Hello, everybody. I'm Kurt Barnhart. I'm the editor-in-chief of Fertility & Serility, and it is my pleasure to host a Fertility & Serility Journal Club Global.
What is a Journal Club Global? Well, we're going to go over an article in Fertility & Serility and have a lot of fun talking to the authors and asking questions about it. That makes it a journal club. Why is it global? Well, I'll give my keynote here.
Good morning, good evening, or good afternoon, depending where you are in the world, because you're seeing this live. And we would hope to have some interaction both here in the audience, along with the panel, and those of you on the web. So Journal Club Global is designed to highlight what I think is an outstanding article that's published in Fertility & Serility, and we have a terrific one.
We have a terrific one for lots of reasons, the topic, the authors, the collaboration, and it's going to make for a great discussion. So it's a lot of fun that I'm going to introduce the article called A SART Data Cost-Effective Analysis of Planned Oocyte Cryopreservation versus in vitro fertilization with pre-implant genetic testing for aneuploidy considering ideal family size. So this is a cost-effective analysis with a really strange first author that I've never met before, Jen Backenson.
And it's also Drs. Flanagan, Mumford, Hutchinson, Chiang, I'm going to, Yves Feinberg is probably watching me, he's going to be angry with me because I'm mispronouncing names, Moreno, Jordan, Feinberg, and Goldman. And it's a wonderful collaboration, and I encourage this.
It's a collaboration from the Feinberg School of Medicine, from the NIH program, from the University of Pennsylvania, from Shady Grove, and from the Kelly Government Solutions in Rockville, Maryland. So you're going to hear a great scientific presentation, and then we're going to purposely take sides. I've divided this group into two groups.
The cons, and that's because they're against the argument, not because they've been convicted. And the cons here are Drs. Sara Morelli from Rutgers, Dr. Jen Kawas from Emory, and Dr. Kenan Omantog from WashU.
And they're going to debate the pros, which happen to have a lot more experience and opinions here on the fellows, where we have Ashley Aluko from Cornell, and I butchered that, Kordicatus, close, not even close. Close, close enough for the work at this point, from Boston IVF. And lastly, I'm going to introduce Jen Backenson, who's the first author of this paper, and I want to congratulate her for an outstanding paper and an astounding inception.
And we're going to allow Jen to have the opening word to present her paper to you so we all know what we're debating. So, Jen, please take the stage. Thank you, Dr. Barnhart, for that introduction.
Just to introduce the paper, as everybody in this room knows, the median age of first birth in the United States has continued to rise over the past 50 years, due at least in part to a nearly six-fold increase in first births to women over the age of 35. In this setting, planned oocyte cryopreservation as a means for deferred reproduction has absolutely skyrocketed, with a nearly 900% increase in utilization in less than a decade. There have been several prior cost-effectiveness analyses, which have attempted to address the effectiveness and cost-effectiveness of egg freezing as a means for deferred reproduction.
And while these were all very well done, they have important limitations. Firstly, in the lack of real-world robust data, most of these analyses have relied on fresh IVF cycles or used single-center data for their model inputs. Second, none of them have utilized PGTA in any of their models.
And today, this is a widely used tool for increasing the efficiency of ART at advanced reproductive ages. And finally, and I think most importantly, none of these studies have looked at the critically important endpoint of achieving a second live birth. And so with these reasons in mind, we sought to pursue an updated cost-effectiveness analysis comparing oocyte cryopreservation versus IVFs and PGTA at a more advanced reproductive age when considering ideal family size using SART data for our model inputs.
And so basically what we did with this study is we looked at an ideal family size of either one child or two children, and we looked at different strategies for achieving either ideal family size amongst patients desiring delayed childbearing. For one child, strategies included either egg freezing at age 33 or not egg freezing. In either situation, patients in a simulated cohort then returned at age 43 to attempt conception.
If unsuccessful, they either utilized warmed oocytes, if they had any banked, versus pursued IVF and PGTA at that time. For patients desiring two children, we looked at four different strategies, two with egg freezing and two without egg freezing. For those who pursued egg freezing, they could have either done one cycle of egg freezing at age 33, returned at age 40, and then if unsuccessful in attempting conception without ART, would then pursue IVF and PGTA primarily, and then warm banked oocytes as needed to achieve a second child, versus they could pursue two cycles of egg freezing at age 33, return at 40, if unsuccessful in achieving pregnancy, would warm all of their banked oocytes primarily.
Strategies without egg freezing included patients who presented at age 40, attempted conception at that time, and if unsuccessful, either pursued IVF or PGTA with embryo banking or IVF-PGTA without embryo banking, and then returned at age 43 as needed to pursue another cycle for a second child. In terms of our model inputs, we used data from over 43,000 SART cycles to determine the number of eggs retrieved per cycle. We also used data from fresh autologous IVF cycles and adjusted it for what we anticipated would be oocyte survival, fertilization, and blastocyst development, using data from the California Cryobank Donor Egg Bank USA, and also adjusted euploidy rates according to maternal age using data from Natera.
