recommended genetic testing if there were a lot of blasts. He gave the example of a patient with 14 blasts! I have also had two failed transfers and I my doctor said he would generally wait until three before considering further investigation (although genetic testing was not mentioned in this context).

I’m planning to do an Access package where I get unlimited transfers (excluding cost of meds) , so not too worried about that. @tulipsandsnow that is a very good point about the emotional impact of miscarriage. My failed transfers were bad enough, but I think I would still want to give a few more transfers a try before going to genetic testing.

To add to all of this, I should also note that I am using a sperm donor and am changing donor for this round, so that may also have an impact.

On the subject of defrosting and testing, I definitely wouldn't do that. When I was considering it for my remaining embryos from previous collection they called and explained that if less than 70% of the embryo survived the thaw then they wouldn't be able to test and refreeze they would have to destroy. Whereas the threshold for defrosting and being able to transfer is much much lower.

I'm currently pg after transfer of an embryo that nearly didn't survive the thaw, along with another embryo. It's possible that first one is the one that stuck and if I had been planning to test it it would have had to be destroyed rather than transferred.

@tulipsandsnow I've read all those studies too but I would ultimately rather be pg with an untested embryo and in the game than have nothing to transfer at all. Nature works in mysterious ways in my opinion. It would still be a really hard decision for me despite 5 failed transfers over 6 months of the last year 😞

Hi @Mouseorchestra7 I'm nearly 36 and will be having genetic testing with my next IVF cycle (when I'll be 36). However, we're having our embryos tested for a genetic condition I'm a carrier for and do not want to pass on anyway, so we may as well have PGT-A at the same time. My husband and I also have no known fertility issues, as we're doing IVF for solely genetic reasons.

We had a previous IVF cycle earlier this year and out of the five blastocysts we got only one was chromosomally normal, one was mosaic and the remaining three were abnormal. After having this experience I think I'd have testing even if we didn't have to due to the genetic condition I carry. I'd much rather know we were transferring a normal embryo with a good chance of working than one that was abnormal and highly unlikely to implant, or highly likely to miscarry.

That said, a transfer with a chromosomally normal embryo still only has about a 50% probability of leading to a live birth. Our embryo implanted but sadly ended in a biochemical pregnancy. Around 10% of chromosomally normal embryos miscarry, but this is lower than would be expected if the embryos were untested.

Hope that's helpful.

@tulipsandsnow

I've read those studies too.

What they can't explain however is the women who are allowed to transfer abnormals and mosaics regularly in the USA and who go on to have perfectly healthy babies - I joined a lot of groups when I got my results and I did actually transfer my low level mosaic in the end with the agreement of the clinic

My friend in the U.K. retested some of her no result/abnormals and on the re test they all came back normal!

The "risk" in the U.K. of testing every embryo is that we aren't allowed to transfer abnormals here so they get destroyed. And had the embryologist doing the biopsy picked 5 different cells out of a possible 100 or more the result could have been vastly different ie it could have been classified as euploid

I've had 5 miscarriages - I agreed with my clinic that if it was a choice between destroying a precious embryo which could have the potential to become a healthy baby (remember they only test placental cells not baby ones) or going through another miscarriage then I could "cope" with the miscarriage

I get where you’re coming from @tulipsandsnow but the problem for me is that when they do PGT-A they test 5-10 cells (of an embryo that’s over 100s of cells). The results then tell you about only those 5-10 cells, it doesn’t tell you about the rest of the 100s of cells. And embryos have been proven to self correct.

Also, while it may reduce the chance of implantation failure or miscarriage - it does not prevent it. So you can spend the money having the PGT-A and then still have a failed transfer or miscarriage anyway.

And as someone who’s had a miscarriage after IVF, yes it was heartbreaking and traumatic but I’m personally glad I got to experience what it was like being pregnant at all after years of infertility and the time I had with that baby was precious to me, even if it didn’t get to stay.

I guess what I’m trying to say is it’s a personal decision and I suppose I’m one of those who would always want to give an embryo a chance, even if if those chances were small. IVF is a massive gamble anyway, whichever way you look at it.

@Mouseorchestra7 I think a new protocol and lab is a good call. What was your fertilisation and drop off rate from day 3-5 like?
I personally would see if your new clinic tests progesterone before and after transfer so they can up your dose if it’s low. I also took ubiquinol before and during stims. There’s only low level evidence to say this helps with egg quality but I figured it couldn’t hurt.

@RiverRiot its for sure a personal decision no doubt! Myself, I am risk adverse personality, having had things go very wrong in life (including medically) in the past, come from a place of flat out fear a lot of the time. For me, a 1% or less chance of something working is not worth what I perceive as a bigger chance I will have to go through something that could impact me profoundly physically or emotionally! But that is me!

(I will say though, that as a scientist (a mediocre one though maybe lol), I am mostly swayed purely by the most recent empirically evidence and published literature. The 2021 study where not one of 201 embryos tested aneuploid managed to be a live birth, is really strong evidence that self-correction or mis-testing happens incredibly rarely, if at all! The literature published on mosaic correction, any time this successfully happened, the embryo started out as categorised as mosaic, not aneuploid. It's one thing to say 'well maybe they can self correct', but if that isn't actually being observed in clinical practice and reflected n the literature, I'm not sure if they actually can in these situations. But more work with bigger sample sizes an studies is for sure needed to be clear. For now, for my sort of personality, I'll do just about anything to reduce the likelihood of BNF, chemical, and MC. Euploid transfers as you say doesn't at all eliminate these, but it massively reduces them! )

*empirical not empirically, *BFN not BNF. Wish could fix typos!

@tiggerwhocamefortea
The low level mosaic situation is totally different though, as there is published evidence that clearly shows that these can result in live birth (not at great rates, but at least that it does happen). When you test in UK, I'd only do so with a clinic that lets you transfer mosaics, so that they let you choose to shoot your shot or not rather than decide for you. I guess I should have mentioned that before- as if you were with a clinic that doesn't allow transfer of mosaics, it totally changes things.

The actual gold standard here is RCT and published work, not FB stories. So far it suggests that aneuploid could self-correct or be mis tested and actually euploid could be less than 1/100, potentially lower. Perhaps when evaluated for frequency in the population, the amount of women reporting on FB/reddit in the USA that have had a success from aneuploid embryos (NOT mosaic) is actually something like 1 in every one thousand that has transferred an aneuploid and didn't get the LB. To me, I think its important that women making these decisions are aware just how low the chance is or isn't. As the 'it could self correct' but only for 1/100, 1/300 or 1000 woman, might really change the choices someone makes versus if it was much more common (which it doesn't seem to be by any metric, but people seem to THINK it is). Luckily it seems like this is a super active research area and more RCTs and data is on its way in the coming years to allow women to weigh the personal decision for them knowing actual probabilities. And also maybe weighing this against he probability of having a complication from a MC that diminishes chances of live birth outcomes, or having diminished results from EC from getting pushed due to being pushed back months or a year from aneuploid transfers.

@whatcangowrong I am so sorry you have had to go through 5 in 6 months. Congrats on your current pregnancy!

(And I agree the thawing to test seems like it should be avoided as any sort of routine practice- Clear undisputed evidence that a non-trivial amount of embryos won't survive the re-freeze and rethaw, I was shocked to hear any clinics ever do this, I don't think many do but surprised any do. You can biopsy at time of original freezing and hold off on testing the biopsies until later, so can avoid the routine practice of thawing the actual embryos just to test and re-freeze again in most cases I would think)