Post-Thaw Evaluation of Embryos

March 23, 2014Carole 109 Comments »

I received this email from a reader who wanted to know more about the process for thawing and assessment of embryos that have been cryopreserved.

This last cycle involved a FET of a day 5 and day 6 blastocyst from an earlier IVF that we were not able to complete a transfer for.  The embryos had been vitrified and when defrosted, we were told they did not expand, and remained shrunk.  The embryologist said there were a few cells in there that were still alive but their assessment was that these were not viable.  I haven’t found much on the web and I didn’t see it in your blog, about defrosting embryos, the process, and how an embryologist makes the call on a defrosted embryo, and how long the process takes, etc.  I did find a study that had compared transfer of blastocysts that had expanded and those that did not, and the pregnancy rate among those that did not was zero.  Thanks for considering this as a topic.

Taking a few steps back in the process, let’s start with the decision of which embryos to thaw. In speaking with other embryologists over the years, the majority or programs will as a matter of policy pick the embryos for transfer that scored the highest among the still living embryos. It is routine for some embryos to stop growing between fertilization and the time of transfer, probably due to genetic issues but not always. So, the remaining non-transferred embryos may have slightly lower quality based on having scored lower-assuming scoring is a good sign of quality–which is not always true. These possibly second tier embryos are frozen. Of course, if you have a large number of good quality embryos, you will be freezing high quality embryos too. The reason I say this is to explain that not all embryos start off equal at the time of freezing. Embryo quality is not improved by the cryopreservation process; the best outcome is no loss in viability.

The method used to cryopreserve the embryos makes a difference too in the quality (and hence the scores) of embryos post-thaw. In the bad old days, we used slow freezing which was relatively poor in preserving embryo quality. If better than half the cells in the embryo appeared clear and shiny after thaw- and thus alive- we called it a good outcome. Now, with vitrification, we expect to see the embryo reappear from the thaw looking as good as it did going in.

When preparing for a frozen embryo transfer cycle, the lab needs to coordinate well with the clinical staff so that the patient’s uterine lining is synchronized with the thawed embryo’s stage of development at the time of transfer. The embryo needs to be ready to implant and the uterus needs to be ready to receive the embryo. The “window of implantation” is only open during a few days in every menstrual or artificial cycle.

The clinical staff “runs” the cycle, educating the patient in how and when to take the medications that will make the uterine lining thick and ready for the embryo. Clinical staff will use test results from blood work and ultrasound visualization of the uterine lining to adjust medications and decide when the patient is ready for transfer. Clinical staff need to keep the lab apprised of the patient’s progress so that that embryo can be thawed at the right time. For instance, if the patient has embryos frozen at the zygote (fertilized egg stage), the embryo will have to be thawed several days in advance of the actual transfer to allow the embryo to continue to grow to the 8 cell stage (for a day 3 transfer) or the blastocyst stage (for a day 5 transfer). If the embryo was frozen as a blastocyst stage embryo, it will be thawed close to the time of transfer, at most, the afternoon before but most likely the morning of the transfer day.

When vitrification is used, the term “warming” is used instead of the term thawing. This naming convention probably arises from the fact that the process of vitrification bypasses ice crystal formation, moving the embryo right into a solid phase- glass-like -state. Ice thaws but glassified embryos warm from a colder state to a body temperature state.

In any case, the first step in removing any embryo from storage is verification of identity of patient embryos and physician  orders to warm the embryo. Every good clinic will have a process to ensure that the right patient’s embryos are removed from storage and among those embryos, that the right one or two embryos is warmed and readied for transfer. All storage systems have some method of identifying embryos that is physically adhered to the smallest storage unit- the straw or the vial. Often, a waterproof permanent marker is used to print patient name or and ID number or both with date of freeze or other info on the straw or vial. Newer methods use bar codes. In any case, the right straw is recovered from the cryostorage tank. A second pair of lab eyes must verify that the right cryostorage unit is removed or thawed at one or more stages of the process. At transfer, usually someone at the clinic and lab side verifies that the right patient is matched to the right straw.

The process used to freeze the embryo dictates the process that must be used to thaw the embryo. That is why when frozen embryos are shipped between labs, thawing or warming instructions must accompany the embryo so that the receiving lab can recover the embryos successfully.

