How Women Can Improve Their Fertility & Hormone Health | Dr. Natalie Crawford

Dr. Natalie Crawford:
Everybody should get an AMH test. I think it's a very important marker. If you are listening to this and you want kids one day, ask your doctor for this test. It is not a test of egg quality. And we talked about what egg quality is, right? Genetics and egg competency. But it is a check of how many eggs you have, and that knowledge can be really impactful for how you view your future and your plan.

Andrew Huberman:
Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Natalie Crawford. Dr. Natalie Crawford is a double board-certified physician specializing in obstetrics and gynecology, fertility, and reproductive health. Today, we discuss the actionable steps that all women can take to improve their reproductive and hormone health, both to enhance probability of successful pregnancy, but also because fertility and hormone health are strong correlates of general health and longevity. Dr. Crawford shares what all women, regardless of age or reproductive goals, can do to enhance their health using lifestyle, nutrition, supplementation, and prescription medical tools that she indeed uses in her practice. We also have a very honest discussion about biological versus chronological age and fertility, why age is not just a number, but also why it is that many women do successfully conceive in their 40s. Of course, there's a lot of information online nowadays about women's hormones, fertility, and health. Today, thanks to Dr. Crawford, you'll learn what is known and documented and what she has herself consistently observed clinically in her practice about women's health and fertility. Few, if any, people have Dr. Crawford's training, clinical acumen, understanding of the new research, and incredible ability to communicate the well- and lesser-known actionable steps for improving female health. Dr. Crawford also has a new book out entitled The Fertility Formula: Take Control of Your Reproductive Future, which, again, focuses on reproductive health, but also hormone health and how both of those things impact female health in the short and long term. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public. In keeping with that theme, today's episode does include sponsors. And now for my discussion with Dr. Natalie Crawford. Dr. Natalie Crawford, welcome back.

Dr. Natalie Crawford:
Thank you so much for having me. I'm thrilled to be here.

Andrew Huberman:
And congratulations on your new book-

Dr. Natalie Crawford:
Thank you

Andrew Huberman:
... The Fertility Formula. It's no small feat to complete a book, and it's especially a big feat to complete a book that offers people so much advice, not just people who want to get pregnant, but also looking at things through the lens of fertility as an important health metric.

Dr. Natalie Crawford:
Yes.

Andrew Huberman:
So, yeah.

Dr. Natalie Crawford:
Thank you so much. You know what goes into writing a book, and it's always been this aspirational goal of mine. And after educating and talking about fertility with patients and people online, it's been something I've wanted to do. But I will say it is a much bigger feat to go through it-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... to work with editors, to try to refine within your word count, I was 20,000 words over and try to bring it back in. So thank you for having me and for holding it up and reading it early and sharing your endorsement for it, too. That means so much.

Andrew Huberman:
Yeah. I am insisting as much as one can insist that various people in my life read this book, including family members and other people, because again, it's not just about people who want to have children or who already have children, but fertility as a way of kind of knowing where one is in their health arc, in their life arc. So if you don't mind, how should people think about fertility purely as a readout of health? Just how do you frame this for-- If somebody comes to you and says, listen, they have kids, or they don't want kids-

Dr. Natalie Crawford:
Mm

Andrew Huberman:
... or they're not sure if they want kids, but why use fertility as a lens on general health?

Dr. Natalie Crawford:
Yeah. Fertility is a health marker, and I love that you bring that up the top of the episode here, because so often patients, women specifically, think fertility is only the ability to get pregnant. We really simplify it into this one phase of life. But if we want to zoom out, your fertility is a sign that you have good hormonal health, good cellular, good metabolic health, because it takes so many different moving parts to ovulate, for an egg to allow a sperm to fertilize, to implant, to get pregnant. But also your hormonal health and the ovarian function is really going to impact your entire life, how you feel on a day-to-day as a woman. But if we want to be really specific, if you have infertility, you have increased rates of metabolic syndrome, cancer, heart attack, stroke, and dying early. Those are extremely scary statistics, and you know I had my own infertility journey, so I fall into this category. But the reason why is not that infertility causes any of those things directly. It's that for most people, it's one of the first warning signs that something is not right in their body and that there's higher levels of chronic inflammation or insulin resistance that we know can impact long-term health outcomes.

Andrew Huberman:
For women who are still of reproductive age-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... and I realize there's no strict cutoff, we can and certainly will talk about what are the measures, direct and indirect, of fertility that can give them a window into their kind of health span risk factors, lifespan risk factors. For women that have already reached menopause or in perimenopause, how should they think about fertility as a health marker? Meaning, if somebody is past the point where they can safely get pregnant-

Dr. Natalie Crawford:
Mm-hmm

Andrew Huberman:
... does that mean that their periods are no longer informative? I imagine their periods, features about their menstrual cycle are still very informative about their general health.

Dr. Natalie Crawford:
As long as you're having a menstrual cycle, it is a sign that you're ovulating and you theoretically could get pregnant. So I think it's really important to say that even in perimenopause, which is the transitional time between having regular, appropriate hormonal function, that reliable Characteristic of the ovary responding to the brain. This is the transition time as you're starting to get to a lower egg count, that you will eventually start to see some cycle changes, but you also have a lot of hormone dysfunction. But you can still get pregnant. And in fact, I see a fair amount of patients who said, "I thought I was past that stage of my life based on my age." But if you're still having periods, it's a really important window into your hormonal health. It can tell you a lot about your body, especially if you know when you ovulate, and we can look at the distinct phases of the cycle, the follicular phase and the luteal phase. When we're a little bit past this, menopause by definition, which I hate, is 12 months without a period. So menopause is one single day in time. Really, it means you've been in ovarian failure for 12 months before you'll magically get this diagnosis. But menopause at its purest is ovarian failure. The ovaries no longer have the capability to respond to the brain signals. You're not going to make estrogen or progesterone anymore. At that time, a woman's metabolic health completely changes, but the age of which you went through menopause really can impact your reproductive health outcomes long term. And some of the characteristics you might have had in your cycle when we look backwards can inform us some about your cellular health now. So it's still really important to think back and move forward. And then on a bigger scale, we're seeing the tide turn on hormone replacement therapy, and I know that's not what this entire episode's about, but as a reproductive endocrinologist, I love estrogen. I love hormones. And I think it's really important for women to know that you can start hormone replacement therapy at any time. So even though a long time ago we felt really comfortable starting it right at the time of menopause, we're starting to see benefits starting it in the perimenopausal period. We see a benefit starting it once you have menopause. But I think it's a disservice to women to make them have no period, ovarian failure for 12 months, no estrogen, feel terrible, before we'll allow them to have hormone replacement therapy.

Andrew Huberman:
Yeah, this is such an important theme and if I may, I realize I have to be very careful- ... to not draw parallels to men's hormonal health when talking about women's hormonal health, because it's not a one-for-one. They're very distinct processes. On the other hand, I think thematically what I'm about to say, I believe holds, so hopefully it won't upset too many people. Which is, for many years now, for reasons that are unfair, hormone replacement therapy sort of became widely available for men before it became-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... widely available for women. There are reasons for this. We don't have to go into it, but they're the kind of obvious ones, that things were pushed to market more quickly and so forth. But there's been this idea, there it's usually testosterone replacement therapy, right? And there was this idea that unless somebody fell below 300 nanograms per deciliter-

Dr. Natalie Crawford:
Mm-hmm

Andrew Huberman:
... for a male, that they shouldn't get testosterone replacement therapy. Now it's kind of understood that if somebody chooses, they can usually find a doctor that if they're at the low end of normal, they can push to the high end of normal or to the middle of the range, so that they can get their symptoms away-

Dr. Natalie Crawford:
Optimize

Andrew Huberman:
... and just feel-- Right, to optimize within the normal range. And so I'm relieved to hear that you're saying the same is true for women. And I'm relieved to hear it because I think that having these strict cutoffs of no periods for a year, well, I mean, it could take a long time to reach that. I mean, what if it's two periods per year, right? Does that mean that that person-

Dr. Natalie Crawford:
Exactly

Andrew Huberman:
... doesn't deserve the therapy? Which is essentially what-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... I think you're saying. So the R in hormone replacement is the dangerous letter, in my opinion, because there is this notion of augmenting hormones.

Dr. Natalie Crawford:
Exactly.

Andrew Huberman:
Okay, so forgive me for going long, but I think the two situations, it would be great if both women and men could augment their hormones to be at the high end of normal or wherever puts them in a place where they're not experiencing symptoms.

Dr. Natalie Crawford:
Absolutely. We know that as humans, we now have longer lifespans, we outlive our reproductive hormones, yet they are essential for our day-to-day function and to feel our best, and we should at least be given the opportunity to have our symptoms evaluated, to be offered hormone therapy if we want it, and to not have to have these harsh cutoffs, especially for something that can be so protective long term. I mean, for women, we see it be cardio protective. It can help lower the risk of Alzheimer's disease. Of course, it can be protective for your bones. So I love this greater discussion, and it really stems from learning about your body, knowing what's normal so you can advocate for what's not normal, and really feeling like you have your own agency over your health and your own future.

Andrew Huberman:
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Dr. Natalie Crawford:
Mm-hmm

Andrew Huberman:
... replacement therapy for people that are out of range, that are too low, out of the normal reference range. Hormone augmentation therapy for people that want to push within the normal range. And then, of course, there's super physiological stuff, and that's kind of how all of this got here was there were a bunch of mainly guys taking tons of anabolic steroids.

Dr. Natalie Crawford:
Mm-hmm.

Andrew Huberman:
And then estrogen's a steroid, testosterone's a steroid, and then it just became a long road to get to this point where people like you are able to even talk about this, right? I think 10 years ago, I think the medical profession was not open to the idea that a 40-year-old woman, for instance-

Dr. Natalie Crawford:
Right

Andrew Huberman:
... who had not yet undergone menopause by the strict definition, would take estrogen. It was seen as a risk as opposed to a benefit.

Dr. Natalie Crawford:
Isn't it interesting? And by professional organizations, they would even call it menopausal hormone therapy, MHT-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... not even just hormone replacement therapy. And I talk about this a lot with my patients, the difference in replacing a hormone, we'll use in an embryo transfer cycle. If I'm going to give you estrogen, you haven't ovulated, I now have to replace your progesterone, or I have to give it in a certain format that it can get to high enough levels, versus supplementing. Your body's making some, and we're supplementing that or augmenting it, like you said, to get it to the appropriate level or to make sure we have enough. I've given hormone therapy for a long time. I've been out of practice for over 10 years. And what's so interesting is that we'll use premature ovarian failure. So going into ovarian failure before age 40, well accepted that these women need hormone replacement, even when they still have the low end of hormonal function. So in this population, we've been doing it for a really long time. But for menopause, it's been so frowned upon because of the WHI and fear-based tactics about what would happen with hormone replacement. So it's interesting, and I'm really glad to see the tide is turning, and we're really allowing people to stand up for themselves, to also know what's normal within their body, which sounds so common. But if we think about it, many women have been dismissed and gaslit for so long. And if you go to your doctor and you talk about your painful periods or your irregular cycles or your bloating that you have with your period and some of these red flag warning signs, the spotting, the this, and it gets pushed to the side. When you start to go through actual hormonal change later, it's really hard to then believe yourself.

Andrew Huberman:
Mm.

Dr. Natalie Crawford:
And so I think it's really important. I have a whole chapter in the book about how to learn to track your cycle and your ovulation and really learn to see the red flags your body gives you, not just if you want to get pregnant now, but to know that your hormones are really functioning as they should. And that's going to help you stand up for yourself later when you're in this transitional period, because perimenopause or diminished ovarian reserve, like we call it in the fertility world, that can last five to 10 years. That can be a really long transitional period that women are going through, and they deserve support if they're not feeling their best.

Andrew Huberman:
Now I want to call it hormone augmentation. Let's just call it hormone replacement for sake of simplicity. Hormone therapies for women, do they always start with estrogen when it comes to trying to encourage fertility or push fertility or wellbeing out into more years?

Dr. Natalie Crawford:
That's an interesting question. I think when it comes to hormone replacement therapy in general, we've got estrogen, progesterone, testosterone.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
Most women, when they start not reliably making estrogen, that's when they really start to feel bad. And so typically, some type of estrogen replacement, and there's many different ways. There's patches, there's pills, there's vaginal inserts, there's vaginal cream, often helps some of the symptoms they're having. But progesterone alone or in combination can be a big player. Progesterone also is not made if you're not ovulating well, so there's this tandem where often you need both of them. But I have some perimenopausal patients who feel great on just progesterone. To me, testosterone's the last one we add to the mix, and it will always depend on clinical scenario. There's nuance. Estrogen and testosterone can convert back and forth. So for most women, if they are adequately being replaced on estrogen and they still have functioning ovaries, so in this transitional period, they tend to not need testosterone.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
But that's never 100% of the time. I think greater to your question about is there a way for us to extend the ovarian lifespan is a really good one We know that women who go into ovarian failure early, so when we look at that, we call it POI, the premature ovarian insufficiency group, their ovaries have more inflammatory markers. They have more chronic inflammation and fibrosis inside the ovary. There's a higher prevalence with autoimmune disease or chronic inflammatory disorders. So I think there's also something to be said, despite not having the perfect paper to sit here and say that we know a variety of different things that increase chronic inflammation, cause you to have a lower egg count, and are associated with earlier menopause or earlier ovarian failure, that paying attention to these factors earlier in your life, whether it's controlling an autoimmune disease, earlier diagnosis of Hashimoto's, whether it's treating your endometriosis or cultivating a lifestyle that's decreasing inflammation, right? Avoiding certain toxins, eating anti-inflammatory foods, the type of exercise, and how we deal with those lifestyle tenets, that that likely has the capability to extend our ovarian lifespan to the degree that it can.

Andrew Huberman:
I know these days people are very concerned about plastics.

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
And you mentioned toxins, so I was going to get to this later, but I'll just ask now. How concerned are you about plastic water bottles and-- We can't avoid exposure to plastics, and I think one thing that Dr. Rhonda Patrick has done nicely is to highlight the fact that the really small, hence microplastics, are really the ones that we worry about the most because they can get into so many tissues. But we're constantly ingesting plastic. Some of them are just excreted because they're big, but some of them get into our cells. Are there any data that have you, or observational data that have you genuinely concerned that plastics are becoming more of an issue vis-à-vis fertility?

