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The mindbodygreen Podcast
644: Why the ovary is key to women’s longevity | Natalie Crawford M.D.
00:51:20
Dr. Natalie Crawford is a double board-certified reproductive endocrinologist and fertility doctor, based in Austin, Texas. She’s also the author of the brand new book, The Fertility Formula, which comes out on April 14th.
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Welcome to the MyBodyGreen podcast. I'm Jason Wakab, founder and co CEO of MindBodyGreen and your host. This podcast is sponsored by Abdokare. Some days demand more from you, whether it's a workout, back to back meetings or just staying present with your family. Spark Energy and Focus Provide stable, functional energy Mix it up before a workout or even mid afternoon when you feel that dip coming on. It's so easy. Shake, sip and within minutes you feel more dialed in. Not wired or jittery, just clear, focused and ready to power through. The drink has a well rounded and balanced formula that goes way beyond just a quick energy boost. You get 120mg of caffeine paired with amino acids and taurine so the energy feels steady, not spiky or jittery. It also includes choline for mental focus and clarity plus B vitamins and L carnitine to support energy metabolism and vitamins C, A and E help support your immune health and everyday wellness. There's also zero sugar which makes a real difference on how you feel later on when you right now Spark Energy plus Focus is offering 30% off and free shipping. Go to drinkspark.com and use code mindbodygreen at checkout. That's code mindbodygreenrinkspark.com if we knew more
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What if the key to women's long term health was hiding in plain Sight all along. Today's guest is on a mission to change the way we think about ovarian health, not just as a fertility issue, but a window into women's overall longevity and well being. Dr. Natalie Crawford is a double board certified reproductive endocrinologist, fertility doctor, and co owner of an IVF clinic in Austin. She is also the author of a brand new book, which we absolutely love, titled the Fertility Formula. In today's show, we get into why ovaries are essentially the command center for women's health. Why what's driving early puberty and early menopause, what egg quality actually means, and why IVF needs a lot more humanity and a lot less factory medicine. My wife Colleen and I went through the wringer in our own fertility journey. We were lucky enough to come out on the other side with two beautiful daughters. But this makes us so deeply appreciative of the work that doctors like Natalie are doing. This episode is a favorite of ours and I know you're going to love it. Let's dive in. Can we start with ovarian longevity and how it's a window into a woman's overall health and well being? Can you help us understand that more?
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B
Yes, Jason, that's a lovely question. And just to frame, I want to think about the ovary as more than just making eggs and getting pregnant. And I think oftentimes that's what the ovary is simplified to. We think about it as a utility to grow eggs, and that's one of its jobs. But women are born with all the eggs they're going to have. And the magic of an ovary isn't in the egg itself. It's in all the cells that surround each egg. And those cells are called the granulosa cells. So one egg grows inside a follicle, around the follicle are granulosa cells, and the ovary is this metabolic, mitochondrial dense factory that loves to make hormones. And this is the hormone producing factory for estrogen, progesterone, testosterone for women. So when we think about the ability of the ovary to function, the ability of the ovary to properly respond to the brain, and the ability to ovulate appropriately, and the importance of cycle awareness and understanding our ovarian health is reflecting a state of overall health. And to expand upon that a little bit, women who have infertility, and this is a scary stat, but women who have infertility have a much higher rate of metabolic disease, cardiovascular disease, heart attack, stroke, cancer, and earlier death. And I had infertility myself. So saying that stat out loud feels really scary. But I think it's very important for people to understand that it is not the act of infertility that causes these things later. And it's not going through fertility treatments. It's actually the underlying predisposition for which many people might experience infertility. And this is higher rates of chronic inflammation, insulin resistance, poor metabolic health that can drive both infertility and later risk of disease. And we see so many health outcomes tied to ovarian function and estrogen production. Whether it comes to you go into menopause early, you have a higher risk of a heart attack, you have a higher risk of osteoporosis. And we see that the longer your ovaries last, you're more protected against a lot of these factors which significantly impact your lifespan. But also we want to think about this as a health span. So when we think about longevity for women, the ovary truly is the key and that piece of the puzzle. And it's something we should be paying attention to much more in a proactive approach. I love the emphasis on menopause that we see in the medical community right now because for years it has been ignored and it's bringing awareness and the language of how to have these health discussions to the public. So I think it's incredible. But the truth is women's health and women's health in midlife and beyond that discussion should start much earlier thinking about how do we understand our ovarian function, how do we try to proactively extend that lifespan to the degree that we can. And there's data showing, if we want to put it in a one line sentence, that decreasing chronic inflammation and improved metabolic health improvements your ovarian reserve, your ovarian function and likely have the opportunity to extend that ovarian lifespan, which is really that key to longevity in women.