We also then used data from 10 geographically distinct IVF centers to obtain median cost data, which we then used as inputs for our cost analysis. And so, what did we find? Well, when we looked at one live birth, we found that pursuing egg freezing at age 33 decreased the average cost per patient by over $30,000, and that the likelihood of achieving at least one live birth increased dramatically at 73% versus only 50% when pursuing IVF and PGTA at a more advanced age. And when we looked at the end goal of two live births, what we found is that egg freezing with two cycles at age 33 was the most cost-effective strategy, and furthermore, was the most effective strategy in achieving at least two live births, with an efficacy of 77% versus just 19% when pursuing IVF and PGTA without embryo banking.
We also conducted a number of sensitivity analyses, including adjusting and varying the age at oocyte cryopreservation, and what we found in these sensitivity analyses was that egg freezing remained cost-effective over a wide range of ages at cryopreservation, and furthermore, we found that egg freezing was most successful when pursued before ages 31 to 32, but remained more successful than the alternative strategy of IVF and PGTA at more advanced ages, provided it was pursued before age 39. And so on the basis of these data, we would conclude that egg freezing at age 33 is an effective strategy and a cost-effective strategy compared to IVF and PGTA at a more advanced reproductive age when considering ideal family size. So thank you, Dr. Backenson.
That was elegant, mature, very well done, and I'm going to translate it back into epi-speak. What they just performed was a cost-effective analysis looking at two potentially good strategies. You could choose each one.
And unlike most cost-effective analysis, I didn't make this word up. This is the correct word. The egg freezing dominated the other model.
So it wasn't a question of it's better but more costly or worse but cheaper. This was both better and cheaper. That rarely happens in a cost-effective analysis, so it teaches us something very important there.
The great part of this methodology was it wasn't just the primary analysis that showed this, but looked at it from a lot of different angles called sensitivity analyses, which basically says, you know, we can vary some of these things, and I'm still getting up in this right place. So I hear the conclusion of this is that if you're considering fertility at a later age, you really should bank your eggs early at age 33, which begs the question, should all women bank their eggs at 33? What do you guys think? So there. Argue against that.
Okay, I'll start. That was an outstanding synopsis, and I appreciate that very much. And congratulations on an outstanding paper.
But to answer Dr. Barnhart's question, I'll start the con side in that I think it's difficult for us to justify, to make a justification for universal recommendation at this age. It's important, I think, to go back to the choice of the reference group, excuse me, the comparison group, which is women at the age of 40 and 43. So if I understood it correctly, the model assumed that women were returning at the age of 40 and 43, and I understand that it did account for the chances of natural conception at those ages.
But those are the limits of reproductive biology in most women using autologous oocytes. And so it did not account for natural conception between the ages of 33 and 40. And so if you're going to compare 33-year-olds with 40- to 43-year-olds, I think it has to be probably a patient-specific decision.
And understandably, a woman cannot often come back and say, well, I'll be back in 10 years, so tell me what to do. But it's a challenge to make a blanket recommendation considering the comparison group. Oh, good argument.
I'm convinced. No women should freeze their eggs before 33. You guys want to counter that? Well, to address the idea of the fact that the patients in this study returned at ages 40 and 43, we did consider that, and I realize that you might hear that and think, wow, that's really late.
But actually, that was rooted in some real-world data that we have out of one of the only longstanding, like 10- to 15-year follow-up single-center cohorts that we have amongst women who pursued planned oocyte cryopreservation. And what they found, first of all, was that nearly 40% of women did actually return to use their eggs, which, while not 100%, is a significantly higher number than I think what has been quoted previously, according to some of the more preliminary analyses, which really didn't have the same horizon of that 10- to 15-year follow-up. So according to at least the data that we have available, a lot of women do return to use their eggs.
And the second piece that I would say is that according to that, again, single-center data, but the mean age at return was 43.9. That's old. But I think what we would say – It's certainly a more advanced age, I think, than what we have – than what has previously been modeled in some of these other studies. But I think the important thing there is that, you know, it's possible that these patients knew that they wanted to defer childbearing until 43, 44.
It's possible that maybe they're using these eggs as a last resort. But the fact is is that they had them. And that's an age at which ART is not bound to be successful.
And so we might be potentially saving these patients from undergoing futile ART cycles or being one of the 17,000 patients per year who undergoes a donor egg cycle. Convincing. What do you guys have to say to that? Your points are very well taken.
I think there is some data that maybe has emerged since you guys did your original LICH search. We did publish outcomes of national autologous thaws using SART data. I think it was done in the interim between when you guys prepared your paper and maybe developed the analysis.
But it does look like, for the vast majority of situations, patients have not come back to use their eggs. And there is also a paper that Ann Steiner was the final author on around 2015 that showed that looked at a similar model that sort of incorporated likelihood of marriage using vital statistics. And if a woman were single in her 30s, what was the likelihood of her partnering? And unfortunately, the likelihood is actually dramatically low.
And when they incorporated the likelihood of marriage into their model, all of the benefit actually disappeared. So I don't know if you guys considered that. Or in their model, if the woman was willing to use a sperm donor, the benefit remained.
But if they were planning to use their eggs actually with a partner, a lot of the cost benefit did not. So the old argument that your date is out of date after two months. So how are you going to respond to that? So I think this kind of gets to the topic of utilization rates and how that affects cost effectiveness.
