Second Chances: Should You Rebiopsy Your Embryo?

Have you ever heard of giving an embryo a second chance at genetic testing? In this episode of Taco Bout Fertility Tuesday, Dr. Mark Amols dives deep into the fascinating world of embryo rebiopsy—what it is, why it’s performed, and whether it’s the right choice for your IVF journey.

When genetic testing of embryos (PGT-A) yields unclear results, such as inconclusive findings or mosaic diagnoses, the decision to rebiopsy can be difficult. Is rebiopsying embryos safe, or does it pose unnecessary risks?

Join us as we discuss:

• What embryo rebiopsy entails and how it differs from the initial biopsy.
• When you should consider rebiopsy, including cases of inconclusive or mosaic embryo results.
• The latest research findings on embryo survival, pregnancy success rates, and potential risks associated with rebiopsy.
• Practical considerations, such as whether rebiopsy actually hurts the embryo or reduces your chances of a healthy pregnancy.
• Insights on how often rebiopsy results differ from the original test, providing clarity when making tough decisions.
• Real-world scenarios and patient-friendly insights to help you weigh the pros and cons confidently.

If you’ve ever faced uncertainty due to ambiguous embryo test results or are curious about your options, this episode provides the clarity you need. Embryo rebiopsy could give you a crucial second chance—but is it worth the risk?

Keywords: embryo rebiopsy, IVF embryo testing, mosaic embryos, inconclusive PGT results, fertility podcast, embryo biopsy risks, genetic testing IVF, second embryo biopsy, Taco Bout Fertility Tuesday, Dr. Mark Amols

Join Dr. Amols in this insightful episode and empower yourself with the information you need to make informed decisions on your path to parenthood.

Thanks for tuning in to another episode of 'Taco Bout Fertility Tuesday' with Dr. Mark Amols. If you found this episode insightful, please share it with friends and family who might benefit from our discussion. Remember, your feedback is invaluable to us – leave us a review on Apple Podcasts, Spotify, or your preferred listening platform.

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Join us next Tuesday for more discussions on fertility, where we blend medical expertise with a touch of humor to make complex topics accessible and engaging. Until then, keep the conversation going and remember: understanding your fertility is a journey we're on together.