- [07:15]
A
So in summary, whether you're looking to conceive a child or not, if you deeply care about extending your health span, then you need to care about your ovarian health specifically. I'll just stop there. That, that's what we're, that's it. And so I want to get on timing and duration. So there are two, in my view, there are two big milestones. There's puberty and there's, there's the question of what when that happens. And I think the duration is more or less the duration. But I'll. You're the expert. And then we've got menopause and there's the timing of menopause and potentially the Duration, which is much longer window, depending on a variety of factors, including ethnicity. So if we talk about. Are those the two? The two in your view?
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B
Yes, and it's really interesting. So the third one, the third one that's really important is the one that we don't control and that would be the fetal environment when you're a baby inside your mother. So if we want to think about this, people think puberty and menopause are opposite ends of the spectrum, like a ramp up and a ramp down. And they're actually two very distinct things. So let's walk through this. A woman is born with all the eggs she's ever going to have. I like to imagine them as being kept in a vault inside your ovary. So you have all your eggs in a vault and every month since you are a baby inside your mother, a group of eggs is sent out of the vault every month. So you have a group of eggs released. Now, all of the years before puberty, nothing happens. The eggs just die. And a really fascinating idea that we have to grasp when it comes to longevity and health span is that the number of eggs that get sent out of the vault is proportional to how many are inside. So let's just think about the vault's really crowded, the door opens and more exit because it's so crowded. And then as it starts to get emptier, there's fewer inside and fewer exit. And to hop for people to understand if anybody's ever done egg freezing or IVF or had a fertility evaluation, we measure the eggs outside the vault with blood tests like AMH or ultrasounds, where we call it a follicle count. And those are the eggs you can get in that month. So if you're doing fertility treatments and you say, why did I get nine eggs and my best friend got 20 eggs, everybody's on a different rate of decline. Based on how crowded their vault is or how many eggs they have left, you're going to have a different number released every month. And so we call this our ovarian reserve, walking it back to being a baby. So we're losing eggs even before we're born. Peak egg number is when we are 5 month old baby. As a woman inside our mom, we have about 6 to 7 million eggs by the time we are born. We have 1 to 2 million. Most our eggs are lost when we have not even been born yet. From then, the second greatest loss is from birth to puberty, where you'll go from 1 to 2 million to less than half a million. And what we're seeing here is that the ovary is constantly losing eggs. What puberty is, is an activation of the brain. Puberty is turning on the brain. So now the brain is mature enough to allow it to send out hormones. And FSH is the primary hormone from the brain that drives egg growth. So it's follicle stimulating hormone. Quite well named because each egg grows in a follicle. And I always say this is the only time in science, because men have FSH and LH2 that the hormones are named for what happens in women. But so the brain is sending out fsh, follicle stimulating hormone gets that follicle to grow, that starts making estrogen. As we're a young girl in puberty, estrogen is going to grow breasts. And then after it's been around a long time, your body will start ovulating, you'll send out LH and you'll ovulate. So in that circumstance, from puberty on, one egg is selected to ovulate. We are making estrogen and progesterone. The eggs outside the vault that are not ovulating just die. And then next month, another group, menopause, on the other hand, is ovarian failure. So the ovaries started losing eggs, losing eggs, losing eggs. Brain turns on in puberty, it works. And then menopause or ovarian failure is now the ovary no longer responds to the brain signal. The brain starts sending out stronger and stronger, higher levels of fsh. The ovary has such a small egg pool left that it does not respond anymore. So we see extremely high FSH levels, eggs out of the vault. There's not enough to do anything with. And in the in between perimenopause or diminished ovarian reserve, we see a stubbornness to the ovary where we have a variable response. And women do start to experience different cycle changes throughout this. And that's why understanding your menstrual cycle and learning to track it, which is a skill many women never are taught, can give you a lot of insight into am I starting to enter into these lower stages of ovarian reserve? The red flag warning signs. So I think it's important to frame aging both at its onset and deset as it's not an on ramp and off ramp of the ovary working. It's really one is the brain turning on and one is the ovary getting so low in eggs that it no longer responds. The reason why that's important to what I think you're getting at here is that the decision of the brain to turn on is often directed by external forces. A lot of these is the feedback our body is given. So the modern world has seen a decrease in the age of which puberty is starting, meaning girls are going through puberty earlier and people who are at higher risk, women who are higher risk of going through puberty earlier tend to be more, more overweight, they have higher rates of insulin resistance, they tend to have more inflammation in their body, they're exposed to certain chemicals. So a certain, essentially, let's say the brain is getting signals that it is more mature than it actually is and decides to turn on early. And those factors themselves that turned the brain on early predispose you to also have later health risks also. And that's why we see early puberty associated with, with health risks later. But it's not because you're going to run out of eggs earlier. And that's a common misconception that because you started having periods sooner, you started losing eggs at an earlier age. The truth is you were losing eggs the whole time. Starting your period sooner didn't change the rate of loss of eggs at all. But it is a red flag that metabolic health is not ideal. That then predisposes you to these other things. And one of them is earlier menopause.