Dr. Natalie Crawford:
There definitely is concern. I always want to frame this, and you did a nice job of it, so I'll double down. The goal when we talk about toxin avoidance is you can't avoid everything. You cannot avoid every toxin in this world, nor should we try to have this all-or-nothing mentality, which is what so many people do. "Oh, if I can't avoid it, I just will totally ignore it then in general." When we want to think about toxins, there's many different mechanisms why plastics can be harmful. When it comes to microplastics, as you mentioned, we know they can accumulate in the ovary. So if we want to be really transparent and simple, your ovaries must function in order for you to make estrogen and progesterone, in order for you to ovulate, in order for you to get pregnant. So if microplastics can accumulate inside the ovary, that's obviously detrimental towards fertility or ovarian function. On a greater scale, we know that some of the endocrine-disrupting chemicals that are in plastics have been associated with worse IVF outcomes, lower live birth rates, longer time to pregnancy. And these are population-based cohort studies, so there's no randomized control trial. So we have to limit it. And there's some truth to the fact that people who might be more exposed to plastics may have other lifestyle factors, such as we know plastics can also be in food wrappers, right? So maybe they have more of an ultra-processed food diet. So it's never one specific thing, but I look at all of these lifestyle factors, and I include toxins as one of them. These are all either contributing to your inflammatory burden or they're helping you. And when we start thinking about optimal hormonal health and fertility, it is your decision every single day. Am I drinking water out of this cup or out of a plastic bottle? Am I going to lift weights, do nothing? Am I going to run? How much sleep am I going to get? What foods am I going to eat? How do I deal with stress? And these choices, even though one single one's not going to make it or break it, together they can add up to that inflammatory burden, or they can help decrease it.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
And that chronic inflammation does in fact matter to your fertility and does worry me.

Andrew Huberman:
I realize I'm jumping around here a bit-

Dr. Natalie Crawford:
Mm

Andrew Huberman:
... but in just thinking about what seems to be on a lot of people's mind, I took an informal poll of some people heading into this because obviously I only know my own experience as a male. So to a number of women, I asked the question, "What are you wondering about?" And a common question was, it seems that for some women, if they've been pregnant once before, they have it in mind that it's going to be easy for them to get pregnant again later. Or easier. And of course, they understand the logic that they were younger before, by definition, even if it's a year, right? And that fertility drops off with time. But there seems to be this kind of belief that if one was pregnant before, that it's going to be possible to get pregnant again within the normal windows of biological windows for getting pregnant.

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
Is there any evidence that having been pregnant before makes it easier to get pregnant again that's separate from the fact that obviously they were pregnant before? I realize that it's a convoluted question, but it's not a perfect experiment, right? Because if they've been pregnant before, obviously they can get pregnant. If they haven't, the control group is not a very-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... it's not a good control group for an experiment. But within the person, if they've been pregnant before, can they exhale a little bit that, yes, they can get pregnant?

Dr. Natalie Crawford:
I did fellowship research with the primary investigator on a large cohort study, one of the biggest ones we have on natural fertility, and this study was called Time to Conceive. And it was looking at women who did not have a history of infertility, who were trying to get pregnant, who were 30 and older, and then we looked at different variables of them. And one of the most startling pieces of data is that there's a huge age-related impact of fertility, right? This data set set the standards for the numbers that we quote, meaning if I will sit here and say, "If you're trying to get pregnant with your first child and you're 30, you'll have a 20% chance per month," right? The finest point we look at in natural fertility studies is called fecundability, the probability of pregnancy per month. But as you age, when you're 35 to 36, that number will be 11% to 12% per month. At age 38, it'll be 5% per month, and at 40 and beyond, it'll be 3% per month. Importantly, for the person hearing this, none of those numbers are zero. And so by no means do we mean you can't get pregnant but in the group who had a child before and were trying to conceive with the same partner that number stayed between 18 to 20% up till age 37-

Andrew Huberman:
Wow

Dr. Natalie Crawford:
... and then it dropped. So we do see that there is this protective benefit for a multitude of reasons, right? You conceived with that person, so they had sperm, right?

Andrew Huberman:
Yeah.

Dr. Natalie Crawford:
Sometimes I find out some patients the male partner has no sperm, and we didn't know all that time they were trying.

Andrew Huberman:
Oh, my goodness.

Dr. Natalie Crawford:
Right? Oh, I've had patients try for years, be dismissed by their doctor.

Andrew Huberman:
Because men and women mistakenly think that because there's semen, there's sperm.

Dr. Natalie Crawford:
Exactly. There's ejaculate, so there must be sperm-

Andrew Huberman:
Mm

Dr. Natalie Crawford:
... inside of it.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
And then when we find out there's none, it's heartbreaking. It's a big reason why we can segue and say one of the things I really hate the most right now about my field is that by definition, infertility is a failure, and we don't even recommend testing or screening or talk about a preventive approach at all until you have failed. Yet, if we look at the population, say, okay, the definition of infertility is trying to get pregnant for 12 months, and then once you've reached that point, well, now we'll check a semen analysis. Now we'll do an anatomical investigation. Now we'll check your ovarian reserve. Now we will discuss if you're ovulating. So we're making you go through this period of time where you're trying, and yes, maybe the majority of people will get pregnant, but most people who do will get pregnant in the first six months. So 72% of people will get pregnant in that first six months of trying, and only 13% will get pregnant in the next six months of trying. That's why if you're 35 and older, we will shorten that testing interval down to six months. But sitting across from so many people who've tried and tried, went to their doctor, their doctor said, "Oh, you're fine. You're young. You're this, you're that," forced them to try longer and fail, and then to find out fallopian tubes are blocked. They had a birth defect of the uterus. He had no sperm. She had low ovarian reserve. And they would've intervened differently back at time period A had they had that data, really makes me feel like we have to switch how we approach infertility in the world where infertility rates are rising, women are waiting later to get pregnant. It doesn't really make sense to make people fail first before we'll even do an investigation. We should test things, and if it's all normal, maybe you do just go try your six or 12 months.

Andrew Huberman:
Yeah.

Dr. Natalie Crawford:
We would capture people who don't get pregnant and be able to help them at a sooner time period, which is so valuable. So to your origin question, there is data that having a child previously puts you statistically at a higher chance of getting pregnant again. But secondary infertility is real. This is where you've gotten pregnant before, and now you're having a hard time conceiving your second child. I want to acknowledge that it's really hard for people who walk it because they weren't expecting it. They're a little underprepared for it because they said, "Oh, I got pregnant so fast before." They come into it just assuming it will be as easy. They watch their children have a longer age gap, a bigger age gap than they wanted. But also, they don't really fit into the community, meaning there's a really robust infertility community, and they support each other. And so many patients who have secondary infertility say they feel caught in between feeling guilty that their child's not enough for wanting more. Of course, they're thankful for their child, but not really fitting into that category, yet also simultaneously feeling left behind their friend group or their family group or watching their family start to look differently. And so even in women who've had a prior child, age does become impactful. It's not the only variable. We also see that sperm counts change with age, so your partner's sperm count will change with age. We see egg quality starts to change with age, largely because metabolic health changes with age as well. And then we see things like endometriosis and adenomyosis, which are tincture of time diseases. It's simply you've had more time, so there's a higher probability that these diseases could be present. So I think it's important to say, yes, you can probably take a sigh of relief that most likely you won't have trouble again. But if you've been trying those six months after and you're not pregnant, I would say kind of at the longest, go and get an evaluation. And if you're a little bit older or maybe started your journey a little bit later, it's never too early to get an evaluation for anybody at any time because you can't make decisions on data you don't know.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
I'm a big fan of knowing the data and then making the choice that's right for you and your circumstance versus taking population-based data and just applying it to every single person.

Andrew Huberman:
Yeah, all excellent points. And with respect to the sperm testing, since clearly there are men who think they're making sperm, and they're not, there are at-home tests of that as well. So once again, men have it a little bit easier. They can do it at home. Although, I don't know how high quality the at-home tests are.

Dr. Natalie Crawford:
There are some that are just telling you almost like a pregnancy test, plus, minus, are sperm present, are sperm not.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
Of course, that's not really telling you the full picture. There are, though, some mail-in tests that go to a true lab that we would even take as valid.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
So it's called a CLIA certified lab, C-L-I-A, for somebody listening, and you can find some of these online mail-in sperm tests and collect a sample. They send you the whole kit. You mail it off. It's very valid.

Andrew Huberman:
Mm.

Dr. Natalie Crawford:
And you get all the sperm parameters that we would then look for. So that's a great way to get data yourself and not have to have your doctor tell you no or go to a fertility clinic. I mean, we'll do a semen analysis for anybody who calls, and most clinics will. It's usually earlier that patients are getting roadblocked, whether it's their PCP or their regular OBGYN. They're getting dismissed and just, "Oh, just try first. It's probably fine."

Andrew Huberman:
Mm-hmm. You mentioned that if a woman has had a successful pregnancy that the probability of getting pregnant again is significantly higher-

Dr. Natalie Crawford:
Mm

Andrew Huberman:
... although with the caveats you mentioned. Is there any data about if someone has been pregnant and either terminated or lost the pregnancy, whether or not that's related to ability to get pregnant again later?

Dr. Natalie Crawford:
That's a good question. Most of the data that exists is looking at prior live birth. So I think there's a couple things. If you've gotten pregnant, regardless of the outcome of that pregnancy If it's with the same partner, we can feel confident that they had sperm present, so that's already one leg up over never getting pregnant. If it was an intrauterine pregnancy, we know at least one fallopian tube was functioning, so that's also in the camp of we're checking some mental boxes of some of the things that we think about. And we know your body could accept an embryo implanting, at least to some degree. The top cause of pregnancy loss is going to be random genetic abnormality.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
This wasn't the right embryo, or the embryo didn't have the right capacity or capability to truly implant. So I think that should give you some sigh of relief-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... that it's probably going to be a little bit easier because certain boxes are checked. I think it's also really important to say, I had four pregnancy losses myself. I don't know if you know this. So I had four pregnancy losses.

Andrew Huberman:
From your book.

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
Yeah. And by the way, I really appreciate the personal story sharing in the book because it really clearly was in service to your patients and to the reader. And even as a male who-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... can't relate certainly to certain aspects of all this, it was not only very moving, but it was really a testament to just how that sort of thing lands, and then the process of trying to sort out what's real. And it just made me even more grateful for the other information. Because otherwise, it would sort of be like if I'm talking about ovarian health. Right? Which I've talked about on podcasts, but-

Dr. Natalie Crawford:
Which we're talking about.

Andrew Huberman:
Yeah, right. With all the caveats, but of course, how could I possibly know? So your personal experience, while the reader in I feel and felt for you in reading it, it is super impactful because there's a level of trust that just comes from somebody who's been through that whole jungle.

Dr. Natalie Crawford:
Thank you. I'll try not to cry on this show about it, which is funny because it's so long ago, right? I have two children now, had them after this journey, and it was terrible for so many different reasons. Of course, going through pregnancy loss is an emotional rollercoaster. I started to have a lot of self-blame against myself, felt like it was my own body, something was wrong. And professionally, what I was unprepared for is this was the end of OBGYN and then the beginning of my reproductive endocrinology fellowship. So I felt like, how am I going to be a fertility doctor, Andrew, if I can't even get myself pregnant? Right? The professional impact of how it made me view myself and my space, I was so unprepared for, right? Especially in an era where you separate your personal and professional life, which is what was 100% accepted back then. My last pregnancy loss was an ectopic pregnancy. My fertility nurse had to give me my methotrexate shot. Everybody knew about it, and I felt like a really big failure. And when I sought help to say, "It'll happen, just relax, there's nothing you can do," or even, "Just do IVF," felt so dismissive of what I felt like was true as the patient experience. Say, "Well, what about this symptom?" or, "What about this question?" And just really, really pushed aside. And I'll be honest, my whole career is different because of it, which, isn't that interesting how sometimes things happen to us that are not ideal and that can be really terrible. I have the two kids I'm meant to have, but also I have forever viewed fertility differently. In fact, all my fellowship research was on natural fertility because of it. Because I said at the core, I want to know why some people get pregnant naturally and why other people don't. I really want to know that. I want to do epidemiologic research. I got a master's in clinical research because that research is very complicated to understand, and most fellows do an IVF lab project, which is great, but it's a lot more of a controlled environment. And then I've been so passionate about talking about it since then. And so I think to walk back what I wanted to say, though, is if you've gone through pregnancy loss, I don't want to ever dismiss how terrible that experience is, and sometimes it can feel that way by me sitting here as a professional and saying, "Oh, you had a pregnancy loss, so that could be a good sign for the future."

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
And I don't want anybody to ever feel that hearing it, but it does tell us that certain systems are intact. On the other hand, after two pregnancy losses, you need an evaluation. The evaluation is for certain blood tests, a semen analysis, a sperm fragmentation, and a uterine and tubal evaluation. That can be moved up to one if you had heavy blood loss, needed a D&C procedure, if your periods have changed afterward. If anything was really off, you can always get tested. And we never want to be in the world where we used to make women go through three pregnancy losses before they would get an evaluation. And I fell into that camp. After two, I said, "Shouldn't we do tests? I'm starting to fall off the curve here. Is something wrong?" And I was told, "You need to have another pregnancy loss before we'll do those tests." And that's the worst thing, the worst feeling, that I had to fail again to a certain degree and lose a pregnancy before they would even investigate why.

Andrew Huberman:
Yeah, this theme, it seems, of it's only menopause when you haven't had a period for a year. You have to have two pregnancy losses, and then we can put you into this category of amenable for treatment. It's something really backwards about all of that.

Dr. Natalie Crawford:
It is.

Andrew Huberman:
I imagine with your book and you being public facing with health information, and hopefully others with you in your field, that eventually this will change. If I were to draw the parallel to psychiatry, which isn't a fair one, should someone really have to be waking up at 3:00 in the morning for an entire year and have no hope for the future and be near suicidal before they get whatever the adequate treatment is?

Dr. Natalie Crawford:
Right. Before we'll treat them for depression or whatever's going on.

Andrew Huberman:
Yeah.

Dr. Natalie Crawford:
It doesn't make sense. I don't think it serves us. And I will say this, too. We're starting to see a change.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
My big lofty hope for the book is that it changes the entire field of fertility. I understand why OBGYN used to take care of this. And then at some point, they said, "Some people have infertility. Let's draw a line in the sand and have some people specialize in this." Right? And I did three years of training in that after OBGYN. But at the same point, it doesn't make sense to practice that way. It doesn't make sense to force people to fail. And I might tell you, "Hey, the greatest likelihood is all the tests will come back normal," but we should do them because sometimes it doesn't. Right? If I look across somebody who has recurrent pregnancy loss and I say, "80% of the time, every test will come back normal." But 20% is a big number. That's a lot of people who maybe it's a simple medication, maybe it's a procedure. Something can markedly change what they're going through. And in the same breath, the 80% really need specialized care because what's really going on if we don't have an easy test for it? So I agree with you. I think the whole field needs to change. I think we need to change how we define terms, how we address women, how we approach reproductive health and hormones and fertility, and really in a more proactive, patient-centric approach. And women and men are driving this really by talking about it. Ten years ago, when I started on social media, nobody talked about fertility, and patients who did had nameless, faceless accounts. And now you see celebrities talking about IVF, talking about endometriosis, talking about their termination for genetic reasons or whatever happened. And those stories are so powerful to drop the stigma, but also highlight how wrong it is that we force women to fail before we'll even evaluate what's going on, let alone treat.