And I think it is intuitive that the more likely women are to come back to use their eggs, the more cost effective freezing up front in an earlier age is. I think earlier sort of older cost effectiveness studies on this topic have shown that if women freeze their eggs early, like 25 or between 25 and 30, that's clearly not cost effective. And so I think back to what Jen was saying about that recent NYU paper, we are seeing utilization rates in the 40% range.
I haven't seen this new data from SART yet. But I want to comment on older data where utilization rates were in the 10% or sort of like the lower percentage ranges. And I think that part of the issue there is that a lot of these studies looked at oocyte cryo over a certain period of time, say like the last 10 years or so, and used the number of patients who came in to do oocyte cryo as the denominator.
And then the numerator would be during that exact same period, how many people came in to warm or thaw their eggs. And so you clearly have this bias where the patients who froze their eggs toward the end of that time period aren't really included or haven't had the opportunity to demonstrate the fact that they are going to come back to use their eggs. So I do feel like as we get more data on utilization moving forward, especially after this sort of boom in oocyte cryo over the past few years, we will find that it is more widely utilized.
What do you want to think about? Well, I think that's a good point. I don't have anything to say to that because it's a good point. Touche.
But I'm going to take the conversation in a different direction. I'm going to take it to a policy level. I think we all agree that every 33-year-old should have a conversation about their reproductive future.
And part of that conversation has to be a discussion about the role of egg freezing. And I think this data actually supports that idea. Now, the question before, I don't think anyone in this room would disagree with that.
People use the word we want to empower, we want to provide an insurance policy. You'll hear these kind of terms talked about. But really we want to give people information so that they can make decisions about their own individual reproductive futures.
The question is, should we take it a step further and have policies in place or advocate for policies that should actually provide people with access, probably through their employer-based health plan, to pay for them to have egg freezing? And I would say no because that is blatantly anti-family. I'll go there. Because this is basically saying to the employer, yeah, man, I don't want to pay for you to have IVF.
I'll pay for you to have IVF. I'm sorry. I don't want to pay for you to have IVF benefits, but I'll pay for you to freeze your eggs because then you don't have to go on leave.
You can stay and work all the time. This is not a new argument. This was the argument when Apple, Google, Facebook, when they all added their benefit.
So I'm not saying anything that you guys haven't already heard, but I'll bring it up for the funsies of this journal club. So I think it's interesting that you brought it up, and especially in this time of the Great Resignation, when employers are having such a hard time capturing employees and keeping them. There are studies showing that offering egg freezing as a benefit increases recruitment and retention.
And there was a study by Mercer that surveyed employers that added egg freezing to their benefits, and 95% concluded that it didn't significantly increase any of their costs related to insurance coverage. So I think that it shouldn't end here. I don't think that we're advocating that employers should just fund egg freezing.
Why not stretch it? Why not increase maternal benefits for those that are ready to have a family or provide options for women who aren't ready to have a family? So I think that restricting it to egg freezing is not the answer, but I think it's definitely a step in the right direction. I'm really interested in that we got into insurance coverage relatively quickly. Years ago, when I was doing more contraceptive research, we would argue with insurance companies, why not pay for family planning? You're going to save so much money on the cost of maternal complications and such.
And I finally got somebody to admit it's because when that woman is pregnant, they're not going to be on our insurance. So they were really that short-sighted in terms of saving money. So at least now we're arguing about a longer-term view of keeping people in the same place, but I'm fascinated by this argument that I'll pay for you now because I'll retain you, but it's really not for the benefit of the woman.
So do you think this data is helping for the benefit of the woman? I'll ask you guys just however you want to answer it. Do you think this data, how can this data be used for the benefit of the woman, not for the benefit of the employer? Specifically about insurance coverage? Well, I'm trying to get away from just cost of insurance. How can you spin this paper to say this is good for that patient in front of me? I mean, for me, this all comes down to reproductive choice.
I mean, as REIs, we are tasked with helping our patients achieve their reproductive goals. The goal for most women is not one baby. In fact, there was a Gallup poll in 2018 which showed that less than 4% of Americans felt that one or fewer children was the ideal family size.
That's a staggering statistic, and I think that's what we see in practice. I mean, it's not surprising, probably, that the vast majority of Americans felt that two to three children was considered ideal, and almost 25% considered more than three children to be ideal. So when I think about this data, and I think about the value of egg freezing, to me, it's not just talking about baby number one.
It's talking about baby number two and baby number three. And on the basis of this data, we saw that egg freezing was the best strategy for women desiring deferred reproduction to achieve at least two live births. And so, again, when we're talking about this data, we're talking about empowering women to have that kind of autonomy over the reproductive decisions and to achieve their ideal family size.
I think we all will agree with your statement, and I think it comes down to what Dr. Omertag said before, that I think everyone on this panel, whether we're arguing for or against, is for reproductive choice and for women making educated decisions. I think we're sort of arguing against this global push towards prioritizing egg freezing, maybe over building a family in the moment. So I think all of it comes down to sort of patient counseling and individualized decision making after having an informed discussion.
I thought I could maybe change the topic a little bit, and one of the aspects of the paper in the methodology that I thought we could talk about was how you sort of calculated your blastulation rate. From what I understand, you used a donor egg bank as your sort of data from which you sort of said, from these number of eggs, we anticipate that we will have X number of usable blasts. And I would say, anecdotally, I'm not sure that autologous eggs that are frozen perform as well as donor eggs from an egg bank.
