Are Day-7 Embryos Doomed to Fail? The surprising science of late-blooming embryos — and why they still deserve a chance.

Are Day-7 embryos doomed to fail — or are they just late bloomers? In this episode of Taco Bout Fertility Tuesday, Dr. Mark Amols explains why embryos that don’t reach blastocyst until Day 7 have lower implantation and live birth rates compared to Day 5 or 6. Using a marathon analogy, he breaks down how timing reflects embryo quality, metabolism, and chromosomal health. You’ll also hear the surprising history of Day-7 embryos — from being discarded in the early 2000s to becoming a viable option thanks to advances in culture systems and vitrification. Most importantly, Dr. Amols puts these odds into perspective: while Day-7 embryos aren’t front runners, many healthy babies have still been born from them.

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Transcript

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Today we talk about a controversial Are day seven embryos doomed to fail? I'm, Dr. Mark Amols, and this is Taco about Fertility Tuesday. Now, if you weren't aware of this, you are now day seven embryos do not have the same implantation potential or live birth ratete compared to day five or day six embryos. Now, this isn't the controversy. This is already known. That has been known. The real question is, should we be freezing day 7 embryos and transferring them? And why is their pregnancy rate lower? Why is our live birth rate lower? I think one of the easiest ways to understand this is to think of this from the analogy of runners in the marathon. Let's call the finish line. The embryo being a blastocyst and how fast they get to that finish line is the quality of that embryo, just like the quality of a runner. The people who come in first and then the top, let'say 100 are going to be better, probably more athletic, probably healthier than the people who end up last. Now, to be honest, I wouldnt even finish the marathon. So these finishers still have meaning, just like the blastocyst that makes it the blastocyst by day 7th. But on average, the people that are not as competitive are not going to finish first. Theyre going to be finishing later. And so in the same principle, the same thing is happening to day seven embryos. Theyre making to the blastocyst stage. They are getting to the finish line, but they are taking longer to do it. And the reason it is taking longer is there are biological things going on that, are making the embryo grow slower. So in this marathon analogy, think of it as the day five finishers are the front pack runners, fast, resilient and the most likely to win. The day six finishers are still strong contenders, just a bit slower. But the day seven finishers are the late arrivals. They made it and that's what matters. But statistically speaking, they don't win as often. So in the end, crossing the line matters. But the timing tells us something about the resilience and the underlying biology of those embryos, just like it would for those runners. So then it brings up the question, which is what would make blasulation slower and lead to lower success? Well, one of the most common things is going be chromosomes. We know that day seven embros are more likely to be anaploid, meaning abnormal chromosome numbers. Even when confirmed euuplooid with PGTA, they implant less often than day 5 or day 6 upoids. Now that's rather interesting. Because, yes, we can all understand if the chromosomes are abnormal, why they won't work as well. But why, if they are on day five or six versus day seven, would duploids be different? We'll get back to that in a minute when we start talking about clinical pregnancy rates. But for now, if you went and grew emyo and they went the blastocis by day five, six or seven, what you would find is the highest number of anapoid embryos would be in the day seven embryos. Which again explains why they are slower. Other things that affected are the metabolism. Faster embryos tend to have more efficient energy use, less stress and better cell communication. Just like you would think a runner would have more energy, the architecture could be affected, meaning early blastill shows stronger cell junctions and better coordination between the inner cell mass and the trophctoderm. One possibility is repair mechanisms may be going on that the Day 7 EMS may be buying time. The correct errors, which can help but often reflect weaker potential. This may even explain why there is higher miscarriage rates with day seven embryos. Because they may be repairing things, but maybe its not completely repaired by the time we freeze it. And so by the time we thaw it, its still struggling. Now, whats interesting is freezing the embryo isnt worse with day 7 embryos than day 5 or 6. Im'not saying their app pregnancy rates are the same. What I'm saying is that when you freeze a dayary embryo, it survives just as well as day five or six. So now we get to the clinical pregnancy rates where I talked about. We would go in a little more depth about why day seven embryos don't work as well. So what are the odds for a day seven blastocyst? Well, it's about a third the odds of a day five blastocyst and less than half the odds of a day six blastocyst. Now, when we're talking about live birth rates, we find that if you put a euoid single embryo, you get about 68% for a day five embryo. And again, this is average across the board. Now, for day six embryos, it's closer to 55%. But for a day seven embryo, the live birth rate generally is around 36%. Now, keep in mind, every client is going to be different and they have their own numbers. At our clinic, we quote around 40% for day seven. But again, every clinic can be different. Il give you an example. Our day 7 embryo as a group didnt do as well until we started noticing that a certain group of day 7 embryos didnt do as well. Once we removed those, we started seeing a higher pregnancy rate for the day seven in whole. So its important for clinics to always look at their pregnancy rates and their live birth rates to make those adjustments. So as you can see, day seven embryos do lag behind, but that doesn't mean they can't work. And this is where the history comes in that matters. Back in the early 2000s, most IVF labs stopped culturing at day six. And if an embryo hadnt reached blastus by then, it was considered non viable and discarded. Day seven embryos werent even given a chance. Now its important to understand that back then we werent as good at culturing embryos out to day seven. So a lot of them