No matter the method used, the embryo is thawed or warmed and transitioned from being immersed in media that is incompatible with life and growth to being moved into a nutritive, warm, proper pH culture medium for a period of hours or days to recover and then grow. In the case of the day 5 or day 6 embryo, the embryo would typically be thawed in the morning of the day of transfer, especially in the case of a day 6 embryo because day 6 embryos really can’t tolerate much more culture time- they need to be moved to a uterus. If you look at pregnancy rates for transfer of day 5,6 and even day 7 embryos, by day 7 the pregnancy rates have dropped to unacceptably low levels (less than 10%). Whether this is due to the fact that culture conditions aren’t optimized for what the day 7 embryo needs or because there was something wrong with an embryo that was growing so slowly that it needed 7 days in culture to become a blastocyst isn’t entirely clear. But I think most clinics would agree that when you thaw a day 5 or 6 embryo, you want to give it a few hours to recover and re-expand, then transfer quickly.

Blastocysts have a large space in the middle of the embryo that fills with fluid. This fluid-filled space or blastocoel is not helpful for vitrification and embryologists have found that if you make a tiny hole in between two cells to let the fluid leak out- collapsing the embryo- the embryo will vitrify more effectively.  Blastocyst stage embryos are often “collapsed” on purpose before freezing to allow the cryopotectant agents to infiltrate the cells in the embryo more effectively.

After warming, we expect to see the embryo re-expand and re-fill that space with liquid. Re-expansion is an active process that requires energy to pump fluid into the cavity and requires that the embryo be alive. So failure to re-expand is of concern. What is not clear is how long should we give an embryo to re-expand before we consider it to be dead? Often times, because we want to thaw and transfer quickly, we might only allow the embryo a very short time, an hour or less to recover in culture medium –and this may not always be enough for an embryos to re-expand. The re-expansion of a live embryo will happen in the uterus after transfer if the embryo is alive but we don’t get to see and document that.  I am not sure that anyone has ever determined what the average time for human blastocyst re-expansion is.  But a failure to re-expand by the time of scoring–perhaps just one scoring event right before transfer-  may or may not indicate that the embryo is non-viable.

For a good idea of some of the factors that effect the outcomes of thaws, you can read this article by clinicians at the Cleveland Clinic’s IVF program, which covers many of these issues in greater detail.

The scoring methods used to assess embryos after thaw are the same ones used to assess fresh embryos. I describe the Gardner method with pictures for scoring blastocysts in this previous blog post. The problem with blastocyst scoring of post-thaw embryos is that the scoring  includes an assessment of the size of the blastocoel. A blastocyst with an collapsed blastocoel will score more poorly and it might not be obvious whether this will be corrected by full expansion in just a few more hours- or not. So scoring post-thaw is problematic.

What embryologists like to see in an embryo that is reviving from cryopreservation are shiny clear cells, not dark opaque cells. Dark opaque cells are dead. Clear shiny cells are usually alive. This sign of life, while not as definitive as active re-expansion, might be all that can be scored immediately after thaw or warming, when the transfer procedure is imminent. Also, the time taken to score an embryo is a matter of seconds. Scoring is accomplished by a quick visual of an embryo that is rotated in culture under a microscope by the technician using a sterile pipette so that all sides are visible and takes less than a minute. The new real time continuous imaging of embryos in culture from fertilization to blastocyst stage using systems like Eeva, will change many of our procedures. Visual manual scoring techniques may be replaced one day by algorithmic scoring of real time embryos but most clinics currently use the old inexpensive methods.

For now, your embryologist will likely still need to make a visual assessment and make a decision based on past experience to decide which embryos survived thaw and are suitable for transfer. More often than not, this will be enough to pick viable embryos.

 

 

© 2014, Carole. All rights reserved.

109 Responses to this entry

  • Carole Says:

    HI Molly,
    I think that sounds reassuring- I don’t get too excited about fragmentation- especially if there is good cell number in the inner cell mass. ! Good Luck!! Carole

  • Jenni Says:

    Hi Carole! Your blog is fantastic and I can’t believe the time you take to respond to the comments. Thank you!
    I have a question. We had our lone frozen embryo put in today. It was a 6 day blastocyst, frozen after PGS. We have a son from the same cycle :). However, the embryologist told us that while the cells were alive, the blastocyst had not started to re-expand and they had hoped to see signs of this. It was just over two hours since they had thawed. However, we popped it in and now we just have to wait.
    In your experience, are you aware of many pregancies resulting from similar situations when the blastocyst has not started to reexpand before replacement? I’m being very pragmatic about this and would appreciate some information based on your experience.
    Thank you!