I'm sure that that's something you all considered and have probably had conversations about, but I'd love to hear how you incorporated that or what made that sort of what you ended up deciding to do. Absolutely. You know, when we had decided to use the SARTCOR's oocyte cryopreservation cycles, we were hoping to use the warming cycles that were linked to those initial cryopreservation cycles, but there weren't enough warming cycles to actually draw meaningful analysis.
And so, you know, we are kind of strapped with, like, okay, well, how do we actually get to the point of, like, how useful these eggs are actually going to be down the line? And you're absolutely right. We did ultimately end up using donor egg bank data, which may not be applicable to autologous oocytes. I think there was some study, there have been some studies that have shown that autologous and donor eggs actually perform pretty similarly, but there have been other data that show that that's not true.
And I think, to your point, it is absolutely something that we will be following closely and hopefully updating this analysis down the line when we do have that data. So I would love to, you guys are all thinking, right, we all agree that this should be presented. I'm going to ask either of you guys as a team or individually to say, how do you present this data? I want to hear what you would say to a woman balancing all these choices between we can freeze your eggs now and definitely incur cost versus perhaps you don't need the cost but you might spend more later, or many of the other things that come into it.
So I would love to hear how we should be using this data. Sure. Well, I think those of us that see patients do this every day, right? I mean, this is a conversation that we all have, and that sort of comes back to exactly what we were saying in that it is very patient-centric, and it depends on that individual's current situation, social situation, professional situation, their long-term goals, their short-term goals, their barriers that are preventing them from wanting to build a family at the moment, and then also how they feel about alternatives.
So that's something I actually do discuss with my patients that are considering freezing eggs. So let's say you do this. Let's say you don't do this, and you find yourself in a position where you have infertility at 42.
How do you feel about donor egg? How much of a priority is it? And, you know, so much of what we do is weighing risks and benefits. And in that pool, that bucket, there's what's your ovarian reserve? What's your insurance coverage? What risks are you incurring by doing this that are balanced against what potential gain might you get? And I actually do share some of these papers that have been published that have tables, sort of average number of eggs frozen at certain age and likelihood of one versus two live births. And I give patients that chart, those papers, when they're considering freezing eggs for that exact reason.
I tell them, you know, I've read too many op-eds in the New York Times that are some really sad 44-year-olds that put all their hope in these frozen eggs and then felt like they were duped. And so I think the truth is that you have to be as concrete with the data as you can be, and to that effect, this paper adds to the data and is something that we can share. Let me do that in a 20-minute consult.
Sure. You guys want to add to that? How would you like to counsel someone if you could? Starting, you're going to start to do it next year, right? Exactly. So I think one way to put it that could make it more sort of easier to digest for patients is to compare it to an insurance policy.
Obviously, I don't think we can ever sort of guarantee someone, you know, a child in the future, but you can think of it as an insurance policy. And with any insurance policy, you think about things like how much protection am I going to get, and you also think about things like how much is this going to cost me. And so from kind of balancing those two things, you figure out if it's worth it to you, whether it's worth it financially, emotionally, or sort of psychologically, et cetera.
And so I think the question will become for these patients, like when should I freeze my eggs if I'm thinking about doing that? And the way I would put it is, you know, there's no guideline, first of all, so it really depends. And right now we're doing it on a case-by-case basis. But you want to kind of tread that middle ground between freezing too early to the point that you run the risk of it really being not cost-effective at all because you're unlikely to use the eggs versus freezing too late where it's really also not cost-effective because, say, you're in your late 30s and requiring multiple cycles, dipping tons and tons of eggs to get comparable outcomes to someone who's younger.
So I think kind of also keeping in mind kind of the family size that the patient wants and kind of settling on where that would be. And for us, we think it would be around 33, exactly. Just to add to that, it's not really an insurance policy for future fertility, but an insurance policy for future choice.
There is a survey study in 2018 by Greenwood that showed 89% of women felt that they derived benefit from freezing their eggs even if they never returned to use them. So egg freezing could in of itself provide benefit, even if it's not guaranteeing a future pregnancy. Knowing that you have that door open, even if it's not a guarantee, it can be beneficial.
And oftentimes this isn't addressed in studies. And from personal experience hearing patients freezing their eggs, they often describe that a weight is lifted off their shoulders, even if they're well counseled about the potential of future pregnancy down the road. I would echo all of that.
I think just to take a line from one of the sponsors, co-authors, the sweet spot for egg freezing is probably 33 to 36. I think that's as far as cost effectiveness goes is what it seems to be the takeaway. Egg freezing at 28, sure, go for it.
But is it really that cost effective? Probably not. So 33 to 36 is a sweet spot. Your AMH is 4. You want to do it? Here's how it works.
I think we need to move away from talking people out of it and presenting people with the options, how it works. How many eggs do I need to get? Well, at year 33, 10 eggs and X percent chance of taking home one live birth. This paper suggests if you know now that you might want to have a larger family, then this makes more sense.
So here you go, mull it over, and let us know when you're ready to start. I mean, I think this just adds to the conversation that has evolved over the last decade that honestly in the last five years I think has come to a place of here's all the information, you ready? Let's go. This is the cost.