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A
Yes, a lot to unpack there. But to, but to clarify that last point, essentially it is a misconception that if puberty comes earlier, the clock starts ticking and accelerates on egg loss. That is not, not true.
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B
Correct.
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A
Okay. And so puberty, so my understanding is the, the duration hasn't really changed. It's the timing. So the duration on average, I think is around two years of onset of puberty and menstruation. Do I have this correct?
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B
Correct. Meaning from this first puberty signs into when menstruation is the last act of puberty.
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A
So that's like approximately two years. Ish. Hasn't really changed, but timing of that event has shifted significantly earlier. Yes. So where is it today? Where was it in the past? And what's your view on what's driving this?
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I mean, honestly, I think what's driving this is a lot of the modern world, the same reason we're seeing a lot of the other diseases of chronic inflammation and insulin resistance. It's going to be increase in obesity, dietary sources of inflammation, ultra processed foods in our diet, toxins that young children are exposed to. There's definitely some ethnicity or genetic ties. So we see certain groups going to puberty earlier. When we really step back and we think about it. We used to say that we would consider the onset of puberty. So thinking about breast budding is typically one of those first signs that you start seeing then axillary hair. And to your point, it's about two years before you get menstruation. Those early signs used to start between age 10 to 12, meaning that we would see kind of the period start between 12 to 14. But now those early signs have shifted and we're seeing an average range of them from about eight and a half to ten and a half at a much younger age and going through starting menstruation much earlier. I have a young daughter who's 11. It's interesting to watch her friends go through this and going through it at a much younger age even than I did. Right. As a woman who's now 44. So it's not just, oh, we think it's happening, it truly is. And it largely is due to the modern world that we live in and certain things that we have overall accepted as standard or normal. That really is not how our body is meant to function.
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A
So essentially, I think what we're talking about environmental, if you go beyond diet. Endocrine disruptors.
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B
Exactly, both of those. And they go really tightly together because many endocrine disruptors enter our system through ultra processed foods, food packaging and, you know, kitchen sources, dietary choices. So when we think about food, we'll just say food is general. Food can be helpful, have a lot of fiber, antioxidants can combat endocrine disruptors. Think about fruits and vegetables. Folate is protective against bpa. So we can have this good category. And then we have things that cause inflammation, that disrupt hormone signaling, that change your body's interpretation of hormones. And a lot of these are those ultra processed foods. But then you get a double hit because they often contain environmental chemicals as well, which are also inflammatory or endocrine disruptors themselves. So, well, we see all the food marketed to children, you know, and the foods that eat, even we probably ate as children, which were suboptimal, but so many kids, that is their day to day diet. It's not a diet rich in whole foods. It's not a nutrient diverse diet. It is one that is rather quite limited and ultimately on the inflammatory spectrum and causes exposure to endocrine disrupting chemicals.
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A
And so if you're a parent listening and you're doing all of the right things, you know, kids eating whole foods, you're probably avoiding microplastics, you're doing everything you can to avoid endocrine disruptors. But you're still concerned. Is there anything else a parent could do to potentially slow this down? There's also an impact. Not that this is maybe the top of everyone's list, but it also impacts height.
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B
It does. You're exactly right. For, for girls, when we want to think about the, the puberty span, we have that brain activation, the follicles start making estrogen. That's about two years. As you said, we get the breast budding, but we're also going to get our growth spurt and then we'll start our period. And by the time we start our period and we start making progesterone, that closes the growth plates. And so women, young girls only give up one more inch max after they've started their period. So that girl who might be really tall in fourth or fifth grade, it when she actually might end up being quite short in the grand scheme of things because her height is getting capped earlier. The thing I think people don't think about when it comes to drivers of earlier puberty, some of them are going to be early life stress, trauma, chronic stress and also sleep disruption and how they play in to that chronic inflammatory environment and also contributing to insulin resistance, which so many people think about insulin resistance as some a disease of being older, something that's associated with diabetes. I hear so many patients say, I don't have diabetes in my family, so that's not something for me. But when we really think about this mismatch in insulin, which is a hormone, it's a growth hormone, but its job is to help your cells use glucose, which is what your food is getting broken down into. And when you start to, we'll use simple analogy, start to eat more, eat those ultra processed foods and you have higher glucose levels, more insulin is going to be released and your cells don't want to respond to it. And I use the bad analogy. If a salesman comes to your door every single day, Jason, what are you going to do? You're going to ignore him, Right? And that's essentially what your cells start doing, meaning it's going to require the salesman banging on the door for you to finally open it. And that is your body giving higher insulin levels. But that promotes gaining weight and your body starts storing glucose because the cells inside are getting so hungry and starved. So it's a mismatch in energy and we can think about that. Well, I don't serve my kids lucky charms or let them have dessert, so I'm not doing those things, which is great. That is fabulous. But other drivers of Chronic stress and the sleep disruption drive inflammation and insulin resistance. So we really think about kids especially, their bodies are doing so much and they really need sleep. So even though we as parents, I mean, I do this, the Olympics are on. So sometimes we're staying up late and we're watching them. And the goal, though, is to have such a good sleep schedule where they're getting enough sleep, they're going to bed, they're getting up, cultivating a good sleep environment so they can handle the resilience. But when your kids are chronically tired, they're going to start to be more insulin resistant, and that's going to predispose them to earlier puberty. And then also we talked about that stress and stress is really, really something to think about here. We don't always think about kids don't have stress because they don't have jobs, but how stressful interpersonal relationships can be, family dynamics and stress, how we approach difficult situations because it's difficult for them. And really cultivating a place where maybe we give space for how humans are supposed to lower stress, meaning, let's go sit outside, or, oh, we had a hard day, let's maybe we should go for a walk. And modeling good behavior, right? Not stress eating, not stress drinking, not worsening that environment. But those are two, I think a lot of parents, and when I see adolescents or I'm talking to moms who are thinking about this for their daughter, are not always really thinking about that. Those things can impact puberty itself.
