2-day, 3-day or blast transfer?

When you do IVF, it is possible to transfer your embryos

  • on Day 2 after egg collection (usually 4-cell embryos),
  • on Day 3 after egg collection (usually 8-cell embryos) or
  • on Day 5 (after the embryos have reached blastocyst stage).

If you have only a small number of embryos and plan to transfer them all, the usual procedure is to put them all back on Day 2 because the uterus is the best possible place for them. However, if you’re doing assisted hatching, you usually need to keep them out for one more day and transfer on Day 3.

If you have a large number of embryos, and particularly if several of them are high grade, you will usually be encouraged to take them all to blast because that turns your ‘longlist’ dilemma (which to choose, which to choose …) into a ‘shortlist’ of embryos that are more likely to be viable.

As any specialist will tell you, odds of a pregnancy with a blastocyst transfer are higher than the odds with a Day 2 or Day 3 embryo transfer. This is an undisputed fact.

Some specialists will also tell you the extreme version of this (which is not actually proven, and is IMHO quite questionable), i.e. that if your embryo doesn’t make it to blast it wouldn’t have been a viable pregnancy anyway.

At virtually all NZ clinics (from what I have heard), the default is to make any leftover embryos go to blastocyst stage before they are frozen. The kicker is that many (and sometimes all) embryos don’t make it as far as blastocyst, i.e. they die in the petrie dish some time between Day 3 and Day 5.

Why does my clinic want us to take our embryos (or leftovers) to blastocyst stage?

The main reasons for these policies (as I understand it) are:

1. For women and couples with a large number of embryos, it is often difficult to tell which are the ‘winners’ that should be put back to give the best odds. By taking them all to blast, only some will make it, and in the ones that do, quality differences will hopefully be more obvious, thereby making the choice easier.

2. There are loads and loads of frozen embies that will never be used and no-one knows what to do with them. Ethical dilemma, and a logistical storage dilemma. Getting people to take their fresh embies to blast, and/or making any leftovers go to blast, cuts those numbers down.

3. More frozen embies means more TERs, which means greater expense for the govt (if you are publicly funded) or greater expense for couples (if you go private) – and more stressful 2wws with lower chances of a BFP each time (compared to a blast transfer). If those embies aren’t going to make it, they think you are better off finding out during the 2ww of your fresh cycle than prolonging the agony and expense. [Personally, I think this is a trade-off each couple needs to consider for themselves; having all frosties tank while you’re in the 2ww makes a VERY stressful time even worse.]

4. They don’t want to give people the “false hope” of thinking that their spares in the freezer are potential children because most of them are not. Quite apart from the points made in #3, above, if you’re an older mum, the months you spend doing TERs that end in BFN are months you are getting older before trying another fresh cycle. [I know some women overseas who cycle and freeze several times before transferring ANY for this reason; if they do get pg on the fresh cycle they will be too old and very low odds by the time they try for a sibling, so they bank several embies up front in the hopes that they might get 2-3 kids out of the lot. I have a friend who banked about a dozen embies at age 43-44, got pg on her last fresh cycle at 44, now is 46 and looking to do TERs, thankfully using embies made at age 43-44, not the near-zero-odds ones she’d produce now (if any).]

5. If you’re transferring blasts it’s easier to talk couples into transferring just one (because of the higher odds) and this reduces the number of twin births, which reduces the burden on the taxpayer, health system, the pregnant mum (twin pgs are sooooo not fun, trust me!), and the parents (possibility of losing one or both is higher, health problems are higher in twins than singletons, the first few months in particular are really really gruelling).

So, what are the main arguments against making your fresh embryos or leftovers going to blast?