  • Carole Says:

    HI Jenni,
    Yes, it can take longer than two hours for a blastocyst to expand so I think the two hours post-thaw without expansion is not necessarily a bad sign. Especially since your embryos had undergone biopsy before freezing on day 6, they might be a little sluggish at first. Some embryos just take a little longer. I would remain hopeful at this point. Good Luck!! Carole

  • Jenni Says:

    Carole, thanks so much for your speedy reply! I’ll let you know the outcome! X

  • Molly Says:

    Thank you Carole for your response and opinion; I appreciate it. So in your opinion you think I should not be too worried about the fragmentation because there was good embryonic tissue in the inner cell mass (is this the same as good cell number in inner cell mass)? I apologize for all my questions and thank you in advanced.

  • Carole Says:

    Hi Molly,
    Yes, that is how I interpreted it so I think you will be all right- but as always, the best expert on your care is your IVF team. 🙂 Wishing you Much Good Luck!! Carole

  • Katie Says:

    Very interested in this post…

    Recently underwent first cycle of ivf, no luck with fresh ESET of a 5AA hatching blastocyst. Just had FET#1 last week- blastocysts had scored 5AB and 3BB before vitrification on day 6 but had only expanded to 2BC and 2CC between warming and transfer (a few hours). I had hoped for ESET but based on my day of counseling, agreed to DET because of the lower grade.

    After reading your posts, it seems expansion was an ongoing process and implantation chances would more likely reflect grade before vitrification than after- is that correct? Do you alter your counseling based on post-warming grade or just report that expansion is occurring and the cells appear viable?
    Thanks!

  • Ange Says:

    Yesterday I did a 5 day frozen blastocyst transfer with a 5BB embryo with no fragmentation. In all the nervousness, I didn’t get some questions answered.

    1. Apparently the embryo was 50% expanded in the first 15 min of thawing – is this a good thing?

    2. The lab also mentioned that the thawed embryo looks exactly as it did when it was frozen; is that what is supposed to happen or the embryo is supposed to grow some more?

    Thank you!

  • Carole Says:

    Hi Katie,
    Practices and policies vary between clinics. We did not regrade post-warming, simply noted that expansion was occurring- or not. We rarely saw cell loss with vitrification so the AB part of the grade didn’t change. And re-expansion occurs over a period of hours and once we confirmed expansion had started, we did not see any advantage to prolonging time in culture prior to transfer just to ensure full expansion. Good luck with your transfer!!! Carole

  • Carole Says:

    Hi Ange,
    50% expansion in first 15 minutes is just fine. Yes, absolutely, the embryo should look exactly the same before and after vitrification and warming- that’s how you know all is well. 🙂 At the supercooled temperatures, the embryo is in stasis, all metabolic functions are on pause so there is no growing happening. Seems like you are in good shape. Good Luck!!! Carole

  • Hopeful mum Says:

    Hi Carole,
    Thank you in advance for your time and help with all the questions from everyone.

    We have a FET with a day 5 blastocyst, but the day we were booked for the transfer we were told first thawed embryo didn’t survived (which made us dissapointed) but 2nd hasn’t fully expanded, but was still “viable enough” for the transfer.

    We saw it definitely looked empty some areas in the microscope but were too overwhelmed to ask any questions or if that was normal.

    We are due for a pregnancy test next Wednesday but since leaving the clinic were not very hopeful. Do you think a not fully expanded embryo has a good chance of development/success? Many thanks for bringing some light.

  • Carole Says:

    Hi Hopeful Mom,
    A partially expanded embryo at transfer has every chance to become a pregnancy because it will almost certainly continue to expand inside you. So I would not lose a moment of sleep over the extent of expansion, because it is only a snapshot in time. I think you have every reason to be hopeful at this point. I wish you MUCH GOOD LUCK!!! Carole

  • cherry Says:

    Hi,

    I was scheduled for a FET with one 3BC PGS tested normal embroyo and was told it did not survive the thaw. Is this a lab issue? What other things could cause a PGS tested normal embroyo not to survive the thaw? Thank you.

