Exploring Approaches for Addressing Age-Related Female Infertility

Hello listeners, welcome back to the podcast "Disease Versus". Today we're tackling a topic that your future self-might thank you for listening into. So sit back, relax, stay tuned and we'll get stuck straight into it. Okay, so imagine this. You were tired, you've built your career, you've traveled the world and now you're finally ready to have a child. But slowly you realize that perhaps it's not quite that easy, you know, months might go by and nothing happens. And that's the reality for an increasing number of people and much of the time it does come down to age-related female infertility. Yeah, so I think most the majority of us kind of grow up being told to have kids later and to worry about it later. I think what most people don't realize is I think the reality of that and the actual biology and science of age-related female infertility and the fact that it doesn't always corporate with us. So people with Obreas, which we will refer to as females for this podcast, have a limited number of eggs and both the quantity and quality of those eggs will naturally decline as we age and that's significant, especially after 35. And this is natural of course, but it's inevitable and it makes it harder to conceive. Yeah, totally agree, Lincoln. So I was doing some research and I found that the Australian Institute of Family Studies found that the average age of first-time mothers actually rose from 26 to 31 over the past three decades. Oh wow. Yeah. And I'm just kind of strolling how society has changed right? Yeah. And more people are delaying their parenthood to focus on things like their career, pursue higher education, or just simply enjoy life a bit longer before settling down. Yeah, and look, like I think that gap between you know what biology expects as you said, Linkar, and how we live our lives as you said, Govind, creates this growing challenge right? Yeah. And that's where science steps in you know, are helping people protect or extend their fertility. Yeah, that's right. So in this episode we're asking what nutritional, pharmacological and fertility treatments can I guess low or compensate for age-related female infertility? And so to explore this question, we'll first look into the science behind the Mediterranean diet, vitamins and some awesome antioxidants. Yeah, definitely. So then we're going to shift gears and take a deep dive into what solutions pharmacology is coming up with for delaying age-related female infertility. Yeah. So we're going to closely examine our particularly exciting drug, called rappermysin, which is actually being used in a clinical trial ongoing right now. Yeah. And then for wrapping up, we quickly explore the issue from a new perspective and consider whether we can not only delay age-related female infertility around, but address it in a different way and through fertility interventions like IVF and then freezing. Yeah, yeah. So look, if you've ever wondered whether there's a quote-unquote right time to have kids or how to even just keep your options open for the future, then this episode is for you. Perfect. Let's get started. Okay. So let's dive into the nutritional interventions and how nutrition can I guess slow age-related female infertility. So first, the Mediterranean diet. This is a huge factor when it comes to fertility and I think general health as well. Right. So I've actually never heard of it. What is it, Linger? So the Mediterranean diet is a way of eating. So it's a diet consisting of lots of vegetables and fruits. Okay. So it's low in meat compared to the normal diet, I guess. And apparently it has many benefits on human health outcomes of IVF and age-related infertility. Yeah, well, that's really interesting, right? Because there was a general article by Carrianna Edel in 2018 that found that the Mediterranean diet helps increase the chances of successful pregnancy for women undergoing IVF, right? Yeah, exactly right. So that study you're talking about, Joel, was trying to link and kind of understand the association of adhering to the Mediterranean diet and relating that to the outcomes of IVF. So interestingly, the young women who better adhere to the Mediterranean diet had better IVF outcomes. So it was actually really evident and interesting to see that better adherence to the Mediterranean diet had better outcomes. Wow, that's that's actually quite interesting. So the Mediterranean diet is not only important for the general health, but it also can delay age-related female infertility and improve IVF, right? Yes, and look, I've also heard that the Mediterranean diet is, you know, rich in antioxidants like vitamin C, which contribute to better reproductive health by serving as kind of this protective factor against oxidative stress and the damage it causes. Yeah, you're so right. So essentially, I guess eating healthy has many positive effects on health and can delay and improve age-related female infertility. And I also want to touch on vitamin C now that you've