420: Democrats’ midterm victory, and a questionable fertility procedure

0:06Daniel Payne: Welcome to The Read Out Loud, a weekly biotech podcast from staff. I'm Elaine Chen. And I'm Damian Garda. Adam Foyerstein is out this week. Today on the podcast, women over 40 who have exhausted their options to have children are turning to international clinics promising success with a questionable and expensive genetic procedure.

0:27Megan Molteni: Egg quality is a key determinant of fertility. Healthier eggs lead to higher chances of successful conception and a healthy pregnancy. Mitochondrial donation involves using healthy mitochondria from a donor to support egg quality, enhancing the chances of fertility in older women.

0:44Daniel Payne: There is no published study showing that any of this works for women above 40. If they have their own research. They haven't published it, which in itself is a red flag. They're presenting this as if it is established and it is not. That story and we'll dive into the biggest news of the week, the massive midterm victory for Democrats across the country. What a seismic change in the makeover of Congress means for health and medicine. But first, a word from our sponsor.

1:18Daniel Payne: Okay, listeners, I know the podcast looks a little different this week. Allison is no longer on the podcast. And Adam is out this week. We have Damian, our former co-host, filling in to help out. Thank you, Damian, for coming on. Thank you for having me. It's great to be here. So let's just get straight into the biggest news of this week, which is, of course, the midterms. We're going to bring on one of our D.C. reporters, Daniel Payne, to discuss what the results mean for the healthcare industry. Daniel, welcome to the podcast. Thanks so much for having me. So starting with, I mean, we're not breaking this news to anyone listening, but there was a seismic result on Tuesday for Democrats across the country.

1:59Daniel Payne: The Democrats will now control the Senate and have a very large majority in the House. I mean, there's so many implications of this within policy in the United States, but specifically in health and medicine. What's the biggest takeaway in your mind from Tuesday's results? I think the biggest headline is we have had two years of sweeping unprecedented changes to the federal health care infrastructure under the Trump administration and Republican trifecta in Washington. The biggest top line is that is all changing. Come January, there's going to be a big handbrake on all these changes that have been happening over the last couple of years.

2:37Daniel Payne: That can be seen in the way that HHS has changed substantially. That can be seen in some of these private deals that the government has been making with the health industry. And also just the politics of the Maha movement, which, of course, has been a huge force in American health care. So let's focus on one of the biggest issues, which is drug pricing. Trump has talked about lowering drug costs as a key priority for him. That's also a key policy issue for Democrats. Now that Democrats have the majority in the Senate and the House, do we expect any more movement on drug pricing? I would certainly expect some movement on drug pricing.

3:18The Trump administration has been pushing for these most favored nations drug prices

3:23Daniel Payne: for a long time. they've been sending Dr. Oz and a bunch of their top officials to the Hill to have private meetings to try to get legislation passed that would codify some of these deals that they've made that they claim will bring American drug prices down to the level of what other countries pay. That has not yielded the result that they've wanted. A lot of Republicans have resisted that. they feel it goes against the grain of a free market approach that they've championed for decades. Now, with Democrats in control in Congress, many of whom are not shy about having more government control over drug pricing, a lot of Democratic leaders want to see more government involvement in American health care to be able to push prices down or increase access.

4:17Daniel Payne: a sweeping result like this in their favor will perhaps fuel more bravery in their policy outlook. And Daniel, I wondered, for members of the C-suites of major pharmaceutical companies around this country and around the world, we saw CEOs of these major drug firms parade one by one into the White House to sign these most favored nations agreements. And that followed what I think could be fairly described as a cozying up to Trump. CEOs were making trips to Mar-a-Lago in an effort on their part to avoid being subject to the tariffs that they were being threatened with and to ameliorate any kind of bad effects on their businesses that the MFN proposals had.