The big issue here is, of course, could a potentially viable embryo die in the lab when it would have lived in utero? It’s unlikely but possible, in my view. Here’s why:

1. The number of embies that don’t make it to blast seems to me to be far higher than you’d expect for the age of the woman. Just an observation. This not only raises suspicions for me that viable embies are being lost this way, but in all those cases where there are none left to freeze (so many recently, it’s heartbreaking), it also massively increases the stress when you are in the 2ww and find out that EVERYTHING now hinges on your fresh cycle. Even if the day 3ers aren’t viable, some couples would rather have the psychological comfort of knowing there was another non-zero chance if they get a BFN.

2. There are some absolutely clear cases where people have had babies from embies that any self-respecting embryologist would stake their career on their not making it to blast. Case in point a board buddy of mine who put back four including two 5-cells that were so fragmented they looked like dollops of oatmeal, in her words. The embryologists gave them NO hope of surviving, so she just thought what the heck, put them all back. She’d had 5 failed IVF cycles already and was 35. She got pg with quads including one set of identical twins, so one of those oatmeal dollops turned into a baby (or two!). They are now 6yo, BTW.

3. The research apparently shows that blast pregnancies are more often boys, yet this is not the case with IVF pgs from 3-day transfers. This strikes me as extremely compelling evidence that SOME genetically normal girl embryos for some reason don’t make it in the lab but DO make it in utero.

It’s not an exact science of certainties; it’s a mix of probabilities and possibilities. Each couple is going to weigh these considerations quite differently. A lot depends on the woman’s age, how many cycles and TERs you can do without going broke or insane, how many kids you want eventually (and how you feel about ‘surplus’ embryos once you’ve achieved your quota), how stressful the various scenarios are to YOU, how many eggs you get each time, etc etc. Also, the aforementioned downtime (with the woman getting older) while you try multiple low-odds TERs instead of moving onto another fresh cycle.

The major issue I have with this is that IMHO (and based on reports from women all over the country I have spoken to) clinics in New Zealand consistently fail to consult adequately with patients, particularly on whether leftover embryos are taken to blast. The vast majority of patients are left with the impression that they had no choice in the matter. Frequently, ALL leftover embryos die before making it to blast, and patients are upset and dismayed to find out that they COULD have asked for their leftover embryos to be frozen on Day 3 instead. Here’s a typical comment from an IVF patient:

I had no idea we had the opportunity to freeze embies at day 3. This has NEVER been offered to us. From what we understand they are to be frozen day 5. We unfortunately have never had any to freeze as we’ve waited to day 5 for them to get to blast. I didn’t even know it was possible? I wonder why [my clinic] have never mentioned this?

This situation is especially upsetting if you are on your last IVF cycle and can’t ttc any other way (e.g. because of no tubes or MFI/sperm issues). When you’re standing in those shoes, it can just feel like the clinic has done everything it can to get you off their books (or onto another fresh cycle and more $$ in their coffers). I’m not saying that’s the motivation behind what clinics do; I’m just saying that can be what it feels like for patients who haven’t been offered the opportunity to give genuine informed consent on an important aspect of their treatment.

So, how should we tackle this and make sure we get what we want?

  • Think through these issues ahead of time and discuss them as a couple – there are trade-offs for either choice and there’s no single right answer
  • It may also be useful to ask the clinic lab/embryologists for some concrete data on what % of embryos make it to blast for women your age
  • Discuss the issue with your doctor and state clearly what you want
  • Write on your IVF consent form exactly what you want – make sure the nurse is clear on this too
  • Confirm this with the embryologist when you meet with them (e.g. at egg collection)
  • Confirm this AGAIN with your embryologist when you go in for embryo transfer
  • If you get any resistance from the embryologist, call in your doctor and refer them both to your consent form – INSIST on what you want. It’s your right!

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11 Responses to “2-day, 3-day or blast transfer?”

  1. Jo says:

    Hi there

    We have had two children from 2 separate ivf cycles. They were both day 3 embies.

  2. Eve says:

    Congrats to you, Jo! Fantastic to have BFPs on both cycles! Did you have any leftover embies?

