The Scariest Part of IVF—And Why It Terrifies Me as a Doctor

There’s a lot to worry about in IVF: Will you get enough eggs? Will your embryos be normal? Will the transfer work?

But for Dr. Mark Amols, there’s one part that truly keeps him up at night—fertilization.

In this deeply personal episode of Taco Bout Fertility Tuesday, Dr. Amols shares why fertilization is the most unpredictable and emotionally gut-wrenching step in the entire IVF process. You’ll get a crash course in reproductive biology—meiosis, pronuclei, 0PNs, 2PNs, and more—and learn what really happens the night sperm meets egg.

He explains:

• Why even perfect sperm and eggs can fail to fertilize
• The terrifying uncertainty of ICSI and why it doesn’t guarantee success
• How fertilization failure happens—and why it feels like a blindside
• What embryologists look for when checking for normal fertilization
• The brutal truth about age, egg quality, and cellular death

Whether you’re preparing for IVF, recovering from a failed cycle, or just want to understand the science behind the scariest moment in the lab, this episode delivers the insight—and honesty—you won’t hear anywhere else.

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.

Stay connected with us for updates and fertility tips – follow us on Facebook. For more resources and information, visit our website at www.NewDirectionFertility.com.

Have a question or a topic you'd like us to cover? We'd love to hear from you! Reach out to us at TBFT@NewDirectionFertility.com.

