How Inflammation Hijacks Your Fertility | Dr. Natalie Crawford

I was dismissed by my own doctors, traumatizing, thinking, how can I be a fertility doctor if I can't even get myself pregnant? I started really saying, what if my infertility is a symptom, that something else is going on in my body? I am Natalie Crawford, a board-certified OBGYN and fertility physician. Nobody talks about mitochondrial health or lowering inflammation. The first chapter of the book is called How Inflammation Hijacks Your Fertility. Even when I announced the book, I still had this narrative that I was using it as a fear tactic. From peers? From peers. If you don't get consistent sleep, that plays in to worsening reproductive outcomes. And they say, oh, I only need five hours of sleep and I can function. You can function, but you're not functioning well. So how much sleep should a woman or man be getting every single night? Okay, great question. So let's try to hit the high points really quickly. There was a study came out that did get a lot of internet press. And let's talk about it a little bit because what you're saying is half true. Raising your eggs is an investment, and it pays off for some women. It's like putting your money in the stock market. I wanna be pregnant soon, what should I start doing? All of these lifestyle factors that we just talked about. But also, number one thing most people are not doing, which is where we need to start to your question, is every single day I have women say, I wish I'd known this sooner because I would have done something different. Natalie Crawford, welcome to the show and welcome to Biohack It. Thank you. I'm so excited to be here. This has been a long time coming. I know. I have followed you for, I think, almost two and a half years when I started my own holistic fertility journey. And you have just been such a beacon of wealth and knowledge and education and cutting through the bullshit with your videos. I have been dying to bring you onto the show. Well, thank you so much. And let's dive in. So Natalie, tell me, where was a time in your life where this journey became personal for you? And you're like, this is what I want to do. This is a career that I'm going to embark on. You know, it's really interesting because my personal and professional life overlapped when I had my own infertility journey, but I was already on this pathway somewhat, meaning I was in OBGYN residency when we started trying to get pregnant. And I already was matched for an infertility fellowship or in that process. I first actually went into emergency medicine. You may not know this. So I did a year of emergency medicine and I loved the diagnostic puzzle in the ER. Somebody comes in, you have to listen, figure out what's going on with them. But what I missed was that personal connection and getting to follow them and see them through to the end of this problem. So I did a year of ER, then switched to OBGYN. And because I still love the diagnostic puzzle. Nothing is as big of a puzzle as your hormones. So I was immediately drawn to reproductive endocrinology because the hormone puzzle of the body. But in training, when we started trying to get pregnant, I was really faced with a shock when after taking care of pregnant women, deciding to go into infertility, we started having pregnancy loss after pregnancy loss. And it was really traumatic and eye-opening because I was dismissed by my own doctors. I was gaslit. I was told to just relax. I was really put in the place where despite taking care of women who had been in this position, when you're in it yourself, everything looks different. And I'm an OBGYN-AMON and I am Googling online and trying to research what am I doing wrong? What do I need to do next? How do I track my cycle? Things that we as women don't learn. When did you learn to track your cycle? Right. Not until you're having trouble. Not until I started. Right? And even as an OBGYN, this wasn't really something we're taught because we're focused on such high-end things, saving lives, surgery. So I started realizing I didn't have the tools, even myself. And if you don't even know what's normal or what you're supposed to do, it's really hard to advocate for yourself. I ended up going into fellowship and starting fellowship, had my third and fourth pregnancy loss, and it was really traumatizing thinking, how can I be a fertility doctor and do this for a living if I can't even get myself pregnant. Do it for myself. I can't even do it for myself. And that was really kind of soul crushing in a moment. At the same time, when you're in fellowship, so you may not know this, it's three years long. You do a year and a half of research and a year and a half of clinical work. And so go get all my testing done. Everything's normal. Have this recurrent pregnancy loss unexplained. I asked, what can I do? And I was told IVF. And I was like, well, what about other things? What about lifestyle or food or this or that? And I was told IVF is the only thing you can do because everything else is normal. Well, I was the clinical fellow in charge of IVF. So I couldn't be a patient because I was the one doing IVF. So I was in this place where I had to wait to do IVF and I didn't really love this idea that nothing mattered. And at the same time, we were choosing our research projects. And everybody does or the majority of people do a project in the IVF lab because it's very controlled and that's what we do a lot of. And I remember going to my fellowship director and I said, I don't want to study that. I want to study natural fertility. I want to know why some people get pregnant and some people don't. I want to know how the world around us impacts our fertility. And they said, well, that's a much harder project to defend. You have to get it published and sit and defend your thesis. So you'll have to get a master's in clinical research. I said, sign me up. I'm there. yes, sounds great. So I studied in fellowship the luteal phase and cycle tracking and vitamin levels, ovarian reserve, environmental toxins. And despite all these different pockets, I saw inflammation over and over again. And despite the fact that we learn about inflammation in medical school as a disease process, you know, once you have endometriosis, you have inflammation, but nobody really talks about it as the precursor to disease and I started really saying what if my infertility is a symptom that something else is going on in my body and what am I going to do about this how am I going to decrease inflammation and as my own in of one experiment started throwing out things in our kitchen based on research on PFCs and toxins started changing how we eat stress levels sleep thinking even in IVF you can only work with the eggs and sperm you're given. So I'm going to do everything I can to have a success. And we got pregnant before. And one of the really interesting things is when I was really learning to listen to my body, I realized that gluten was inflammatory to me. And I was told I didn't have celiac disease, that gluten didn't matter, no food categories mattered is what I was told. But I conceived both my children when I wasn't eating gluten, was eating a very whole food, vegetable rich diet. and then 10 years later got diagnosed with celiac disease. So I think that sometimes we have to understand that the medical system exists as it is based on the research that's available. And just because something doesn't have perfect science doesn't mean that it's not important and that testing protocols are just a starting point, that it doesn't mean that nothing is wrong if everything comes back normal. But that is a very eye-opening experience to be on the other side of the table and certainly has changed how I approach fertility, why I'm so passionate talking about this, but also how I approach patients every day. You know, it's crazy to me listening to, hearing you speak, and for you coming from the inside out, the fact that we have the highest percentage of mitochondrial density in our oocytes and our eggs is like 600,000 to above. And nobody talks, when you go to a fertility clinic or see a fertility specialist, nobody talks about mitochondrial health or lowering inflammation. Right. But that's one of the key baselines of having a healthy pregnancy and obviously going through a healthy IVF cycle. But yet nobody's talking about supporting that and lowering inflammation even before you do a round of IVF. And there's buckets of research. And you'll hear some fertility doctors say people are trying to scare you with inflammation. There's no need to focus on lifestyle. You still hear the same narrative from a lot of people. And why is that? I think because there's a few different reasons. I think one reason is that we see a change in how fertility is practiced. There's a lot of large practices. There's a lot of private equity. There is an emphasis sometimes on making money. And I also think that a lot of times people are trained in medicine. Medicine can be like a cult. You know, you get broken down in training. You are trained to think the way the people above you think. And thinking outside the box is not valued or rewarded. So I think we're living in a time now where thinking outside the box is mandatory. We have patients who are asking really important questions. The world around us is changing. And to still practice medicine like we did 40 years ago doesn't make sense. The first chapter of the book is called How Inflammation Hijacks Your Fertility. And what's so interesting is even when I announced the book, I still had this narrative that I was using it as a fear tactic and that I'm trying to scare women. From peers? From peers. And what's fascinating is that's the opposite, right? Because if you- You're empowering women through it. So women are so smart. If you help educate somebody why this one decision, how it is changing inside their body, what's happening, they're then going