This is not. This is what your expectation is going to be with your AMH of 0.6 and you being 33. Like, I might get four eggs.
Not an indictment on your ability to have a live birth on your own in two years. But it's part of a conversation. Just in the spirit of debate, I want to caution us against using the words insurance policy is my personal feeling because I think we all agree in a general sense that this is allowing for reproductive choice and we're in favor of that, but I worry that when I'm sitting across from a woman and using the word insurance policy, what she takes from that is a guarantee, although you said very clearly it's not a guarantee.
We can take the data. We can show them live birth rates over time as a woman ages, but we all know that nothing that they do, even at the beautiful young age of 33, is not a guarantee of building their families by X number of children. So, again, I think it goes back to what a specific woman envisions for herself or thinks she envisions.
I know there was a lot of thought, I'm sure, put into the choice of the comparison group based on the data, but those papers also showed that the average age of an egg cryo was, I think, between 36 and 38. So, yes, those women didn't come back until they were 40, 43, but they actually froze their eggs much later in reproductive life. So, again, we can certainly use this paper in counseling, no question, but I think we have to acknowledge the caveats of any model.
We've had a good debate going so far. I'm going to get up and see if you guys have questions, but it does remind me we are, to use clichés, we are preaching to the choir, right? We are a biased group here that believes in intervention for helping people get reproductive choice. The joke I was presented with when I worked with Luigi Mastroianni and Celso Garcia, who one invented the birth control pill and one was the second or third person in the United States to put out the F, was their whole goal in life was to allow women to have sex without getting pregnant and get pregnant without having sex.
So I think that we have to realize where we're going and what we're telling women, and with that as a preface, I want to hear what you guys have to say to this illustrious panel. So while I get up and find some questions, let's see if you can continue challenging each other for a second. Anybody? Yeah, great.
Great talk. I think the other thing that this paper makes me think about is kind of separate from cost effectiveness and how eggs and embryos are not equal things, and something that I think we're going to have to continue to grapple with as a field and as people that are doing these interventions are that because of the inefficiencies of human reproduction, the limitations of our technology, and the changing legal landscape, we are basically okay as a field with creating a lot of excess, and this is an ethical conundrum and it could also become more of a legal issue because if we have all of these supernumerary embryos, which I like to call limbrios, I just think that it does create potential problems, whereas if you freeze eggs, it's not the same as having these extra embryos. So I think there's another cost here that's really important, and I feel more comfortable having patients freeze eggs that they might not use versus embryos, not because of my own personal beliefs, but I've had patients that really struggle with what to do with all of these extra embryos after a few years.
Comments? No? Yeah, I mean, yeah, I mean, I think we all echo that same sentiment. The idea of excess and excess embryos just now got a little more sweaty for everybody in the room, and it's going to vary from state to state. So I think right now, I think the point is something we need to consider moving forward.
Great point. This is a question for Dr. Omotag. You mentioned a 28-year-old coming for elective egg freezing, so I want to take it a little further.
Yes, you said that you would give the pros and cons, but would you tell the 28-year-old, based on this paper, since we are debating this paper, that if she could potentially come back in five years' time and if she has still not found a partner, at that time it might be a reasonable time to consider egg freezing? Yeah, I think that's a good point. This paper helps kind of reinforce a recommendation, perhaps, for that particular patient, but we all know that if the chief complaint is, I am going to freeze my eggs with you, tell me how to do it, you still need to have that conversation. But in spite of that conversation, I will personally say, okay, you know what, you have agency.
You've heard all the pros and cons. I've cited this wonderful new paper and given you the reasons. I really don't think this is in your best interest.
I don't think you need to do this now. I don't think you need to invest in this. You're asking me my opinion now, so I'm going to give it to you, but you have ultimate agency over this decision.
I've empowered you with all the information available. Call me with cycle day one and let me know when you're ready. You know, I think that one thing that this paper doesn't necessarily address is the likelihood of utilization of oocytes, and so I think we need to be very clear with patients about what this data does and does not tell us.
Our data was able to evaluate the efficacy or effectiveness of egg freezing, and we found that it started to decrease around age 31 or 32. So I think reasonably you could probably tell a patient that if you want to wait a few years it probably won't hurt you, and I think that is helpful and that is data that we can get from this analysis. I think the other thing that I just want to call attention to is that our own society, when giving recommendations for selection of an oocyte donor, says that that individual should be at least of legal age to consent, but ideally between ages 21 and 34.
And so I think when we're thinking about, you know, what is the optimal age to freeze our eggs, I think a lot of us will say like, oh, you know, at 35 fertility starts to decline more precipitously, like maybe consider starting to egg freeze around then, but to me that's a double standard. Why are we telling our patients to do something different than we would ideally like for an ideal situation with an egg donor? And so again, just trying to shift the mindset and thinking about when is this going to be maximally effective for our patients, and maybe considering a younger age is actually a very reasonable thing to do. Julie Lamb from Seattle, and I just wanted to make the comment, like, you know, I think we think of medical indications when counseling patients with this new excellent data.