Andrew Huberman:
As many of you know, I've been taking AG1 for nearly 15 years now. I discovered it way back in 2012, long before I ever had a podcast, and I've been taking it every day since. The reason I started taking it, and the reason I still take it, is because AG1 is, to my knowledge, the highest quality and most comprehensive of the foundational nutritional supplements on the market. It combines vitamins, minerals, prebiotics, probiotics, and adaptogens into a single scoop that's easy to drink, and it tastes great. It's designed to support things like gut health, immune health, and overall energy, and it does so by helping to fill any gaps you might have in your daily nutrition. Now, of course, everyone should strive to eat nutritious whole foods. I certainly do that every day. But I'm often asked, if you could take just one supplement, what would that supplement be? And my answer is always AG1, because it has just been oh-so critical to supporting all aspects of my physical health, mental health, and performance. I know this from my own experience with AG1, and I continually hear this from other people who use AG1 daily. If you would like to try AG1, you can go to drinkag1.com/huberman to get a special offer. For a limited time, AG1 is giving away six free travel packs of AG1 and a bottle of vitamin D3 K2 with your subscription. Again, that's drinkag1, with the numeral one, .com/huberman to get six free travel packs and a bottle of vitamin D3 K2 with your subscription. One theme that I heard over and over again was women would say, okay, they thought that they might have been pregnant before, or they knew they had been pregnant once before. Circumstances varied, but they sort of had it in mind that they could get pregnant at one point.

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
And that their mom had either them or a sibling let's say at age 42 or 43, and they're in good health themselves. And so they have in mind that there's time. I think this is not uncommon.

Dr. Natalie Crawford:
Mm-hmm.

Andrew Huberman:
And given that life is very expensive, most people in the world seem to be underpaid nowadays.

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
And people are waiting longer to get married and have children. And the other common narrative that I was hearing was that there are people that want kids, but it's under the, "Well, if I found the right person, I would do it, but otherwise I wouldn't do it on my own."

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
That's not always the case, but it's pretty-

Dr. Natalie Crawford:
It's a true statement

Andrew Huberman:
It's a common theme, right? So for those women, which I think is quite a few, whether or not they're in their 20s or their 30s or their 40s, what sorts of things do you recommend they would add to that rather just kind of real-life analysis? Those are not meaningless metrics, like how one's mother had a child-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... for instance. But things have changed. Microplastics, maybe certain things have gotten better, right? We're no longer eating margarine. I'm not trying to be facetious here. I think that-

Dr. Natalie Crawford:
No, I know

Andrew Huberman:
... there's so many variables. People are living longer, yet there are more environmental toxins, perhaps. People are smoking less. So it, the-

Dr. Natalie Crawford:
Are they, though?

Andrew Huberman:
Are they? We'll talk about nicotine for sure. So for those women in their, let's say 20s, 30s, and early 40s-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... what's the level of urgency that they get certain things checked out, and what should they get checked out? Oh, and I should say that they'll say that they're having regular periods.

Dr. Natalie Crawford:
I'd love to answer it, and I'm going to, but for the person who's maybe coming to this discussion, let's explain egg quality really quickly-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... because it really is going to tie into what we can test and what we cannot. As you know well, women are born with all the eggs they're ever going to have. The eggs are kept, I like to think about it, as in a vault inside your ovary, and so they're stored there. You have the most eggs when you're five months old inside your mom. You have six to seven million eggs. By the time that you're born, you have one to two million. By the time you start your first period, you have half a million. So you lose eggs over time. A lot of the determination of that starting number will be influenced some by genetics and some from your mom's health while she's pregnant with you, things she's exposed to, her current disease state. What I want people to think about is every single month, you are losing eggs. So I like to imagine and describe to my patients a group of eggs is coming out of the vault. Each egg grows inside a small fluid-filled structure called a follicle. The brain sends out follicle-stimulating hormone, or FSH, well-named, gets a follicle to grow. As the follicle grows, it makes estrogen. This is called the follicular phase. Estrogen levels talk back to the brain. Remember that the brain does not see what's happening anywhere in the body. It is simply waiting for the hormone signal. That's what hormones are. They're communication signals. I like to think about it like text messages between friends. When estrogen is high enough for long enough, 200 picograms for 50 hours And that's the level it'll tell the brain it's time to ovulate. The brain will send out a surge of LH, a follicle within rupture, egg will be released. It only has 24 hours to be fertilized, but that follicle will actually reform and become the corpus luteum. Now we're entering to the back half of the cycle called the luteal phase. The corpus luteum makes progesterone stimulated from LH pulses from the brain. So then it makes progesterone pulses throughout the luteal phase, can only live for about two weeks unless a pregnancy occurs. When you have an embryo come in an implant, it makes HCG the pregnancy hormone we check in a pregnancy test. Fun nerdy fact, HCG and LH share a receptor. So HCG comes into the corpus luteum and now stimulates a constant production of progesterone. But if that doesn't happen, corpus luteum will die, progesterone will drop, and you'll get a period. Okay. Also back to the vault, you have a different number of eggs that come out every month that is proportional to how many remain. So when you are younger, when you have more eggs, more eggs come out of the vault every month. As you get older and you have fewer eggs, fewer come out every month. That explains why you go from six to seven million to one to two million, and why you go from one to two million to half a million. Because you had more, you're losing more. At some point, everybody will be out of eggs, right? We're going to call that ovarian failure and not menopause for the sake of our discussion.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
But so everybody will go into ovarian failure. Now, the timeline once you have, your clock is now up because at that point, there's no more eggs. You cannot get pregnant with your own genetic child. You still have a functioning uterus. It's just not being stimulated. So importantly, those women can get pregnant with donor eggs or donor embryos. They can still carry a pregnancy. That's sometime a myth that people think about. But once you're out of eggs, that's kind of the end of your clock. Now, two things are happening with time that are really important because your eggs are inside that vault inside your ovary, is that they absorb the wear and tear of your life. And your egg has many different functions. It has to respond to hormone signals and make estrogen, make progesterone, and ovulate. The mitochondria inside the egg, which everybody knows the mitochondria, the powerhouse of the cell, gets exclusively passed on to the embryo. It completely controls embryo growth and development. In fact, the male genome doesn't even kick in until day three after fertilization.

Andrew Huberman:
Oh.

Dr. Natalie Crawford:
Those first few days are 100% maternal. The egg also has to hold the chromosomes in correct position. So an interesting fact is that inside the egg, it is frozen in metaphase of meiosis II for whatever reason. And so the chromosomes have met in the middle and they're held apart by those meiotic spindles, and they do not separate until you ovulate. And so then you get your egg that has what we think about as your 23Ls. The other part goes into a polar body. Okay, this means that when you're 25, your eggs have only been held in metaphase for 25 years. Your chromosomes are, for the most part, still in the right position. Your proteins are strong that are holding them apart. Most people have better generalized metabolic health. Their mitochondria are stronger. When you are 40, 40 years have passed. We've asked those chromosomes to hold there longer. I always say if I have a line of kindergartners and I ask them to stand for 40 years, somebody's going to get out of line. So tincture of time adds up. But the other thing that happens as we get older is as a population, we get more metabolically unhealthy. So we see more chronic inflammation, more insulin resistance, more obesity, and all of those factors influence oxidative stress, mitochondrial health, DNA damage. They can damage the meiotic spindles holding those chromosomes apart. So we also see more genetic abnormalities as we age, but that is worsening as metabolic health worsens, too. Okay. We don't have a direct test for egg quality. That's what we call egg quality, genetic normalcy and egg competency. How good are the mitochondria? Can it do its job? We approximate it to age, which has some faults because not all 40-year-olds are created equal. When we think about ovarian reserve, this is how many eggs you have remaining. So this is how many eggs are inside the vault, and we can approximate it with a blood test called AMH. AMH stands for anti-Müllerian hormone. It's made from the granulosa cells that surround each follicle. So in its purest form, more eggs inside the vault, more come out, more AMH. Fewer eggs in the vault, fewer come out, lower AMH. Not a perfect test. The vault also is not perfect, so there's some month-to-month variability in how many exactly get sent out. And in prolonged periods of not ovulating, AMH can be suppressed, whether it's from birth control pills, pregnancy, postpartum, whatever the reason is. So AMH is imperfect, but it is something, and it's a very simple blood test. It's not telling us if you can get pregnant or not, but it is telling us how many eggs do we have outside the vault. And the way I like to frame this is that every woman who wants to have children or understand her own reproductive timeline should get an AMH checked. That is against medical advice, meaning the American College of OBGYN says that women should not get an AMH checked unless they have infertility. Okay, this is wild to me, right?

Andrew Huberman:
I mean, to me as well. I mean, it just seems like this failure criteria-

Dr. Natalie Crawford:
Again

Andrew Huberman:
... it just seems just very extreme and unnecessary. Unless there's some hidden agenda to try and prevent people from maintaining fertility or-

Dr. Natalie Crawford:
Which doesn't even make sense

Andrew Huberman:
... or having children because-- And that doesn't square with at least my assumptions.

Dr. Natalie Crawford:
The idea here is that it can be really stressful. This is what they say in their document, American College of OBGYN, that it can be very stressful for a woman to find out she has a low AMH and that it doesn't predict fertility. And there's some truth to that. So let's think about I have two 30-year-olds. One has 20 eggs outside the vault, which would be age-related norm, and one has five eggs outside the vault. Well, if every single other factor is the same and they each are ovulating one egg They have the same chance of getting pregnant. So that's not a faulty statement. However, the person who has five eggs will not have as long to grow her family. She will not get as many eggs if we're doing advanced treatment like egg freezing or IVF because I can only get the eggs outside the vault to grow. So it's hugely impactful for what your journey may look like in treatment. But more so than that, Andrew, so many of the causes of a low AMH directly contribute to infertility. Things like autoimmune disease, insulin resistance, endometriosis, smoking cigarettes. So if there are factors, some of which you can control, some of which you can treat, if I have a woman who has a low AMH, I'm not going to sit here and say, "Okay, well, you can still get pregnant, no worries." I'm going to say, "I don't know that you'll have infertility, but some of the reasons your AMH is low can cause infertility. You will get fewer eggs if we're freezing your eggs or doing IVF. You will go into menopause earlier." So we need not wait. To your point, the woman who's 20, 30, 40, thinking about this, she might make a very different decision when she knows she's really faced with a timeline that is less than ideal. And why should we allow time to be making that decision for us instead of at least playing an active role? I sit across from women every day who find out they have a low AMH, and I say this, "Let's do the investigation and see if we can find out why." Probably 50% of the time, we find an autoimmune disease. I can't reverse the clock, but I can slow down the rate of inflammation.

Speaker 3:
Mm-hmm.

Dr. Natalie Crawford:
Say if it's Hashimoto's, suddenly we can do thyroid replacement, we can work on decreasing inflammation. If inflammation harms our ovary, maybe we can slow down that rate of egg loss. At least she's being treated and probably feeling better and will have improved fertility outcomes because her Hashimoto's is treated. So we should look at why. Why is it low? And treating that why very well may impact fertility. We also might say, what should we do about this? I have a lot of couples who are partnered who are just waiting for the right time to get pregnant. So sometimes we say, "Well, we could get pregnant, but I'm in medical training. I'm going to law school. I'm doing XYZ. It's not a good time." Well, when faced with their perfect time, they may not have eggs anymore. Suddenly, we reevaluate where we are, and there's no one right answer. We might choose to try to get pregnant now. If we don't have a partner, we might buy donor sperm and try to get pregnant. Maybe we freeze eggs. Maybe we freeze embryos. Maybe we do none of those things. But we made the active choice. Sitting here saying, "I chose not to pursue treatment, knowing my AMH was low and that I might be in ovarian failure at the point when I was planning to have a family, and I know that," makes the journey so much easier to walk because you made that active choice from a place of knowledge. That was your autonomous decision versus saying, "I asked my doctor for an AMH test five years ago. They told me it wasn't medically recommended because I don't have infertility. And had I known that information, then I might have done something different." That was the longest discussion to say everybody should get an AMH. I think it's a very important marker. It's a newer-ish test. We've only been checking it for about the past 10 years. It's not a perfect test. I don't have the nomogram for exactly how it should drop over time, and I like to think about it as categories. Normal, above average, below average, critically low. And based on your category, we should probably talk and do different things. If you are listening to this and you want kids one day, ask your doctor for this test. If they say no, you can order it yourself at a LabCorp quest. Many of the online platforms like Function Health, you can have an AMH check through them. You can ask your doctor for it and say, "Well, if it's low, I know I'll talk to a fertility doctor to find out more information." Or call a fertility clinic and just say you want fertility testing, the end. Okay? I think it's such-

Speaker 3:
Mm

Dr. Natalie Crawford:
... an important marker. It is not a test of egg quality. And we talked about what egg quality is. Genetics and egg competency. But it is a check of how many eggs you have, and that knowledge can be really impactful for how you view your future and your plan. So I think everybody should get an AMH. I think we've got to learn to track our cycle, and I know you said in the vignette that these women have regular cycles. Having a regular period is really good. It's much better than having an irregular period. But knowing when you ovulate and tracking ovulation is a much more sensitive health marker than simply when you bleed or when you have a period. Because tracking ovulation is going to allow us to know how long is your luteal phase and how long is your follicular phase. And ovulation disorders progress through a very predictable pattern, and we know this well. The first stage of an ovulation disorder is a luteal phase defect, meaning a shortening of your luteal phase. So you're ovulating, but the brain and ovary have a miscommunication, and we don't make progesterone long enough to sustain the luteal phase. Less than 11 days is a short luteal phase. But you'll still have regular cycles. So if I sit across from somebody and I just say, "Are your cycles regular?" And they say yes, and we carry on, I've missed the fact that they actually have a shortened luteal phase, and that warrants further investigation. Prolactin, thyroid, AMH, PCOS, looking at different causes. The second stage of ovulation disorder is a long luteal phase. Takes the ovary longer to actually respond to the FSH stimulus from the brain. And then from there, we'll progress into irregularity and true amenorrhea or absence of periods. But those first stages, you might miss the little red flag warning sign that something's wrong inside your body because you are just tracking when your bleed is, and it's every 34 days, so you think it's normal. But if we were looking at when you actually ovulated, we have more data. So learning to track ovulation as opposed to just cycle tracking, I think is one of the most important skills a woman can have for Learning to listen to her own hormonal cues.