to be in a place to really make educated and different decisions. But to your point, there's buckets of research showing that mitochondrial function is very important and essential in both just hormone production, so the granulosa cells that make hormones, in egg quality, so the genetic normalcy, and how your eggs function, their competency. Can they accept a sperm and divide normally? And we have simplified female fertility to be age. Totally simplified it, saying your egg quality equals your age. And there's some truth to the fact that your eggs are in your body your whole life. They do absorb the wear and tear over time. And chromosomes do degrade over time, right? Proteins that hold them apart do degrade. But also this metabolic competency factor, we see that women who are over 38 have more abnormally shaped mitochondria, have more inflammatory products in the follicular fluid inside their eggs, because more women are unhealthy at 38 and above also than they are at 28. So to just say it's your age, you can't do anything about it, I think it's really not serving anybody. Instead of saying there might be some level of chromosome damage based on tincture of time, and I can't change all of that. But what I can change is the metabolic health of my cells, look at the mitochondrial health, thinking about how the choices that I make every single day, how chronic inflammation and insulin resistance are impacting hormone function and egg quality. And it's more than just getting pregnant. Getting pregnant is one piece of the puzzle. Yes. But if we think about the later you go into menopause, improved health outcomes later. So if we can extend your ovarian longevity, if you can help your body make hormones better from your ovaries because you're lowering inflammation levels. Why are we not talking about that? So talking about extending ovarian aging and keeping you out of perimenopause and menopause and delaying that whole process, what is your take on things like mesenchyme stem cells or PRP for the ovaries? Okay, we're going to get into that, but I do think it's important because you and I already talked about this. Preventive care is key. So the first thing we need to be thinking about is, you know, not majoring in the minors, but the big things that are really causing, you know, chronic inflammation in the majority of our cells in our body. Stress and chronic stress can be so traumatic, not just, oh, it's bad for me, but really on a cellular level. Let's think about what happens when you're stressed. If you experience stress, which I know you and I both have in the past, your body goes into this fight or flight response. Cortisol is known to be an inflammatory hormone, but the reason why is glucose, which is the fuel for your cell, is freed up from your liver. And this is because if you saw a bear, your body wants that glucose to feed your heart and your lungs and your muscles so you can run away from it. But we're not running and using up that glucose. We're just exposed to the bear. But your body is wired so that glucose is broken down from the liver, goes into your bloodstream. It's ready for you to use. But stress now happens in conversation, at our computer, at our phone, in a relationship, at work. And we're not using that glucose. We're just elevating our blood glucose. We're causing insulin resistance. Chronic stress can cause insulin resistance. This means your body now can't use that glucose very well. And high insulin levels in your body then cause you to put on fat in the midsection. They actually change how your ovaries make hormones directly. So you see this hormonal cascade happening for your reproductive hormones directly from chronic stress. And that doesn't even count for the fact that it changes how your hypothalamus in your brain can even interpret or respond to hormones. It's your control center. It says, Iman has too much going on. I'm not sure she can be pregnant right now. So my protective mechanism is going to be to change what's happening. It causes interference right at the level of the brain. As someone who's always drawn to wellness products that are simple, effective, and actually help you understand your body, which is why I'm so excited to share the Hormone Zuma by Vibrant Wellness, a company I love and trust. It's an advanced at-home test that gives you real insight into your energy, mood, and overall balance. That's why I trust Vibrant. It combines standard of care labs with genetics and innovative biomarkers backed by over 400 researchers and more than 40 peer-reviewed studies. I took the Hormone Zoomer myself and finally getting clear answers behind signs and symptoms I'd always blamed on stress or too much travel, which was extremely empowering to me. It measures up to three times the markers of typical hormone panels, including hormones, adrenal and bone health, oxidative stress and endocrine disruptors and toxins like glyphosate and phthalates. Essentially five tests in one. And with Vibrant's network of over 30,000 trained providers, you get expert interpretation and a plan that makes sense for your body and your needs. If you're ready to understand what your body's been trying to tell you, ask your provider for the Hormone Zoomer or find a Vibrant certified provider at vibrant-wellness.com slash biohackit. because understanding your body changes everything. So how important would you say is somebody having a regulated nervous system and a woman feeling safe in her body and her environment? I think it's one of the top things that we don't talk about that needs to be done for longevity, for hormonal health, for fertility. Because this is really your body is made and wired to protect you first and foremost. It wants to feel safe and protected. It also, I would say it's like a toddler sometimes, It wants to know that it can rely that we're gonna get the things that we need. We're gonna get the nutrients we need. We're gonna get the sleep that we need. We know that even for every hour of sleep that you don't get, we see pregnancy rates go down. We see decreased- In men and women? Men and women. We see sperm counts go down. We see fewer eggs with IVF cycles when you get less sleep. And we know that sleep variability has a negative impact. If you don't get consistent sleep, that plays in to worsening reproductive outcomes. So how much sleep should a woman or man be getting every single night, especially if they're trying to conceive? This is great. At least seven hours. That's the low end. Really, the perfect amount is going to be closer to seven and a half to nine hours of sleep. The vast majority of people are not getting that. Most people are getting under seven. Over a third of people get under six hours of sleep on the average night, which is a huge number to me and startling. And I see patients wear this like a badge of honor. They say, oh, I only need five hours of sleep and I can function. And I sit here and think, you can function, but you're not functioning well. You're setting yourself up for a day where you're already in a deficit. Sleep is when your body heals from inflammation. It's when your body's able to lower some of that insulin resistance, become more sensitive. It's really important for hormone production. So cortisol and melatonin go hand in hand, but also your gonadotropins, the hormones sent out from the pituitary that talk to the ovary, FSH and LH, they're released in the early morning hours after a certain amount of sleep. So if you're cutting your sleep cycle short, you're also impacting your brain's ability to send out hormones. And yet we know that when you're stressed, you also tend to sleep less. It becomes this really nasty cycle where I always say the foundation of your day, the number one thing most people are not doing, which is where we need to start to your question is focusing on how do we reduce stress? How do we get better sleep? And how do we move our body in a way that is hormonally friendly for us? And those tenets is where we need to start first if we want to be thinking about hormonal health and longevity. Talking about sleep for a second as well, do you follow this idea of the, you know, the Chinese cycle of like certain organs regenerate at certain times during the night, therefore you have to go to bed by a certain time? I do think our bodies are meant to work in a certain way. And certainly your body's going to prioritize organs that it views as more important. But also what's so nice is that your body loves the sun, right? In the sun cycle. And when the sun goes down, those are the cues that your body should go into a rest and a heal state. And when the sun comes up is when you naturally are going to be at a more energetic state. Modern world is incredible, but we're on devices. We have artificial light. People stay up so late. And so thinking about our circadian rhythm and how we're timing our sleep, how we're exposed to sunlight in the morning, getting enough sleep for all of our organs to really get to a state of healing and balance, that's really important because we're cutting it short. We're making an active choice to start our day in an energy deficit and with inflammation on board. And that's a recipe for disaster right there. And that's why I always tell people, my show is all about telling you guys to fix your baseline health, the things that are free, your sleep, what you're consuming in your body from the media to your relationships to the food that you taking in Fix those things before you invest in a super expensive supplement or a cold plunge or anything else Exactly And we can talk about like the fancy little add I love some of these and there exciting things coming but for the average listener we have to rewind and we need to start with the choices we're making on the free stuff, how we're sleeping, how we're dealing with stress, how we're moving our body before we start going into some of these other things that might