You know, we think of those medical indications as mainly cancer, but we certainly see a high volume of patients with severe endometriosis or the 28-year-old that's lost an ovary with a dermoid that has a small dermoid on her remaining ovary, and we have to be careful to really include that long list of other medical indications when we're counseling these patients with this data. While I'm walking over to the other side of the room here, we were doing cost of benefit by dollars only. What other costs were in your model, safety, medical problems, things like that? I think for simplicity, we ended up omitting a lot of things like, for example, the medical costs associated with an admission for OHSS or the medical costs associated with miscarriage.
And so to that point, there were some things that were eliminated from our models. But that being said, I think, you know, in today's day and age, egg freezing tends to be a very safe procedure, and the medical costs associated with some of those things is quite low. And again, I think it comes down to informed consent, but I think that we need to trust patients with informed consent, and to suggest otherwise, I think, is paternalistic.
Jen, thank you for the great paper and the great presentation. I had two questions. The first question is regarding your decision tree.
I was curious. I know you based the, I guess, returning at age 40 based off the data that people come back at that certain age, but assuming that people are considering freezing their eggs in their early 30s, did you think about also looking at women coming back in their late 30s? Because that, to me, is more real-life scenario, anecdotally, what my friends are looking at right now. Like, most of them are working at, like, tech companies, and this leads to my second question.
And so if one of my friends is trying to freeze eggs because her company, she's, like, is getting fired from her company and only has the benefits from her tech company for the next two months, but she's thinking about having kids, like, two kids after the age of 35, and I know she has a current partner who most likely she'll get engaged to and, you know, probably start her family with. So she's feeling the pressure because she has two months left, but she's also probably going to be starting around 35. So I was curious because I know your model looks more towards age 40 versus 33, but I was thinking why not look at early 30s versus end, like, late 30s.
Thanks, Esther. It's a good point. I think that we did not actually look at varying the age at return to actually use those sites, and again, it's grounded in the best available data that we have.
We did make it so that patients who wanted more than one child would turn before the age of 43, and I don't know if you caught that in our models, but patients who were desiring two children did return at 40 as opposed to 43, which, again, I think we selected on the basis of just trying to mirror what was more realistic in terms of when patients would actually return considering ideal family size. But, again, I think it's, you know, in terms of using this data to counsel patients, I think it's important to exactly what you're doing is really note what assumptions we made in our model and whether that might be applicable to the patient in front of you. My question is a little more broad.
I think, like Dr. Barnhart said, you know, preaching to the choir, we, you know, see this data in and out and can really analyze it, but I think the people and the physicians and providers who really need to understand this more are the generalists that are seeing these patients at annual visits and might be kind of like the first line before a referral. So I'm curious as to people's opinions as to, like, how to get this information across to the generalists that are referring and things like that. I think it's an excellent point, and actually, you know, there is a set of guidelines for generalist OBGYNs in terms of what should be covered at an annual well-woman visit, and there is an absence of fertility in those recommendations.
And so I actually wrote a commentary with Dr. Kara Goldman, one of my mentors, in AJOG earlier this year about why is fertility omitted as part of a well-woman visit. It's essential. It's health care.
And yet I think we're missing a very key point in time where this could be addressed, and if it's addressed at every annual visit and not in a threatening way, not in a, you need to freeze your eggs now, but just something to think about, because I totally agree with you that, like, I think having it as part of these guidelines that are disseminated to our generalist colleagues is a first step and one that I hopefully, I think, you know, wouldn't be too hard to take. Shout out to you guys for writing that commentary because that is actually the most important part of this conversation. The U.S. Preventative Task Force needs to include reproductive counseling so that the generalist, the family practice doctor, they are having this conversation at 33, just like they're having a conversation about a colonoscopy.
Like, that conversation needs to be normalized for anyone with ovaries. I wanted to echo the sentiment. I think that, you know, surveys have shown that women are very unaware of sort of their age-related fertility decline as well as the options that are available to them for fertility preservation.
And so I do think that outreach and making sure that this becomes sort of more general common knowledge is very, very important. Thank you so much for presenting this. In this paper, it's always nice to see something that has a dominant strategy as the outcome.
It seems like the model was designed and sort of the counseling is around patients who are primarily cisgender and straight and likely to have a goal of partnering with a cisgender man and having children with his sperm. How do you think your model would change or that the dominant strategy might change if we're thinking about a broader patient population? If we're thinking about our queer and trans patients who either, A, may know that they want to use donor sperm and for whom actually embryo cryo might make more sense, or B, who might have a different pathway to parenthood or multiple different pathways to parenthood? I think it's an excellent point, and definitely some of those thoughts are a little bit outside the scope of what we actually accomplished in the paper that we had in front of us. But to your point, I mean, I think the real-world data suggests that many patients do use donor sperm, and whether it's because they are in a same-sex couple or because they don't have a partner, you are right that I think the conversation changes, particularly if you know right off the bat that you are planning to use donor sperm.
I think in that case, you know, Brent might not agree about making embryos, but I think, you know, it's something that could be considered. That being said, you know, age-related fertility decline and reproductive aging is universal for all patients who have ovaries, and so I think, like, the central tenets of the paper probably wouldn't change too much. I also think there's a tremendous research opportunity to better describe the transgender, non-binary populations and their reproductive desires, both short-term and long-term, and I think there's a huge knowledge gap that there's a great opportunity for you guys to help uncover.