  • Carole Says:

    Hi Cherry,
    I am sorry that you are having such a hard time. Unless the embryo was already non-viable before the freeze, it should normally survive thaw- assuming that vitrification methods are used (as opposed to older slow freeze methods). So failure to survive the thaw are more likely to be technical. Embryos can be easily lost as they are moved from the storage container to the various wash dishes if the technician is not experienced- and sometimes even experienced techs encounter issues like equipment failure or failure of the container (eg, cracked straws). I think it is perfectly fine to ask for more details about what happened. The consent form you signed typically includes a list of everything that can go wrong. The chromosomal status of the embryo has no effect on the ability of the embryo to survive. Good Luck!

  • cherry Says:

    Thank you so much for your response. One more quick question – I also had two of my PGS embroyos come back as no result. Any idea what would cause this? Does this say anything about the quality of the embryo? Thank you so much!

  • Carole Says:

    Hi Cherry,
    Sometimes you can get no result if the chosen cell is missing the nucleus which can happen during preparation or maybe the cell was starting to break down. One bad cell does not mean the embryo is bad at all. The embryo naturally dumps cells along the way. You can also have technical problems which result in no signal. But this is a good question for your PGS lab team- usually there is someone who can explain the test to patients. Good Luck!!

  • Jen Says:

    Hi Carole,
    Thank you for all the wonderful information. I am considering a FET. I have three blast embryos and was tryig to understand the grading. They are 6CB & 6CC (2). I was wondering about the ICM grade of C and what the chances of a successful implantation would be over a ICM grade of B. Is there a huge difference between B&C? And does the ICM grow if the implantation is successful? Im trying to decide if I should to the transfer and what my odds are. Your opinion would be greatly appreciated – Thanks

  • Carole Says:

    Hi Jen,
    Thanks for your question. I did a whole blog post on this topic: http://fertilitylabinsider.com/2011/12/understanding-the-gardner-blastocyst-grading-scale/ The difference between B and C is the number of cells in the ICM. More cells is better so B is better than C. It is not a huge difference in that pregnancies can be achieved from either B or C, but the probability of implantation is likely somewhat greater with more cells. The ICM will continue to grow as long as the embryo is alive– the ICM is the beginning ball of cells that give rise to the entire baby- with time- so yes!!-every baby started from an ICM that continued to grow! 🙂 Good Luck!! Carole

  • Rachael Says:

    I had a successful single embryo transfer in 2009, which resulted in the birth of my first child. I was 24 at the time (PCOS; I don’t ovulate) and thankfully we had very good quality embryos. 12 made it to day 5, 1 transferred, 11 frozen (vitrification). We would like to do an FET with PGD to select for opposite sex, if this is possible.

    I loved our clinic and found them to be very knowledgeable and up to date. Their fresh transfer success rates were/are very good. However, I was absolutely shocked when I looked at their FET stats. ~10% success from non-donor FETs for two years running. Numbers were higher for donor FETs but nowhere near the national average. It did not appear to be an obvious thaw problem to me, since all of the cycles where a thaw was attempted resulted in a transfer (according to SART.org).

    I emailed my RE about this and he replied that they previously let people freeze any embryos for later transfer, even if they were poor quality, and that is what accounts for the low numbers. (He said they don’t allow this now, although recent stats are not yet available). I am having trouble wrapping my head around this. They did ~100 fresh transfers and only 24 frozen transfers in one year. Only 2 FETs were successful out of those 24. So that means a truly huge number of FETs should have “not happened” due to poor embryo quality.

    I’m not sure where to go from there – is this a red flag, or should I just trust that the stats reflect a different patient population? Are there additional questions I could ask that might shed some light on where things are going wrong? I don’t want to switch clinics, but I am suddenly feeling uneasy.

  • Rachael Says:

    Oops. I typed my comment in word and pasted over – my copying missed the first paragraph. Just wanted to add, thank you SO much for keeping such an informative blog! The Q&A here is particularly helpful – thank you!

  • Carole Says:

    Hi Rachael,
    Even if they haven’t published final rates yet, they are keeping track of their rates since changing their policy about what to freeze.So if they want to , they can share them. The logical next question is–so what are your rates since you changed your policy? Even with freezing everything, these rates (10%) are abyssmal. I think it does raise some questions. How many FET cycles have you performed using embryos frozen under the new policy? OF these frozen embryos, what is your rate of survival post-thaw. (For eg., if you thawed 5 embryos, how many of those on average would survive the thaw? It should be at least 80%. What is your pregnancy rate now that you are freeing better embryos? It is also possible that the fresh embryos were decent (since you said they have a good fresh rate) and they are simply not good at performing freeze/thaw procedures. So unless they are more forthcoming, I might consider changing clinics. Good Luck!