make a really good impact. But none of that, none of that money is going to be worth it if you're sleeping five hours a night. So if somebody comes to you and they said, you know, Natalie, I want to do a cycle in, I don't know, two, three months, or they, you know, become a patient of yours, where would you start them? For anybody listening, they're like, we want to start trying naturally, or we even decide to go for a round of IVF because we want to test our genetics or something like that. What are the baseline things that they should start with? So we have sleep, we have diet, reducing stress. Is there anything else they should be supplementing with or taking into account? Okay, great question. So let's try to hit the high points really quickly. So number one, we already mentioned sleep, at least seven hours per night, really trying to have a good circadian rhythm, good timing, and making sure your sleep environment is conducive to this. I love a sleep mask, a sound machine, a cool temperature, a weighted blanket. Also, your partner matters too. If you sleep in the bed with another human, we can't ignore the fact that if they're staying up hours later and coming to bed. It's one, disrupting your sleep pattern. But two, it's impacting their reproductive health too. So if we're talking about a man coming, sleep is essential for male fertility and male hormone production and sperm production. So fertility is a team sport. We need both people to come to the table here. Number two, stress. It's really unrealistic for me to sit here and say, let's live in a stress-free world. That's not. We wish that was true. Right? But that doesn't mean that we just take it off the table and say stress doesn't matter or my least favorite don't stress about being stressed i think we have to say the world is stressful how am i going to build into my day protective mechanisms to combat this so number one i recommend at least 20 minutes a day of time to drop your cortisol which is seeking that feeling and we're all wired a little bit different and it doesn't have to be the same thing every day but this could be feet in the grass time outside a walk journaling red light the sauna acupuncture yoga meditation mindfulness therapy calling your friend you know there's many things they all do not involve your phone or the internet they're a disconnect from they're free yeah they're free things that you can pay money for things but it's going to be what can you show up for how can you show up for yourself in those 20 minutes that day, and you're searching for that cortisol release. So that's number one. The second is back to this idea about the bear. Because we have baseline stress, we have chronic stress. We also have these really, you're going to fight with your partner. You have a bad meeting at work. You come out of a fertility appointment that's terrible. And you can feel yourself stressed. You feel the anxiety. What I want women to think is, okay, glucose is now in my bloodstream. Okay, my body thinks there's a bear and there's not. And what we know is we already talked about is glucose levels are going to raise. Insulin is a hormone made from the pancreas that allows glucose into the cell. When your body is meant to eat food, have glucose spike, have insulin released, glucose then goes into your cells and comes back down. So this is meant to be this really beautiful system. But when you're chronically stressed- It's staying up there the whole time. Yes, it's staying up there. And then you have these other stressful encounters. The pancreas doesn't know the difference. It sees glucose, sends out more insulin. So then your cell is getting what we call insulin resistant. To simplify this for people, because I think sometimes they zone out when they hear this term, they say, I don't have diabetes. It doesn't really matter to me. Correct. But a lot of people are insulin resistant and they don't really know it. If you had a salesman coming to your door every single day, same time, what would you do? Stop answering. You're like, go away. Go away. I'm not answering. That is what your cells are doing when they see insulin coming. So when insulin comes every single day, all the time, constantly released, your cell says, I am not answering. I'm not going to let glucose in because I'm sick of this salesman. So your body has to send out more insulin. So the salesman can bang on the door really hard, and the cell finally goes, fine, let it in. And as we talked about, that high insulin makes you deposit fat, that visceral fat under your organs, changes ovarian hormone production, worsens inflammation and creates this cascade. Well, back to the fact that your muscle, so we didn't even talk about really movement and exercise. Exercise can have a lot of benefits. It can help with the stress pathway, of course, but also building and using skeletal muscle is the number one thing that women are not doing enough. Your skeletal muscle, if we want to be very simplistic, we don't have to talk about longevity and osteoporosis and other health benefits. Muscle has a transporter in it called GLUT4. And this is like giving glucose the key to the cell that doesn't need insulin. So if you build skeletal muscle and you use it, your body can now use glucose without needing insulin. So then your glucose levels can lower, and then your insulin levels can lower. So when we say we can fight insulin resistance by building muscle, this is what I mean. We now have the key to lowering this insulin, fighting against visceral fat, decreasing inflammation, but you have to build it and use it. So if we walk back to stress and you see a bear. Glucose is released into your body. Well, most people are going to stress eat or drink or scroll on their phone. They actually do things to worsen the cycle. But if we get up and we take a quick walk or we do some squats. Or call a friend. Call a friend. But really, if we use our muscle in some way. So if you move around and use some skeletal muscle, we can get that glucose into the cells really quickly, lower it, stop this insulin stress cortisol cycle. And also using skeletal muscle releases dopamine, which can counter some of the stressful event. So that's one thing that I never learned until much later in life, saying, if you have these stressful moments, take a couple minutes out, use your muscles, you know, even if you're just right there at your desk, do some squats, do something, anything, say, okay, I'm going to get that glucose eaten up. But these are little tools that we're not taught or talked about. So thinking about building muscle, how we are going to build in protective mechanisms against stress, but then also what are we going to do when we are stressed and getting more sleep? Second part of your question is diet. We know that diet is one of the top causes of inflammation in the body. And we can talk about diet the entire episode. Your gut health, your gut microbiome is very important in hormone production, very important in controlling your inflammatory levels. and your gut microbiome, its food is fiber. So we live in a really protein obsessed world and protein can be, is very important, but fiber is what feeds your gut microbiome and it's what's actively going to fight against inflammation. So fiber is found largely in those fruits and vegetables that have lots of antioxidants and other nutrients. We also can see fiber in protein based sources that are vegetable based. So your legumes, your soy based products, what doesn't have fiber is going to be your animal meat. And that doesn't mean that animal meat's off-limit, but it does mean we need to balance our diet much more effectively. And we need to avoid things that only cause inflammation, especially with limited nutritional value. Your altered processed foods, your added and artificial sugars, your processed meats, you know, and when it comes to meat or animal meat, we need to be very careful about where it's sourced from and how much we're consuming. Because it can be inflammatory as well. It can be highly inflammatory. I mean, especially red meat and especially with certain conditions, like endometriosis is a good example. So I think paying attention to the foods you're putting into your body, the vast majority of people are just not eating enough fruits and vegetables, to put it simply. And anybody who tells you a banana or an apple is bad for your health is just wrong. It's just truly wrong. When it comes to your hormones, more servings of fruit, specifically fruit, increasing your fruit servings, increase your fertility. That's done in big prospective studies. And how much fiber should somebody be taking? At least 25 grams of fiber a day is the minimum of what people need. And we see that a lot of people on the standard American diet get less than 10 grams. So huge difference there. So really these subtle shifts, which doesn't have to be huge, but thinking about eliminating things that are toxic, building a base of a diet high in whole foods, fruits, veggies, legumes. and then you can, there's nuance with, are we sensitive to dairy? Are we sensitive to gluten? If you're struggling with inflammation, so if you feel- Well, sugar, we know you're going to be inflamed. That one needs to go. But when it comes to some of the dairy and the gluten, there's a lot of people with sensitivities, even if they don't have true lactose intolerance or celiac disease that I recommend, especially if you're falling into infertility, unexplained infertility, low ovarian reserve, you do a trial of removing them and see how you feel. And if you feel better, you're probably sensitive to it and should keep it out of your diet the majority of the time. And if you don't notice any difference, then it's probably neutral to you. I'll say this about diet for the average person wanting to do IVF or to get pregnant. The goal is to set your core diet away that you don't think about this all the time. You're