SART Fertility Experts - Vanquishing Multiples

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Hello, and welcome to today's episode of SART Fertility Experts, the podcast for people trying to build a family. I am Dr. Kelly Lynch, and my guest today is Dr. James Toner of Emory University School of Medicine. Dr. Toner is Professor of Obstetrics and Gynecology, and he is here to talk to me today about vanquishing multiples.

Dr. Toner, welcome. It's a pleasure to be here. So can you talk to us a little bit about why multiple gestations are a concern for patients with infertility and why they were so common in the past with in vitro fertilization treatment? I'd be happy to.

Now, in the early days of IVF, we were lucky if one in 10 embryos attached. So we were kind of forced into a position of putting in many embryos all at once in hopes of getting to any pregnancy at all. But things have changed.

And as they've changed, I think we've become much more aware that in a way there's more than one patient in front of us. There's the couple or individual we're working with, but also their future offspring. And kind of in line with the edict to first do no harm, I think we've come to recognize that for children, it really is best for their health to be born one at a time.

And that's sort of changed the balance. And as an example of the risks of even twins, children born as twins have about five times as much cerebral palsy. They have somewhat lower acutes.

They have much more problems with learning disabilities. And these are really lifelong conditions, right? They're not just, oh, I was born a month early. And then you kind of get out of the NICU and go on with a normal life.

These are long-term issues that we now can adjust our treatments such that they occur much less often than before. So, really, on behalf of the children's health, I think it's generally understood within our society and within our practice these days that embryos should best be put back kind of one at a time. Otherwise you would kind of lose the opportunity to put a lid on how many multiples are being created.

And again, the multiple pregnancy situation puts the children at some risk. Right. What about the risks to the mother's health as well? The mothers also are at increased risk, but they're sort of, in my mind anyway, in a somewhat different class because those are risks that are transient.

I mean, you know, yes, there's more diabetes. Yes, there's more hypertension in pregnancy. But once the pregnancy is behind that woman, they resolve.

And again, so that's a different sort of an issue, I think, as opposed to the lifelong things that can happen to children that flow from being born, you know, two at a time or three at a time. Even, you know, even when we put back just one, we know one in a hundred times we're going to get identical twins anyway. That's unavoidable.

So even when we're doing, quote unquote, the right thing, we know we're still going to have an occasional twin. But that also kind of means by extension that if you put in two, sometimes you get three or four. And that's incredibly risky to the health of the children.

We now have a tool, and we can talk about how we got here, a tool for doing what can be done to protect the health of IVF children. So what do you think are the ways that IVF programs have been able to help improve pregnancy rates while reducing the risk of multiple gestations? Yeah, the treatments that we now can do are different than before. And many, several of them have led to our ability to have high success rates and low multiple pregnancy rates all at the time.

I think probably the most significant one is the ability to allow embryos to develop in the lab for much longer than in the early days of IVF. In the early days of IVF, you would put sperminate together in a dish. And initially, one day later, you'd put back anything that looked like it had fertilized and hoped for the best.

Then it became possible to culture embryos for three days in the lab. But now it's possible to culture embryos five days. With extended culture, the embryos are able to sort themselves in a way that wasn't possible before into those that are still growing well after five days and those that have fallen behind or stopped growing altogether.

So embryos that now get to day five are much more likely to be healthy and competent than in the early days when we couldn't achieve extended culture in the lab. So that's a huge change. The other thing that has allowed us to reduce multiples is the safe freezing of embryos and high efficiency; probably 99, 95% of embryos that are frozen thaw and look and behave just like they would have had they never been frozen.

And also, you can test the genetic status of embryos. And that's especially helpful for the cases where the women who are providing the eggs are perhaps above age 38 because even a healthy-looking embryo from a 40-year-old doesn't attach as often as a healthy-looking embryo from a 30-year-old. And that's because much higher proportion of them, even though they look good, have the wrong number of chromosomes, and they would have just been a miscarriage.

So if you can do the genetic screening, even for women who are 40 or 42, you can find the ones that are likely to work. And that allows you to stick with this one embryo at a time policy, even for women in their 40s. Right.

So extended culture is what you're saying is it allows us to be more selective about which embryo to transfer. So we have a better idea of which embryo is most likely to implant. So we can put back one embryo with greater confidence.

Yeah. And these days, if you have a good-looking embryo that's developed for five full days and achieves this stage of development called blastocyst, they attach half the time, especially under 38. And then look, they'll still attach half the time in women over 40 if you know that they're also normal genetically, that they have the right number of the 46 chromosomes that they should.

Right. So genetic testing can allow those patients who are older to know that they're transferring a normal embryo, which can also allow them to transfer a single embryo with confidence. Right.

Because it used to be that there was this need to transfer more and more embryos as women got older because those embryos were likely to have trouble that you couldn't see by just looking at them. But now the ability to test their genetics makes a huge difference. Dr. Toner, what do you say when you see a couple that says we can only afford to do one cycle of IVF? We want to put back two embryos.

We want twins. How do you counsel them? Well, we do counsel them and those concerns are legitimate. So I don't brush them off lightly.

I guess what I tend to describe the fact that it's the initial effort to get eggs. That's the very expensive part. Whereas the use of any frozen embryos is a much less expensive step.