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A
We'll move on from kids to older age groups. But my last question here is what labs would you recommend for a parent to administer for their child to get a sense of, hey, potentially we're not on the right track.
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B
There are. So your pediatrician and then pediatric endocrinologists really do specialize in this. And one thing that they do that most people aren't aware of is they actually do an X ray of the hand and do something called bone age. And if they start to see that the age of the bones is accelerating, then there's definitely an evaluation why. And there's something called precocious puberty, which is going into puberty early. And sometimes these have nothing to do with any of those lifestyle factors I just mentioned. Maybe there is a reason in the brain, maybe there is a genetic reason. There can be factors why puberty can start earlier. We can do ultra sensitive fsh, LH and estrogen tests. So there's specific labs. We always usually check other brain hormones like thyroid and prolactin, and Then we check the age and there are some medications that block some of the hormones at the brain that you can give to halt the puberty process. And that can sometimes help kids maybe have a longer time span, achieve a greater adult height. If we are really worried about the way things are going.
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A
Got it. Moving on to us grownups. So is it safe to assume that everything you just outlined so articulately in terms of the drivers for early onset puberty hold true for early menopause?
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B
They do. There is a genetic predisposition. So one, you can be born with a lower egg count. So some women are born with a lower egg count. Some of this is a true genetic syndrome. There known genetic links that can cause you to go into menopause early. There is also certain exposures your mom had when she was pregnant with you that might have depleted your egg count more. There's nothing you can go do to change that. But there's also. The bigger drivers are going to be chronic inflammation, autoimmune disease, inflammatory diseases like endometriosis, exposures that we know induce this inflammation and insulin resistant environment, endocrine disruptors, smoking cigarettes. So there's a litany of things that are associated with going into early menopause. But if we really want to tie them all together, it is this metabolic dysfunction kind of this chronic inflammation. And chronic inflammation hits our body in so many different ways when we think about female reproduction and what we've talked about, chronic inflammation. So again, inflammation normal part of your immune system. You get a cut, your inflammatory system is going to go heal it up. And interestingly, inflammation is good for our body. We want to ovulate, we have to have our inflammatory system comes in and helps us break open a follicle and allow an egg to be released and reform. So the goal is not to go take some anti inflammatory medication to get rid of inflammation, but it's to proactively prevent these drivers that increase what we call our inflammatory burden. But on a reproductive spectrum, chronic inflammation. So constant activation typically is by exposures that we have. So the food we eat, the amount of sleep we get, the stress levels we have, the type of exercise we do or don't do, and then toxin exposure, which includes these endocrine disruptors, these can increase that inflammatory burden. This can interfere with the brain. Brain has a hard time understanding hormone signals, so it starts to misfire. It can impact directly at the ovary. The ovary has a hard time interpreting signals, so it stops working correctly. It actually changes how the ovary works. So inflammation in the ovary actually changes how the ovary responds. And so if we want to have our ovary respond better, we want to decrease our inflammation so that it can respond better and longer. But bigger than that, a couple big keys. Chronic inflammation is going to get inside the vault. It can drop our egg count directly. It also can impact the quality of our eggs. And the quality of the eggs is the genetic normalcy, which, that's a piece of the puzzle when it comes to fertility, but it's also the metabolic response, how the mitochondria work, can the egg start to grow and can those cells around the follicle actually make estrogen? And then later here on the spectrum is you actually can get fibrosis in the ovary as well from chronic inflammation. So then even if it wanted to respond, it can't because it gets more fibrotic, which we want to think about as a scarring inside the ovary. So this long standing chronic inflammation, let's just imagine the young girl who's exposed to it to start puberty earlier, never kind of gets it addressed, you know, might have infertility along the way. Also those are her body giving her red flags, might have some abnormality in her menstrual cycle, but was dismissed or not taught about them, is now on a pathway to go into menopause earlier, have less ovarian function and at a higher risk for heart attack, stroke, earlier death, all the things we talked about. So this is a long standing problem that spans our entire life. But I think to answer Jason, the question you actually asked, it's yeah, it's the same thing. It's all connected together. It's not coincidence or one magic thing here and one magic thing there. Our body is all tied together. And to put it simply, chronic inflammation is one of the primary pieces that we can control because a lot of that inflammatory burden is is from our daily exposures and choices in addition to some inherited risk.