4:55Daniel Payne: Now there's this changing of the Guard in Congress, specifically these powerful Senate committees that have subpoena power. Do you imagine there could be repercussions to sort of score to settle on behalf of the Democrats who maybe didn't love watching pharma CEOs stand and backslap the president in the Oval Office last year? Absolutely. I think that is going to be a huge issue, and not just for pharma companies, even though they may be among the top targets in healthcare. We've heard some of the most powerful Democrats who are expected to lead some of the top healthcare committees say explicitly for months that they want more information about these deals or other healthcare matters.

5:31Daniel Payne: Ron Wyden, who has led the Finance Committee for the Democrats, he tweeted on election night subpoenas. So there's a lot of action from this administration that the Democrats will want to investigate and make hay of. So I think it's pretty safe to say that that's top of mind for them. With the Democrats in power now in the House and the Senate, what does that mean for the sweeping Medicaid cuts that are coming from the One Big Beautiful bill that was passed earlier in this term. In the immediate aftermath of the results on Tuesday, we heard a lot of Democrats saying that this was one of the top issues they wanted to tackle very early on to undo some of these cuts, reverse them.

6:17Daniel Payne: There's been some talk of delaying them even just to offer more time to do something about it. So I think we can certainly expect some action on this. At the same time, and I think this point applies to everything we've talked about so far, it's really easy, particularly in healthcare, to talk about whatever policy goal you have on the campaign trail and a stump speech. It's easy to say you're going to lower cost and expand access. But, you know, as we know, and our listeners and readers know, the policymaking is so much more difficult and complicated and how they might pay for the changes they want to make or for how they reconcile reversing these cuts and also not giving the money directly to these big healthcare conglomerates that they say that they want to hold accountable.

7:06Daniel Payne: That maybe is a tougher task going into this Congress. I want to ask also about the administration's attacks is maybe too strong a term, but approach to the NIH over the last two years. And there have been moves to politicize it, there have been moves to limit its ability to spend. So what might lie in store for basically the administration's approach to NIH now that leadership is changing hands? I think there's going to be a much stronger check on the administration's agenda for NIH and for science broadly. I think if you look back, even to when there was a Republican trifecta, There were a few instances where a policy was announced that would change NIH funding in some substantial way that would offer tools for political appointees to have more power about what research is funded and how it's funded.

7:59Daniel Payne: And shortly after, Susan Collins, a Republican from Maine, the top appropriator at the time, would push back on it. Shortly after, a lot of those policies were reversed. So now imagine you have someone in that seat who is a Democrat, who is maybe not facing the sort of political pressures that Susan Collins was. I think we will see a much, much sharper approach from Congress to push back on those policies. And particularly because research and NIH at its core has largely not been a controversial federal program. So taking this all in just through the lens of industry, the goals of biotech and pharma writ large, and this might be kind of a vulgar simplification so people can be upset with me if they'd like, but is to a return to normalcy at FDA where regulations happen in the normal regulation way in the Federal Register and not by fiat that is confusing and frightening.

8:58Daniel Payne: to be left alone on drug pricing would also be their dream and to not have any kind of retribution for any actions they might have taken over the last two years in the Trump administration. But the other major ask, something that some of the CEOs have said on the record, which is for Robert F. Kennedy Jr. to be fired, asked to resign, otherwise just depart his role as secretary of HHS. So what do you think this election result portends for Kennedy? I think Kennedy faces a difficult road now. His movement, the Make America Healthy Again movement, in the aftermath of this election, lots of its leaders have just said, we're not so sure that aligning with Republicans and the Trump White House is exactly where this movement needs to go in the future.

9:47Daniel Payne: That puts Kennedy in a difficult place. And there are some Democrats in Congress who have already said immediately, we want to see him fired or resign. Whether they have the power and votes to do that, we shall see. Overall, Daniel, any other thoughts you have about the implications of the elections? I think there is a sense that a lot is about to change in health policymaking. One, in that Washington is changing in all the ways that we've discussed. There's no more Republican trifecta, and the Trump administration does not have nearly the power come January that it has for the past couple of years.