Andrew Huberman:
Amazing. And I don't say that lightly. You just explained egg quality, the biology of the ovulation cycle, and how it links to the actionables, and I'm just struck. It's awesome. And it has me asking a couple of practical questions.

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
Some people will have insurance, some won't.

Dr. Natalie Crawford:
Mm-hmm.

Andrew Huberman:
What's the cost of an AMH test? Let's assume insurance doesn't cover it-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... and they just have to go completely out of pocket. And before you answer, I will say, whatever it is, I think it should probably be compared against what it would be to try and, I don't want to say rescue, but to not take the test and then three years later you're trying to harvest eggs. It could be-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... multiple cycles-

Dr. Natalie Crawford:
Exactly

Andrew Huberman:
... because you realized it was only five eggs per month as opposed to-

Dr. Natalie Crawford:
And what could have been three years ago

Andrew Huberman:
... age matched, right? 15, right, exactly. So, are we talking hundreds of dollars, thousands?

Dr. Natalie Crawford:
79.

Andrew Huberman:
$79.

Dr. Natalie Crawford:
Yeah. We're withholding a $79 test, and I feel really strongly about this. I do not view myself as the gatekeeper of information about your body. Do you want hormone levels checked? Do you want an AMH? I do not think that is the role of a physician. And now I can say your insurance doesn't cover it. You can make the decision if $79 is worth it to you.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
But in the age of information, where that's an easy test to do, every lab runs it, and it's relatively inexpensive compared to freezing your eggs or IVF. I mean, right, multitudes. $79. We're throwing a fit over a $79 test.

Andrew Huberman:
Wow. I'm going to make sure that message goes far and wide- ... because I thought you were going to say maybe in the high hundreds-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... or thousands, which for some people is going to be-

Dr. Natalie Crawford:
Would be cost-prohibitive

Andrew Huberman:
... prohibitively expensive. Yes. So get AMH checked. I think I'll avoid going into too much editorializing here because I'm really just interested in how you view this. But how you describe the way your field has originated and where it's headed reminds me a little bit of, I remember in the '80s, genetic testing was starting to become possible, and a lot of it was happening at Stanford. I happened to grow up near campus, and I remember hearing you could get tested for Huntington's disease-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... which can be a devastating disease. And the idea was people don't want to know. I think everything I've observed, I can't speak for everyone, but everything I've observed about people's interests in their own health and genetics and what genetics does and doesn't-

Dr. Natalie Crawford:
Mm-hmm

Andrew Huberman:
... mean tells me that people are actually much more interested, and they're much smarter than, let's just call it the traditional medical field, certainly medical genetic testing gave them credit for.

Dr. Natalie Crawford:
100%.

Andrew Huberman:
It's like people aren't idiots. You can sit someone down and say, "Hey, listen, you have this gene. There's an X probability. Here are the things you can do to protect yourself." But there was this assumption like people don't want to know because now they're going to live in dread, and their life is going to be destroyed if they know they're going to get full-blown Huntington's or something like that.

Dr. Natalie Crawford:
Yeah. It's so paternalistic.

Andrew Huberman:
It borders on unethical.

Dr. Natalie Crawford:
Mm-hmm.

Andrew Huberman:
People are smart. People can take in information, and they can make decisions that don't necessarily crater them on the basis of just knowledge. It feels like we sort of treat people like little children. Even little children would probably want to know certain things, although you don't want to give them genetic information, but certain things like, "Hey, you have a challenge with X, Y, and Z-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... and you can overcome it in the following ways."

Dr. Natalie Crawford:
Look, technology's advanced.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
It has. How we counsel and how we approach healthcare needs to advance also, meaning we don't live in a universal healthcare system. We don't have only X dollars to spend on every single patient. And in certain circumstances, when that's the case or a patient has limited money, we do have to make very judicious decisions about the best use of those dollars. But for the majority of people who will be listening to this, they are willing to spend money on their health, and it shouldn't be a society or a physician or somebody standing in the way of getting data that can dramatically impact your life. And because you mentioned Huntington's, I should say, autosomal dominant disorder, people have very strong feelings on if they want to know they have it or not, and I've had patients, because we can test for this with IVF. So we do genetic testing of embryos, and we often do screening to see if the chromosomes are in the right position, which we talked about for age. That can be really beneficial. But we can do single gene testing as well, PGT-M for monogenetic diseases, and Huntington's is one of them. And I've had some patients say, "My mom had Huntington's. It was the worst experience to watch her go through that. I would love to test my embryos, but I've committed to myself that I don't want to know if I have it or not." Okay? And I think it's really important just to mention that disease to say, "We can blind test you. You can make a probe to see if you carry it or not. You don't have to know, and we can still test the embryos." And I've had a few patients who then themselves did not want to know, but we went through the steps to make a probe in case they did. In both cases, the patient did carry it, didn't find out that they did, but they could assuredly transfer an embryo that did not have it.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
Because often, these people have felt so strongly watching a family member die from a terrible progressive disease. They've said, "Children are not in the cards for me," or, "I'm not going to have genetic kids." Or sometimes they'll come to me saying, "We have to use an egg donor or sperm donor because I might carry this and don't want to know." So again, it's the idea that that should be your own individual choice whether you want to know or not, but it shouldn't be the society or somebody else putting this roadblock up. And it's such an antiquated approach in the era of technology and access, where you really can get so many data points. Why should somebody be making the decision on if that information's valuable to you?

Andrew Huberman:
And I think with blood testing, the price coming down, it seems to me maybe it's just the circles I run in that people want more information as opposed to less. But I'm glad that you raised these cases where people don't want to know certain amounts of information. One thing that, well, I'll just pose this as a question. How many women out there do you think know if-- I have to be careful how I word this, if doing an egg harvest cycle decreases their ovarian reserve or not?

Dr. Natalie Crawford:
The majority of patients that I sit across from will tell me, "I'm afraid to freeze my eggs or do IVF because I don't want to go into menopause earlier." So the myth that doing that is going to tap into the vault and pull out eggs is inaccurate and a fear that really does need to be busted, because it doesn't. It's a limitation of the science that I can only get the eggs outside the vault to grow. If I could tap into the vault, it would change the game. But right now, I am limited by the eggs you give me, the number of them controlled by whatever's outside the vault. We in IVF, we just give FSH, the same hormone your brain makes, trying to stimulate more than one egg to grow. Your body doesn't want to have five kids or 12 kids or 20 kids, so it has checks and balances to prevent that from happening. I, however, would like every egg outside the vault to grow, because in nature, you will ovulate one and everything else will die. You are constantly losing eggs no matter what. When you're pregnant, when you're breastfeeding, when you're on birth control, before you start your first period. Constantly losing them. I cannot change that right now. So doing IVF or egg freezing is not going to decrease your ovarian reserve. It is simply going to influence one month in time trying to not have all those eggs die.

Andrew Huberman:
And I think the myth is that by doing a cycle of egg freezing, that you're taking more eggs from-

Dr. Natalie Crawford:
Mm-hmm

Andrew Huberman:
... your reserve. But as you pointed out, women are losing the same number of eggs each month, or follicles each month, regardless. You're maximizing on that process by just maturing more and taking them-

Dr. Natalie Crawford:
Exactly

Andrew Huberman:
... as opposed to letting them die.

Dr. Natalie Crawford:
Exactly.

Andrew Huberman:
Yeah.

Dr. Natalie Crawford:
We are not running out of eggs early. I think it's just based on, again, nobody understands basic biology, so we think in our brain, "I'm just losing that one egg since I'm ovulating." We're not thinking about all the ones that were sent out of the vault who weren't chosen.

Andrew Huberman:
Yeah, and I think people will also assume because they haven't been told that if you do an egg-

Dr. Natalie Crawford:
Mm-hmm

Andrew Huberman:
... if you stimulate for more to mature-

Dr. Natalie Crawford:
Mm-hmm

Andrew Huberman:
... that you're somehow taking away from eggs that you would've had stuck-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... around somehow. So we're saying the same thing three different ways.

Dr. Natalie Crawford:
Yeah. So you're giving-

Andrew Huberman:
Right

Dr. Natalie Crawford:
... It's fascinating to me if you think about it, because we are allowing the possibility for you to have children in your family that likely you would not. Because if you were to get pregnant naturally that month, the greatest probability is it would just be one that you would ovulate. Yet for IVF, we can sometimes take one month's group of eggs in time and have a couple different embryos, and those become a couple children for you that you have from this one exact cohort. I think it's so fascinating. Early IVF days, IVF's not that old. It's only been around 46 years, I think, the oldest IVF babies. We didn't have gonadotropins. We didn't have FSH that was synthetic or purified, and so we couldn't get multiple eggs to grow. So original IVF patients had to go live at their IVF clinic, and they had urinary-based hormone measurements done every day so they could try to gauge, as estradiol was rising, when they were getting closer to ovulation. And in those days, this is just science, they went and they did abdominal surgery to aspirate the egg. Now we do a vaginal egg retrieval where we take a needle attached to a vaginal ultrasound. It's a minimally invasive procedure. But back in the origin IVF studies, they had to go and do an abdominal incision to put a needle into one single follicle to get the follicular fluid and the egg out. So it was very low odds of working. It was crazy to even think of. But the advent of gonadotropins, the ability to first start it by purifying FSH and LH and be able to give that to people to stimulate more than one egg, understanding this concept that there's so many more eggs that you have outside the vault every month, that has changed the game, and it's such an amazing advancement in science that we can leverage that physiology for egg freezing or IVF.

Andrew Huberman:
A very practical question. It's clear that the younger that a woman is, the more eggs-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... that could be frozen in a given cycle. But I think it's fair to say that many people, either because of finances or life circumstances, that could be not having a partner and wanting a partner before having kids, this sort of thing, are waiting.

Dr. Natalie Crawford:
Right.

Andrew Huberman:
They're just waiting. What stands between us now in the United States and egg freezing being covered by insurance 100%? I don't hold any superpowers, but there are pretty powerful ways to lobby all the administrations, regardless of who happens-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... to be in office when that actually happens. It is possible, right? The phone is a powerful tool. Advocacy is a powerful tool. I do think that things can happen if there's a lot of advocacy. So first question is, what would that require?

Dr. Natalie Crawford:
Mm-hmm.

Andrew Huberman:
And is that a good idea?

Dr. Natalie Crawford:
I am a fan of knowledge and options, and egg freezing is not a guarantee. So how I pose it to patients is we are going to keep the door of opportunity open longer for you, and that is our goal. If we want to compartmentalize it, as some people will falsely sit across from me and say, "Oh, egg freezing's an insurance policy for my fertility," and it's not, because an insurance policy always pays off, but it's an investment in my fertility.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
Like investing in the stock market probably will pay off. But depends on external factors that we don't have yet. So the ROI is yet to be determined, but in general considered to be a good thing. I think it would be absolutely incredible to be in a place where egg freezing could be covered, and there's definitely countries where it is, that they have said, "Well, the birth rate is dropping. We want to keep the reproductive lifespan open for some patients. We want to offer this." I think to be honest and transparent, the number one restriction against that that we see as a field right now is the camp of people who are ethically or morally opposed to IVF for reasons of embryo disposition.

Andrew Huberman:
Embryo disposition?

Dr. Natalie Crawford:
Yeah, like the personhood of an embryo. Is an embryo a person?

Andrew Huberman:
I see, because embryos that are not used are going to be either kept frozen or discarded, and to those people, that's seen as essentially killing a baby.

Dr. Natalie Crawford:
Correct.

Andrew Huberman:
Right. That's their view.

Dr. Natalie Crawford:
Yeah. And we should acknowledge that I have many patients right now who are donating embryos when they are done with their family, which is an amazing way to kind of pass forward the opportunity and for other couples to have a family. And I also just want to say at the top of this is that IVF's incredible. Seventeen million babies have been born in this world because of IVF. So I think this technology's great. Does that mean everybody has to do IVF? No. You are allowed to have your own feelings and decisions about anything that you do, IVF included. And there's often things we can do within the procedure for patients who might have religious or ethical concerns to limit the number of embryos that we make or only transfer embryos that are created, and that's important to know to bring that up if that's your line in the sand, is that we can often do things differently based on your beliefs. It might be less efficient, it might cost more money, it might have a lower rate of success. But I've had patients walk that road, and that's the way it felt comfortable to them. In this country, there's a camp, not to get too political, and they're really pushing something called restorative reproductive medicine, and they're opposing a lot of the American Society for Reproductive Medicine's attempt to get fertility treatment and fertility preservation covered. And their rationale, even though a lot of RRM I'm a huge fan of, it's about teaching women cycle tracking and getting to the root cause and really supporting understanding your fertility. Like bullet point 10 on their list is that IVF is unethical.

Andrew Huberman:
But these people are ostensibly pro-child, so that-

Dr. Natalie Crawford:
I agree with you

Andrew Huberman:
... my political stance-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... people often speculate. I'll be really honest, I don't like politics.

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
And I'm very disappointed in the current state of politics, on both sides. And I try and go issue by issue, and I realize that itself is a controversial statement. You're supposed to take a hard stance for or against. But I think that as a biologist- ... I look at certain things and I go, "All right." And I look at other things, I go, "Oh, my goodness. Like what Stone Age are we living in?" And so I think that to argue whatever it is that one believes about-- It seems to me that IVF, at least to me, maybe I just am too through my own lens, but the whole notion of freezing eggs and creating embryos seems very pro-child to me.

Dr. Natalie Crawford:
I-

Andrew Huberman:
So it doesn't square with-

Dr. Natalie Crawford:
It doesn't square with points-

Andrew Huberman:
... with number 10 on this list.

Dr. Natalie Crawford:
I agree with you. I agree with you, and I think a lot of the people who are a fan of RRM might actually agree with you and I, but there are definitely people who are very adamantly opposed to IVF who put number 10 in there because they have a different agenda.

Andrew Huberman:
Okay.

Dr. Natalie Crawford:
I'm a fertility doctor, right? I want as many people to have a family as they desire. I want you to fulfill your life's dreams. If having a child is a part of it, I want to do everything I can to help you have that. I am not here to sell IVF or force IVF. At the end of the day, it impacts me zero what you individually choose to do. But I believe that across the board, people deserve the tools in the toolbox. They deserve to be presented with all the choices. We could try Clomid. We could try IUI. We could try surgery. We could try IVF. Oh, you're getting older. We could freeze your eggs. There are just more tools. There's more opportunities. And then based on your circumstance, your financial, your beliefs, you should be allowed to choose. I feel very adamantly that one's own beliefs that cause you to want to put it at number 10 on the list should not be the beliefs that we enforce on everybody, especially when we know that IVF can be so powerful to help so many people have a family. It should be something that is offered to you if indicated, and you get the choice. And so back to the origin, it would be incredible to live in a world or a country where egg freezing was offered to women as we do see people are waiting longer to start their families. It would allow more people to feel less pressure, less pressure with a partnership and on their relationship, not to feel like, "Oh, this better work out because my clock is ticking," and be able to really feel like they could chase one dream and not at the expense of another.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
I think we're further in this country than we want to admit from that. We can't even get fertility treatments covered for patients with cancer when we know that chemotherapy is going to deplete their ovarian reserve. We have some states that we can't even get egg freezing covered for them.