Transcript

0:01

Today we talk about embryo reoppsy, giving embryos a second chance. But is it worth the risk? I'm, Dr. Mark Amols, and this is Taco about Fertility Tuesday. Have you ever heard of an embryo getting a second chance at genetic testing? Well, today we tackle what embryo rebopsy is and whether giving embryos a second chance makes sense for your IVF journey. When you get an embryo biopsy, what you expect from that is to get a result. And that result is going to help you then make decisions. But sometimes that result isn't what you expect. What you're expecting is either it euloid means genetically normal, or unemployed means genetically abnormal. But you probably didn't know this. Sometimes you can get a result that says inconclusive or mosaic or no result. And the question is, what do you do in that situation? Well, one option is you could biopsy the embryo. Again, a rebiopsy. But as you would think, is it okay, meaning is it going to hurt the embryo? And so what we're going to talk about today is this idea of rebopsing embryo, what we're going to expect from those results. Is it worth rebopsxing an embryo? Now, when they take a biopsy, we are taking a few cells. We're not trying to take a whole bunch, may maybe like three to five cells, because we don't want to harm the embryo. And so in ar riopsy, there are two things that have to happen. The first is we have to thaw the embryo. The second thing is then biopsy. Now we have to refreeze that embryo because you can't put it back right away because we don't know the results. And so it's going to take time for those results to come back. And so essentially you are thawing biopsy and refreezing. So what's happening is two things are happening, the biopsy and the refreeze, which normally wouldn't happen on the embryo that was biopsied once. Now, your first thought is going to be, well, that probably harms the embryo because you're taking another biopsy. And a matter of fact, most people think biopsies hurt embryos, but in reality, we're not actually biopsying the baby or biopsy the placenta cells and embr actually do very well when you do, a biopsy. When you compare it to people who don't do biopsies, they do very well. Similar with regards to live birth rates when you factor in euoid status, meaning the embryo was normal. So let's talk about these Situations of when you would want to re biopsy. Well, let's say the test shows that it's inconclusive or no results. If an embryo comes back with no result, it's saying that they weren't able to get the information from the cells. Now, that could be for several reasons. The biopsy might have been traumatic to the cells and they didn't survive. Sometimes the cells when they're inside the buffer do not survive. And so when they go to amplify the cells later, it's not able to be amplified. And what that means is that they lys the cells to get the DNA from them, and then that DNA is amplifified so they can run tests on them. Sometimes they do that and they say there was no DNA. That doesn't mean there's not DNA there. It just means that maybe the DNA was not intact enough because it wasn't protected by the buffer. That then led to the cells not having quality DNA that could be amplified. So in this situation, you don't get a result at all. In the inconclusive result, what they're talking about is that they got some information, but the information wasn't clear, and so they can't make a decision. And so I tell people kind of think of it like someone giving you clear directions on how to get somewhere. If it's clear, you can get there. But if someone's kind of not being very clear, they're like, well, I think you go to this place and then maybe you take a turn here. You may not get to the place you want because it wasn't clear. Sometimes the dad is very noisy and it's very difficult to interpret it. And so in that situation, they call it inconclusive. The last situation is going to be an embryo coming back mosaic. And the mosaic embryo is when the embryo has both normal and abnormal cells in it. There can also be what's called segmental anuploid, which is where instead of the whole embryo being abnormal, it's just a small portion of the embryo being abnormal. For example, if the whole chromosome is missing, we would call that monosomy, meaning it's missing the chromosome. But if a segmental monosomy was there, it would be like a small portion of chromosome 9 of the letiss, say short arm was missing. So why am I telling you all this stuff? Well, because you need to know this to understand the next question. Do I biopsy that embryo or do I put it back in me? Now, the answer to that question, you need to know some other things will Reboiopsy hurt my embryo. What's the chances of me even getting results from the rehbopsy, and would I be okay with just transferring the embryo without the results? Now, at first glance, it seems scary to put an the embryo back that you don't have results for. But keep in mind, the chance of you actually having a baby with a chromosomal problem is very small. I actually did a podcast on the specific topic. When you think about it, the risk of putting back ambryo that's untested is the same thing as everyone else putting back embryo, not doing testing. So it's not a big risk. Now, this only pertains to if you have a no result. If it comes back mosaic, then the question is, is that mosaic embryo a concern? For example, what if it's mosaic for down syndrome? Well, that may be a little scary to put back, because then you may be worried, what if it really does have down syndrome? Because it could potentially be an embryo that has down syndrome. And then the other concern you may have is if it comes back inconclusive, does that mean it's more likely to be abnormal or the same thing? If it comes back mosaic, is it more likely to be abnormal? Now, if you have no problem putting the embryo back without retesting it, then that's always going to be your best choice. Anytime you read biopsy and freeze and thaw, it's always going to add a little risk to that embryo. Even if there is zero risk from thawing it and bombing it and refreezing it, there's always a risk that you're