10:30Daniel Payne: I also think if you were listening to these up and coming candidates for the Democrats who are seen as potentially the future of the party, who are putting up huge, almost unimaginable numbers in states that were not considered competitive for Democrats, you see a new party vision emerging. That maybe is not going to be immediately seen. But I think if I were a CEO of any major health organization, I would be concerned about how Washington is going to change in the next decade. And I imagine it's going to be pretty substantial changes. Like I said, the policymaking is so much harder than going out and giving a victory speech.

11:15Daniel Payne: So we'll see what happens when they actually have to put text to paper. Daniel, thank you so much for coming on. Thanks so much for having me.

11:33Daniel Payne: For women as they age, and especially those over 40, having children may no longer be an option. Many have tried traditional IVF treatments with no success. But one American company is promising these older, would-be mothers a chance for a healthy pregnancy. The company connects them with international clinics that are using a novel and unproven treatment known as three-parent IVF, which is banned in the U.S. Stat reporter Megan Molteni spent eight months investigating these clinics, and she joins us now. Megan, thank you for being here. Happy to be here, Elaine. So to start off, what is MRT, and why is this procedure so controversial?

12:11Megan Molteni: So MRT stands for mitochondrial replacement techniques. It's kind of an umbrella term that encompasses a couple different ways of constructing IVF embryos that winds up being a combination of DNA from three different individuals. Essentially what it entails is combining mitochondria, the batteries of cells. Everyone gets all their mitochondria from their biological mother. And so it is combining the genome of those mitochondria with nuclear DNA, so this would be chromosomes from biological mother, biological father, and then mitochondria from a third person who would be an egg donor. And the reason it's controversial is because we just don't know a lot about what the long-term health impacts are of combining DNA from three different individuals.

13:15Megan Molteni: This is still a very new technology. How new? It was shown for the first time in non-human primates in 2009. And some of the first human tests of this are currently underway. The first clinical trial of this is taking place in the UK for families that have a history of mitochondrial disease. And that means there's a mutation in the genome of the mitochondria carried by the mother. And that if that were passed on to any of her children, it would result in a serious or sometimes fatal disease. There was data published last year after about 10 years of them running this study. And that resulted in the birth of eight children.

14:04Megan Molteni: And so they're still quite young and there's just still a lot we don't know about the long-term health impacts.

14:10Daniel Payne: The companies you're writing about, they are marketing this procedure not for a mitochondrial disease, but to help older women with fertility. So tell us about what the companies are saying about how it might affect fertility.

14:27Megan Molteni: So we took a look at a number of different fertility clinics around the world who have started to advertise mitochondrial replacement techniques as a fertility treatment. We focused particularly on one U.S.-based company called International Fertility Group. It's what's known as a medical tourism agency. So it connects patients with clinics overseas. What that company in particular was advertising was that mitochondrial replacement could be a silver bullet for a problem that arises due to maternal aging. Around age 40, so-called egg quality starts to take a big nosedive. And what that means is that it gets harder and harder for women to produce eggs that when fertilized develop normally, like a normal number of chromosomes.

15:29Megan Molteni: This is a problem called aneuploidy if you have an abnormal number of chromosomes. And so what this company IFG has been advertising is that a boost to your mitochondria, what they've described as recharging your eggs batteries by swapping out the mitochondria in your own eggs for the mitochondria from a younger donor, that that can be a solution to overcoming this problem of aneuploidy. The underlying assumption is that aneuploidy and other egg quality issues are caused by aging mitochondria and that by swapping them out, you can fix that. And the data is really lacking across the board. Certainly there have been no clinical studies in humans that show that mitochondrial replacement techniques can overcome aneuploidy issues.

16:24Megan Molteni: There are some studies in mice suggesting that it is possible. And there is one group of academics in Europe who are hoping to study this in a small trial in humans. But I think just what we learned from talking to dozens of scientists is not only is there a lack of evidence, but also that the underlying assumption doesn't have a lot of direct evidence either.

16:50Daniel Payne: So this company that you focus on, IFG, they're based in the U.S., but what they actually do is they connect patients to clinics abroad because MRT currently is not available in the U.S. Patients are spending upwards of$30 ,000 to do these procedures, to go abroad, a huge amount of money, despite this lack of data. Why are women spending so much money to do this?