eating anti-inflammatory most of the days, most of the time. And this gives your body the nutrients and the tools it needs to fight against inflammation, but also to say, hey, if I go have cake on my birthday, I can now process that inflammatory burden and get back to baseline much easier because I don't have this inflammatory burden at baseline that's so much higher. So the difference there is how we're structuring our life with an anti-inflammatory approach. And I think sometimes toxins get left out of the discussion. I was going to ask you, what do you think one of the biggest things for disrupting female hormones is right now? Like what is the biggest disruptor? I'm going to think that, well, twofold. Things that we're adding in is going to be in your kitchen products. This is largely going to be in to go. What I'm seeing right now is to go containers, right? People are starting to swap over in their kitchen. You know, nonstick pans are a huge one. Cutting boards. Cutting boards. There's still a lot of plastic in kitchens that we really should get rid of. people are still drinking hot beverages out of to-go containers that have plastic in them and even if you get something from somewhere switching it over to a better container is better than nothing right we have to make the best decisions which we can you can't eliminate every toxin to live in that world really is going to drive you crazy but we have to say that doesn't mean that none of them matter we know that these forever chemicals your pfcs this is what i did a lot of my research and fellowship on these are probably some of the most concerning because they live in your body, they build up and they can impact your endocrine system, how you make hormones. So we really want to be mindful that's in your nonstick coating, a lot of your food packaging and wrappers, but also it can get through the soil and into your water system. So I think your kitchen's a great place to start, but also the water you're drinking, I recommend a water filter, making sure that it is filtering out what's in your area. And you can actually go to the EPA, they do a really good job of you can put in your zip code, see what's in your water. You'd be shocked by the results. It's crazy. It's wild. But also you can see what type of filter you need. So it's really great information, but you don't know this unless you go look for it. Air filter for your home, we're exposed to so much ambient toxic exposure, both with air pollution, depending on where we live, fragrance, other people coming in. But the biggest toxin that I see impacting health right now is actually what I call behavioral toxins. So alcohol, cannabis use, and smoking cigarettes and nicotine. These are things that we're choosing to do. And I hear this narrative every day. So-and-so did it and they're fine or this N of one. But if you're looking to optimize your reproductive health, your hormones, your sperm count, we've got to start by eliminating the things that we can control. So the top thing that I'm seeing is cannabis use. And even by just the male partner significantly impacting the ability to get pregnant. So we know that if the man is using cannabis, we have decreased testosterone, decreased sperm production. We're also seeing longer time to pregnancy. Most concerning to me, though, is going to be the higher rate of miscarriage, even if the female partner is not using or not around it. This is showing us direct damage of the sperm DNA. I also find men will have normal sperm counts on semen analysis. And I told you this story before we started. But I am seeing patients who, when they're going through IVF, everything looks relatively normal from a male side. And yet when we are in the lab, all the embryos stop developing on day three when the male genome kicks in. And when we go back and talk about it, more times than I can count, I have a male partner now endorsing that they're using cannabis in some form. And they didn't disclose it prior to. Oh, so their sperm counts were normal. So they're like, it's okay. It wasn't that big of a deal. But this is telling us it is a big deal. A semen analysis is only telling us count, movement, shape. It's not telling us about the DNA inside the sperm. And so when we think about what a sperm has to do, yes, it has to swim and get where it needs to go and you need to have enough of them, but its real job is to protect that DNA. And unlike women who have their eggs inside their body their whole life, sperm are created. They're brand new created. 1,500 sperm a second. So this is completely influenced by your environment. That DNA is packaged into a sperm head. And the sperm life cycle is only about three months in total. So it takes about 72 days for sperm to be made in the testes, then about 18 days for it to get out the ejaculatory system. So that means a single change right now can influence things. Three months from now, we can have a very different sperm count if we make life changes right this second. For female fertility, it's not quite that profound, right? We can improve things, absolutely. but we can't see such a reversal as we can for men. So the top toxin I'm seeing is actually going to be cannabis. I'll say this last thing you asked before is about for women. The egg lifespan, yes, they're in your body your whole life. I like to think about them as kept in a vault inside your ovary. However, we know that before you ovulate, the 290 days prior to when you're going to ovulate, the eggs are going to start to be reactivated. I like to think about them as getting lined up to come out of the vault. And the 60 days prior to ovulation is that true follicle cycle. So I often have women say, well, it's too late to make a difference because my eggs have been in my body my whole life and I did all these crazy things, so I can't change it now. And I want to counter that and say that's inherently a false narrative. Yes, maybe we can't undo everything we've done in the past. We can't rewind the clock. But we should feel like we're in a position of power to influence the eggs that are coming out of the vault now. And that is why focusing on all these things that maybe seem small individually, right? Oh, Natalie said get more sleep. But when we put them all together, this is hugely changing how we face our day-to-day life, how much inflammation we have. How we respond to stressors in our life. Exactly. These things matter a lot. And so this is what I want. No matter if you're doing IVF or you're trying to get pregnant, this to me is must do. When I always say, I give you data and you make decisions, so you should know, though. Where I take problem is this idea that people aren't given this data. They're not explained it. So how can they even make the decision to make these changes? If they don't know. Yes, or they're in the position I was. We said, oh, it doesn't matter. That's an inherently false narrative because they do, in fact, matter. Last thing I'll say is I do think women should start tracking their cycle before they want to get pregnant. So if you are in the stage where you say, I want to be pregnant soon. What should I start doing? All of these lifestyle factors that we just talked about. But also, are you ovulating? And tracking your cycle is more than just marking day number one in an app. Really thinking about when are you ovulating? Do you know what your fertility signs are, your cervical mucus, your body temperature, your hormones? And what are some of those signs? Yeah. So really quickly to understand these signs, let's talk about just what happens very briefly with your hormones across your menstrual cycle. So I always like to think about you have a group of eggs coming out of that vault. Each egg grows inside a follicle. The brain sends out a hormone called FSH or follicle stimulating hormone stimulates one follicle to grow. As that follicle grows, it makes estrogen. This is our follicular phase, time when a follicle grows. We love estrogen. The female body thrives off of it. So as estrogen levels rise, you feel your best, you have more energy, more concentration, increased sex drive, you're doing great. That estrogen is actually what tells the brain that you have a mature egg. People don't think about it, but your brain doesn't see what's happening in your ovaries. It is relying on your hormone to be a communication system back to the brain. So when it hears a strong enough estrogen signal, now it sends out a surge of a hormone called LH. LH, your luteinizing hormone, tells the follicle that the egg grew in to rupture, allows the egg to be released. It's captured by the fallopian tube within 20 minutes. It's crazy. It only lives for 24 hours if it's not fertilized. But I digress. The follicle reforms and becomes a corpus luteum, which now makes progesterone. And this is now the luteal phase. So in the luteal phase, the brain sends out pulses of LH, telling this corpus luteum to make progesterone. It can only live for about 12 to 14 days unless you get pregnant. Fun fact is that the pregnancy hormone, HCG, structurally is similar to LH. So it can bind to the same receptor on that corpus luteum and keep it alive. we call it rescuing the corpus luteum. But if you don't get pregnant, corpus luteum dies, progesterone drops, you'll get a period, all the eggs that weren't chosen to ovulate die, and you have another group coming out of the vault to start over So thinking about that information allows us to step back and think about these fertility awareness signs So number one one of my favorites is going to be cervical mucus This is probably one of the most underutilized signs but we know that if you are tracking your cervical mucus, you have a twice as high likelihood of getting pregnant. So cervical mucus is based on the idea that the cervix is the entry point to the uterus, and it's meant to prevent anything from getting inside. So it is usually thick or creamy and you're not