- [27:23]
A
This podcast is sponsored by Abdokare. Some days demand more from you. Whether it's a workout, back to back meetings, or just staying present with your family. Spark energy and focus. Provide stable functional energy. Mix it up before a workout or even mid afternoon when you feel that dip coming on, it's so easy. Shake, sip and within minutes you feel more dialed in. Not wired or jittery, just clear, focused and ready to power through. The drink has a well rounded and balanced formula that goes way beyond just a quick energy boost. You get 120 milligrams of caffeine paired with amino acids and taurine so the energy feels steady, not spiky or jittery. It also includes choline for mental focus and clarity, plus B vitamins and L carnitine to support energy metabolism. And vitamin C, A and E help support your immune health and everyday wellness. There's also zero sugar, which makes a real difference on how you feel later on. Right now, Spark Energy plus Focus is offering 30% off and free shipping. Go to drinkspark.com and use code mindbodygreen at checkout. That's code mindbodygreenkspark.com yes. And so let's pivot back to the important group of people who want to conceive. And you touched on eggs, and there's quantity and there's quality. What does egg quality really mean?
- [28:39]
B
This is a great question. And I think that the problem here, and I'll be honest, right, I'm a fertility doctor who owns an IVF clinic and my peers as a field, we've really simplified egg quality to genetic normalcy. We've talked about. Right? And that's a piece of the puzzle, but not the whole puzzle. So here's my way to think about it. Our eggs are inside our body our whole life. We've already well established that they are exposed to the wear and tear of the world around us. What we may not realize is that for women, our eggs are held in a stage of cell division called metaphase of meiosis. And if we think back to biology, metaphase is when our chromosomes meet in the middle. So we have all of our pairs of chromosomes lined up. A woman would be 46xx. So we have 23x and 23x held apart by proteins, these meiotic spindles. And not until you ovulate do they split apart. And then that's when you get your 23X. That's in an egg. And that's an important idea to think about half of egg quality, this genetic idea, because that's a very vulnerable state. So this is where some of that inflammation and time can add up. I like to imagine your chromosomes are a line of kindergarten or sitting in alphabetical order. The longer I ask them to stay in alphabetical order, the higher the odds somebody's going to get out of line. So tincture of time alone does impact genetic normalcy. But also if inflammation is bringing puppies into the room, it's distracting. It's eating away at some of these meiotic spindles. More kids are going to get out of line if there's puppies everywhere. And that's what this chronic inflammation is also doing. So we see a doubling effect the older we are, we've asked them to wait in line longer and we've had more time for inflammation to come in and interfere with the proteins holding our chromosomes apart. So genetic normalcy is a piece of the puzzle for egg quality. But the other part of that is the egg has the mitochondria. It's going to get passed on to the embryo. The egg allows fertilization or not, and controls all embryo growth from up until day three, when the male genome kicks in. Male genome doesn't even do anything those first three days. Everything's dependent on the metabolic health of the egg. And I consider this the egg competency, the ability to do its job and to function. And that is clearly associated with our metabolic health. So again, chronic inflammation, insulin resistance, is going to impact egg quality. And this is why women, even though they may be young, might have poorer egg quality. And some women who are older might have better egg quality than their stated age. Because age is a piece of the puzzle. We, we can't rewind the clock. But when we start to think about as a population, as we age, we will have fewer eggs to work with. They will have been exposed to more inflammation just from tincture of time. But as a population, we get more metabolically unhealthy as we get older, people tend to feel the damage of, you know, living this metabolically unhealthy life more. So that's why it's just markedly harder when we get to 40 or older to get pregnant, because we have multiple factors impacting us. But it is not just a numbers game when it comes to getting pregnant. It really is. There's the quality and the quantity. And that quantity again is the ovarian reserve, the how many eggs you have left to work with.
- [31:59]
A
And I also don't want to underestimate the male role here. Here it takes two to tango, so to speak. And then there's embryo quality. But before I, before I go there. So you mentioned genetic normalcy, and I saw a wild theory online that essentially stated that couples who share the MTHFR gene that there's something with the, that they maybe tend to struggle with infertility a bit more. And I thought it was interesting just solely because I am MTHFR C677T, my wife is. We were metabolically fit, we, everything was right and we really struggled with fertility. Nine embryo transfers, four IVF cycles. You know, we got through it, we just. Happy ending. But what do we really know, like does that even hold up? Do you think it's like. Do you think there's something happening potentially genetically?