Andrew Huberman:
So this is state by state.

Dr. Natalie Crawford:
This is state by state right now.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
We would love federal protection for everybody. We would love to be able to see-- I don't know. To me, that's my litmus, what your state or your country would do for patients who have cancer or are in this position. And if we're not even willing to move to help them, the idea that we could cover it for everybody, we're still ages away from that, I think.

Andrew Huberman:
Yeah, because none of what we're talking about is forcing anyone to do anything.

Dr. Natalie Crawford:
No.

Andrew Huberman:
Nor is it necessarily the destruction of an embryo. I mean, there is a world where the embryos are created and kept frozen, right? There is no-

Dr. Natalie Crawford:
No.

Andrew Huberman:
Like-

Dr. Natalie Crawford:
We call that embryo banking. I mean, to specify-

Andrew Huberman:
Mm-hmm. Yeah

Dr. Natalie Crawford:
... maybe for somebody who doesn't understand, right? Egg freezing, getting those eggs outside the vault to grow, taking them out of your body, and we freeze them right there at the egg state. Making an embryo is going to be thawing that egg, fertilizing it with sperm, letting it grow out to the implantation stage, which is day five or six. Not every egg will survive, fertilize, grow. There's a ton of attrition in culture. So 90% of eggs survive the freeze thaw. 75% will fertilize, 50% will make it to the implantation stage, and then not everyone will be genetically normal based on your age and other factors. And then even a genetically normal embryo only has a 65% chance of live birth. The science has come far, but we're not there all the way. With that being said, they do morally really feel like an embryo could be a potential life, and they do struggle with what to do if they have leftover embryos. And I have some patients who've told me, "Every embryo we make, we're going to transfer." Okay, well, we want to be really mindful what we do in that circumstance. And even though it's unlikely, I have a patient right now with four children and one embryo in the freezer because we froze five knowing that everyone shouldn't implant based on that 65% number, but we've gone four for four. Okay? So, we have to know that if that's what we're doing, we're prepared for-

Andrew Huberman:
Mm

Dr. Natalie Crawford:
... how the data may fall, because data just helps us guide decisions. Right? Especially when it comes to live birth. It's zero or 100. It happens or doesn't. Now, if I freeze them as eggs, for some patients who have really strong beliefs and they are afraid of that number five, we might take more time or more money, but we might say, "Let's thaw them and only fertilize two."

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
"Let's leave everything else frozen, and then whatever makes its embryo, we can transfer." And yes, that's not a cost-effective way to go through the process because we might be having to pay for thawing and the fertilization and the transfer more times because there may be nothing to transfer based on that attrition. It can let some patients say, "Okay, I feel better with that process." So just freezing eggs, to your point, is not making embryos. Right? And there's different things we can choose along the way to make an individual person feel comfortable, but we shouldn't be dictating how the field has to function. I think it would be incredible if we could encourage egg freezing earlier. I think it would open the door of opportunity. And not everybody who freezes eggs will need them, but the peace of mind knowing that there's a chance is really impactful on the human mind.

Andrew Huberman:
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Dr. Natalie Crawford:
Most insurance doesn't cover IVF.

Andrew Huberman:
Mm.

Dr. Natalie Crawford:
You're not wrong, right? In principle, if I freeze a 25-year-old's eggs, I will have three times as many eggs to work with than I would if she's going through IVF when she's 37.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
So if I'm going to pay for her to do IVF at 37, it'll take so many more cycles. I'll spend so much more money. That one cycle of egg freezing is much more cost-effective if I'm covering them both. But we don't even cover the latter, so many times patients, this is such a hard stretch for everybody. And look, the technology is incredible. As somebody who has an IVF lab, as somebody who keeps embryos on site, it's outrageously expensive. Our generator alone is a million dollars. Right? Because if the power goes out-

Andrew Huberman:
Mm

Dr. Natalie Crawford:
... what do we have to keep going? We always say, "If there's zombies coming, come to the clinic." The technology to keep up with all the advancements, to have trained embryologists, their micromanipulation skills, it's impressive. So it costs money to run a lab like that that will provide results. So the process and the technology is really, really expensive. That being said, I shouldn't be the one sitting here making assumptions again on what you're going to do with your money. And if somebody's in a position where they know their egg count's low and they should freeze their eggs because they're not partnered or they're not ready to get pregnant and they don't have the financial resources, we can sometimes find more money, right?

Andrew Huberman:
Mm.

Dr. Natalie Crawford:
We make decisions every day when it comes to money. We can't find more time, we can't find more eggs or more ovary. So again, this idea that, well, what are they going to do about it if they find out they have a low AMH, or, oh, they can't afford to freeze their eggs anyway, or, oh, it's too expensive. We all make individual choices on how we leverage our different resources-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... which I consider to be your time, your money, your physical energy, and your emotional energy. And every day you're leveraging them. But when it comes to reproductive health, having a family, I feel strongly, you feel strongly, which I love, that we should be giving more access and more options to people so that they can pursue this. And so the arguments across the board, too, like why not check an AMH in somebody who's younger? Well, they can't afford egg freezing anyway, so what are they going to do about it? Again, we shouldn't be making the assumptions of what somebody will or will not do with their resources or with their data. We should be ones helping them get the data and interpret the data, understand what resources or options exist, and then the individual has what they need to make the decision.

Andrew Huberman:
In the Bay Area, where there are a lot of tech companies-

Dr. Natalie Crawford:
Mm

Andrew Huberman:
... my understanding is there's an opportunity at many of these companies for female employees to freeze their eggs. That landed much more controversial than I thought it would.

Dr. Natalie Crawford:
Isn't it crazy?

Andrew Huberman:
Because to some people, the tacit message there is, "Don't have kids now."

Dr. Natalie Crawford:
Yeah. Don't have kids now. Work for us.

Andrew Huberman:
"Work like crazy, and then have them later," right?

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
But having known some people that worked there and froze their eggs in their late 20s or early 30s, the ones I know would say, "Yeah, I'm really grateful that I did that, and that the company I worked for paid for it." And they got to keep their eggs, even though they don't work for the company anymore.

Dr. Natalie Crawford:
Yes.

Andrew Huberman:
So there's that. But it was kind of interesting. So anyway-

Dr. Natalie Crawford:
Yeah. I mean-

Andrew Huberman:
... we're getting kind of-

Dr. Natalie Crawford:
We are

Andrew Huberman:
... sociological here-

Dr. Natalie Crawford:
But what we can say is-

Andrew Huberman:
... but I think it's important

Dr. Natalie Crawford:
... yeah, what data supports is that when companies do leverage a fertility package in their benefits, they retain employees longer, employees are happier, and more people utilize the service than would without it, meaning people freeze their eggs when it's offered to them through their company, and that gives them that peace of mind. Understanding it's not everything, but they feel more comfortable exploring bigger opportunities, and they are grateful to the company. They stay with the company longer because that is an investment in your employees. I think it's incredible. In Austin, a lot of these tech companies have second homes, so we see a lot of these patients also. And I do think that has changed the game for so many people to be able to have access. Because for many, it's not ethical or moral, it's financial.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
Often, the time when you would freeze your eggs, when it would give you the highest rate of return, you don't have the resources to do so. So having a company that's able to come in and do that is really, I think, impactful. I wish more companies would do that. Maybe we can change their minds.

Andrew Huberman:
I tend to get pretty loud and pretty consistently loud about the things that I believe in, once I understand the landscape. So I plan to be vocal about it, for what it's worth. You mentioned that birth control can reduce AMH levels-

Dr. Natalie Crawford:
Mm-hmm

Andrew Huberman:
... on a month-to-month basis. And we should define birth control-

Dr. Natalie Crawford:
Mm-hmm

Andrew Huberman:
... because it's such a broad category. But is there any evidence that taking hormonal birth control can lower chances of pregnancy when somebody comes off birth control? In my friendships and knowledge space, and this isn't I have a friend, I know a number of people who have kids now-

Dr. Natalie Crawford:
Mm-hmm

Andrew Huberman:
... who were on birth control, came off birth control, and got pregnant right away.

Dr. Natalie Crawford:
Right.

Andrew Huberman:
So I think a lot of people assume that's how it works. But are there any good examples of how certain forms of birth control can actually suppress fertility in women long after women come off birth control?

Dr. Natalie Crawford:
Excellent question. Okay, let's break the data down from big to little. Number one, big studies looking at all different types of contraception, no higher rate of infertility, again, defined as failure to get pregnant at 12 months. So you come off your contraception, at 12 months later when we look, there's no higher rate of infertility than we would have on the population base level. So that data leads us to comfortably say birth control is not causing infertility. Now, if we go and we look more nuanced at different types of contraception, if you look at the birth control pill, what most people are talking about, the birth control pill is a combination of synthetic estrogen, ethinyl estradiol, and a type of progesterone or a progestin. These work by telling the brain, essentially tricking it, so the brain doesn't send out FSH or LH. And as we described earlier, those are important in getting you to ovulate. So you don't ovulate when you have taken the birth control pill, and that's why it's a very effective contraceptive choice. However, the half-life of the birth control pill is only 28 hours, so it's actually quite short. So you can miss even just one pill, and you could ovulate. So when you stop the birth control pill, your period should come back that next month. So immediately you should have resumption of ovulation. A couple of problems with this one is that the birth control pill has some valid medical uses, has some non-valid ones, but very often, especially in the generation of women that we see right now, they were given the pill, potentially for a valid medical reason, without any investigation of what it was. So maybe a woman had irregular cycles or some acne, and her doctor said, "Well, here, take the birth control pill. It will help." And it did help. But just based on that history, I would sit here and say, I bet she has PCOS. And the woman, though, never was told, "I think you have PCOS. Here's what it is. You probably will not ovulate when you stop the birth control, and your acne will come back, and you should talk to a fertility doctor, and here's lifestyle things we can do to decrease insulin resistance." Never had that discussion. So in her mind, had some symptoms, started the pill, those symptoms resolved. Now we stop the pill, and we're not getting pregnant, and we have irregular cycles. And we start to blame the pill as the reason why, instead of understanding that the pill was maybe masking it or treating certain aspects of it. So we do see failure to get to a diagnosis in women who were prescribed the birth control pill young, and then with the idea, I'm going to stop the pill and get pregnant right away. What I like to say is, you're not ovulating on the pill. If ovulation and knowing when you ovulate is one of your most sensitive health markers and really essential information in trying to get pregnant. If you are trying to get pregnant, the egg only lives for 24 hours. The fertile window is the five days before and the day of ovulation, meaning sperm can live in the reproductive tract for up to five days. Most will stay around for two days. That's why the two days before and the day of ovulation have a 20% to 30% chance of getting pregnant compared to a zero day the day after ovulation, 0%. So very defined fertile window. So if you know when you're ovulating and you target intercourse, you're going to have a higher odds and get pregnant faster. Data supports that very much so. But you don't know how to track your ovulation because you've been on the pill, so you don't know how to do that. So I recommend that you stop the pill three to six months before you're really wanting to start your family so you can track your cycle, learn to detect ovulation, and if you do have an abnormality, you're not now six months of trying or one year of trying before it's evaluated. You can say, "Oh, I can't detect ovulation," or "My cycles are irregular. Let me go get that investigated now so we're not kind of behind in our own timeline." The progesterone IUD is another one that we talk about a lot. The progesterone IUD is local progesterone that is placed inside the uterus There's different types that can release progesterone in different amounts. It typically suppresses ovulation in the first two years, but then progesterone levels drop, and it tends not to suppress ovulation. But that chronic progesterone exposure thins the endometrial lining to the degree that many women do not have periods anymore.

Andrew Huberman:
Hmm.

Dr. Natalie Crawford:
That can be great if you don't like having a period. That can decrease the chance of anemia or menstrual cramping. So it can be very lifestyle positive during those years. But when you stop the IUD, we do see a change in endometrial receptivity, at least for six months after it's been removed, and it can take time to build that lining back up. So I always recommend that a progesterone IUD is removed at least six months before you want to get pregnant. Give the endometrium time to rebuild and regrow, and then you'll have better odds at conceiving. We do see a little bit of lower pregnancy rates in those first six months of conceiving in women coming off of the IUD. More of them are getting pregnant in the back six months. So kind of shift your own timeline. And the birth control, I think it's always important to mention in this conversation, is one that's not as common, but it's the Depo-Provera shot. So this is a high-dose intramuscular progesterone shot that can prevent ovulation for three months. On population-based levels, to use it as an effective contraceptive must get every three months. But one single dose can prevent ovulation for 18 months. So this is that one exception where if you want to get pregnant potentially in the next two years, please don't get Depo-Provera.

Andrew Huberman:
Great. Incredibly thorough and clear. Is there any evidence one way or the other that intentional termination of a pregnancy can disrupt chances of getting pregnant again later?

Dr. Natalie Crawford:
No study supports that having a termination is going to negatively impact your fertility later. One caveat I just want to mention is that any intrauterine procedure has the potential to damage the endometrium and result in scar tissue. So that could be having an IUD, could be having a fibroid removed, it could be a prior C-section, it can be a prior DNC because you had a pregnancy loss, it could be from a termination. Where we see the greatest risk in all of these circumstances is from heavy bleeding or from an infection associated with it. So in general, most terminations are done early, very routine. Where we are fearful is when they are accessed in non-safe environments. We're seeing more infection or heavy bleeding, or even when women are having to travel statewide to access care, and they're getting the procedure done later with a higher risk of complication. In Texas, where I practice, there's obviously an abortion ban, and so women who need an elective termination for a medical reason. I had one patient who's been very open about her story. Her baby had anencephaly. So she went through IVF and had a baby that had no brain develop. And they made the decision that they wanted to terminate that pregnancy since that's not compatible with life. They didn't want to have to carry the entire pregnancy. They had to travel out of state to access care. Their first appointment was canceled, so they had to make another one in a different state. Took them much longer than they wanted. Had the procedure much later. And then she had residual scar tissue inside her uterus that was because it was done at a later term that we then had to fix before she could get pregnant again. So I think it's just important to say that across the board, any intrauterine procedure poses a little bit of a risk. No matter what it is, if your periods are different afterward, the hallmark sign is going to be a lighter cycle. So no matter what thing on that list you had done, if your cycle is now lighter afterward, I am worried there could be scarring inside the uterus. And we'd rather evaluate that in the clinic. We can do a saline sonogram to just check and make sure there's no scar tissue because that will impact your fertility.