  3. Mil says:

    Ive done 5 IVF cycles and have only ever had one embryo to freeze (frozen at day 3 which didn’t manage to thaw). Of the five fresh cycles we have transferred two embryos each time. The first two cycles transferred at day 3 and the the last three at day 2. We have had two pregnancies from the day 2 transfers. One ended in a miscarriage, the other in an ectopic. I have just read from an EBB contributor that day 3 (or day 2) embryos have higher chance of ending in ectopic pregnancy. Can you confirm this?

  4. Vinni says:

    I have a 2 yr old girl from a 5 day frozen blastocyst and soon to have twin boys (fraternal) who were transferred fresh on day 2.

  5. Tilly says:

    Hi Eve, thanks for this discussion. We are currently trying to make this crucial decision. It is Day 1 and we have been told we have 8 normally fertilised embies.
    With respect, IMHO, I think you have missed listing the main reason that clinics encourage the policy of taking to blast. The main reason, as I understand it, is that, in cases where there are a whole lot of good-quality Day 3 embies, taking them to blast enables the scientists to choose the one (or two) embies that are most likely to make it, and thus pregnancy rates are improved.
    Otherwise, at Day 3, if there are a whole lot of normal embies, how do they know which one (or two) to put back? By taking them on another 2 days, they can have better information as to which fresh blast to put back. The strongest, most high grade one (or two), on Day 5 is replaced.
    Otherwise it is just a lottery at Day 3, they have to select one or two, put them back, and hope for the best.

  6. Eve says:

    Tilly, thanks for this, and you are right – I’ll edit the post accordingly. I did end up focusing more on why leftovers are taken to blast, rather than why the fresh ones are taken to blast. Good point!

    And good luck with your cycle too. 🙂

  7. Tilly says:

    Thanks Eve for the good luck and your comments 🙂

    I hope you don’t mind if I make another couple of points. Point 1 above: you say that by “taking large numbers of embryos to blast, quality differences will hopefully be more obvious”.

    I think possibly this statement should be worded more strongly than this. The scientists at Day 3 can only make a visual assessment of the Day 3 embies. They may look perfect, but their genetic worth has not been proven. By Day 5, blastocysts are proving their genetic “get up and go”. They have evolved into a new form of life, and thus that is why pregnancy rates are so much improved by replacing a blastie versus a Day 3 (63% versus 46% at FAW for 2009, respectively, for women 37 and younger).

    You also say that some specialists would tell us the extreme version of this , that a Day 3 that didn’t make it to blastocyst in the lab , woudln’t have made it back in utero. However, I do wonder if phrasing it as an “extreme version” is the best way to represent this statement.
    I wonder this because the FAW updated handbook (January, 2010), states that :

    “Our current understanding suggests that if an embryo does not develop into a blastocyst in the laboratory, it is highly unlikely that it would have done so had it been transferred into the uterus on day 3”.

    I asked an embryologist this morning if she agrees with this claim,and she says yes. I did not push her on the evidence, but I do feel that they would not write statements such as “highly unlikely” (very strongly worded for science, as they never use the word “certain”!) if they did not have evidence to support this.

    Thanks again for your blog and the opportunity to have these discussions in an informed manner, I totally agree with your ethos of us being as informed consumers as we can be, and questioning our treatment protocols as much as we can.

    Cheers, Tilly:)

  8. Eve says:

    Hi Tilly,

    Thanks again for your comments.

    Point #1 is in fact worded more strongly than the snippet you paraphrased. I said, “By taking them all to blast, only some will make it, and in the ones that do, quality differences will hopefully be more obvious, thereby making the choice easier.”

    So, when you take day 3 embryos to blast, several (hopefully just a few, maybe most, maybe all) won’t make it. So, as I said above, this cuts your numbers down. Now your longlist has become a shortlist (as I said above), which makes the choice slightly easier from a pure numbers perspective.