  • Rachael Says:

    Thank you for your response!

    It is very confusing. The clinic is very good, and connected with a medical school/university. My RE communicated in the original email that their pregnancy rates were “similar to what you report for other clinics” – which, in my email, was 40-50%. I will call tomorrow and see if I can find the actual numbers

    This situation is further complicated by the fact that the clinic is actually on the other side of the country – we moved. We were not sure whether to ship the embryos here to a new place or do the cycle from afar. My RE said he had seen some “shipping disasters” and therefore would recommend keeping the embryos with them (hardly an unbiased opinion). Before I saw the stats, I was totally fine with that. We were planning to do monitoring here and then I’d fly out for transfer.

    Have you ever experienced shipping problems? I am actually a scientist and I *have* had problems with cells sent on liquid N2, so this does make me nervous.

  • Rachael Says:

    I spoke with the lead embryologist and she very much put my mind at ease. She pulled my chart, and there’s some good and bad news together.

    Unfortunately they were slow-freezing embryos in 2009, so mine were not vitrified. They were day 6 and at least half were hatched or hatching.

    The numbers: their current FET implantation rate is close to 70% with ~60% ongoing pregnancy rate. The explanation: they switched to vitrification right in 2010 and the thaw protocols were not correct for two years. They had a huge staff turnover in 2013, and now they have no problems with thawing. (It sounded like they ousted someone who was messing things up big time). I wish my RE had been more forethright about the actual issue, but I trust the embryologist’s explanation and it lines up exactly with their stats (pre-2010 FET numbers were fine).

    The bad news is the slow freezing part, since we will be expecting a higher rate of embryo loss. She did not recommend attempting a thaw with fresh biopsy and transfer, as they are already day 6. We actually have two sons (one surprise/natural pregnancy), and the sex selection is part of our choice to attempt a third… we will not transfer if no female embryos are available. We also cannot afford another IVF, so we will just have to hope for the best.

    With all of this, it looks like we should feel comfortable going back to our original clinic. Thank you so much for the advice!!

  • Carole Says:

    HI Rachael,
    Slow-freezing can certainly account for a lot of bad outcomes. I am glad you went back to get more answers– and that the embryologist spoke with you and gave you more information so that you could trust them again. Doctors often either don’t know or think too many lab details will confuse the patient- maybe because they don’t understand it either. I am biased but I think it is always best to go back to the lab for answers to lab questions. 🙂 Good Luck !! Carole

  • Vicky Says:

    Hi Carole,
    What a fantastic blog, congrats! I’ve got a question about the timeline of a five-day blastocyst transfer. My RE initially told me that it would be done on day 6 after ovulation. Today I got my blood test results and had a scan and the verdict was that I ovulated yesterday (let’s call it Day 0). The transfer will be on Day 7. Is there any rule on when exactly a five-day frozen blastocyst transfer should take place? I’m a little worried that Day 7 may be too late. Thank you.

  • Carole Says:

    HI Vicky,
    I would ask your doctor what the pregnancy rate is for his transfers done on day 7 (compared to day 5 and 6) – and how many patients are in that rate. If day 0 is day of retrieval, day 7 seems latish,although pregnancies have been reported on days 5,6 and 7, but 7 typically is less successful. I would follow up with your physician. Good Luck!! Carole

  • Rachael Says:

    The verdict is in from the clinic with the strange FET stats… Of 11 embryos, only 3 survived the thaw for biopsy. Two were boys with monosomy, and one was a chromosomally normal girl. Unfortunately the female embryo is low quality – 4CC – but it was vitrified and we will transfer in 6 weeks. I’m not sure what the quality really means, if the blast will be less likely to survive a vitrification/warming or if we should just forget about grading at this point. I can’t shake the embryologist’s original comment that the blastocysts were not expanding “as well as we’d like”, although I suppose with a grade of 4 that means something.