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

0:00

Today we talk about the scariest part of ivf. And no, it's not the shots or the retrieval. It's something no one can predict. Fertilization. I'm, Dr. Mark AML, and this is Taco about Fertility Tuesday. When going through ivf, there are many things to worry about. Whether you'll get enough eggs, whether you'll get enough embryos, whether those embryos will even come back genetically normal, or whether your transfer will work. There are so many things to worry about. It seems like it's countless, but there's actually only one thing that keeps me up at night, and that is fertilization. And it's not because it normally goes bad. It's because it's one of the most unpredictable parts of the entire IVF process. Almost every step of IVF can be predicted. When it comes to the, ah, eight number you're going to get, we can predict that how many will be mature. Again, predicted. Once you have embryos that fertilize, we know by prediction about how many will become blastocyst. And once you get slow blastocyst, we know how many will probably be genetically normal. We know the percentage of the transfer working, but the one thing we can never know is whether fertilization will work. No matter how good the sperm is, no matter how good the eggs are, there are times where the, fertilization just goes wrong. To understand this, we need to go back the high school biology ivfition. This is where sperm meets egg and either magic happens or total silence. Now, if you've listened in my prior podcast, you've heard me talk about the concept that all the eggs you have are made in the womb. But what a lot of people don't understand is, is that those eggs undergo a process called meiosis. Again, that's different than mitosis, which is the normal division of cells. Meiosis is where there's the vision to get to half the amount of DNA, so that way it can combine with a sperm which also has half the DNA. But what's really interesting about eggs that's different than sperm is that eggs stop halfway in the first division of meiosis compared to sperm, which complete the full two meiosis stages. So that means your eggs are stuck in that phase halfway through until the day you're going to ovulate that egg. Now, because meiosis has two stages, your eggs are arrested in the first phase of prophase, and we call that prophase one. Now, when you're taking medication to cause your follicles to become mature, what we're talking about is we're getting the eggs ready and then we give HCG to restart the process of meiosis. And that will carry it all the way to meiosis II metaphase. So that now becomes metaphase ii. At this point, the egg is just waiting. It's waiting for a sperm. If a sperm is present, then it will penetrate the zona pelucida where then the egg will then complete meiosis II and inject what's called a second polar body. The polar body is the leftover cytoplasm and membrane when the cell divides unevenly, creating a bigger egg and a small polar body. At this point, the male and the female DNA form a pro nucleus. This proucleus can actually be seen when you look under a microscope. If we see two pronocleases, then we know we have normal fertilization. Therefore, when the embryologist is going to look for fertilization, they look for a couple things. If they see two polar bodies, they know that they egg fertilized and now is an embryo. The next step, then they look at is the pron nucleus and find out if there's two and if there are again, normal fertilization has occurred. What's interesting is that this fertilization doesn't occur right away, meaning the fertilization may occur. But when the embryist needs to look for these pernial clears is during a certain window and they time it to make sure that they can then see this fertilization. And so they could potentially miss it if they look too early or look too late. The pronuclei only show up for a period of time and then they disappear. Which means if you don't see the prouclei, it doesn't mean it didn't fertilize. It just means that either it didn't fertilize or you missed the window. When the 2pm fades, we call that a 2pm fade because it disappeared before we got there. And so when you see a zero pronucleic called as 0pm but you see two polar bias, you know it fertilize, but you wonder did it fertilize abnormal or did we miss the window such as a 2pm fade? This is usually not a usable embryo. If it doesn't start dividing, if it does divide, we know then we must have missed the window. Now another situation can be a one pro nucleus. This is called a 1pm this could be abnormal. Where only male or only female DNA formed a proucleus this can also be parthogenesis, where the egg activated without the sperm. We don't usually transfer these. However, if you are able to watch them and they make it a blastocyst, you can biopsy them and then test them to make sure that there is not a monoploy embryo. Now, the gold standard, as we talked about, was the 2pm this is one piece of DNA from the sperm and one from the egg. This tells us that fertilization occurred as we expected. Now, after that, you can have multiple PN, 3 PN, 4 PN, 5 PN. And this could happen when either two sperm fertilize one egg, causing polysermy, which can lead to polyloidy in the embryo. There's also the possibility that the egg could have extra DNA in it and could have caused the increased PN number. These are typically discarded. If they are kept, they are kept separately. And then what will happen is with PGT testing, they can determine if it truly is a polyploidy embryo. So what does this actually mean? It means that even if you are told you had 100% fertilization, the question is, did they fertilize normal? If it's a 0pn, a 1pn, a 3pm or greater, they're not always usable. Only two PN's are, considered normal fertilization. Now, common sense would say, well, then let's do icsi, because if we bypass nature and inject the sperm directly, then nothing can go wrong. But that is not true. Even when you inject the sperm in, you might prevent polypermy. But that doesn't mean you can't get polyploidy embryos because the egg could have extra DNA. You can also not have fertilization. That can happen. And the other thing is, is the actual cell can die. So sometimes when you go to thexe, the cell itself can start leaking and they can die. Even the next day. The cell can undergo atresia. And that's because when older patients, sometimes the egg quality is poor and it dies after the ici. I've seen cases where there are fragile membranes where they stick the icine needle in and everything starts leaking out. Now, ICSI is great when you've had the history of failed fertilization where you did conventional fertilization and none of the eggs fertilized. But it's important to understand it does not guarantee that you will get fertilization or even normal fertilization. There are some cases with conventional fertilization where you may fertilize 20 