even quite aware that you have it. But as estrogen gets higher and your body is preparing to let sperm through, the cervical mucus changes. And your type 4 cervical mucus is seen with peak estrogen levels. And this is going to resemble an egg wipe. So it's sticky or stretchy, kind of clearer. You'll actually notice cervical mucus when you go to the bathroom. You don't have to insert fingers or do anything, you just wipe before you go to the restroom. Look at the toilet paper, and if you have anything that resembles an egg white, type 4 cervical mucus. So intercourse on a day with cervical mucus has the highest odds of getting pregnant. So if you want to get pregnant, boom. If you're just trying to say, well, when do I ovulate? How long is my follicular and luteal phase? The last day of your type 4 cervical mucus is considered your ovulation day. So it might be a single day, but if you have two or three days, mark that last day as ovulation day. Second is going to be urinary hormone monitoring. So we call this OPK or an ovulation predictor kit, which is a urinary LH hormone. Although to be honest, there's some very expensive hormone systems that check LH in addition to many others. They check estrogen, progesterone, metabolites. Those are fine. They're great, but you don't need something that fancy. You can just use an LH only test. And these resemble a pregnancy test where you pee on it and you're trying to capture that LH surge. Remember that LH will be pulsed the whole luteal phase. So you're just trying to see when did it go from negative to positive. So you want to start them four or five days before you think you're going to ovulate. Use an OPK one time per day. I recommend between 10 a.m. to 2 p.m. because LH, as we talked about earlier, release from the brain in the early morning. So you want to give it time to get through your kidneys and get into your urine. But the day of a positive LH is the day before you ovulate. So if you're trying to get pregnant, we say intercourse day of the positive and the next day. And then if you were just marking ovulation, it would be the day after the positive. And then lastly is basal body temperature, BBT. Premise here is that the corpus luteum, when it makes progesterone, progesterone is fascinating, but it totally changes your body temperature. Yeah. Your entire metabolism, you are shifting to go into gestating mode. It is the pro-gestational hormone or the pro-pregnancy hormone. So your body temperature is going to rise at least 0.4 degrees Fahrenheit when progesterone is made. So if you can capture when progesterone has risen, you now know that you have ovulated. There's some nuance about when it was at its lowest and when did it cross the threshold. And I used to say, as somebody who lived and breathed BBT back in my own days, that it's really hard and can be very stressful. And I will amend that statement now because with wearables, we live in a really different world where you have natural cycles pairs with your Oura ring. There's other options where you can get these micro temperatures throughout the day and they have such high sensitivity for actually knowing when your shift is happening. So this is one that I love and it's a little bit more passive because this is where technology really makes it easier for us. You don't have to use all of these, but any of them can improve your detection of ovulation. If you're trying to get pregnant, using any method of fertility awareness will get you pregnant faster than using none. And using two has the highest rates of getting pregnant. So pick what works for you, but have some awareness. And what I'll say is that many times people just dismiss the menstrual cycle. It is really one of your first or your biggest outward signs that your hormones are communicating properly. But you have subtle changes before things get crazy wonky. And I always say there's this spectrum of ovulation. Perfect cycle. There's a textbook, perfect cycle. But then there's stages of ovulatory dysfunction. So if the first stage might be a short luteal phase, that's typically the very first sign of ovulation disorder. So that's a luteal phase that's 11 days or less. But if I just say, Aman, do you have regular cycles? And you say, yes, I actually don't know anything about your luteal phase. The second stage is actually having a longer follicular phase. So it's starting to lengthen out. You're getting those longer cycles. But again, if I say, Aman, do you have regular cycles? You're going to say yes, and we're going to miss it. The next stage goes into that really more irregular i don't know when it's coming right kind of stacking on to every few months and then amenorrhea or absence of a period but the biggest time for intervention are these subtle cycle abnormalities that you need to be paying attention but you have to know when you're ovulating to know how long that luteal phase and that follicular phase are and definitely if i tell you one of the biggest things i'm looking for is i'm concerned about any change from your baseline. Okay. Okay. And we change from baseline, meaning a longer ovulation window, a shorter ovulation window. Exactly. Or my periods used to be every 28 days and I would ovulate on day 13, but now they're 25 days and I ovulate on day nine. But you have to know what's normal for you to tell me about this change. And this is not, not to get on this pathway, but this is where I do think hormonal contraception has done a little bit of a disservice. We see women who are on contraception for a really long time. They don't have any idea of their cycle, what's going on in their body. Right. And I want to be clear, that's wonderful. It serves a job if you're trying to prevent a pregnancy. But the narrative that we've gotten wrong is, well, just stop it when you want to get pregnant. Instead of saying, hey, let's stop it three to six months beforehand. Let's learn to track your cycle. Let's see if you have any cycle abnormalities that need to be addressed before you start trying to get pregnant. Instead, women are stopping the pill. They're saying, I'm not trying, let's just see if it happens. I'm not preventing. They are trying to get pregnant, nothing happens. Then they start tracking their cycle because they're not having success. Now we see something's abnormal, but we're a year into this game and it's really frustrating. So I really think we've got to have a more- Educated approach. And preventive in a way, right? A proactive approach to fertility. The fertility field exists as a reaction, meaning here is OBGYN. People weren't getting pregnant. They said, let's create a specialty to help these people? How do we define what infertility is? Well, 85% of people get pregnant the first year. So let's say it's a year of not getting pregnant. It truly was an arbitrary definition to begin with to decide who should see this extra group or who needs help. Understanding that, 72% of people get pregnant the first six months of trying, only 13% in the next six months. so we make people women we make women fail before we're in a position to even do testing to even draw a lab to even check a semen analysis to even talk about their cycle it doesn't make sense to me especially when for so many having kids might be a life goal and not everybody will be in the position to have them but i would rather you make that choice based on knowledge and what is right for you and what are your options at different stages of your life because But some point time will make it for you. And that's the worst place to be in for me. Because every single day I have women say, I wish I'd known this sooner because I would have done something different. And I really think we have to start saying, you deserve to know this information sooner. So you can then make the choices. And that doesn't guarantee everything will work out, right? No one thing causes or cures infertility. Even IVF is not a guarantee. Absolutely. And this is the other thing people tell me all the time. They're like, well, at least if you freeze your eggs, it's a guarantee. I was like, no, it's not. And if you have embryos, you have a higher likelihood. But still no guarantee. But freezing your eggs is no guarantee. So this idea that you have a backup plan, that there's not the backup plan. You know, if we're freezing your eggs, we're taking one month's group of eggs and we're getting them to grow, right? We can't tap into the vault. We're only working with the eggs we're given. So I also think we see a lot of women freezing eggs who are not optimizing lifestyle and they're spending money, time, and effort. And maybe they could get better eggs. but also it's not an insurance policy on your fertility. I hear so many people come to me and say, I want to freeze my eggs so I have some insurance or a backup plan if life doesn't go the way I want it to. Freezing your eggs is an investment and it pays off for some women. It's like putting your money in the stock market. It is generally considered a good thing based on your goals, but the ROI on that investment is going to depend on things we do not know yet. So we have to make educated decisions and guesses, but there is tangible risk involved and zero guarantee. And that needs to be our mindset when we're freezing our eggs. I think the biggest investment women can make into themselves is lowering inflammation, getting their sleep cycle right, the diet that they're taking in, making sure the quality of their relationships is healthy, tracking their cycles to be educated on their bodies. I think that is better insurance than just going and freezing eggs. I agree with you. And I think there's, I freeze women's eggs every day. Of course. And there are circumstances where it makes perfect sense. Certainly, we see patients who are about to go chemotherapy and their egg count might be depleted. There's women who know they want children and it is a life goal for them and they