didn't even make it. But this will start to change in the late 2000s. A 2008 case report described a twin pregnancy from three frozen, thawed day 7 embryos. Suddenly, the assumption that too late means no chance was being challenged. Then in 2010, two innovations changed the practice. One, better lab systems. Now the incubators, the culture media allowed safe growth to day seven. The second, vitrification. Now all of a sudden, fast freezing made it possible to preserve any good blastes even on day seven with high survival rate. And this is because there was less stress on the embryo with vitrification versus the slow freezing method in the past. Around the same time freeze all cycles became the common. So labs werent pressured to transfer fresh embros on day five. They could watch embryos longer, freeze them and then pick the best embryo to transfer in the future. This also meant that some late bloomers could be frozen. By 2020, the consensus had completely shifted. The meta analyses were confirming that while the prognosis was a little poorer with day seven embryos, they do not support the discharge of slow blastulationation embryos. In non medical terms they were saying dont discard the embryos just because they day seven. And now its the common practice for most clinics to watch the day seven. So in the marathon terms that we talked about 20 years ago, day seven runners werent even allowed to finish the race. Now we know some of them can cross the finish line and win even if theyre not the favorites. Now earlier I talked about how most of these embryos on day seven are going to be chromosomally abnormal. So you would think that PGTA would let us know which ones are good and we won't have to worry about the chromosomal abnormaly and then they would be the same chances at Day five and day six embryos. But you would be wrong. What we find is Yes, a UP PL Day 7 is going to do better than randomly selecting a day seven embryo that wasn't tested. But what we find is it's still far behind a ah, day five embryo that's euloed. Matter of fact, that our clinic, when we started looking at day seven embryos, we found that our day seven embryos that were CC grade had almost zero chance of working if there was no testing done on them and they were just randomly picked. And then even with pgta, we found that almost rarely did anyone ever get pregnant with the day seven RO if it was a CC grade. So taking longer to become a day seven embryo and having poor morphology showed us that these embryos, although would do well on day five or six, were not doing well on day seven. So we adjusted our criteria. But the point here is PGTA cannot fully erase the disadvantage of slower development. Timing itself carries some type of biological meaning and if you think about it, it just makes sense. Its going slower because its struggling. And Ive brought this concept before. If I'm going to die in 10 days and you freeze me for 10 years, when you th me I'm still going to die in 10 days, you just postpone my death. And so when we see these embryos on day seven and then we freeze them, are we just postponing their death? Were they maybe not going to make it anyways? Now, although we don't have the full answer to that, we do know they do have a lower implantation potential and lower live birth rates. But what I would tell you is 40% is still pretty dang good. Sure I like hearing 60 and above, but 40% isn't that bad. When my wife and I went through IVF, we put back two embryos on day three and the chances were 40%, which means a day seven embryo, which is the lowest success rate of all the embryos, has as good of a rate as putting back two embryos that were considered good quality back when I went through. So I absolutely believe you should be transferring day seven embryos if they make it to that point and it's one of the embryos you have. Clearly you want to put back your better embryo first. But I dont even think its'wrong to pick a day seven over a day five or six if maybe the gender is the one you want. That's not unreasonable. Just understand your pregnancy rate will be a little bit lower. So if you are one of those patients who does have a day 7 embryo the way you should look as this if you have a day five or day six embryo start there. Those are your front runners in the race. If all you have is a day 7 embryo, dont lose hope. Many healthy babies have been born from day seven embryos. Think of it as lower probability but not no probability. As I mentioned before in prior podcasts, because the media is becoming so routine to be made and lab are making themselves, almost all clinics are getting better and better and what that means is maybe someday we well be doing day eight as we get better and better at culturing. Now just because your clinic doesnt freeze day 7 embryos doesnt make them bad. Every clinic can to have different policies, but if yours does freeze by day seven then that may be just another opportunity for your embryo to have a chance. Unlike back in the past when we didn't even give day seven numbers a chance. Another important point is that when you have a day seven embryo, you still do the transfer with five days of progesterone or based off of your era. And that's because we control the uterus clock. But the difference is embryo biology, not the uterine receptivity. So the embry took until day seven to get to the end, but the moment where it's at, which is the blastocys stage, is timed with the uterus still. And this is true for day five and day six embryos. The stage at what they are re at is when we're putting in the uterus but we don't adjust the progesterone just based off of the day that they are re frozen on. So we go back to the original question. Are day seven embryos doomed to fail? Absolutely not. But there are late finishers in the marathon, less likely the win, yet still capable of a victory. The point is if youre holding on to a day seven embryo its hope worth holding on to. If you or someone you know has a day seven embryo, let them know about this podcast. It might help alleviate some of their fears and maybe give them some insight they didnt have before. As always, if you like this podcast please give us a five star review on your favorite medium. Tell your friends about us and you have an idea for a show please let us know about. You can Send it to TVFT or talk about Fertility Tuesday at new DirectionerTtility.com'Be sure to add it into my future podcast. But most of all keep coming back. I look forward to talking to you again next week on Talk about Fertility too. U.