    Yes, it is a major achievement to have made it to blast, and the ones that do make it have significantly better odds. So, the shortlist is a better quality set on average than the longlist of Day 3 embryos.

    It is also likely that of the ones that have made it to blast greater differences may become apparent than were evident in those same blasts when they were at Day 3. Embryologists can still only make a visual assessment of the quality of blasts (unless you have done PGD) – all they know is that blasts are more likely to be viable than Day 3 embryos (based on the simple fact that they made it this far), but beyond that they are still grading based on looks. Here’s a great web page about how one U.S. clinic grades blastocysts and some examples of grading Day 3 embryos.

    As you correctly point out, clinic manuals use language like “highly unlikely” to describe the chances that a day 3 embryo that dies in the lab trying to make it to blast would in fact have made it in utero. I don’t disagree with that, and neither would any competent embryologist or fertility specialist. Highly unlikely – yes. Zero likelihood – no.

    However, some specialists use language like “wouldn’t have made it anyway” which IMHO is an “extreme version” of what is in the manual because it implies to patients that there’s basically NO chance they would have survived. If this was the case, obviously ALL cycles would be going to blast. They don’t do this. Why not? Because SOME embies (yes, a small percentage, and we don’t know the number because it’s simply unknowable) will make it in utero that wouldn’t have made it in the lab.

    We are all very different in how we feel about the trade-off here. It’s not at all easy because by taking them to blast there’s a risk that a potential baby is lost in the petrie dish between days 3 and 5. But if you put one or two back and freeze the rest, there’s still the risk that you’ll lose a potential baby in the thaw process (thankfully this is becoming less of an issue due to vitrification, but it still happens quite a lot, and is of course highly dependent on the quality of the lab).

    All I am trying to do here is highlight that these are very real possible scenarios that people need to know about because I have talked to so many women and couples who had no idea they could end up with no blasts to transfer, or only one (and would therefore be facing a whole new fresh cycle if they got a BFN or wanted to try for a sibling). I think it’s best to go into this with our eyes open about the possible scenarios and make the best choice we can.

    Obviously you are in the lucky situation of having too many Day 3 embryos to choose from and hopefully you’re also going to end up with a lot making it to blast as well. It’s quite a different situation for a couple with lower numbers or more mixed quality, or who’s older and wanting 2-3 kids (in which case frosties frozen now will have better odds than freshies in 2+ years’ time – once you’ve gone through a pregnancy, breastfed, weaned, got your cycles back to normal so you’re ready to cycle). And all this is assuming the couple doesn’t have some unknown problem whereby great-looking embies or blasts won’t stick, or won’t stick for long

    All fingers crossed for your blasts! 🙂
    Eve

  9. […] pretty sure that assisted hatching can be used whether you are doing a 3-day or a 5-day transfer, but generally not for 2-day transfers (the embryologists say the embryo is usually too small then […]

  10. Tracey says:

    We had fresh IVF cycle, were overstimulated and coasted for four days. Despite over 30 folicles doctor only retrieved 3 eggs. We were shocked when all three fertilised and at day three we have 2 x eight cells and one a bit slower at four cells. We were all set to put two back on day three but I was at too high a risk of OHSS so they decided to delay a few days and take the embryos to 5 days blastocysts and see if I was then ready for a fresh transfer and if not the embryos would be frozen. Day 5 arrived, went to the clinic for my scan, was told it might be a possiblity to have one fresh transferred but would wait for the days blood results and check on embryos. We were devastated to learn that none of the embryos had made it. So fresh cycle all finished with absolutely nothing to show for it. We are upset that we didnt insist that at least one of the embryos was frozen at day three.

  11. Eve says:

    Ohhh Tracey, it’s so heartbreaking to go from all the hope of a high-yield cycle to the devastation of nothing being available to transfer. I really hope you can find some answers and some luck on your next round, if you are able and wanting to go there. (((hugs)))

    Eve

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