have the ability to do so. But we're seeing a narrative where women froze their eggs thinking it was an insurance policy. They go to use them and they don't pay off. One, they probably didn't have full disclosure about the rate of success per egg. It's less than 5% per egg frozen as far as getting to a pregnancy. They maybe didn't have enough to play the odds well, but also to your point, they weren't given the tools they need to even have the best egg quality possible. And so it's another one of those things where we're saying you're majoring in the minors and we need to walk everything back and say the best investment you can make is in you, right? And in your health, learning to listen to your body, learning to decrease your inflammation and hear your cycle and prioritize your own wellness, that then impacts your fertility, your hormonal health, your longevity. I also want to talk about this whole idea, and we were discussing it before we started shooting for the show, about how men also now have a biological clock. Yes. And how we had this idea that men can have kids at any age and it does not matter. Well, the research is showing otherwise. And is it true or not, as a lead on from that question, that women's egg quality doesn't necessarily have to go down with age. Yes, the number of eggs you have in your body you're born with and that's it. But that is not as directly correlated anymore. Okay, let's break it down in twofold. Number one, male fertility, first of all, is 50% of infertility cases. So this idea that everything falls on the woman, not true. We know that male fertility matters. We already talked about some of the lifestyle factors. But just like women, there's a delicate communication system between the brain and the testes where the brain has to send off hormones and the testes have to interpret and send hormones back. And testosterone and sperm are produced together. Men absolutely have a biologic clock, and this is because the ability to package and create that sperm diminishes with age. Now, we know that if you are trying to get pregnant and the male partner is older, you have lower pregnancy rates, even if the woman is young. So we see this directly as far as functionality, even when sperm counts are normal. So when men get over age 45, we see lower pregnancy rates than if they are younger. When men get older too, there's also more errors in the DNA. So I think it's really important to note that we see higher rates of new onset autosomal dominant mutations. We see something called imprinting diseases, and we see polygenic diseases like schizophrenia and autism. Okay, so advanced paternal age absolutely impacts child health and outcomes from treatment cycles. But all men will go through a time where their testes will go into failure as well. Fibrosis from chronic inflammation, insulin resistance, they add up in all organ systems, including inside the testes. And so men will stop making testosterone and stop making sperm at some point. Yes, it's much later than women. Women do run out of eggs before men stop making sperm. So there is a discordance there. But we will see that it will happen. And in addition, the quality will become so detrimental that it is harder. And even when we do IVF, when I have men who are 50 and older, their sperm quality starts to play a significant role in getting to an outcome regardless of female age. So men have a biologic clock. Their lifestyle does influence it. So in the same idea, focusing on decreasing inflammation and avoidance of toxins is a really important idea. Even for men. Even for men. Now for women, there was a study came out that did get a lot of internet press. And let's talk about it a little bit because what you're saying is half true. This study looked at the mitochondrial DNA. So let's remember inside your egg, you have your nuclear DNA. This carries the traits that you're going to pass on to baby. So when we think about an embryo being 46XX, getting 23X from mom and 23X from dad, that 23X is coming from the nuclear DNA within a cell. This study actually looked at the mitochondrial DNA, which has its own DNA. Extremely important because an embryo gets all its mitochondria from the mom. So that egg, that mitochondrial DNA, and why we say mitochondrial health is so important in women is because that mitochondrial DNA gets passed on to the embryo. Mitochondrial DNA does not age at the same rate as nuclear DNA. Okay, nuclear DNA does still age. So the idea that, oh, you don't have a biological clock or egg quality is not impacted by age, that's not going to be a true statement. But it is, in my opinion, a very empowering one to say, but if the mitochondrial DNA doesn't age at the same rate, and we already know how important mitochondrial health is for the egg to function and for the embryo to function if you're trying to get pregnant, this is something that we do influence more dramatically. So it says, hey, if mitochondrial function less as we get older, right? We have more abnormally shaped mitochondria, but this DNA isn't damaged the same rate that our nuclear DNA is. This is just adding to the conversation that decreasing inflammation and focusing on mitochondrial health can preserve female fertility to some degree. I like to say that the average woman has a double hit with age. We have a drop in our genetic normalcy, our nuclear DNA, and our metabolic health, which influences our mitochondrial function in DNA as well. Well, if this DNA isn't damaged as much, okay, yay. But then if we can improve our metabolic health, we can counter that narrative. And even though we maybe can't reverse all changes in our nuclear DNA, we can help with how the eggs are going to function, their competency, their hormone production, and have overall a higher chance of getting pregnant. So there's nuance in that. We were expecting mitochondrial DNA to age at the same rate as nuclear DNA. So the idea that it is preserved longer, I think, gives us more hope that we probably could influence nuclear DNA more if we start talking about this earlier. Because if we can decrease inflammation at an earlier rate, if we know things like chronic inflammatory diseases and endometriosis and autoimmune disease have high levels of inflammation, impact egg quality and genetic normalcy, if we can learn to decrease inflammation and take this shift that we're seeing right now in our discussion. Then we have better outcomes. and apply it to women who are earlier, and you can have a longer time period where you really are focusing on decreasing inflammation, we probably can extend the genetic normalcy of some of that nuclear DNA. So from your perspective, we focus for so many years on women freezing their eggs and having this like backup for themselves and insurance policy. Do you think more men should start freezing their sperm when they're younger and healthier and using that as an insurance policy then? I think that certainly there are circumstances where you should. So number one, if you have cancer or you're going to get chemotherapy as a man, you absolutely should consider. Number two, if you're giving testosterone for hormone replacement therapy, testosterone itself talks to the brain, stops it from sending out FSH and LH, and then you're not going to make testosterone. You're not going to make sperm. Testosterone causes azospermia that is sometimes irreversible. So I think it's important to say my testosterone is low. Ideally, you try a different alternative that tells the brain to send out more FSH and LH, things like Clomid or HCG. But if for some reason testosterone is the best option for you, and I have some patients who are in this camp, free sperm verse, because you might be in a position where you don't have any. Second from there, the average man who is maybe going to grow his family before age 40, we're probably in a place where we're fine. However, if you are not the average man, or if you're looking at your life and you're in your thirties and you say, I really want to have kids one day, but I don't know when that is. It is so much easier and cheaper for men to freeze their sperm than it is for women to freeze eggs. You know, it's under a thousand dollars. You ejaculate into a cup and we freeze it. One deposit can give you multiple samples that you can use later. To me, it's a no-brainer. Although I will say this. We talked about the sperm lifespan. It's three months. If you're going to spend the money and time to do something, take care with those three months. Be straight and narrow. Don't be drinking a lot of alcohol or smoking marijuana, eating lots of processed foods. Or doing hot yoga. Exactly. Don't be in the sauna, the hot tub. Things that we know are detrimental to sperm production. If you're going to preserve, I mean, you're going to freeze your eggs or freeze your sperm. Do it from a place of you're trying to put the best sperm or the best eggs into the freezer. So don't ignore the lifestyle factors, which is what I see. You know, I'm not against egg freezing by any means. And I think there's a place for both. You need to be decreasing inflammation and being this more proactive, preventive approach. And at some point, if kids are a life goal, freezing your eggs may come into your plan. But why are we just talking about this one without the other I was also going to ask you earlier you said you know women are born with a certain amount of eggs And as you age that goes down Then women who don have a cycle how are we hear these crazy freak stories I had it happen to older friends by the way They think they in menopause. They're not ovulating anymore. And all of a sudden, bam, they're pregnant. How does that even happen? Okay. If we go back to my analogy that inside the vault are all the eggs you're ever going to have. Every month, a group of eggs comes out of the vault. And what's very interesting is that when the vault is more full or more crowded, more eggs come