mentioned the job. So vitamin C is an antioxidant, which basically is like a little guardian of the body. So it protects your body and eggs against the unstable molecules that are produced naturally in the body called reactive oxidant species, also known as ros. So the guardians in the body, the antioxidants, like vitamin C, protect the body and eggs from ros damage, which is oxidative stress. Right. Wow, so vitamin C is important for improving age-related infertility because it reduces the oxidative stress from ros. Yeah. And so essentially, I'm guessing, damages the body and decreases the quality of the oocyte, which is more commonly known as eggs. Yeah, I spun on. So the take on message for everyone is that antioxidant rich foods, the Mediterranean diet and vitamins can help with infertility by reducing oxidative stress and increasing oocyte quality. Right. So I really do think that eating healthy and a balanced diet are, you know, really underlying factors for many things, not just age-related fertility, but also the general health as well. So it reduces the risk of diseases such as cancer. Yeah, yeah. That's exactly right. And, you know, I think it's as easy as just even eating a bit more greens and less animal protein right, to kind of constitute one of the solutions to age-related female infertility. Yeah. And like Linka said, it's like a balanced diet, like vitamins and low less meat is a long-term solution. And it allows you to take advantage of the many benefits it has for health and fertility. Yeah. Yeah. So the Mediterranean diet sounds fantastic, right? But look, my favorite part about it would definitely have to be the red wine. So look, it's not just the fact that, you know, I love my Friday night sure as, but also the fact that there there was some awesome stuff in red wine. No, look, I agree, but personally I'm not a red wine girl. Yeah, fair enough. But I love this mix of it, but I shouldn't be not talking about the alcohol, but no, no, no. So one of my favorite molecules in red wine is it's probably resveratrol, which is another awesome antioxidant with a pretty awesome name too. Yeah. And look, I'm just going to preface quickly. For the listeners, I don't recommend drinking insane amounts of red wine just for the resveratrol. But look, even so, resveratrol, it's kind of awesome. Yeah, wait, I remember there was this paper looking at resveratrol and fertility. It was published by Lille and Collewein, these colleagues in 2016, right? Yes, yes, that's the one. So the research just gave resveratrol to the drinking water of young mice for up to 12 months. And in the mice that were given resveratrol, their fertility lasted longer. And actually, in the eggs of these older mice given resveratrol, the eggs look very, very similar to those of younger mice. Yeah, wow. That actually sounds pretty cool, Joe. So I'm guessing I'm going to guess should we all go out and start drinking red wine? Well, I wish we could. The water of the mice were drinking had a much higher concentration of resveratrol than a red wine. And look, your liver is definitely not going to thank you for drinking the lead as a red wine on a daily basis. But there is still a lot more to explore when it comes to resveratrol. And we've got to remember that this is all happening in mice, right? This results. And so not humans. And the processes that are occurring in mice, underlying this might not exist in us or work in the same way. But like, but even so, it is really cool to see that an antioxidant can have such a profound effect on fertility. Yeah, for sure. There's a whole bunch of stuff, oxidative stress, really messes with, right? Including mitochondria, which you might remember your e12 biology as what the powerhouse of the cell. So Rose basically prevents them from working as well as they should be? Yeah, pretty much. So, you know, mitochondria are like these tiny little micro machines in our cells that basically produce energy. And if you damage them, they start to make stuff that also damages them in turn like rods. So when you have an antioxidant, you can reduce the rose in the cell and prevent the egg from being damaged to such an extent. But I don't get one thing. How can the cell even deal with that defective mitochondria? Is there a way we can treat the problem from the source? Yeah, there actually is. And it's called autophagies, basically like the cell's way of dealing with its broken bits and bots. Oh, okay. Oh wow, that's crazy. So how does autophagie actually work though? Like, is the cell eating itself? Like, actually, you're pretty much spot on. No, great. So, autophagie is, yeah, this cell's way of cleaning up any broken pieces inside it and then recycling into new components, right? Okay. So the usat's pretty much start to gobble up its old and defective mitochondria, yeah? Yeah. And so I'm going to guess you'll produce the less rice? Yeah, that's the idea. Oh, okay. I think I'd get it. So we want the cell to eat itself. Cause. If I'm thinking, right, if I broke my finger, I definitely wouldn't