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B
Yeah, I think it's a really good question and I don't think science has the true answer here because what we know is that the mthfr gene, right, so this is important in folate metabolism, is that many different people, there's different types of mutations. So I guess we have to say that there's different types where you can have a problem with the function of MTHFR because it's an enzyme. But 30 to 40% of people will carry that now. Only 10 to 15% carry two copies of it, and they're probably more impacted in their functioning.
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A
That's both of us. Both of us carry two copies.
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B
Both of you carry two copies. So you're probably in a smaller subset of people to have magically found each other in that way.
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A
I love your perspective.
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B
I mean. Right. It's just like, what are the odds? I. I mean, I. I have a. I have a couple that she went in, she was a patient of mine since she was 16. She came to me to see. With no period and she was in primary ovarian failure. She. She never started a period and never would her ovaries fail. Failed before they ever started. And he. And he has no sperm. He's got an obstructive azoospermia where he'll have to have a procedure. And it's. They are lovely. They love them so much. And we're walking through this road together. But they were like, what are the odds that I have no eggs and he has no sperm in his ejaculate and we found each other. Like, we must be meant to be because, like, nobody can understand maybe this viewpoint. Like we can back to where we are with this is all the scientific studies don't support that having. Even having both copies coming together, that that's a true cause of infertility. I always like to say, though, that science can only get us so far and studies can only tell us what they've really looked at and in what small population. So just because something doesn't exist, proving it in literature doesn't mean there's not some truth to what we're seeing in clinical practice or what patients might experience. And I think what we might say here is that you are more predisposed to inflammatory states. Even if you are living healthy. There might be other barriers that can be impacting egg quality. We don't have the magic answer for it yet, but it probably is significant in You. Even if we don't have the exact mechanism of why.
- [35:13]
A
Well, on that note, I also had obstructive azoospermia, which to this day was a bit of a medical mystery. It was very uncommon. Ultimately had to get surgery. Happy ending. But back to your point with science, a couple things I want to call out. Also very painful and I think problematic that my wife went through a couple cycles before they even decided to test me.
- [35:37]
B
Jason, it's wild. I mean, that's highly. I just want to say that's highly unacceptable because 50% of infertility is male factor and 50% of female. There's a huge amount of couples that have both. That's wild.
- [35:49]
A
And like, men have all sorts of issues with sperm right now for a variety of reasons, which we won't get into. But like, all. So getting back to. So this hits home and we. And we, you know, ultimately, happy ending. I'll give a shout out to NYC ivf. Like, it was just. It was a terrible experience, but a very. But. But then turned into a wonderful experience with our provider. And we had two beautiful girls, were very blessed. So with that said, I want to touch on embryo and what we know is science. I'll never forget when we started going through this. We did the transfers, we would do the embryo test and we'd examine the quality. And my wife had perfect egg. Look at these beautiful embryos. And they would rank them. We didn't get to like, our first daughter was like the fifth one. And like, when we did the transfer, we, we. We put in because we failed so many times. We put in four eggs. And the person assisting the doctor at NYC IVF was like, doc, like, you sure you want to do this? Like, this is like, doc, doc. And the doc's like, look at her chart. Look how many times this has failed. And with the four. And so like, she was like quality number six. And she ended up one child, not four. And I think of our oldest daughter, who is like such an unbelievable child, like, super athletic. Like, we joke. She probably eliminated the other three embryos in the womb because she is that tough of strong of like a physical girl. She's probably going to be like 6 foot 3. Like, she's just like genetically like a force. And we're like. And she was like, number six. And then we look at her other child, the second one, who also is genetically good. Like, she was number eight. Like, both gifted, special. I'm like, what do we really know about testing embryo quality? If we have like two, in our view, we're like exceptional kids.
- [37:41]
B
Your story's not isolated, though. And something I tell patients all the time is that, quote, ugly or bad? Embryos make beautiful, perfect children. Because there's a limitation to what we can do when it comes to thinking about embryo quality. Let's just think about, we have got an egg, it gets fertilized by a sperm. It goes from this one single cell into the implantation stage, which now we're taking almost all embryos to the blastocyst stage, which is day five or six. The embryo will be about 300 cells. It expanded, it'll be like a ball. Spherical cells that become the placenta and a small bundle of cells that become the baby on the inside. And they can be frozen, they can be genetically tested. And most of the time we're doing genetic testing. At this stage, we're looking for aneuploidy, meaning does the embryo have the right number of chromosomes? Well, before we could do this type of pre implantation genetic testing where we could take some cells from the placenta and see if the embryos were normal. The only way we could judge how good an embryo was was to give it a morphological grade. And I call this the embryo beauty pageant score. Right? It is really a human is looking under the microscope and deciding how expanded is the soccer ball, is it deflated, is it expanded? And it gets a number score. It then is how even and symmetric is the inner cell mass, the little part that will become the baby, how even and symmetric is the outer cell mass that will become the placenta. And it gets graded like school on those aspects. A, B, C, above average, average, poor. And most of the times, embryos that are less than that, you tend not to see because they didn't develop into a structure well enough to quantify. So we really want to think about, you can have these AA embryos all the way down to CC embryos. And in general, if I send them all off to a lab, ones that are AA have a higher likelihood of being genetically normal than ones that are cc. But it's not all or nothing, meaning poor looking embryos can absolutely be genetically normal. They can have a lot of. They can be very normal functioning. It's very subjective. Many studies have shown that embryologists who look under the microscope will grade even the same embryo seen on a different day, the same embryologist will grade it differently. So there's. Right, so there's a lot of, you know, beauty's in the eye of the beholder and in the moment of which you see it. So I Always give it with a grain of salt. If we do genetic testing, having that. That normalcy trumps. I don't care now what its morphologic grade was. We'll. We'll transfer it no matter what. And if we don't have genetic testing, like, there are no embryos that we wouldn't transfer based on that morphology, we might strategize to try to get you pregnant faster by transferring some of the, quote, better ones first because overall they have more odds.