handling it and something can go wrong. When you handle embryos, something can go wrong. So just in inherent nature, doing it can cause problems. It'd be no different than like taking planes. If you fly a lot, the landing and the taking off is the scariest part because it's the most dangerous part. Being in the air is not the most dangerous part. So the more that you take off and land, the higher the risk it is. That's why direct flights are technically safer than taking a flight that has multiple stops. Well, what if you don't feel comfortable? What if you feel like you need a clear result? Well, the good news is that with doing a rebopsy, about 95% get a definitive diagnosis. For example, if you just take the general embryos that you biopsy and get inconclusive, what you find is about 50 to 60% of them come back eulooid. Even embryos that rec called mosaic will come back. You plo it. So if you're the type of person who says, I'm never going to put this embryo back unless I know it's normal, then the re BPSY would be very good for you because now you can make that decision to use that embryo and it is not lost. The way I look at this is if you will never use that embryo unless tested, then who cares if it's going to have a risk of being killed or something when reboing? You weren't going to use that embryo regardless. But for those of you who are on the fence where you feel like I'd like to do the biopsy but I'm worried going to hurt my embryo, then this is where we're going to talk about the next step. Does it hurt your embryo by doing the rhiopsy? Well, as we talked about with the planes, yes, there is always a risk, but surprisingly, it's not as bad as you think. We do know that the survival rate after the second thaw is lower than people who have a single biopsy. After a single biopsy and a single freeze thaw, it's around 95%. And again, that's for the entire country in these studies, not looking at our specific clinic or your specific clinic. And then when they looked at for the second thought after being frozen, again, it was more around 70, 80% survival. They also saw the same thing in studies showing that clinical pregnancy rate and the libipirth rate were slightly lower after the re biopsy, with most clinics being around 50% for a single biopsy and around 30 to 45% after a second biopsy. Now, it's important to note that all the babies are still healthy. That second biopsy has never led to a baby having more problems. And it's also important to note that other studies have actually shown almost no difference in the live birth rates from the second biopsied embryos and the single biopsied embryos. In one study, they actually found that the biopsy itself wasn't causing any issues, but it was just the freezing and thawing a second time that actually compromised the embryo a little bit more. When they dig deeper into it, what they found is the embryos that didn't expand as well on the thaw were the ones that didn't do as well when it came to live birth rates. Meaning if it was slower to expand and it took longer to expand, then that may show that the embryo wasn't doing very well. Embryos that were slower to expand were already showing signs of some poor growth and maybe Some difficulty. And so even though they were re biopsied, the embry was already showing signs that it was not as good as other embryos. This is kind of like day seven embryos. We know that they have a lower pregnancy rate and that's because it took them longer to get to the blastocyst stage. Even when looking at things like day five or day six, BPsy made a difference because again, it took the embryo longer to get to that point. So that could also put that embryo at higher risk, not because of the biopsy, but because, that embryo was already not doing well. This is a very important concept to understand in your mind. You may be thinking, oh, well, the day sixmer are going to do worse. Yes, but not because of the biopsy. The biopsy doesn't harm them in any way. It's just that those embryos were always slightly compromised because it took them longer to get to day six or day seven compared to the ones on day five that were ready for biopsy. This is why many clinics will actually advise you whether you should re biopsy or not. So for example, at our clinic, we do not recommend certainrn embryos being biopsied because we know that they're going to have a lower chance of then surviving the thaw later and leading to a live birth. We know that the miscarriage rate is slightly higher on these re biopsied embryos, especially the ones I talked about that were like day six or that didn't re expand right away. But the reason isn't so much because of the embryo being biopsy, but the stress, on that embryo that was already compromised and making it worse. I wish I could tell you which embryos is the biopsy and not. But the problem is every clinic grades things different. Even the way embryologist bops dambryos can make a difference. So when it comes to wanting to a re biopsy, you really need to talk to your clinic, talk about their experiences with it and whether they recommend you byiopsite embr or not. Now, go back to that point. If you're never going to use the embryo, then what's the harm? You're not going to ever use it. So if it hurts it, it hurts it. But if you're on that fence, then I'd say talk to them. And if you really don't care, then just put the embryo back. That will always give you a better chance than even rebiopsing it, meaning not hurting the embryo. Obviously, if the embryo is abnormal, your chance won t be low. If you Test andhi as normal it will be higher. But the testing doesn't make the chances better, it just helps you know that the embryo has a higher chance. So when it comes to ranking the embryos and determining if they are going to come back with a good result, what you find is, is that no reeds usually do come back with normal results. Meaning if we're expecting 60% of the embryos to be normal and you had no DNA or no results, you would expect the same 60%, the comeback normal. So there's nothing that is being told in the no result like there's something wrong with the embryo. The results would be