I'd also say that that sort of mirrors the point that Dr. Lamb was making, in that I would put that in the medically indicated category, meaning that if it's someone who's committed to using IVF, in the long run, you're not going to tell them to wait until 33, right? Then you're going to say, at some point, you need to harvest these eggs anyway, so you might as well do it sooner rather than later. It's a little bit of a different scenario. Thank you so much, Jen, for your paper and discussion.
My question involves your comparison group with really 43-year-old women that did tall egocycles with PGT. Did you look at or have the data looking for not doing PGT for non-tested blasts? And I wonder if that's included. We all know that it's difficult for a 43-year-old to get a euploid blast.
Would that aid your cost-effective analysis if you include all IVFs, like those cycles, that maybe did not have a euploid embryo transferred, just to aid, again, the cost-effectiveness? Thanks, Michael. Obviously, I think PGT is one of those topics that can be controversial in our field, particularly when we're talking about the extremes of reproductive aging and the utility when you're talking about a patient who's already 43 and the low likelihood of getting a euploid blast. I think if you look at practice patterns nationwide, there are many centers that are doing PGT on all of their embryos.
You could make the argument that this is just mirroring clinical practice for a lot of centers. But for us, I think really why we chose to include PGT in the comparison group is just coming down to reproductive planning. Because thinking about two children was a central goal of this paper.
I mean, really, if you have a patient who's 40 who's coming back, and you know definitively that this patient would like to have two children, some people might argue that you're doing that patient a disservice if you do a fresh embryo transfer, knowing that they're going to come back at 43 and want a second baby at that time. Really, by knowing exactly what you have banked, if you go through PGT and you know you have several euploid embryos and you have this statistic likelihood of having a second child with those embryos, it really did come down to reproductive planning. That's why we made that choice.
I have a question. Raise your hand if you're aware of the recent ACOG practice bulletin saying that IVF is a risk factor for IUFD, and as a result, there needs to be twice-weekly monitoring in IVF pregnancies starting at 36 weeks. Okay.
Who's also aware of the practice bulletin from ACOG that says that an IVF pregnancy requires cardiac fetal monitoring with high-level ultrasound at 20 weeks because there's an increased risk of cardiac anomaly? Okay, pretty much everybody is aware of that. That's good. Are we telling our egg bankers that? Who's telling your egg bankers that when they have this conversation about banking eggs at 33? Are we telling them about that? Are we telling our IVF patients about that? Should we be? Should.
Where does this land in the discussion about egg freezing? So, again, was that a rant or were you looking for an opinion? I'm just trying to make it fun. I'm just trying to make it provocative. So does that mean? I guess the question is the risk of IVF as it relates to anomalies.
This is a conversation we've had about for a long time as a specialty. What role does that data and conversation have in the conversation of egg banking, if any? I haven't looked at the data backing up that guideline recommendation specifically, but I guess my question back to you would be is the increase in IUFD and cardiac anomalies related to the IVF technology or is it the indication? We're looking at infertile patient populations that are going through ART in the first place. So I think we need more studies to be able to validate and say that egg freeze population has the same risks.
I'll push back on that because if you're using your eggs at a later age, by definition you're infertile because you're at a later age and you need to use your eggs. So I would be careful of the distinction that might not be that material. And I also happen to think scientifically that it's not just the woman.
I think it's also the process. Anyway, I'm usurping. I have another thought-provoking question that this kind of made me think about.
From a workflow standpoint in the embryology lab, if let's say hypothetically we had all 33-year-old women given the choice and had the means to freeze all their oocytes that they wanted, obviously that would put an increased strain on the laboratory process. In a field where the need for fertility care doesn't quite match up with the supply, to pivot that thought to a policy standpoint, if you were to try to pick, let's say, mandatory oocyte coverage for women that wanted that versus trying to focus efforts on improving fertility access to couples that already struggle with infertility, where would you strike that balance? I don't know if anybody has any thoughts on that. Sounds like a reproductive justice within the specialty.
Yeah, I mean, if you had Sophie's choice of the REI moving forward, would you rather make sure that everyone has access to IVF, or would you rather make sure everyone has access to egg freezing splitting hairs? I mean, they're kind of the same thing, but it's a very difficult question. You could set up an apparatus where egg freezing removes itself ultimately outside of the quote-unquote fertility clinic, and you can have your own operations that are, do you need a lab to freeze eggs? How big does that lab need to be? Do you need a place to store them? I mean, are you going to store them? Is someone else going to store them? You guys know what the models are. This isn't new to you guys.
Very good question. So if we were able to move egg freezing outside of the IVF lab, I think that would also help from a cost-effectiveness standpoint, because I think a lot of the costs associated with egg freezing are lab costs, because the labs do bear the burden of the costs of IVF and all of those procedures as well. Great point and a great question.
The thought I had also related to cost, not exactly what you're speaking to in terms of the cost of the labor, is I think one of the great strengths of your study was its geographic diversity and incorporating multiple centers. But as you recognized in the paper, your model was based on self-pay, understandably. I imagine it would be challenging to do it otherwise.
But how does this affect decision-making? I'm in a mandated state, certainly. I think we can all agree that there is much, much, much room for improvement in terms of insurance coverage. That goes without saying, even in mandated states.