- [40:29]
A
That is such helpful perspective because I can't help but think of the psychological weight it puts on a woman at a couple, because you're, You're. You're essentially saying to someone, well, this is. These are the. These are the winners. If, if you're not framing in the right context so there's more pressure, and if that doesn't work psychologically, you're already losing hope, like, to some degree.
- [40:52]
B
Jason, you went through ivf, so you understand this. And the one thing I want to say, if anybody, is, is that it is so important to educate yourself on what is supposed to happen and what things mean so that you can ask the right questions. I recently saw a patient who was told none of her eggs fertilized and she had bad egg quality by an outside clinic. And when she came to see me and we looked at the records, none of her eggs were mature. And that is a thing with the. The IVF protocol, how big they get. And not all eggs are always mature. And sometimes you should try another cycle and make some changes to try to get them. But an egg that is not mature cannot fertilize. So she's been walking around for the past year since this cycle, thinking, all of my eggs are bad, because she was told, your egg quality is so bad, none of them fertilized. But the truth is that none of her eggs got to maturity in the cycle, and she should have been told, let's do another one and see if we can get there. But the mental impact of thinking all my eggs are bad, that's profound. And even. And her hearing that for me, I mean, she started crying, just thinking, I have been feeling like I'm the failure. This is my fault. What have I done? And it really speaks to the fact that the words we use as physicians with our patients matter so much. And framing things in a way. I mean, not just that they understand, but it's also, you know, that is rooted in truth, not quantifying embryos as good or bad. I tell all my patients, there's all of these Embryos, we would transfer. I mean, not at once, but saying these are all options for us. I don't want us to feel like one is lesser than the other, nor should we go into that with a mindset that would make us feel that way.
- [42:35]
A
You know, I'll just give a shout out again to NYC IVF. Dr. Alassar, husband and wife. The husband unfortunately passed away, but we. We started out at a factory and like, things went really south. We ended up there. And Dr. Lasso, they kept on saying that to Colleen, my wife, like, you're, like, this is going to happen. Like, there's nothing. Like, we just need to get more at bats. Like, like there was a message of hope. And the bedside matter, even on some of those really rough days was, you know, I know this is like, sat there, listen, but, like, continued with this message of hope. And I think that's just so critical versus, I think, look, I love science. I know you love science too, but I think you can get lost in the. In the weeds, so to speak, as you start going down this rabbit hole of, well, the embryo ranking. And this is what dehumanizes this process, which science does matter and is like, 50 years ago, like, our options were very limited. But you just can never underestimate the role that psychology, like having a physician who actually cares and listens and understands the nuance of communication and how vital it is.
- [43:49]
B
A thousand percent. Yes. It also, this field is rapidly changing. It would be so naive to act like we have all the science that exists on it or that it's not constantly changing, meaning we've got to approach that with respect. I always tell my patients I can't always control the outcome. I mean, I'm going to try because I love data and science and I'm controlling. But what I can absolutely control is your experience on the journey that you have your questions answered. You know, why we're doing the things we're doing. You feel like we're moving in the direction we should and we feel optimistic about the future. Like, those are things we can do together. And I think as we are in an era, we've got to be frank about it. Medicine is not great. There's a lot of private equity buying medical practices. We see a lot of IVF specifically being turned into IVF factories and tons of patients. You barely see a doctor. I mean, I own a fertility clinic in Austin with my partner, so that there can be two of us. We're very small. We do things very differently because we worked at a prior place. We know what it's like. But if you're the patient and you're just out of place, you may not know that that's not the experience you have to have. So one of the things I love most about what you shared is that you left somewhere where you weren't having maybe the experience that was ideal and went somewhere. And a lot of that is how the patient or experience, how the doctor's talking to you, how the whole team is interacting. And people hopefully should feel empowered to please, please, please. If you're in the midst of infertility and you hear this or you have somebody who is, get a second opinion, send your records out, meet with somebody else. It's. This is too important and too personal to. To not feel confident in the plan ahead.