And I try to, again, encourage them to think perhaps, in addition to the finances, which are a valid concern, about the health of their future children. And by, I think, focusing, drawing attention to the fact that there are real risks to children born as twins that are essentially avoidable by just using that second embryo a little later. Most couples end up deciding or individuals end up deciding to go with the one embryo at a time approach.

And remember that once an embryo is frozen, it never gets older. So if you went through an IVF cycle, had two embryos produced, put the first one in, froze the second one when you were 35, for instance, and then came back three or four years later for another try with the second, that embryo is going to act 35. It's not going to act 38, 39.

So there isn't any medical advantage to putting them back together or urgency because time is going by. The eggs and the embryos will not get a day older, and the uterus doesn't really age either until women are in their late 40s. So a 40-year-old uterus can carry an embryo just as well as a 35-year-old.

So you're giving your offspring the best possible chance and lowest risk of complications associated with multiples by transferring singletons. Right. I think the field is, again, now that these new approaches are available to us, coming to embrace the goal of having the healthiest children possible.

Risk of multiples puts the children at risk, and most of that risk is now avoidable. So as a field, there seems to be a consensus that on behalf of the health of the children and in line with sort of our oath to first do no harm, it really has become a policy of single embryo transfer in most clinics. And it's a good one.

I think it is. I think it really does benefit the health of the children. Just as kind of maybe a reference point, until about 15 years ago when these new approaches started to become more popular, more than half of the IVF children were born in pregnancies that were at least twin, if not triplet, then quadruplet.

And again, that 50%, 60% of the born children were all of them at some risk because they had come in the form of a multiple pregnancy. In the most recent year where we have information about outcomes, it's now not higher than 5%. So we've taken a risk that was at least 50% of a multiple pregnancy and driven it down to 5%.

And the natural rate is 1%. So we're getting close to an approach that hardly produces any more multiples than would occur in people with no fertility challenges. It's a dramatic improvement.

What do you think about the role of insurance coverage in helping to reduce multiples? I think that takes the... You alluded earlier about patients who are worried about the high costs if they have no insurance, that spreading out the transfers instead of just doing multiple embryo transfers, and I kind of get that. I think if people have insurance coverage, that that takes that financial pressure off of their shoulders because there won't be, except for the slight inconvenience of having a few monitoring visits, any additional cost to spreading out the transfers instead of multiple embryos at one time. And there were some insurance companies, I don't know that it's still a common practice, but there were insurance companies that negotiated with the providers to say, we'll cover this service if and only if you put back one embryo at a time.

And I think that's also not a bad policy because not only is our multiple pregnancy risky to the mom and the children, but they also, for the insurance company, presented much, much higher cost. So they had been willing to maybe offer coverage to do the right thing so they won't have to take a big hit to support the NICU stays of triplets by triplets that come if they don't provide some control of how we're putting embryos in. I can speak from some experience with that.

I practiced in Massachusetts for 21 years where there's a very generous insurance mandate and Massachusetts had the highest rate of twin birth in the nation in the early 90s and they instituted Blue Cross and TAPS, I believe instituted a mandate, a single embryo transfer mandate with the help of the medical directors and it did help to dramatically reduce the risk of multiples. As I understand it, you can confirm that the patients would be covered if they agreed to a single embryo transfer, but not if they chose a double embryo transfer. Right.

And they also extended the coverage. If they agreed to a single embryo transfer, they would cover more cycles for them. They would extend their coverage to include more transfers and more cycles, which was a win for both, really.

Yeah. Getting back to one of your original points, I think we all get the feeling of urgency, people with infertility to have their children and maybe have them as quickly as possible. And without knowing the risks of twins, it's certainly understandable why they would say, let's put two in.

But again, now that we know and have acknowledged that there is a real risk there, our general default approach is different than it used to be. And with the relatively high pregnancy rates, even with one embryo going back at it, one at a time, 50, 60, 65%, many people are pregnant right out of the gate. And if the transfer doesn't work, we come back four weeks later and try another transfer.

So it really doesn't even involve an appreciable delay to the first pregnancy. Right. I think patients need to know that IVF, in general, offers patients high chances of success and that they really don't have to transfer two embryos in their first transfer unless they're older and they're not testing.

So single embryo transfer makes sense for a lot of patients. Mm-hmm. Again, based on the national experience, now about 65% of all the embryo transfers are single embryo transfers.

And it used to be under 5% 15 years ago. So it isn't at 100%. There's still some situations where a double embryo transfer might be appropriate, usually in the context of embryos where you don't know the genetic testing results.

But if you do know the genetic testing results, putting back two normal ones at once invites some challenges for the health of the children that result. Well, thank you so much for taking the time to speak with us about your expertise in this area, Dr. Toner. Patients really would benefit from hearing what you have to say.

And this is a really important topic and really represents tremendous progress in in vitro fertilization. The progress we've made in reducing multiples really will help babies and children go on to lead healthier lives. Well, thank you for the chance to discuss this with you.

Congratulations on this really excellent paper. The information and opinions expressed in this podcast do not necessarily reflect those of ASRM and its affiliates. These are provided as a source of general information and are not a substitute for consultation with a physician.