But that also should weigh into our counseling in terms of cost and benefits. So I was just going to say I have a comment about the paper and then sort of something a little more philosophical. But firstly, this is a great discussion, great paper.
Papers are only as good as the data that go into them. And that's not a flaw in your paper, but it's a flaw in the data that's currently available. And some of these things have been brought out, but I think it's really important to think about the egg donor data was based on donors, which was brought out.
And the data, while it is the largest and best available in terms of long-term usage, and the median age of freezing was actually 38 from that paper, and less than 8% froze before the age of 35. So very different patient populations. So not surprising that they didn't come back until 40 or 42 or 43 because they didn't freeze until they were 38.
So when were they going to come back, number one? And number two, the usage was probably higher because they were still single at 38, 39, and 40. And so I think that if you change that to freezing at 33, as was brought up over here, and using them in the late 30s, I think you may have very different data. And that gets to my philosophical comment, which is the problem when things come out like this, and this is a problem with our field in general, is that we tend to be an all-or-none phenomenon.
And so if something comes out and it says it's good, then we're going to do it on everybody. And I think people have brought out, but this is should everybody freeze before they turn 30? Should everybody freeze before they turn 33? I think the world is much more nuanced than that. And I think we have to be very careful before we start counseling that everybody needs to do this.
And that's my concern. Not that absolutely if you're going to have kids at 43, freeze your eggs at 32. That's a no-brainer.
But I think the reality that that's going to happen for most people who freeze is very, very different. And so I think we just have to be careful. The data that went into this paper, while it was the best that's available, isn't the same data that we're now making conclusions.
We're using data with eggs from 20-somethings that were egg donors compared to women who were 43 and telling women to freeze their eggs before they're 33. And so we have to be very careful when you take data from one population and then, A, apply it to a different population, and even more so then try to apply it to the entire population. So everything's much more nuanced than that.
Well, I never disagree with Marcel Cedars at my own peril. Actually, maybe I have once or twice. But I think that's a nice place to sum this back up.
So I think we all recognize, or I'll say it out loud, this was an artificial cost-effective analysis, right? I mean, it's real-world data, but it's not patients in here to find out what happens. And, yes, this theoretical patient knew at 33 that she was not going to have children until her 40s and not going to get married and was going to use her eggs. So just take that for what it is.
So with that wonderful paper, and it caused great discussion, and I'm really pleased that it's in fertility and serility and it's the right place for it and write more papers, let's go back to the panel and just summarize your thoughts. Why don't we give it to Jen and your group first, summarize what you think are the positives out of this, and then we'll give it to the convicted felons for the last word. Well, thank you, everybody, for a good discussion.
I think there's a lot of uncertainty that has been uncovered, but to just bring it back to the certainties that we know we have, there are few things as certain in our field as a decline in egg supply. And so, you know, we talk about prophylactic health care all the time, but I think really this is talking about prophylactic fertility care. And really, by giving our patients the option to freeze their eggs, we are really equipping them with the best tool we have available to achieve their reproductive goals.
And, again, the goals for many patients is more than one baby. And so I think, you know, it's all about options, reproductive choice, and increasing the likelihood of achieving their goals. I'm going to just alternate back and forth and everyone get their last statement.
So if you want to just make a comment. I will go back to the first comment that I made, acknowledging the strengths of this excellent study, but also echoing, again, what Dr. Seder has just said, which is the data is based on the model. And so if we are going to apply this to the woman who's sitting in front of us and she's 33 and she says, I'll see you in 10 years, doc, I'm hard pressed to say, sounds good to freeze your eggs.
But that would be the woman that fits into this model. And so I think it's the data is the data based on the model, which is the model. I guess I just wanted to commend Jen for her excellent paper and also point out that her findings are not dissimilar to other cost-effective studies on the same topic that have been done.
And then also I just wanted to say that it is difficult to argue a sort of like one size fits all policy where we say everyone should do something at a certain age, especially something that's very costly and, you know, is a procedure. But I think that in order to kind of put our patients in a position that sets them up for success and also that kind of puts them in a position where they're able to do something that's cost-effective, I think it does make sense to freeze eggs sometime between, I think we've agreed on between 32 and 36. And I think, you know, we're saying 33, but I think that, you know, sometime during that time frame sounds like a very reasonable time for most patients.
I'm not sure that I have much more to add. Marcel summarized it perfectly. I guess the take home is really that it comes to informed consent and providing data that is specific to the patient in front of you and not making global recommendations that are not patient-centric.
Very similar thoughts. I think that this paper will be included in my toolbox when counseling patients, understanding its limitations and who it applies to. But ultimately, I like to remind myself that the weight of these decisions aren't on my shoulders.
You know, our goal is to provide unbiased counseling and support patients through their decision-making process, but ultimately it's up to the woman to decide for herself, very similar to any kind of healthcare decision-making. So I think that this is something they'll refer to pretty often. I would just echo everything and just really emphasize this push to get the U.S. Preventative Task Force to really make reproductive counseling and planning a milestone for all primary care providers and OBGYNs.
Microphone was off, so I was just saying thank you to all for being part of this. It will be cataloged and you can watch later. And again, good morning, good afternoon, and good night to whoever is watching it online.
And we will have other ones in the future. Thank you for the panel, wonderful paper. Thank you for the audience, and thank you for all the help.