- [45:29]
A
So in closing, where do you think this field is going? I can't help but think. And it's been a while since we went through our process. It's been a decade. There's the movie Gattaca, I don't know if you remember that, with Ethan Hawke and, you know, the Superior Genetic Child. And what's your take on where this is going in the future?
- [45:48]
B
Let's answer this in two part where it is going that I am excited about. I am excited about options to potentially extend ovarian lifespan, improve function of ovarian follicles, or even to mature eggs outside the body. Because right now, if we kind of walk back, we talked about with ivf, as you start to run out of eggs, I can only get the eggs that are outside the vault to grow. So something called in vitro maturation, where we're able to get eggs out of the vault, for lack of a better word, and mature them in a lab that will really open up doors of opportunity for women who have low egg counts or who are older. I love opportunities to think about medications that might extend ovarian lifespan. Think about rapamycin or ovarian prp. So options that are helping ovarian ovaries function longer, slash, improve reproductive outcomes for patients who are finding themselves, you know, at the end of that timeline, so that time doesn't have to be the independent variable. I think that's really exciting. Where I don't love. And this is a problem right now, right. AI and tech are changing things faster than science can keep up. And I don't love what we're right now calling pgtp. Pre implantation genetic testing. That's that embryo testing we talked about. I described it as checking the number of chromosomes an embryo has. That's Called for aneuploidy pgta. That's really, well, standard, well studied. There's a couple other times. One is to check for a single gene called pgtm. For example, if you and your wife both carry the gene for cystic fibrosis, we could go look on that chromosome and see if this child would be affected. We can also look to see if the chromosomes are in the right order. That's called pgtsr. So this is all we'll say, medical diagnosis, pre implantation, genetic testing for a diagnosis. PGTP is for what's called polygenetic diseases. This is what a lot of companies are pushing right now. You might have seen it where they are saying they can take your embryo sample and for the low, low price of $50,000, they can run it to see if your child would be at risk for type 1 diabetes or autism, or if they would be tall or if they would have blue eyes. And what they're using is genetic trait databases, mostly from European adults. And they're trying to apply these embryo samples using AI to stratify risk. By no means is that a proven technology. So, one, we're not close to the place where we can actually do Gattaca, even though that's what companies like this might be selling. I think they're predatory right now on people who, like, I saw patients and he's, you know, a really terrible type 1 diabetic, and he'd really love not to pass that on. So I think sometimes patients are coming from a really vulnerable state or they had, you know, a family member with really terrible autism and they watch that. So I, I don't think patients see this and they think, oh my gosh, that would be incredible. And maybe not understanding that the science doesn't support that as diagnostic technology. And I think it's scary where tech companies can say, we can now do this, yet it's all AI driven from databases not truly held up. So there has to be a little bit of a buyer beware. And this is why when it comes to IVF specifically, you gotta have a doctor you trust, somebody who's willing to walk that line of you're not having standard outcomes with traditional approaches, so what out there, hypothetically can help us, but also to say that is not anywhere near proven nor where we should spend our time, money, resources. So there's this delicate balance to be an IVF doctor where we know things are changing and we want to stay ahead of it, we want to apply it to the individual patient, but we also want to be wary of things that are not going to be proven, slash, don't hold any quote benefit at the current moment and are more predatory in behavior.
- [49:32]
A
Well said. So in closing, the book is the Fertility Fertility Formula. And the book is amazing, I think applicable for women of all ages and men because it takes two to tango. Can you share more about the book where people can find you? What's next for you?
- [49:50]
B
Absolutely. The book, as you said, the Fertility Formula so walks through a couple different parts. The first part is a lot of what we talked about today. Inflammation impacting how your ovaries function, normal ovarian function, what ovarian reserve is and what influences it. Then we talk about cycle abnormalities. And we didn't even dive into, you know, learning to track your cycle as a red flag. But that's all deep in the book. And then what you should do if you're trying to get pregnant or you have infertility. But half the book are those lifestyle pillars and really showing you the data on how it impacts ovarian function from sleep stress, muscle toxins and dietary options, really trying to give people the blueprint to try to improve, you know, their ovarian health and function earlier. And then my, you know, currently, as you and I talked about, too, I have a big passion in ovarian longevity and understanding how we can try to extend this ovarian lifespan and how we help women in the middle when it comes to that. Right now, everybody calls it perimenopause. Clinically, we call it diminished ovarian reserve. It's really the same thing. And I'm on Instagram, Natalie Crawford MD and you can buy the book anywhere you buy books. It comes out April 14th from Penguin Random House. And I'm so excited. I've worked on it for years and years, and it's really meant to help anybody before you want kids, if you're in the middle of the journey and even after, if you're just trying to get a sense of your hormones and what's normal and what you can do and how to advocate for yourself.
- [51:13]
A
Amazing. Thank you so much, Natalie.
- [51:15]
B
Thank you, Jason, for having me.