be chewing it of my hand, right? No. Right. Okay, so I guess cells and eggs can deal with ruzz with either antioxidants or type of food? Yeah, absolutely. You know, the, the reaction is also this drug called rapamysin, which is honestly just awesome. So in 2017 and Dow and colleagues showed that most taking rapamysin short term had a longer ovarian lifespan and their eggs were much higher quality as well. But we're still not sure how these effects happened, right? Yeah, yeah. Although, a clue might be the fact that rapamysin promotes this process of autophagy. Oh, wow. I actually didn't know that, Joe. So, but I got a question. How does rapamysin assist in turning on autophagy? So so basically the drug rapamysin binds this special protein in cells and eggs called mTOR. And look, I know mTOR sounds like a movie title, but look anyways. This mTOR protein is involved in many functions in our cells. But what's really interesting is that the mTOR protein acts kind of like the brakes on autophagy and prevents it from happening. Oh, okay. So if we want to hit the gas pedal, we need to stop mTOR doing what it does. Yeah, yeah. Like your spot on. So that's exactly what rapamysin does. It blocks the function of mTOR and allows, you know, our cells and our eggs to undergo more autophagy. Oh, wow. So if we put it all together, that's exactly what could be happening. So maybe rapamysin might be delaying female infertility by blocking mTOR, increasing autophagy, and destroying defective mitochondria. So essentially reducing oxidative stress. Yeah, like that sounds super reasonable to me. It's already been shown, rapamysin's been shown to preserve ovarian function and female fertility in cancer patients taking hemotheraopinia. So there was a paper published by Goldman and colleagues in 2017 that showed this protective effect right. Look, but of course that's not age-related female infertility. Yeah. But there was another paper by fan and colleagues in 2024 that showed that rapamysin can reduce oxidative stress markers in infertile endometriosis patients too and offer them high chance of IVF success. So look, link to your hypothesis sounds really reasonable. Yeah. But the real question now is what are the effects of rapamysin on mitigating infertility in healthy women? But wait, Joe, now that you mention it, isn't there a rapamysin in the drug they use in that vibrant clinical trial? Yes, yes. So these very researchers at Columbia University are running this trial to see where the rapamysin could delay age-related infertility in pre-menopausal women. So hopefully the researchers are hoping that the drug could decrease the rate of ovarian aging by 20%. Wow. And hopefully increase ovarian lifespan and fertility by up to five years. So look, we're still waiting for results from this trial. It's a trap up next year, but this is seriously so exciting. Yeah, that's huge. Like, imagine this could be the first pharmacological intervention for treating age-related female infertility. That's so exciting. Yeah, yeah, absolutely. And if it does work, the next question will be how? Could it be autophagy and reducing bros? Or yet to find out? Yes. Okay, so we've talked a lot about how pharmacological treatments and dietary changes can aid fertility, but look, honestly, sometimes that's just not enough, you know? So I guess that's where we turn to more advanced options. Yeah, absolutely. So one of the most effective strategies currently is usecrub reservation, which is more called the known as egg freezing, right? Oh, yes. And that's actually not just a backup plant. It's more of a proactive way to boost the chances of future pregnancies. Well, I mean, go for it. You sound pretty keen to cover this topic. And how do you've been digging deep into the research of it on its effectiveness? So talk us through the sides behind it. Yeah. So we all know that fertility in naturally declines with age, right? Yeah. But with frozen eggs, it doesn't age at all. So by freezing eggs early, like around 35, you're essentially hitting the pores in your biological clock. Oh. Yeah. And I also found this study by Mason and Co in 2015. And they found that freezing around 20 mature eggs before the age of 34 can actually give you a 74% chance of actually having one live birth. Well, 74% sounds like solid insurance. Yeah. And exactly. And it's a guess. I guess it's a later like freezing fruit. So if you do it when it's fresh, it'll last way longer, right? Right. Yeah. And essentially later, you can use those eggs and procedures like IVF. And these give women more control of their timelines without giving up too much of their fertility potential. Right. Well, I mean, speaking of IVF, most people know that it's the go to fertility fertility. But it's affecting it's effectiveness does hinge significantly on age, right? Yeah. Exactly. I think I've read somewhere that IVF success rates decline rapidly after the age of 35. Yeah. Yeah. Actually, there was this study by Alpinky and colleagues in 2021 that found that women under 35 have success rates