17:16Megan Molteni: I think the heart of this is that there is a real unmet medical need right now. There are women who have struggled with fertility. They're struggling as they get older. And there just aren't a lot of good evidence-based solutions for that population of patients. The fertility industry in the U.S. and around the world is full of what are these so-called add-ons. So these are things that clinics will sell you for additional charges. And so when options are not available in the U.S., it is a predictable outcome that people who have the means to look elsewhere are going to do so. And so I think at the heart of this is there's this tension between a strong desire for genetically related children and a technology that we just don't know whether or not MRT can provide that, right?

18:22Megan Molteni: Like that's where we're at right now. The evidence doesn't exist. So I think the real question that the reporting raised is what is the responsibility of clinics selling MRT in terms of the information they're providing patients? What I heard over and over from the patients that I spoke to is, I want a chance to try this. I just want to be fully informed. I want to know what my odds are based on my fertility history, based on my age. And I want to be able to make an informed decision and know what I'm signing up for. And the issue that we came across in our reporting was a disconnect between how the technology is being marketed and what the available evidence is.

19:10Megan Molteni: And that's the most concerning aspect of this.

19:14Daniel Payne: You've spoken to people who have used these services, but a lot of them didn't actually want to go on the record and use their name. Why is that?

19:24Megan Molteni: For one thing, there's a certain amount of stigma associated with this. For people who are in the U.S. or in Europe where MRT is not legal, people have trepidation about sharing this with their doctors, sharing this with their family. I think there is a sense that, you know, this is a big social experiment. And how will these children be viewed? Will they be viewed any differently? I think nobody knows right now. We're very much at the beginning of that. But then I think the more concerning aspect for the patients that I spoke to is for the ones who have eggs or embryos banked with clinics that have contract agreements with IFG.

20:06Megan Molteni: There is a concern that if they were to go on the record, that their materials could be compromised, could be held hostage. And so what I heard repeatedly was a willingness to tell their stories in full once they have retained custody of their eggs and embryos.

20:26Daniel Payne: And what are some of the common issues that people brought up in terms of the clinics that have contracted with IFG? Is it that the advertising claims that they were being fed did not live up to the reality?

20:40Megan Molteni: One of the claims that I heard repeatedly was if you are able to get four eggs, then that will be enough to have an embryo that's genetically healthy that you could implant. That was a number that was tossed around in webinars and other communications by this company. You know, a lot of these women are in conversation with each other and trying to track success rates because they're not able to get that information from the company itself. One thing I heard was that especially for women of advanced paternal age, what they expect from a fertility clinic is a very detailed discussion about what their likelihood of success is.

21:25Megan Molteni: That there is disclosure from the clinic in terms of its own success rates, in terms of life birth rates and pregnancy rates. And this was data that women who signed up with IFG were not getting. And then I think the other thing that I heard was that they were receiving subpar care in these clinics in Albania and Slovakia and Georgia, where there were issues with egg retrievals. Whereas if they get an egg retrieval in the US, they're getting 20 eggs or a dozen eggs. They do it at those clinics and they get one or two. And that means that in order to bank enough eggs to do MRT, they have to do multiple cycles.

22:04Megan Molteni: And that adds more costs because every cycle is a couple thousand dollars. And so their expectations were pretty mismatched with what they were getting in reality.

22:14Daniel Payne: So let's come back to here in the U.S. Because there is a congressional ban on procedures perceived as manipulating embryos, that means that MRT is currently banned in the U.S. But as experts you spoke to pointed out, this lack of regulation has ripple effects on the amount of data we can gather from these procedures and the lack of regulation of the fertility industry. Can you tell us more about that? Yeah.

22:42Megan Molteni: I mean, it's pretty interesting. So one of the scientists who's the pioneer of one of these mitochondrial replacement techniques, his name is Shukrat Matalapov. He's at Oregon Health and Science University. And he was the first one to show that it was feasible in non-human primates. He was then deep in conversations with the FDA about doing a clinical trial of this in the US to prevent mitochondrial disease transmission for families with a history of it. And they were in the final phases of that. The FDA had asked for some additional experiments. They were conducting those. This was at the end of 2015.