    We were absolutely devastated to find that so few survived the thaw. I was 24 at the time of our first cycle and our RE literally chuckled when he saw our embryology report, because they were all so high quality, more than half frozen at hatching. I’m having a really hard time understanding how an academic clinic with otherwise fabulous stats could have been screwing up freeze/thaw protocols for so long. I trust their new embryologist, but it is sad to think of how many couples would have been affected by what were clearly bad cryopreservation methods.

    We do feel profoundly grateful that we have one shot at the FET. Just hoping for the best now – it is out of our hands!

  • Lea Says:

    Hi Carole,

    I just had my FET and transferred 2 5d embryos. One survived perfectly and the other one had a 70% survival. Can you explain to me what it means exactly and what I should expect my chances of implantation with that embryo? Both were expanding blasts graded 4AA.

  • Carole Says:

    Hi Lea,
    It sounds like you are in pretty good shape. You’ll have to go back and ask your embryologist what “70%” survival means? It could mean that only 70% of the cells survived which seems low for a 4AA score. Don’t be afraid to ask your IVF team these questions- they may have devised their own scoring system. It’s part of your treatment plan to understand your treatment plan so please feel empowered to ask these questions of your team. Good Luck!! Carole

  • Carole Says:

    Hi Rachael,
    Freeze-thaw protocols are harder than regular IVF procedures- they are less forgiving. Some clinics don’t invest the time or money needed to train their staff appropriately. Older slow freeze protocols were particularly tricky and even a good freeze-thaw some loss of cells. Vitrification is a huge improvement in the freezing technology – but also requires training and expertise. The other thing is that it may be months or years before you realize that something went wrong with the freeze protocol because it may be that long before the embryos are thawed. The good news is that if they were very high quality and started from your 24 year old eggs, they may be able to survive all these manipulations–wishing you MUCH GOOD LUCK with your upcoming transfer. Carole

  • Sacha murray Says:

    Hi there,

    I have just had a transfer of two embryos in my first frozen cycle. They were 4bb and 3aa when thawed the night before. The morning of transfer the 4bb was still 4bb and the 3aa had become a 4aa. I am intrigued that my clinic must have a policy of thawing night before transfer and you seem to recommend the opposite. Do you think it matters that the 4bb has not changed? My logic tells me that the 3aa one that grew seems a better chance. Wild be interested to know your thoughts although slightly nervous too! I have never posted on one of these blog sites before as it always seems to me that they are either going to work or not and there is nothing more that. An be done at this point. But I am curious about the fact that one changed and one did not. My clinic are very positive, I believe one was starting to hatch too

  • Carole Says:

    HI Sacha,
    I don’t know why any particular clinic does things the way they do. Presumably, they have good results with their approach. I would follow up with them if you want to know why they do it the way they do. Growing and producing more cells is always a good sign though and I wish you MUCH GOOD LUCK!! Carole

  • Ripple Says:

    Hi there
    I have just had a frozen embryo transfer and the embryologist said that the embryo had split but is still joint and she thinks it’s two embryos or maybe the embryo has lost some cells. Also she said it didn’t re expand and the term collapsed was use. But she said it’s still viable. What hope do I have?

  • Tegan Says:

    Hi,
    My day 5 embryo survived the thaw 100% and was perfect.
    However, it hasn’t expanded at all in 18 hours.
    How long can an embryo be arrested for before it may start to expand one more?

  • Jeanine Says:

    Hello Carole,
    Wow thank you so much for all your help. The info you provide is priceless. My question is similar to Lea’s who posted Feb 3rd. I had FET scheduled today. The embryo which is 5 day blasto grade A female embryo thawed but 20% of the cells did not survive so my RE suggested thawing a second embryo and putting in both embryos. The 2nd thawed well with all cells surviving so I am hopeful that that embryo which is a boy will stick! However I am concerned about the girl embryo. Do you think she has a good chance at surviving? We have no more girl embryos. I had an FET back in August with our only other female embryo I got pregnant but miscarried at 10 weeks. Needless to say I really want my current female embryo to make it! Twins would be amazing! Would deeply appreciate your input. Thanks for all you do!!