Andrew Huberman:
Thank you. Some practical questions-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... about metabolic health, mitochondrial health, and egg quality.

Dr. Natalie Crawford:
Let's do it.

Andrew Huberman:
In your book, you go into this in some degree of detail, but when you think about the things that can really help support egg quality aside from age-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... in fact, I should say at any age, what are the sort of top contour of those? You mentioned inflammation is the enemy.

Dr. Natalie Crawford:
Mm.

Andrew Huberman:
But inflammation happens all the time-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... and we can't avoid it. But we can certainly avoid exacerbating it. So what are the things that people can do, not do, and take? We can do-

Dr. Natalie Crawford:
Okay. I love it

Andrew Huberman:
... those three. Do, not do, and take. Yeah.

Dr. Natalie Crawford:
Okay. So yes, inflammation is prevalent in our world, and the goal is not to avoid all of it. In fact, acute inflammation is required for conception, right? We need acute inflammation with ovulation. If we just think real physiology, a follicle is rupturing, allowing the egg to be released and then reforming. Like, we need our acute inflammatory response to allow that to happen to the degree that if women take NSAIDs around the time of ovulation, Advil, ibuprofen, Aleve, they'll prevent the follicle from rupturing.

Andrew Huberman:
Really?

Dr. Natalie Crawford:
Yes. So they will go through the hormonal changes of ovulation, but the egg will not be released. So that's why we recommend, and fun fact or important to know, if you're trying to get pregnant, you can take those medications only when you're on your period. So period cramping, fine, but we don't want you taking them for the rest of the cycle because you can prevent ovulation from occurring.

Andrew Huberman:
How many people, in your experience, do you think know that?

Dr. Natalie Crawford:
I don't think very many-

Andrew Huberman:
Okay

Dr. Natalie Crawford:
... honestly, right? Which is why-

Andrew Huberman:
I mean, I feel like it's sort of like banner across the sky. Like you said, you're not going to lose eggs by doing a freeze cycle, a collect and freeze cycle. I mean-

Dr. Natalie Crawford:
Basic facts about our biology that we are never taught.

Andrew Huberman:
So if somebody's trying to get pregnant, NSAIDs can be problematic.

Dr. Natalie Crawford:
They can be problematic. They can prevent the egg from being released with ovulation. So I think that this is important because I will sometimes have patients say, "Well, if inflammation's bad, can't I just take medicine for it?" Right? Like that in our brain might make sense. And I always want to say your immune system is essential for ovulation and also for implantation. So like, I don't want to turn off your immune system. What I want to do, though, is not have it be so burdened with what we call chronic inflammation, that constant activation where it can't even do the job that we need it to do. So I like to think about this as that inflammatory burden, and so we're all exposed to some, but how do we, to your degree, make it better? How do we add to it and make it worse? And really framing ourselves so that we can cultivate, and I like to think about it as resilience within your body. You're going to be exposed to inflammation. Life is going to throw things at you.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
But you want to cultivate these best practices of your life so that you are reducing inflammation to the degree that you had, and this goes hand in hand with insulin resistance, which we'll get into. And I usually divide it into what I call my five non-negotiables of sleep, stress, muscle, food, and toxins, and thinking about how we leverage these to our benefit by giving people the knowledge that if they understand their bodies, they can then be empowered to make choices that are in line with their goals. And so I really also just want to say, really importantly, I hate the narrative that there's nothing you can do for your fertility or that it's all luck. Because the truth is, even if we can't control everything, we have a huge control over our metabolic and cellular health, which, as we just said, plays a huge role in our ability to get pregnant for both men and women. So taking control of what we can, I think, is really important information, and one person can take with that and make the choices they want to make. But the worst thing that I hear every single day is people sitting across from me saying, "Gosh, I wish I'd known that information. I would've made a different decision." Why do we make people go through a failed IVF cycle, they have no embryos form, and only then do they make lifestyle changes when we know the lifespan of a sperm is 90 days, and sperm are so sensitive? And then we know that even though eggs are in your body your whole life, the 60 days before you get pregnant is when the egg is most susceptible to the world around you. So this is this time period that I like to call trimester zero, the time before you're getting pregnant, where the choices you make can influence your egg and sperm quality the most, and to what you said earlier, if we're making them even earlier in life, can we influence ovarian function longer? I think there is good thought to that. But how do we leverage these choices and diving into them? Number one for me is sleep, and I think that this is an important one because it can leverage that inflammatory burden in both ways, and I know you're a big fan of sleep, so this isn't going to take much to convince you. When you sleep, this is when your body's going to get rid of some excess chronic inflammation, lowers our inflammatory markers. We know that when we get less sleep, it's going to cause us to have more cellular stress, more oxidative stress. Your gonadotropins, so FSH and LH, are released from the brain in the early morning hours, so when you don't sleep long enough, you're not going to have the same hormonal response. And we know really directly, men who get less sleep, they have lower testosterone levels and lower sperm counts. Women who get less sleep get fewer eggs at IVF cycle. And we see that if you say you have poor sleep, you have double the rate of infertility. If you just subjectively say, "Yeah, I have poor sleep," you have double the rate. And that people who are not sleeping well, either partner, it will take them longer to get pregnant. They have lower fecundability, that month-to-month pregnancy rate. So it's not just me sitting over here saying, "Oh, yeah, you need to sleep better." Your physiology is meant to sleep.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
It is a sign to your brain, if we go back and we view that hypothalamic response as central command station looking for clues that your life is stable enough, you're healthy enough to carry a pregnancy for a woman, which is a huge metabolic spend. It's looking to make sure you're taking care of yourself primarily, and sleep is one of the most powerful markers that we can move. Seven to nine hours. Most women need closer to seven and a half, especially in the luteal phase. Making progesterone is a big body spend. We really have to cultivate better sleep. All the things you talk about. Dark room, sound machine, a sleep mask, a cooler temperature. Takes two to tango, so if you sleep in the bed with somebody, they need to be on board. You need to go to bed at the same time, and you have similar sleep practices. And we know that day-to-day consistency is also impactful in fertility, so not just the length of time, but really having that good circadian rhythm is so important for your hormones. Melatonin is obviously released before you go to bed. Low doses of melatonin supplementation can impact fertility, so doses of one to three milligrams 30 minutes before you go to bed can improve your odds of getting pregnant as well.

Andrew Huberman:
Interesting.

Dr. Natalie Crawford:
Can influence egg quality. And we know that naturally, you make more melatonin when you ovulate to kind of counter some of the oxidative stress to the ovary. Really have to be careful, though. A lot of over-the-counter products have 10 times the amount of melatonin.

Andrew Huberman:
Yeah, right.

Dr. Natalie Crawford:
So I always want to tread lightly with that one in recommending it to patients.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
Often, a pediatric dose is one milligram, and that's the perfect amount.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
Just to augment. Again, we're not trying to replace your body's melatonin.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
We want to augment it and to kind of help your body, I always like to think about like a toddler. Really get good consistency with your wind-down routine so that you can get enough sleep.

Andrew Huberman:
I don't want to disrupt your flow.

Dr. Natalie Crawford:
You're fine.

Andrew Huberman:
But if a woman is already sleeping well-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... should she take melatonin?

Dr. Natalie Crawford:
I would say for the average person, probably don't need to.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
I would say the exception to the rule would be that if we know we have increased chronic inflammation, maybe we have endometriosis or an inflammatory autoimmune disease, or we're going through IVF with unexplained infertility, or ever been kind of told you have, quote, "bad egg quality," then the anti-inflammatory properties of it might be advantageous.

Andrew Huberman:
Since NSAIDs can disrupt the inflammation requirement for ovulation-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... I'm curious about other things that are known to potently reduce inflammation. I think enough terrible things have been said about cold plunges that we don't need to add any more, but we're seeking reality here. And despite common belief, I don't have anything inherently attached to cold plunges. I do them sometimes. But we know that one shouldn't do them after resistance training or any kind of exercise where you want the inflammation to get the adaptation to the exercise.

Dr. Natalie Crawford:
Mm.

Andrew Huberman:
We know that. And it's a pretty potent inhibitor of inflammation. So Is there any reason to think that in the time where somebody's trying to conceive that perhaps they should avoid the cold plunge?

Dr. Natalie Crawford:
I usually recommend against them for reasons stated here.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
I think there's very few things we have that are going to really turn off that acute inflammatory response to the degree that NSAIDs do, but we should proceed with caution in doing those things.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
Most everything else is trying to just get rid of the excess inflammation we have. But if something's dampering down into that acute inflammatory response-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... then I think we have to be a lot more judicious in saying, "Yeah, go for this." So I'm not a fan of cold plunges when trying to get pregnant.

Andrew Huberman:
A lot of people will be very happy to hear that because I don't-- Unlike the sauna, nobody likes the cold plunge.

Dr. Natalie Crawford:
I mean, I hate a cold plunge.

Andrew Huberman:
Yeah. That's what, that's all-

Dr. Natalie Crawford:
I've tried it one time-

Andrew Huberman:
Yeah

Dr. Natalie Crawford:
... and that was one time too many.

Andrew Huberman:
I always say if you like it, great. If you think you benefit, great. But otherwise, don't worry about it. One thing that's commonly used is curcumin.

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
And it's a pretty potent anti-inflammatory. Do you recommend people stay away from, let's not cooking with curcumin, but the high-dose curcumin that comes in a lot of supplements?

Dr. Natalie Crawford:
Yeah, I don't usually recommend it in a supplement form.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
I never recommend it.

Andrew Huberman:
Right.

Dr. Natalie Crawford:
I think if you have a doctor who's giving it for a very specific purpose, you might be a unique person who has excess inflammation they're trying to target.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
But that's not something that I recommend. But cooking with it is fine.

Andrew Huberman:
NAD and NR-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... are, I get asked about them thousands of times-

Dr. Natalie Crawford:
Oh, same

Andrew Huberman:
... per week. And I'm more or less a fan of NR or NMN if one is trying to, I don't know, I don't think it'll extend lifespan, but it does seem to, at least in my experience, increase energy, these kinds of things. But it's NR in particular, there are data that it can be very anti-inflammatory. So if a woman is trying to conceive, should she stay away from NMN, NAD, and NR? Because I often see it listed in fertility protocols.

Dr. Natalie Crawford:
I know. Animal data looks like NAD and NNM can be advantageous-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... especially for unexplained infertility, which to be clear, is different than, "I just want to get pregnant." Right? In unexplained infertility, you're not conceiving. We do the basic tests, anatomy, ovulation, ovarian reserve, semen analysis. They're all fine. So I view that as chronic inflammation unless proven otherwise.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
And so that's a unique situation that patients may have potential benefit. But unlike certain things across the population that we can feel really comfortable recommending, I don't recommend that to everybody. So I think that there might be utility in certain subgroups who are kind of really falling off the curve and we think there's excess inflammation that it could make sense for. So I don't ever say no, and I sometimes use it. But on the flip hand, we could say like CoQ10, which has robust human data that is advantageous without a negative benefit. That's an easier place to leverage your supplement dollars-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... if you're going to spend.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
Because most of us don't want to spend endless amounts on all the things that we can craft for our supplement list. But the human data is yet to be out, although animal data looks promising for the right patients.

Andrew Huberman:
I'm glad you mentioned coenzyme Q10. CoQ10 and L-carnitine are the two, at least I'm aware of, there's some decent data on supporting sperm and egg quality. So do you encourage patients to start taking that, what, 60 days before trying to conceive and then continuing that through pregnancy?

Dr. Natalie Crawford:
We usually stop CoQ10 in pregnancy just because of lack of data. We're very cautious in pregnancy of not exposing you to anything additional you may not need. So we just want to be really mindful of that. But I think it's in my, like everybody should take before you get pregnant. Yep, at your trimester zero, your, "Hey, we want to get pregnant soon. We should take a prenatal vitamin that has folic acid. We should take CoQ10. We should take omega-3 fatty acids. We should take vitamin D." These are all going to optimize, giving you the nutrients you need for a pregnancy, helping support good mitochondrial health, which is important for egg quality, without risk of harm to any of these specific supplements.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
Those are the universal we're trying. And then for sperm health, L-carnitine we like a lot, and then zinc and selenium can have benefits as well.

Andrew Huberman:
I know you cover specifics in the book, so we'll leave it to people to find it there.

Dr. Natalie Crawford:
I have supplement charts for everybody who's like very curious-

Andrew Huberman:
Dosages and all of that

Dr. Natalie Crawford:
... based on disease state-

Andrew Huberman:
Yeah

Dr. Natalie Crawford:
... and more info.

Andrew Huberman:
I'd like to take a quick break and acknowledge our sponsor, Function. Function provides over 160 advanced lab tests to give you a clear snapshot of your bodily health. This snapshot gives insights into your heart health, hormone health, autoimmune function, nutrient levels, and much more. They've also recently added access to advanced MRI and CT scans. Function not only provides testing of over 160 biomarkers key to your physical and mental health, it also analyzes these results and provides recommendations for improving your health from top doctors. For example, in a recent test with Function, I learned that some of my blood lipids were slightly out of range. As a result, I decided to start supplementing with nattokinase, which can naturally help reduce LDL cholesterol, and it did. In a follow-up test, I could confirm that this strategy worked. My blood lipids are now back where I want them, in range. Comprehensive lab testing of the sort that Function offers is so important for health. And while I've been doing it for years, it's always been overly complicated and expensive. But now with Function, it's extremely easy and affordable. To learn more, visit functionhealth.com/huberman and use the code Huberman for a $50 credit towards your membership. I'm sure there are sort of standards and a lot of communication in your field about how many follicles to try and mature, if one does IVF or is pulling eggs. I don't know if that's the right term. Forgive me. There it is again. I think, pulling eggs. Taking eggs out carefully and for sake of freezing or fertilization. But how much conversation is there at the various meetings and in the journals about things like coenzyme Q10, L-carnitine? I'm not trying to punch holes in these. I'm obviously a big fan of supplements. My friends joke when people ask me, "Which supplements do you take?" They just shout-

Dr. Natalie Crawford:
You like all of it

Andrew Huberman:
He takes all of them, which is not true, I don't take all of them, but I've been experimenting with them since I was in my teens. And they're not the be-all, end-all, but some work. So how much conversation is there about things like coenzyme Q10, L-carnitine? Is there a consensus, or is there sort of a distribution-

Dr. Natalie Crawford:
Hmm

Andrew Huberman:
... of old school, new school? And I am very curious, not trying to be political or politically correct, whether or not this divides on male/female fertility docs. The culture within a field often tells us a lot, so I'm not asking you to throw any of your colleagues under the bus-

Dr. Natalie Crawford:
Oh

Andrew Huberman:
... but if you have to

Dr. Natalie Crawford:
No.

Andrew Huberman:
No.