23:20Megan Molteni: And then this rider was inserted into a funding bill. And this was done by the anti-abortion, anti-embryonic stem cell crowd. So that just cut that program off at the knees. And so that would have been an opportunity for a clinical trial of this that could generate evidence with regard to its safety and efficacy. And it would have been the first time that the FDA would really have claimed some authority over the IVF sphere. Like currently, it really just regulates the drugs that are used for the hormone stimulation during egg retrieval. But this whole IVF add-on that I talked about, the FDA has taken an entirely hands-off approach on that.

24:04Megan Molteni: And that has allowed that to really proliferate here in the U.S. And so, you know, bioethicists looking at MRT felt like this was a really big missed opportunity, both in terms of regulation, but also in terms of the science. The U.S. is the largest funder of biomedical research, and the resources to do those kinds of large-scale studies are less available in other parts of the world. And so to the extent that there have been human studies, They've been small. They've been pilot studies. They've been in places that have a little bit more regulatory laxness, like Greece, like North Cyprus. There's also bans on federal funding.

24:42And so Metalipov and others working on it in the U.S.

24:46Megan Molteni: have had to continue that research with private funding. So all that is to say, that has contributed to the lack of evidence for this procedure. And I think into that kind of void, businesses looking to make some money have been able to step in.

25:04Daniel Payne: So as you started reporting about this company, IFG, they actually took down any mention of MRT on their website. It looks like they're currently, at least for now, not accepting any more clients or customers for MRT services. Do you think that this program will be truly closing or will it just move more underground?

25:23Megan Molteni: Yeah, I can't say exactly where this company will land. My understanding is that they are looking to hire an embryologist who is proficient in mitochondrial replacement techniques to replace the person who was doing it for them. He actually, on the same day that our story came out, he announced on LinkedIn that he's retiring from embryology altogether. So I think certainly there are a limited number of people in the world who have been trained in this and know how to do it. And to some extent, that is a limiting factor right now. But I've heard about there being other operations in Mongolia and in Kazakhstan.

26:16Megan Molteni: And so I think as long as there is this desire for genetically related children, the inability to meet that desire by the standard fertility industry and people willing to spend money to try it out, like I think we'll continue to see this. And I think that reality is creating some urgency with regard to scientists and ethicists renewing a call to regulators that maybe we do want to really study this in the fertility context, you know, renewed debate that is being stoked both by emerging data from some of these pilot studies, but also by the birth of this for-profit industry. And so the thinking is if people are going to be out there trying it, if people are going to be out there offering it, you know, maybe that should create a regulatory environment that would be friendlier to running clinical trials of this technology in the fertility context.

27:11Megan Molteni: Because although the biology suggests it wouldn't work specifically for age-related infertility issues, there is this whole other subset of infertility that scientists think it actually has a higher likelihood of working for. So these are younger women, but who have a history of failed IVF. Their embryos aren't developing, their eggs aren't maturing, various places where the IVF process is failing for them. I think scientists will be learning that there's probably a set of mutations that is driving that, and we'll probably get to a place where you can find out if you have one of these mutations for which MRT might be a good option.

27:50Megan Molteni: There's one trial getting underway right now in Belgium. And what I'm hearing from researchers and ethicists is that there should be an environment that is fostering large-scale clinical trials of that so that we can know whether it works and we can understand what the long-term health impacts are.

28:16Daniel Payne: Megan, thank you so much for joining us. Thanks, Elaine. That does it for another episode of The Read Out Loud. Our podcast is produced by Rachel Gottbaum. Our senior producer is Alyssa Ambrose. Our executive producer is Rick Burke. And our theme music is by Brian Joel. We'd love to hear from you. Tell us what you like about this week's episode, what you didn't like, and how late you stayed up on Tuesday night watching the election results. You can do all that by sending us an email at readoutloud at statnews.com. and if you like what we do leave a review rating on apple podcasts or wherever you get your podcasts see you next week