  • Molly B Says:

    Hi Carole!
    I could really use some advice for our upcoming failed IVF consultation with my RE and lab. I need them to provide me with some explanations on what happened with my case. Here is what went down. I had 34 eggs retrieved in August, 13, 5 day grade 1 embryos made it to freeze. I couldn’t transfer due to over-stimming so we looked forward to our FET come Oct. The day came for transfer and they came in the room and told us they went through 5 embryos. 3 didn’t survive the thaw and we transferred 2. I did not get pregnant. They called us in and said they couldn’t provide an explanation on why 3 died and they haven’t seen that happen in their history. We move to Feb, our second FET. They called us that morning and said “bad news again nothing is surviving the thaw” the technician said at the very end of the thaw my embryos would just start to degenerate. We lost 6 embryos that morning and transferred the very last 2 that were “iffy” but still viable. So we went from 13 healthy frozen embryos down to 0 in 2 cycles. I don’t even know where to start with my questions for them but I need some explanations. We are completely discouraged and heartbroken and at this point my faith in the lab is slim.
    Thank you,
    Molly B

  • Carole Says:

    Hi Tegan,
    I would have expected some change over 18 hours. I would ask your embryologist for more information. Good Luck! Carole

  • Carole Says:

    Jeanine,
    I hope you had a good transfer!! Either one or two is a pretty typical transfer for someone in your circumstances. Yes, I think the loss of 20% of the cells on day 5 is not insurmountable at that point. Good Luck!! Carole

  • Carole Says:

    Hi Molly,
    I am sorry you are having such a hard time. Some questions:
    What is the pregnancy rate for patients like me who transfer embryos like mine? On the day, I had my thaw, were there other patients with normal results?
    Was the technician who performed my freeze/thaw experienced? How many freeze/thaw cycles did the tech have under their belt before our case? How long has the clinic used the freeze/thaw protocols they used in my case?

    These are all questions that they should be able to answer without too much squirming. Though when I hear something, like this never happened in their lab before, my gut reaction is if you want to do this again, search for another clinic with better than average results (check out http://www.sart.org – preg rates for clinics) . All clinics have these bad outcomes from time to time if they have been in business any length of time. The question is do they have the infrastructure and personnel in place and culture to trouble shoot what went wrong and prevent it from happening again. Overstimming is also something that can happen with newish clinics – or bad/inexperienced docs- and overstimming is not good for egg quality. You get lots of eggs but you don’t get MORE good eggs. You don’t mention your age but if you are over 35, IVF may be less than ideal for you. I wish you all the best moving forward!!! Carole

  • M Says:

    We are on IVF cycle #3. Our plan was to do PGD but we didn’t have great numbers so our 1st cycle we did a 3 day transfer instead but ended in twin MC. Then 2nd cycle was cancelled due to poor response. This 3rd cycle they only retrieved 5, 4 were mature, and they indicated 3 fertilized normally. On Day 3 they indicated they were all 8 cell and graded them a 7 on their scale that is 0-8 with 8 being the best. I got the report this morning that on Day 5 one was biopsied and the other two are expected to be biopsied tomorrow. When I asked about grading they indicated all 3 were fair.

    So now I’m wondering statistically do the Day 6 ones have reduced odds of taking than the Day 5 one? Also, I really don’t understand the grading scales. I know ultimately we have to wait on the PGD results since we’ve had recurring losses and the last ones were confirmed as chromosomal issues.

  • Carole Says:

    Hi M,
    I wrote about the Gardner blastocyst grading scale which might be helpful http://fertilitylabinsider.com/2011/12/understanding-the-gardner-blastocyst-grading-scale/
    Here’s an article about pregnancy rates on day 5 and day 6 http://humrep.oxfordjournals.org/content/early/2010/06/11/humrep.deq143.full They noted that some blastocysts reach blast stage on day 5 and some on day 6 but pregnancy rates are comparable, as long as they get to that stage. Good Luck with your PGD results and your next transfer!! Carole

  • Rachael Says:

    Hi –

    Following up from my post above, where we had 1 viable blastocyst left from an original set of 11. Unfortunately there were problems from start to finish, particularly regarding communication between myself and staff but also between the MDs. I received very poor medical care and developed complications from the progesterone that landed me in the ER and unable to walk for two weeks (severe cellulitis; they had been insisting my symptoms were “normal” for a solid week). I was provided with three totally different explanations from three different people for their bad stats. The cycle did not succeed and we probably cannot afford to start again.

    I look back and don’t feel that we should have made any different decisions based on what we knew at the time. We had to go with the embryos that we already had. Shipping them to a new clinic would not have been a good option… I would have attributed the loss of 10 otherwise healthy embryos to the shipping process, if we had done that, and then I just would have blamed myself. So, I can wish things had gone differently, but I do not regret that we tried.