out every month. I always think of this vault keeper trying to keep the room at perfect capacity. But as the vault starts to get emptier, fewer eggs come out every month. So we start to see that the eggs that are outside the vault, which we can test, that's what we're testing when we do an antral follicle count on ultrasound, or we do a blood test for AMH, is a reflection of how many you have remaining inside. Well, every single month you lose eggs. Most of your eggs are going to be lost when you're a baby inside your mom. So between five months gestation to birth, you go from six to seven million eggs to one to two million. And this is because more in the vault, more coming out. The next biggest loss is between birth and puberty. So before you ever start a period, you're going to drop from two million to half a million. Eggs are coming out of the vault. Puberty is not the ovarian activation. It's actually the brain. Puberty is your brain turning on and starting to send FSH and LH. And then your ovary can respond. But it was sending eggs out of the vault that entire time. And same thing happens. If you go on birth control, still losing eggs out of the vault, just nothing is stimulated to ovulate. When you're pregnant, when you're postpartum, eggs are still coming out. So this loss of eggs is happening every single month, no matter what. When it comes to being in a place, and to your point, when the vault gets very low, I always say at both ends of the extreme, really high egg count, like we see in PCOS, or really low egg count. The brain and ovary starts to have some disconnect. The brain sends out hormone signals expecting there to be an average number of eggs in the vault. The ovary starts to get more stubborn as age. You know, the other thing about the ovary, we've simplified everything to being about the egg. The ovary can have fibrosis. The ovary has neurons. So when we think about all the things that start to happen with age, they start to happen inside our ovary too. So at some point when you're in ovarian failure, you actually have just a very low egg count, but your brain is now sending out all the FSH it has, and the ovary is no longer responding. It just says, no, thank you. I cannot interpret these signals anymore. And this is why when you're in menopause, classically defined as a really high FSH and a low estrogen, you're not responding anymore. I can't even do IVF and get eggs because when I do IVF, well, we give FSH, right? People often think we give these crazy synthetic medications. We're giving FSH and LH, same structural compounds your brain is making. So if your ovary is already not responding to them naturally, I can't do anything else. But what's really interesting, and we see this with women who have what's called POI, or premature ovarian insufficiency, that's when you go into menopause before age 40, is that you actually, your ovary goes into failure and stops responding before your egg count is zero. and when you lower fsh notably with hormone therapy so if i give a woman who has poi estrogen replacement which you absolutely should because you are not meant to be estrogen deficient that long so we give them estrogen we say hey i can't freeze your eggs i can't do ivf your ovaries are in failure you need estrogen for your brain your health your heart your bones everything all of it so we give you estrogen well estrogen talks to the brain lowers some fsh levels and then occasionally you can actually get kind of what we call an escape ovulation where you actually ovulate an egg then because of this kind of transient response. Other fun fact is in the interim stage, as you're starting to get into perimenopause, and this is what I see more, you know, perimenopause, I love it. There's so much attention on it right now, but in the fertility space, we've called this diminished ovarian reserve for a really long time. Same thing. You have a lower egg count, brain and ovary, you're starting to be more sensitive. that's what I would say, more sensitive or stubborn, influenced more by the world around you, but a little bit of disconnect between what the brain is saying and what the ovary is doing. Well, FSH levels start to rise as the ovary gets a little more stubborn. And two things we see. One is that you start to ovulate sooner. So classically, anybody of any age, when they say my cycles used to be this long and now they're shorter, the first red flag I think is, do you have diminished ovarian reserve or are you in perimenopause? And that naturally starts happening when you go into your 40s and onwards. It does. To everybody, this is part of the natural process. As the egg count starts to get lower, the brain sends out its signal. You don't have as many eggs, so it's not as diluted. So at first, before FSH even rises, you're going to say, I'm sending out a normal signal, but instead of to 20 eggs, it's to 10. Each egg gets double the amount, therefore grows faster and ovulates faster. That's going to be your early stages. Then you're going to see the ovary gets more stubborn and it takes a stronger FSH signal to get it done. Now your cycles typically start lengthening. What's interesting, though, is that in these two time periods, we actually see an increased incidence of twinning as people get older. Really? Yeah, because that FSH is a stronger signal to each individual egg, you tend to get two ovulating instead of just one. So when you do tend to see these surprise perimenopause pregnancies, you also see an increase in twinnings. Even if it's not genetically in your family? Correct. It's just your body starts. It's just your body starts to ovulate too because of this change in hormone interpretation. Wow, that's fascinating. I did want to talk briefly about things like mesenchymal stem cells and the rapamycin study. So let's do the rapamycin study first. So we were speaking about this earlier. So the new, this study came out, I think it was out of China or Japan, they basically studied rapamycin over a longer duration of time. And it showed really beneficial effects on women, slowing down avarian aging. This is separate to the Columbia study that a lot of people reference, right? What is the truth of it? How does it really affect your fertility and slow down a very nature? Let's say this. This is really exciting data. Rapamycin has been talked about in the longevity space for quite a while. What it does is it slows down cell proliferation and turnover. And if we think about it from the ovary and we take that mechanism of action to what we're hoping, we're trying to say, can I change the rate of loss of eggs out of the vault? So if I have a set number, if I could lose fewer at a time or change some dynamic about how many are dying, can I extend this ovarian lifespan? Everything is experimental right now, but there is promising results showing that this might be something that could be an easy added intervention. It can be an oral medication. And I think from this study, the smaller subset, this is very small, but this is so exciting that I screenshot it and sent it to my work partner because we're so excited about this. Within this study, they did look at IVF. And I think IVF is nice at times because you get very short-term data because longevity, ovarian hormones and function, as we talked about, can be influenced by so many factors. But they did a subset with IVF, and they looked at women who were doing an IVF cycle, and they put one group of them, they did the same protocol, and one group of them had added on rapamycin, and it was just a one milligram pill starting when they started Lupron, part of their suppression, and the other group did not. And they did this during IVF. They froze all embryos. Okay, well, the group that had rapamycin, they had what appeared to be more normal embryos. Okay, well, that's exciting, thinking about if it changed something about how the eggs were recruited, what's happening in IVF. What became even more exciting is they, importantly, they did make them wash this out. So they had to take three months off. I think it was three months before they did an embryo transfer. Because we don't know impact of rapamycin might have if you were to be pregnant or how long it lives in your body. So they came off of it. Then they lined up for the transfer. And they didn't want to influence the endometrial lining or the transfer outcomes by the group on rapamycin. And then they did the embryo transfer. And the group that was on rapamycin, so we'll call them the rapamycin embryos, they had higher pregnancy rates and higher live birth rates and lower miscarriage rates. Fascinating, right? Fascinating. So when we think about something about cell proliferation, how the cell is healing itself, how the cell is metabolically active, I think it's a lot more than just like not running out of eggs. which was this original hypothesis or slowing down how they come out of the vault. I actually think it's changing some of the mechanisms within the cell that can be really optimistic to the point where I think we're going to start to see it as a potential option in IVF cycles for patients who have very low ovarian reserve or who are older. Now, this is an extremely limited study. So we always have to caveat, right? We have to make decisions with the data we have, but this is the study we have to go on. In this study, I think we could consider using it knowing that we don't have long-term data, knowing that this is very small. I think there are less than 50 patients or so in each group, so it was limited. But nonetheless, for patients who essentially come to this end of the road and we have limited options, what we can add for them, it could be an exciting thing to consider. So it's not going to be standard at all practices, but it's definitely something, especially if you've had failed IVF cycles or you're falling into this category. Or you're older and have a lower egg reserve. that we should at