eggs and nothing fertilizes. We would call that, a failed fertilization. And we would definitely recommend doing ICSI the next time. But there are times where you do fertilization and it's a partial fail fertilization where maybe three of 20 eggs fertilized and the rest don't. And that's why it's important to look at the details then and say, well, did they fertilize and fertilize, abnormal, such as zeropn, or did they not fertilize at all? It's also important to know how many eggs were mature. It's amazing when I talk to patients and they'll tell me, oh, I had 25 eggs but only 12 fertilized. And then I look at the report and I realize, well, they only have 15 that were mature, so of course only 12 fertilized. There is only 15 that could even fertilize. So sometimes it may look worse than it is. You can't look at the total number of your eggs. You have to look at the number of mature eggs. You can start with a million eggs. It doesn't mean anything if only 10 of them are mature. At that point, you have to limit your expectations to fewer number of embryos. So why is fertilization keeping up at night is because it doesn't matter if you're young, it doesn't matter if you're older. It doesn't matter if you've even had kids naturally without any help. When you do ivf, it's not natural. And sometimes some people don't do well when it comes at the fertilization stage. Things like egg quality and cytoplasmic maturity can completely change the results. Sperm can look great on every semen analysis, but on the day of, it might have been a bad game day. There are even very rare things like calcium signaling failure or issues with the aossomaal reaction that occurs between the sperm and the zone pelucida. The point is, it's not predictable. I have seen many cases where I expect everything to go well and it doesn't. And this is the stage that ends up shocking me. Now when I see bad sperm, I'll prepare someone and say, hey, you know what? There's a very high chance there could be poor fertilization, maybe only 50% in your situation. And then they'll do amazing. They get 100% and I'm going, what the heck? And yet the person with perfect sperm, they'll have only 25% fertilization. Now, I think it's important to understand fertilization. No plan does go well. And statistically, as I've mentioned before, about 70, 80% of the eggs end up getting fertilized. But the reason it scares me is because it's the one part that's not predictable. As I mentioned, if you have poore egg quality, we're going to expect fewer eggs. If we notice that the sperm is poor quality, we predict there may be lower fertilization. If we know you're older, we know we're not going to get as many genetically normal embryos. But the thing is, fertilization plays by its own rules. And for that reason, I can't predict it. And that's what scares me. Should you be scared? I would say yes. Not because it won't go good, but because good sperm does not guarantee fertilization. Young age doesn't mean you're bulletproof. This is the point where emotionally you can feel devastated when you go through everything and all of a sudden things don't fertilize and you feel like you've wasted an entire cycle. Now, the good thing is there are things we can do that sometimes help this. We can use things like the Zymod chip, we can use ici, we can use Pixie dishes. There are many things we can do to help when we think there's going to be a problem. But that's the part that scares me. Because sometimes when it looks like there's no issues at all, that's when tragedy can sometimes happen. The good news is normally it goes fine for most people. So who are the people who are at the most risk for feed, fertilization or poor fertilization? Obviously this going be people who have poor sperm quality that'going to potentially lead to poor fertilization. As women age, there is also some changes occur such as accumulation of spindle and chromosomal damage that can then lead to poor fertilization. Abnormal pronuculi such as the 1pn or 3pm in early degeneration or abnormal embry development. Basically, the longer the egg has been stuck in prophase I, the more likely something can go wrong. This is why we tend to see women who are more mature have lower ovarian reserves and poor outcomes. So overall, what's the takeaway? Fertilization is very complex. We're constantly looking for new ways to help improve it. Unfortunately, you cannot predict fertilization from the egg count, hormonal levels or even the sperm quality. So that means even with 20 eggs, you may not have fertilization it makes you feel better. But unfortunately this is the one step that God is truly in charge of. In some ways, fertilization is the first true biological test of egg and sperm quality. Nothing is guaranteed until you see that 2pm now the good news is once you see that 2pm we know the prediction of how May will become blastocyst and how May will come back genetically eu ploid. My goal is definitely not to scare you. My goal is just to let you know this is one of the areas I get worried about. Most people are worried about the number of eggs they get. They're worried about other parts of the IVF process. But this is the one that scares me because I know it's so unpredictable. I know that sometimes patients I would never expect to have pore fertilization can have very poor fertilization. And just like I've had, people who have severely poor sperm end up having great fertilization. But the thing is it doesn't matter if you have 100 eggs. If only 10 are mature, then the most you're probably going to get is somewhere around 10 embryos. And the same token, it doesn't matter if you start with 100 eggs and only 10 fertilize, then you're down to 10 embryos. So this is the point where there's the biggest drop for many people. May not be for you, but for many people it is. And that's why it can be scary. The good news is, as always, we can take that information. We can now adjust for your next cycle and be able to give you the best chance. Ivf, doesn't always work on the first try and should never give up if it doesn't. Remember now we can see things and make adjustments and hopefully help in the next cycle. I hope that you never went through this and had a bad fertilization experience, but if you did, hopefully this episode helped you. Or maybe you're going to be going through IVF and this may help you face some of the fears that may come ahead. If you know someone who may be is interested in this type of topic, let them know that we did an episode on this. This may help them. And if you love our episodes, you love the show as always, give us a five star review on your favorite medium. Tell your friends about it, tell your familyies about it, but most of all keep coming back. If you have any suggestions for topics, set that to TBFT and newirectionfertility.com and I'll be sure to add that into my list of topics I look forward to talking you again next week on Talkac about fertility Tuesday.