    Again, thank you for your wonderful blog and advice.

  • Carole Says:

    HI Rachael,
    I am so sorry you are having such a difficult time. IVF does not serve everyone well. There are many pathways to parenthood if that is what you still want. I hope you find yours. I wish you all the best moving forward. Carole

  • Lilai Says:

    hi,
    i have just a quick question, I have undergone IVF 4 days ago, I had 3 frozen embryo’s and all of them survived the thawing, only 1 good embryo was transferred. I had a call on the 4th day that 2 of my thawed embryo’s didn’t survive because the right ingredient wasn’t added? my question is was that because of incompetency of the embryologist? and what is the rate chances that the one transferred to me will survive the implant?

    thanks,
    Lilai

  • Carole Says:

    HI Lilal,
    I don’t know what ingredient they are referring too. I would direct these questions back to the IVF team. Hopefully, they will be honest and make amends (discounted/free cycle) if they made a mistake outside of the risks you accepted in the consent form you signed before beginning IVF treatment. Good Luck! Carole

  • Layla Says:

    Hi

    I had a fet of 2 day 5 blastokysts..the 1st one was good quality and was suitable for cryopreservation,the 2nd one was not fully met the criteria of cryopreservation but finally made it and was frozen..at the moment of freezing they were not hatching.my questions are:
    1.both became of mediocre quality after thaw,even the good one, is this normal?
    2.both were fully hatched before transfer and the embryologists told me that they were evolving pretty fast..are fully hatched more difficult to implant, is it good that they evolved in culture means so much or would it be better in the uterus?
    3. They thawed them one whole day before tranfer and when I persistently asked them if they became 6 Day blastokysts and should have been transferred on the sixth day they assured that the 5 day transfer was suitable,that they remain 5 day blastokysts and need to give them 1 day to recover after the thaw..what is your opinion,shouId they have been thawed later or transfered the next day?will it affect the result?

    Thank you very much for the time,sorry for the long message but I feel really anxious..look forward to hearing from you.
    Best regards,
    Layla

  • Jenn Says:

    Hi, thank you so much for providing such informative answers.
    My question is similar to Jeannine’s:
    We implanted 2 A plus fresh expanded blastocysts, and neither implanted. Fr the same cycle, we froze 1 slightly lesser quality (A hatching blastocyst expanding), and one poor quality F (7/20).
    For both, only 70 percent of the cells survived.
    Are there any data comparing chances of success with fresh perfect embryos (I was told 1/3 for my age group), and these poor embryos?
    Thank you so much, in advance,
    Jenn

  • Elizabeth Says:

    Hi!
    We had PGD done on our 5 day blastocysts. They have thawed 5 of them and over the course of a few hours will see them expand and be shiny and then go dark. They say that the person who did the PGD must have damaged them. We had one transferred that was dark but still had a cluster of shiny cells at one side of the blastocyst. When there are still some live cells, can that blastocyst survive? Or does the entire blastocyst need to be shiny to survive? Thank you! Elizabeth

  • Carole Says:

    Hi Layla,
    There is variation among clinics in how long they culture post-thaw. In my own lab, we would thaw and culture embryos until they got to blastocyst stage- or if already blastocyst stage, we transferred a few hours after thaw, just to confirm viability. Presumably, they have good results with this approach or they wouldn’t do it. I think the fact that your embryos both reached blastocyst stage and hatched are excellent signs of viability. They are a little more fragile if they hatch ahead of time but a good technician can deal with that. Please do not be too anxious. Your embryos have already passed many hurdles and that is every reason to be optimistic. I wish you much good luck!! Carole

  • Carole Says:

    Hi Jenn,
    The scoring system is essentially limited to visual observations which can be misleading. The first IVF baby I ever had a hand in started off as the most poorly scoring embryo you can imagine but the patient was young with young eggs and so got pregnant. A better indicator is timely progression- e.g. that they are hitting embryo development milestones on time. I am concerned that only 70% of the cells survived thaw. With vitrification freezing methods in the hands of experienced techs, you usually don’t see such cell loss. I would ask them if they are using vitrification. IF no, I would find a lab that does. If yes, I would wonder how long they have been doing this. I don’t think older maternal age is necessarily correlated with poor thaw. If you had a transfer, the hatching blast -even with 30% cell loss- still has potential. Good Luck!! Carole

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