of around 48% for IVF. But when you get to age 43, it plants to about 5%. Oh, wow. Yeah. That's why freezing eggs early can really boost IVF success as using eggs frozen at 30 instead of 40 can significantly improve the success rates, you know, from around 6.6% to over 40%. Wow. Wow. That's a massive jump there, right? Yeah. So IVF and egg freezing can really improve the odds. No, that's way. We kind of just sugarcoded like that. There are some death in those. Well, yeah, you're right. You know, we've got to be realistic about it. Yeah. Yeah, I'm just trying to keep it real though. So first of all, there's the massive cost. Yes. So single egg freezing cycle can sit you back around, I think is around 15 to 20,000. Yeah. And, guys, here's the catch. Many women need more than one cycle. So it's definitely a massive investment. Yeah. And look, plus most women only breathe, be in freezing their eggs after age 35, right? Yeah. So that's where the success rates are already on the decline. Yeah, exactly. And only about 12% of those women who freeze their eggs actually even end up using them. So they go through all this stress, yep, and the expense and all their harm treatment for something that might not even need it. Oh, well, I mean, that sounds like a lot for a quote-unquote "just in case." Yeah, Joe, exactly. And then there are these ethical considerations. Egg freezing was initially developed for cancer patients who might lose their fertility due to treatment, right? Right. But now it's often used to delay childbearing for lifestyle reasons. Yeah. When you put a life that, it does blur, I guess, the line between medical necessity and the lifestyle choices only available to the rich, right? Yeah. So look, I guess, while IVF and egg freezing have benefits, they're not perfect. They're costly, complicated, and their success drops, longer weight, too. Yeah. And they don't necessarily stop fertility decline. They just kind of work around it. Exactly, Linka. I guess they're not exactly a time machine, but they're more like modern science as a vision of hitting the pause button. Yes, that's right. So basically, Planned Smart, Eat Well, and Freeze When It Down, right? Okay, so let's integrate and wrap up everything we've talked about so far. I want to go back to our big question, though. What is the big takeaway when it comes to age-related feeling fertility? Yeah, Joe. So, first and foremost, there are many ways to delay or compensate the effects of reproductive aging, right? But I think what we all agree on is that early intervention is very key here. Yeah, exactly. So, let's start with the simplest tools, lifestyle and nutrition. So we looked at the Mediterranean style diet, incorporating key vitamins and antioxidants, which are basically lifestyle and natural strategies that can, I guess, slow reproductive aging. And plus, they benefit your overall health, too, which is a bonus. Yeah, and the best part is, you know, for healthy people, these changes are low risk all beneficial and relatively easy to integrate in today's life. But there is also, you know, this field of pharmacological options for delaying age-related female infertility, including stuff like rapamysin acting through, you know, oxidative stress or autophagy. Yeah. It's definitely promising, but we're still in the early stages, right? Yeah. And a lot of these exciting findings have come from animal studies. So we can't just apply to human strain away. Yeah, yeah, that's right. But there are these trials like the vitamin clinical trials, and they do have a lot of definitely set us to help us understand how these interventions work in humans. Yeah. And of course, let's not forget about the assisted reproductive technologies. So we looked at IVF and Opsychiroprosimation, which offer options to kind of preserve fertility. And these approaches don't stop aging, but I guess they can help compensate for it later on. Yeah. And, you know, this is important. You know, none of these options are magic fixes. They all work best when you start early, right? So really, if you're waiting until 40 to start thinking about fertility, many of the interventions we've discussed aren't likely to really give any benefit. 100% right, Joel, yeah. So that's why we need to invest in more clinical relevant research, like that vibrant clinical trial. And they go beyond that lab and, you know, go into their clinical studies. Yeah, exactly. So wherever you are in your life or fertility journey, we hope this episode kind of encourages you to think critically, ask questions, and also consider taking action earlier rather than later. Because I think right now there's no kind of guaranteed way to preserve fertility at older ages. And your future self will probably thank you for thinking about this stuff. Well, that's. Yeah. So look, to our listeners, thank you for tuning in. We hope today's discussion has helped shed some light on the science and the strategies behind reproductive aging. So look, until next time. Take care, stay tuned and plan ahead. [BLANK_AUDIO]