Dr. Natalie Crawford:
I will say this. Over the past 10 years, we've seen a huge change in how we talk about fertility, even at meetings. The first ASRM, which is the American Society for Reproductive Medicine, that I went to was probably 15, 16 years ago, and it was so IVF heavy. Now, to be fair, the science was rapidly evolving. Genetic testing was just introduced for embryos. But as we also see more patients, and the general public, really curious about, "Well, what can I do?" And I think this is such a good question because I look at people and say, "IVF's incredible, but I can only work with the eggs and sperm you give me. So come to the table with the best eggs and sperm you can." Control all of these variables. That public curiosity drives research to a degree.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
Because if you're hearing it from your patients, that's the formation of research questions that we're looking at. Now, granted, all data that exists is limited in its own form. In general, when we look at cohort studies, of course, people who tend to take CoQ10 have other advantageous lifestyle factors than people who do not. When we do randomized control trials, though, which we often do in the IVF subset because we can look at more distinct criteria. I can say, well, how many eggs were mature, or how many embryos formed, or how many were genetically normal, or the pregnancy rate per embryo transfer, which is a little bit of a finer point than just how many people got pregnant per month. We definitely see robust data that certain supplementation, CoQ10, vitamin D, omega-3 fatty acids, those are clearly associated with improved reproductive outcomes. And we're starting to see more, I don't want to say fringe, but of the specifics. Inositol for PCOS, decreases insulin resistance, huge benefit. N-acetylcysteine for endometriosis or chronic inflammatory disease. So we're seeing more interest in the nuance. It's a hard question on the field. I think there's definitely an old school versus a new school approach. I've always been slightly controversial because I've always been educating, and I think at the end of the day, my job's not to say, "Just do IVF."

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
My job's to explain what's going on, what the options are, and help you make that decision. I think a lot of older-trained physicians practiced medicine in the day where this field specifically, patients did not have knowledge and access to knowledge. Therefore, when a doctor said, "Do this," they just blindly said, "Okay." And they view that as a simpler way to practice, and therefore can be very dismissive of patient questions when they say, "What about CoQ10?" Or any merit of the other lifestyle factors that we talk about. The plethora of research that exists, which is more and more now, is that these lifestyle factors matter a lot, that decreasing inflammation can influence your fertility from how your hormones function, how your ovaries respond, how many eggs you pull out, to what you say-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... how many embryos you form, and that supplementation is one piece of the puzzle.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
It's not the end-all, be-all. I think we probably should always focus first on where we can move the needle the biggest.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
So those more core lifestyle practices should be tenet number one. When we feel like we've mastered those and we want to add to the puzzle, that's when we can start to say what supplements help me. And one thing that I really encourage is allowing ourself space in each patient to be their own N of one experiment.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
Meaning, how can I get so in tune with my body that I can say, "This makes me feel this way," and trust that sense for yourself? Because we are all unique, and our response will be different to different medications or different interventions. And learning to trust that instinct about what's working for you or oh, this isn't, that's really important when it comes to optimizing your own health, regardless of what tenet of health that we're talking about.

Andrew Huberman:
If we'd have been sitting here 15 years ago and I said red light therapy can be useful for skin and for offsetting-

Dr. Natalie Crawford:
Mm-hmm

Andrew Huberman:
... age-related vision loss, any reasonable physician would be like, "That's nonsense."

Dr. Natalie Crawford:
That's bogus.

Andrew Huberman:
I spoke to an ophthalmologist yesterday. There's been a clinical trial using red light and infrared light for what's called dry AMD, dry macular degeneration, to offset age-related vision loss.

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
And it looks promising. It doesn't reverse age-related vision loss completely, but seems to help the mitochondria and the photoreceptors.

Dr. Natalie Crawford:
It makes sense.

Andrew Huberman:
People are holding onto some vision that they would lose. There was a cover of what I am told is the premier dermatology journal exploring the recent studies on red light and infrared light, so it's a common practice now.

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
So it takes time, but this stuff was considered super woo, niche, and nonsense by most, quote unquote, "traditional physicians" 10, 15 years ago. In the field that you're in, how are things like red light, infrared light therapy looked at currently? And if they are used, where is it directed?

Dr. Natalie Crawford:
Mm-hmm.

Andrew Huberman:
Is it actually on top of the ovaries? Is that the idea? Or that it's just more of a systemic effect?

Dr. Natalie Crawford:
Great question. I think, again, let's just think about the fact that chronic inflammation impacts your body when it comes to your hormones and your fertility in multiple ways, right?

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
So if you have chronic inflammation, it's going to interfere with hypothalamic receptivity, so your brain can't interpret your hormonal signals as well. It's also going to send out signals differently. You're also going to have distinct ovarian changes in how the ovary responds, and then, of course, for the egg quality. So the bigger answer of what type of therapy matters maybe depends on the outcome that we're looking at or how we're trying to show benefit. And in short, data is inconclusive, but all appears to be beneficial for the reasons you stated, whether it is to improve ovulation patterns, which we've seen signs showing that. That's more the systemic probably.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
You're sitting in front of your red light panel-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... that's going to decrease some whole-body inflammation. That's the inflammation that's most likely contributing to some of the brain sensitivity, so you're improving the ovulatory pattern. There have been some studies looking at ovarian-directed red light-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... therapy, so through the abdomen. But there is now-- We don't have definitive data, but there's even a vaginal ultrasound wand that's got red light therapy. So we don't have data on that yet, but seeing intravaginally, you're much closer to the ovaries.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
That's why we do vaginal ultrasound monitoring for IVF to try to see if directing the response closer to the ovary can have more benefit or could-

Andrew Huberman:
Mm

Dr. Natalie Crawford:
... potentially benefit egg quality more. I think most people are going to say, "We don't have definitive data yet."

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
Yet everything's pointing to likely benefit.

Andrew Huberman:
Mm-hmm. I don't know if this study could be done, but the one arm of this, my podcast company, funds research, and the one thing I'd love to see the experiment done is either maintaining or doing fertilization of eggs under red light because so much of the proper chromosomal arrangement seem to be dependent on mitochondrial health.

Dr. Natalie Crawford:
Mm-hmm.

Andrew Huberman:
That's a short-term exposure, but the more I learn about the different wavelengths of light and how they impact mitochondria, and I think about the horrible lab lighting that I lived under for many years of my life, I think, oh, such precious embryos, is there a way to put them under beneficial lighting as opposed to either neutral or, I'm not saying detrimental lighting, but I don't know. It'd be a fun study to fund-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... if there's a way to do it.

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
Could it be done?

Dr. Natalie Crawford:
It definitely could be done.

Andrew Huberman:
Okay.

Dr. Natalie Crawford:
We have incubators. That could definitely be done, and where you fertilize, too. I was going to say off-topic, my daughter did her science fair project on chicken eggs, but they looked at blue light, green light, and natural light-

Andrew Huberman:
Ooh, cool

Dr. Natalie Crawford:
... to see if they-- They're all fertilized-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... but to see if their hatchability was different. And the group that was exposed to blue light actually had the highest hatchability, and-

Andrew Huberman:
Interesting

Dr. Natalie Crawford:
... UV light was actually the lowest. But in their research, what's so fascinating is that red light is really detrimental to chicken eggs. So-

Andrew Huberman:
Interesting

Dr. Natalie Crawford:
... anyways, I think, like-

Andrew Huberman:
Yeah, well, that's why science is fun

Dr. Natalie Crawford:
... yeah. So science is cool.

Andrew Huberman:
Oh, congratulations to her. She should write it up.

Dr. Natalie Crawford:
I know.

Andrew Huberman:
There's a journal where kids can write up their-

Dr. Natalie Crawford:
Oh.

Andrew Huberman:
Yeah, I'll send you the link to it.

Dr. Natalie Crawford:
You'll have to send me it after. She would love that.

Andrew Huberman:
She'll be published, and that's what's so cool about science. Sometimes we think, oh, the red light is going to be the beneficial one, or the blue light is going to be the bad one. But then vitamin D production is dependent on blue and UV.

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
So nature's mysterious. That's awesome.

Dr. Natalie Crawford:
It keeps it interesting for us.

Andrew Huberman:
Awesome. Is she going to become a scientist? Or she's already a scientist, but-

Dr. Natalie Crawford:
She's 11, but she's a scientist right now.

Andrew Huberman:
I love it. I'll send you that link. It'd be cool if she would write that up. So red light, maybe.

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
And I should point out, red light and infrared comes from sunlight. And of course, there's good circadian effects of getting sunlight. But-

Dr. Natalie Crawford:
All circadian benefits of getting sunlight are pro-fertility, pro-hormonal health, yes.

Andrew Huberman:
Great. Yeah, I don't want to give people the impression that they have to purchase a panel.

Dr. Natalie Crawford:
Correct.

Andrew Huberman:
There's no hidden agenda here. So those are the things that one can take. The do nots, I think broadly is don't smoke, don't drink. I was shocked, but I need to ask to learn, what I found was that 15, one five, percent of women in the United States report having used cannabis in some form or another while pregnant.

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
Does that concern you?

Dr. Natalie Crawford:
Cannabis use is probably the most concerning thing that I see in clinical practice. So both you can just say if that many are using it in pregnancy, let's extrapolate to how many are using it beforehand.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
And ultimately, something that we are just now getting robust data on because it's hard to study something when it's illegal.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
All cannabis use is hugely detrimental to sperm, for sure, across the board, right? Both production, the quantity of sperm, testosterone production, also the quality of the sperm, specifically the DNA fragmentation inside the head of the sperm, to the degree that female partners who conceive from a male partner who's using cannabis have much higher miscarriage rates than partners who do not utilize cannabis. And I will say clinically in the IVF lab, when I see embryos halt at that male developmental stage on day three, we say, "Oh, here's a young couple. They've got no embryos, and we were expecting them to have some." When we go back, nine out of 10 times, he is using cannabis that he previously denied. So it is one of the most movable factors right now in this country for improving fertility outcomes. For women, cannabis use in the prior year can decrease the eggs you get at egg retrieval by 25% and can decrease fertilization rates by 28% and can increase miscarriage rates, therefore decreasing live birth rates. So huge numbers in science, right? We get excited when something's a few percentage points different, but these numbers are really high to the degree that it's really easy to sit here and say if you're trying to get pregnant the fastest, if you want to have the best pregnancy outcomes, or even you want to have the best hormones you can, have longevity of your ovaries, or have the best sperm counts or the most testosterone, cannabis use should not be a part of that. And THC crosses the placenta directly, and THC levels in edibles are usually the highest. So I think it's really important that sometimes people are like, "Oh, well, I don't smoke it, so I'm okay." We want to be really careful that this is not something your body is meant to be exposed to when we want to think about the core of how your body's meant to function.

Andrew Huberman:
Critical message. Thank you so much. I've been put through the wringer around this cannabis thing because I've hosted people that said it does increase the risk of psychosis in certain, typically young males-

Dr. Natalie Crawford:
Mm-hmm

Andrew Huberman:
... although not everyone. I've been accused of all sorts of things related to that, then had someone on who confirmed that, someone who refuted it. And cannabis, I believe is Recently rescheduled from Schedule 1, at the federal level, it's assigned a no medical application to Schedule III, so there's going to be a lot more cannabis use going forward. It's so critical that people hear this. And the argument I always hear, and it's always dudes, typically on X, they'll say that they smoked a lot of weed or took edibles, and they got their wife or girlfriend pregnant-

Dr. Natalie Crawford:
Oh, yeah

Andrew Huberman:
... X number of times, and it sort of becomes this point of boasting. And then I never want to make the comment, but I'll make it now. It's like, yeah, but you're talking about brain development in your kid.

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
And I'm not saying your kid is dumb, but I'm saying they're maybe not as smart as they could be, or as healthy as they could be. I'll just say that because I'm talking to the guys out there, and that's how we talk to one another.

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
Yeah, you had a bunch of kids, but they could be a lot healthier. And so I think to me, it just seems like anything that one could do, since it's ostensibly a short-term decision, certainly for the man, right? The woman who's going to breastfeed should probably avoid cannabis-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... during breastfeeding, too. You see where I'm going with this.

Dr. Natalie Crawford:
Look, the outcome is so important, right?

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
And when we want to think about even just male cannabis use, yes, sperm count, et cetera, decreases the sperm quality. That sperm quality is important for programming of the embryo, for how the placenta develops. If the placenta's not as good, association with earlier birth. It's just not worth the risk-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... when the outcome is so important, right? We're all weighing risk every day with different decisions. To me, there's a lot harder decisions you have to make. But nicotine use, cannabis use, alcohol use, the data here, none of that is advantageous for your health, especially if we're looking primarily through a fertility lens, a hormone lens, or specifically a pregnancy lens. There's no place for it. You can choose to do what you want with that data, right?

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
And people will always say, "I know so and so who did this, and they got pregnant." And there will always be those people, but you're the one making decisions for your journey. And the recommendation's even stronger if you are having infertility, if you are older, depending on your scenario, because you want to control what you can because you can't control everything.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
So I call those the behavioral toxins-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... that there's really no place that we need to add these to the world if we're talking about how do we get my body to function optimally.

Andrew Huberman:
It's interesting that certain substances get politicized. In the past, I experienced this thing that you can tell with some degree of friction. In the past, cannabis was associated with the left.

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
It was like pro-cannabis was left. Now, pro-cannabis is actually very strongly correlated with the-

Dr. Natalie Crawford:
I know. It's interesting

Andrew Huberman:
... with the laws anyway, of this rescheduling. And you watch the media just kind of pivot, and it's just very clear that the traditional media isn't paying attention to the actual data. It's sort of like, how can we use this as a weapon? On both sides.

Dr. Natalie Crawford:
100%.

Andrew Huberman:
And so depending on where people get their news, it can be very confusing to people. Along those lines, for whatever reason, nicotine has become this right-wing associated thing.

Dr. Natalie Crawford:
I know.

Andrew Huberman:
I recently spoke to about 4,000 young men and women, and I would say about 30% to 40% of them raised their hand that they're using oral nicotine every single day. Anywhere from probably, I did a crude analysis by hand, so these aren't hard data, but it was somewhere between 12 and 70 milligrams of nicotine a day.

Dr. Natalie Crawford:
That's wild.

Andrew Huberman:
So for women in particular, is oral nicotine use detrimental to either egg quality or probability of successful pregnancy?