least be considering. And it's something we're starting to do at our clinic and certain patients. And I'll come back and tell you how it's going. But I think that leads to the narrative of, could it have ovarian longevity function, which we're also seeing preliminary data supporting? Does this mean that everybody should go beyond rapamycin? I'm going to say no, we don't have that to say it. But I do think for the person who has mastered the majors, right and we're proactively controlling everything that we are and now we're at a place that we want to potentially improve that ovarian lifespan it's exciting data i think the generation below us is going to benefit from this more than you and i are based on our current age but i do think it is exciting future and i really more than anything i'm happy to see a focus on women's health because rapamycin after all this time and it's been around for so long but it's only been studied for longevity and on men. In men. So it's been looked at for longevity and for men. And so looking at it through this lens, to me, you know, that's step one. We've got to start doing the research. And so seeing it come out and seeing people investigating it, that's really exciting. And then the last thing I'm going to leave our audience with is also a little bit of research on your opinion on stem cells, mesenchymal stem cells, and PRP for the ovaries. So I have, first of all, I think we'll also say, this is right now mostly experimental, done under IRB studies at certain institutions. I have a two-fold approach to it, meaning I've had some patients, I don't do it, but I've had some patients go somewhere and they've had great outcomes afterward. And I've had other patients have really bad outcomes. So to me- With the PRP and the stem cells. Yes. And I think that we'll say, we'll kind of group them all together. To me, I think this is where we have to, as an individual, understand that fertility more than everything is so personalized. And there are certain things we might choose to do when we get to the end of a road because at this point the potential benefit outweighs you know potential harm or damage i don't love seeing women who are not at that place start to we'll use ovarian prp right we're poking holes into the ovary right injecting you don't need to do it right so i don't think this is something that we should be applying to everybody and i do see some people doing that so i think that's the wrong approach. I think it's something we should say, this has potential in the right patient. I'll say from a scientific standpoint, studies have not shown a benefit on IVF outcomes and population based studies. So what about live birth rates going up for people who are doing stem cells or PRP without IVF? Yeah. When we look at the big, when we put all the data together, we don't see it. That doesn't mean though, and I feel this so strongly to my core, population-based data is helpful to guide decision making but we always have to use it and individualize because we're all in of ones we are all unique beings and how we might respond to something is not going to be always how the population responds and i talk about this to my patients all the time and i think it depends on where you are your goals i do want to say one thing I don't like is people chasing expensive add-on treatments when they haven't had a full fertility evaluation. Yeah, of course. But they do, right? But they do. You know, I'll see that we're doing ovarian PRP and our partner won't even get a semen analysis, okay? We also, that's not fair. Cut out the microplastics from your day-to-day. But also, yeah, to the same point, right? The majority of people need to focus on all the factors that we can control before we're chasing expensive treatments, experimental outcomes. And I think that's the big narrative because sometimes people are looking for a fast, easy thing. It's easier to go pay money and have this themselves versus dealing with the chronic stress that my relationship is causing. Like this feels easier than this. And I think that that's also a false narrative. So we have to understand that these are all experimental and that's exciting. I don't love the narrative that fertility doctors specifically are opposed to change and innovation. If we think about this crazy field that I'm in, the oldest IVF baby is 47, right? Somebody decided like, let's try IVF, right? That would be all experimental. It's all experimental. We are a field that embraces technology, embraces change. So to live on a pedestal now and say the perfect study hasn't been done for this, therefore it has no merit. I don't buy it. Is that correct either? I don't buy So for me, it was really beneficial because I, you know, decided to start late. At the time, I was still married. You know, now I'm going through a divorce. And for me, my FSH was super high. I had a low ovarian reserve. My AMH was, you know, it was just, everything was topsy-turvy, upside down. I had a lot of inflammation. I was really, really stressed. And when I, I said, I don't think I just want to go through a cycle. So I went on the repamycene, which helped me. Then I did the stem cells and my cycle became regular. There was a few months that I didn't even have a cycle from stress. My cycle got regulated. I started having a regular cycle. My FSH and AMH adjusted. It's incredible. And then from there, I started feeling like a human being again. And then I went on estrogen patches and I had progesterone supplementation and things like that. So I was controlling all these different things. And so for me, given that I was in my 40s, things were a little bit topsy-turvy. For me personally, it was really beneficial. But I had gone through guided with a fertility specialist who walked me through everything and said, listen, for where you are, for your case, for your scenario, for everything. This makes sense. This is what we should do with you. And that's the perfect utilization of some of these, what other people call IVF add-ons. It's not a one size fits all. So we can't sit here and be like, PRP for everybody. Or we shouldn't sit here and say PRP for nobody. It really needs to be- Or rapamycin for everybody or nobody. Exactly. It really needs to be individualized when it starts coming to these. But to your point, you felt so bad. You know, your hormones were off and you knew it. I didn't feel good. You knew it, right? Because if you're not ovulating and you're not making estrogen, you're not going to feel like yourself. And these are those clues that we've got to learn to listen to, to our body. But I think that too often, you know, women do get dismissed. And I'm sure there was a period of time where you didn't feel good and people said, oh, it was normal. Oh, it was this. Absolutely. And nobody was tracking it. I would go to the OBGYN, get my regular checkups. Nobody bothered to check this stuff. And yeah, in fact, the recommendation is to not. Correct. And that's crazy to me. Why would you not give me data in my early thirties, in my mid thirds? And one of the other biggest things for me, Natalie, was understanding that the stress and the stress of my relationships, what it was doing to my hormonal health. It was. It was destroying it completely. And yet you probably got dismissed or told it was no big deal or not even addressed at any, in any way. You know, I think we live in a world where not all medical providers are created equal. And to leave your audience with the idea that your health, your hormonal health, your reproductive health, your fertility, it is nobody's journey but your own. And unfortunately, that means you've gotta be a really good advocate for yourself. And that's okay. And we should feel inclined as women to take a space. And empower each other. Right, to ask for what we need, to talk about our cycles and our health so that we can understand what others are going through and break down stigma, but also to give you the tools for how to advocate and what questions to ask for, what labs to ask for. I do not think, you know, I wish we lived in a world where you went to the doctor and they had all this time and they ordered all the tests you need. And they won't do that. But that's why you need to educate yourself. That's not the real world for the majority of people and the current medical system. Yes, there's unique systems and providers, but you've got to come in from a place of really understanding what's going on, knowing what to ask for, knowing the right questions. And that all walks back to you can't advocate without knowledge. So thank you for having me too. And for this show and everything that you do, because you're helping give women that baseline that they need. And you have an incredible show. Can we tell the audience about that, where they can find you? Yes, thank you. So I host the As a Woman podcast, where we talk about fertility and hormones and health every single week. That's on anywhere you like to see a podcast. And I have the Fertility Formula coming out in April. It's available for pre-order now. And it's everything that we just talked about. So we're breaking down everything about your fertility. I wish you'd learned and you never did. what to do when things are abnormal, how to advocate for yourself, what questions to ask when it comes to your cycles, your hormones, or getting pregnant or infertility. And then half the book is all about lifestyle. So how do you decrease inflammation, really giving you tangible items, but all the science behind it so that you can really start to make that change. And you can buy that anywhere. It's the Fertility Formula. And then I'm on Instagram at Natalie Crawford MD. Thank you so much for taking out the time and being in Miami and coming on the show and sharing all your wealth of knowledge and research. in a way that the community can process, understand, and apply to their lives. Thank you for having me. Thank you, Natalie.