exactly the same as if the results came back the first time. Now, like we discussed, if that embryo is not the perfect embryo that be biopsied, it could compromise it slightly and could increase the risk of a miscarriage. But overall the differences are minimal. To give you an actual statistic, around 95 to 90% of previously inconclusive embryos gave them conclusive diagnosis after retesting them. And that result tends to be exactly what the result would be on the first popiopsy. So again, if it was 60% it would still be 60%, meaning it doesn't show any tipping to one side saying that the embry may be normal or abnormal. But what about mosaic embryos or segmentalloidy embryos? What happens when you re biopsy those? I mean, your thought would be probably they're going to come back abnormal because that's why they were mosaic. Well, surprisingly a lot of them come back normal. In a study published in 2023 titled Blinded Re Biopsy and analysis of Non euupoid embryos with two distinct PGT platforms for anaploidy in this study they took 100 donated Blastocys originally classified as abnormal, meaning anaploid or mosaic by next gen sequencing. Then they performed four rebopsins on each embryo, they took those samples and then used a snip array which is a different type of technology. The results were striking. Every embryo that had been diagnosed as mosaic by next gen sequencing was uniformly euoid on themp based retest, meaning snip array. What this means is is that a lot of the mosaics then are not through the whole embryo because the other biopsies showed they were normal. And so it's either possible that the technique before caused the mosaic or they got the cells that were only abnormal causing the mosaic diagnoses. The other good news in that study was that the embryos that were considered fully Anaploid, meaning there was no mosaism were confirmed when they did the SNP array. Overall, if it's mosaic or segmental anyloid they were less concordant versus if it was a whole chromosomal problem it was highly concordant. So this should reassure you that if you are concerned about a mosaic embryo and you don't feel comfortable pointting it back, there's a very good chance it's probably normal anyways. And so unless it's one of those abnormal mosaics such as down syndrome or significant condition, you might feel comfortable just putting it back because it's likely normal. But on the same token you can also biopss it and feel comfortable that the results will give you some clarity and make your decision much easier. In the end, it's a personal decision you need to have with your doctor. But it's important to know that reiopsies can provide results and most of the time do. I've seen patients who have had abnormal embryos and don't believe it and they've re biopsied it. And in at least the history I've had with patients, I've never seen anyone with an anaploid embryo ever come back with a normal embryo after retesting it. Now keep in mind when I say that I'm talking whole chromosome and theloidy, not segmentals, not mosaix, but actual the whole chromosomes missing. In my experience I've never seen one come back normal. That doesn't mean it can happen. We know the test isn'terfect. There's always the possibility that an abnormal embry could be normal, but it's very very unlikely compared to the chance that it's actually correct. So in summary, if you really are not that worried and just want to put the embryo back, you can and the risk of having a child with some genetic problem is very very low. This will give you the highest chance of the embryo implanting and your pregnancy rate and live birth rate would be exactly what it would be if you didn't do testing. If you're someone who would never feel comfortable pointing the embryo back unless's tested, then you really have nothing to lose because if you're playingning to discard the embryo, rebopsy gives your embryo at least another chance without any additional risk since you weren't going to use it anyways. So in that situation I'd always recommend reiopsy. Why discard an embryo if it could potentially have a chance? And if view are like most people where you really are in the gray zone where you really don't know what to do. Part of you wants to put it back, but part of you scared then this episode was for you to help you make that determination. Rebopsies can clarify ambiguous results and can rescue embryos that you are maybe not going to use. But there's a trade off. You might get the clarity, but it does have a slight reduction in the implantation. And that's because as we talked about the thawing and freezing, we also discussed that there are some embryos that are more suitable for re biopsy. And unfortunately I can't tell you that at ah your clinic because each clinic is different. But there are some general ideas that make some embryos better than others. Most of all, the findings are very reassuring. Mosaic embros often come back eulooid, allowing you to use it versus discarding them just like segmental anaploids. Studies have shown that there'no negative neonatal outcome by having a second biopsy. No matter what. The decision is going to be tough, but hopefully this information is going to help you if you run to that situation. I hope you liked this episode and found it helpful. Unfortunately, if you're in this situation, I know it's very tough. I think one thing to remember too is that a lot of time these companies will not charge you to reiopsy these embryos. So if that's the situation like at our clinic, then there's at least no financial repercussion. If you have a lot of embryos then you may not have to worry about this decision. But if you do, I hope this episode was helpful and helped you make a decision. As always, remember to talk to your doctor and your clinic because those situations can be slightly different. If you liked this episode, as I always say, please tell your friends about us. Give us a five star review on your favorite medium is because of you of why this show is becoming more popular and I can't thank you enough for helping me. As always, I look forward to talking to you again next week on Taco about Fertility Tuesday.