Dr. Natalie Crawford:
It's definitely correlated because of how it works in the brain to ovulation, getting pregnant, hormone response. So it should not be something that we're adding to our day-to-day life in any form if we're trying to get pregnant. Most the egg quality data from nicotine comes from cigarette smoking-

Andrew Huberman:
Uh-huh

Dr. Natalie Crawford:
... so I think it's a little bit more nuanced because smoking directly, if we want to look at that, I always say it's one of the few things that gets into the vault and decreases our egg count. And as I say, chronic inflammation can get in there, but nicotine, cigarette smoking definitely does. You go into menopause early, you'll get fewer eggs. The egg quality is detrimental. It makes sense based on what nicotine does to your body and how it changes your cellular response, that it probably is impacting your egg quality also, even with these oral nicotine pouches that we're seeing everybody utilize. And it's tanking sperm counts. That one's really clear.

Andrew Huberman:
And then, of course, everyone's talking about the reduction in just population growth, which when I was growing up, we were told that the Earth is going to be overcrowded. Now we're told that there's not going to be enough people.

Dr. Natalie Crawford:
Yeah. It's funny, right?

Andrew Huberman:
Everyone's going to be alone on their phones. I don't think either extreme is true. But these are vitally important things for people to think about because these are easy decisions to make, and they can be short-term decisions.

Dr. Natalie Crawford:
They are.

Andrew Huberman:
Yeah.

Dr. Natalie Crawford:
We make decisions every day, and you don't have to be perfect, and you don't have to be all or nothing, and it doesn't have to be forever.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
A lot of these things, once you really start making a bunch of them and decreasing inflammation, you will tangibly feel better. I think we are creatures of our own world, and humans by nature adjust to the environment we put our body into. So even things like we talked about sleep, but chronic stress, how it's directly associated with insulin resistance, how building skeletal muscle is one of the top ways you can reverse insulin resistance. It's the best mechanism for hormonal health we have is to build more skeletal muscle. These things can impact your fertility and your health long term. And so once we start to make these little decisions, eating more fiber, anti-inflammatory foods, cutting down the ultra-processed foods, removing the toxins, changing the toxic behaviors, sleeping more, really trying to manage stress in a more productive way Together, when your inflammatory burden lowers, people feel better, and then they get it. Then they say, "Oh, this running on just caffeine and eating whatever food I could on the go and not getting enough sleep, and then using 100 nicotine patch, that was my body giving me 100 red flags that it is working overtime to deal with what I'm handing it." So how is it supposed to do its normal day-to-day function? Which at its purest, that's where your body should try to be, especially when it comes to trying to get pregnant and have the best egg and sperm quality.

Andrew Huberman:
I would never ask you to assign any validity to something for which there's no data. But in your experience, your clinical and scientific experience, is there something that you've heard from your patients and then observed in terms of outcomes that is intriguing to you that you would like to see more science on?

Dr. Natalie Crawford:
Oh, yes. Absolutely.

Andrew Huberman:
And the reason I ask this is there's this incredible intuition that comes from just being in regular contact with a certain process. For instance, any time I've spoken to an embryologist who does the kind of work that they do in your clinic, they read journals and there's a process. They learn protocols, but they develop an intuition to pick that sperm, to wait just a little bit longer, maybe even fertilizing that egg at the end of the day-

Dr. Natalie Crawford:
Oh, I know

Andrew Huberman:
... even though it looks more mature than the-

Dr. Natalie Crawford:
It's a couple of hours. It's a little small, it's a little gray

Andrew Huberman:
This is the art, not the-

Dr. Natalie Crawford:
It's like the je ne sais quoi of medicine

Andrew Huberman:
Right. The art, not the science of it. The same way cooking is chemistry, but there's an art to it, too.

Dr. Natalie Crawford:
Mm-hmm.

Andrew Huberman:
And that nothing can replace those millions of hours in contact with the process. So you've had so many hours in this process at every level. Is there something that intrigues you and that you'd like to see more science on?

Dr. Natalie Crawford:
I love that question. One thing I think I want most people to take away, and then I'll answer the question, is that you can make tangible improvement in your fertility. By looking at these lifestyle factors and coming up with a plan to try to decrease your inflammatory burden, you can have a different outcome. And I think that conversation's even more important if you're waiting longer to get pregnant, or if you're at an older age, or you have lower ovarian reserve because knowing that you are controlling all these variables to put the best egg and sperm forward is really important. The most intriguing part of the conversation for me right now is GLP-1s and their use for potential chronic inflammatory disease like endometriosis. As a field, we quickly accepted that they are hugely powerful for PCOS and states of obvious insulin resistance for reasons that make sense to everybody. They also help, obviously, patients lose weight. Fat cells make estrogen. They impact the ovulatory process. Fat cells are inflammatory. So all the things that we said were negative. So by simply losing weight, we can restore ovulation, we can have improved IVF outcomes, and it is just a more effective mechanism for weight loss. So easy to jump on and say, "I have a patient who needs to lose weight. I have a patient with PCOS." GLP-1 agonist can be a very powerful tool to that. Where I see right now are patients who have known endometriosis or what I call probable endo. They have unexplained infertility. 50% of those patients will end up having endometriosis. One of the problems with endo is gold standard is a surgical diagnosis only. We don't have a lab test for endometriosis. But when we are getting unexplained IVF outcomes that do not match what we would expect, or we have these known chronic inflammatory diseases, I will have patients go on a GLP-1, low dose for three months. We have to stop them and then go through a cycle of different IVF outcomes. We will see more embryos in the lab.

Andrew Huberman:
Hmm.

Dr. Natalie Crawford:
And we don't have the study to say that, but-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... talking to colleagues across the country, we know that GLP-1s can be very anti-inflammatory and the way to kind of target what appears to be that inflammatory burden. And I think that there will be utility there within the context of these chronic inflammatory disease that might be able to help a patient population that we've struggled with, with difficulty to get to a diagnosis or limited data points on what to do with it. So the data's not out yet, but it is a tool I add to the box, especially if we're not getting outcomes we would expect, and we don't have another reason why.

Andrew Huberman:
So do you think there could be direct effects of the GLP-1s on reducing inflammation that are independent of less adipose fat tissue?

Dr. Natalie Crawford:
I do because some of these patients do not have much adipose tissue.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
So I think obviously that person's going to get even more benefit if they have adipose tissue to lose that's causing inflammation. But I think especially if we think about autoimmune disease-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... where people's immune system, their inflammatory response is mis-triggering-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... I think that there's benefit for the GLP-1s in that population specifically that is giving them an added benefit to decrease inflammation in a really profound way.

Andrew Huberman:
It's really interesting because I would've thought GLP-1s reducing body fat for a woman who isn't carrying excess body fat-

Dr. Natalie Crawford:
Could be

Andrew Huberman:
... that might actually be detrimental to getting pregnant.

Dr. Natalie Crawford:
It's a fair point that we have to be really careful when it comes to skinny culture. We are seeing just societal norms shift again to be very thin after being more body positive, be of a healthy weight. We are definitely seeing celebrities go back to being extremely thin, and we know at both extremes of body weight, again, the hypothalamus is your checkpoint. If you don't have enough body fat, we are worried that you cannot maintain a pregnancy, so it can stop how it's sending off hormones. And again, we can see a luteal phase defect is that first warning sign before you're in true hypothalamic amenorrhea. So I think we have to be really careful in that patient group, and it has to be done with the right person who has a lot of experience with GLP-1s that are super low doses. The goal is not weight loss. It's really a different goal. And again, I don't have a paper to prove it, but we are seeing that clinical experience to say At the end of the day, we could say there's merit in trying to decrease inflammation, especially in people who we suspect is contributing to the circumstance they are in.

Andrew Huberman:
And you said low-dose GLP.

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
Yeah. Are these available in generic form now, or are they still under patent where they have to be-

Dr. Natalie Crawford:
I don't know the answer to that one.

Andrew Huberman:
Okay. I don't know. I know compounding pharmacies are making them. I know today, today the gray market for peptides in this country-

Dr. Natalie Crawford:
I know

Andrew Huberman:
... was shut down, so no more.

Dr. Natalie Crawford:
Well, you never can tell.

Andrew Huberman:
You can no longer buy that just for research purposes.

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
But compounding pharmacies seem to be protected. But I just ask because of the GLPs, at least the non-generic forms in their full dosage, my understanding is that they can be rather expensive.

Dr. Natalie Crawford:
Yes.

Andrew Huberman:
But the lower dosages in generic form perhaps have to be more affordable.

Dr. Natalie Crawford:
One would think, yeah. And I think, again, there's a lot of kitchen sink approach we do-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... in fertility medicine. I've used human growth hormone for years and years and years. There's not an FDA approval to use HGH for egg quality, yet we see that it can improve egg quality in the right patient in the lab.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
So if somebody has a cycle and they don't get as many mature eggs, or their embryos don't do as well, my partner actually did a study where she put them through the same protocol, so the same medications in a subsequent cycle, and the only change was adding human growth hormone and had improved embryo development and maturity of eggs.

Andrew Huberman:
Amazing. So this is like an IU a night or something like that? Like some low dose of HGH-

Dr. Natalie Crawford:
Yes

Andrew Huberman:
... during the IC.

Dr. Natalie Crawford:
Yeah, just during the STEM. So it's like two weeks of use.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
And so then now that's starting to be extrapolated, and people are starting to look at it longer or before STEM.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
And so we have to take that-- I love the fact that my field's always viewed cutting-edge research. It's a double-edged sword. There's some good and there's some bad. But we really want to think about mechanistically if it could potentially help having a low threshold to attempt it in patients who are getting at the end of their journey specifically.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
When they've done all the basics. They're controlling the lifestyle factors. I will say one thing I dislike is this just do IVF mentality, meaning nothing you can do can impact your egg quality. Let's just do IVF, and then we're compounding dollars and dollars and dollars, yet we're not eating anti-inflammatory food, and we're drinking wine every night, and we're not getting enough sleep. So I think that we've got to really look at these five non-negotiable areas and optimize them to the degree we can, knowing each day will be different, but building our body the resilience to be able to respond as it's appropriate to. Because sometimes you'll fly to Texas and get less sleep, or you'll go out to eat and you'll eat differently, and your body's meant to handle those challenges, but it can't when it's constantly challenged-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... every single day, all the moments of the day. So there's a ton of experimental stuff that we do that's really cool, and some of it will be introduced into practice in 10 years. Probably 15 years ago, if I had said human growth hormone, people would've scoffed, and now it's commonly added on-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... when we're not getting the outcome we want, and that's how medicine should be. We should not be afraid to say that the perfect study doesn't have to exist. If the physiology makes sense, if there's suggested studies, if we explain it to the patients, we help have shared decision-making with them because if we're always waiting for the perfect RCT, there will be thousands of patients we could've helped in the interim-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... that we didn't.

Andrew Huberman:
What are your thoughts on platelet-rich plasma?

Dr. Natalie Crawford:
Oh, such a good question.

Andrew Huberman:
Which is not stem cells, by the way.

Dr. Natalie Crawford:
No.

Andrew Huberman:
Sorry to just shout out there. People think it's stem cells. Stem cells are not allowed by the FDA in the United States. A vision clinic, they were injecting them into the eye for macular degeneration, and the patients all went blind, and I'm very familiar with those cases. It was that specific clinic that shut down stem cell. You can't advertise stem cells online anymore. But PRP is not stem cells.

Dr. Natalie Crawford:
Okay.

Andrew Huberman:
Forgive me for interrupting.

Dr. Natalie Crawford:
PRP has two potential different mechanisms by which it can be used, and it's different. So one is intrauterine PRP, where we are injecting it into the uterine cavity, similar to how we put an embryo inside or how we would do an intrauterine insemination. So small catheter, not invasive, but kind of goes through the cervix right into the uterus. The other is looking at ovarian PRP, which is a more invasive procedure. This is using the same needle like we do for IVF, yet instead of extracting the follicular fluid and the eggs, I'm putting the PRP into the ovaries. Looking at it for two different reasons, implantation failure or potential Asherman's scarring of the uterus in the uterine PRP group, and looking at it for low ovarian reserve or age-related fertility in the PRP of the ovary group. Where it shows the most promise is intrauterine PRP, which is nice because it's less invasive. That's the minority of people who are having recurrent implantation failure. Most people don't have success because they don't make enough embryos. That's the rate-limiting step for most people with IVF, meaning if you have three genetically normal embryos, almost 95% of people will have a live birth. So we're talking about a very small subset of the population here, but showing the most promise, though not universally accepted and isn't done everywhere. Ovarian PRP is a little bit more nuanced because clinics can charge a lot for it. It's a procedure. You need anesthesia. I'm putting a needle in the ovary. I'm always a lot more skeptical of potentially damaging the ovary or potential developing eggs. Although no study has supported that it does do that. There are some more hypothetical concerns with that versus uterine, where you're not really damaging any structure, you're just adding it. That being said, ovarian PRP is currently being studied. We don't have definitive data. Potentially could be something to consider if you're really approaching that end game. You're really not getting the outcome you want. You are older. You have low ovarian reserve. There are people who have some success stories. So I think it's, again, the exception, not the rule. Has potential benefit, but yet to be determined.

Andrew Huberman:
A few years back, there was more discussion about the age of the sperm and the probability of autism.

Dr. Natalie Crawford:
Yes.

Andrew Huberman:
Could you update me on the The data?

Dr. Natalie Crawford:
Yeah. After age 50, we see a few different increases for sperm specifically. So advanced paternal age is real, both when it comes to how you make sperm, but also the quality of that sperm. We see overall, in a population base, increases of autism, of autosomal dominant new mutations, specifically certain types of dwarfism or very specific diseases that are ultimately overall rare that can happen. And then you also can see an increase in some other mental health diseases, like schizophrenia.

Andrew Huberman:
Hmm.

Dr. Natalie Crawford:
That data's scary, not the end-all be-all. At the end of the day, when you have an opportunity to bank sperm younger, it would make sense, and utilize that preferentially. If somebody came to me and let's say they had banked sperm and it's gone now, and I have a 52-year-old man across from me, I mean, this is who we want to have children with, then this is who we want to have children with, and we accept that risk because on a population it's still very low, right?

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
A small percentage point increase means still the most probable chance is you're going to have a very healthy baby. It plays more into, though, the idea that nobody's fertility is finite, that age-related impacts impact everybody. I would say the same thing is that if the mechanism is the DNA essentially or the quality of the sperm, then those lifestyle tenets in the 90 days prior to getting sperm or banking it or using it in an IVF cycle probably matter the most, and I would make sure I would want to be controlling all of those factors I was, so I wasn't adding to risk.

Andrew Huberman:
No cannabis-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... reduced heat, all the things that mutate DNA.

Dr. Natalie Crawford:
Exactly.

Andrew Huberman:
Yeah. Nicotine out, that kind of thing. Yeah, it's interesting. I think about the sort of high signal-to-noise anecdotes, things like, "Oh, so-and-so smoked weed every day and has eight kids," or-

Dr. Natalie Crawford:
Oh

Andrew Huberman:
... or, "So-and-so had another kid when he was," whatever. I'm thinking of some actors or something. I don't follow this stuff closely. It was when he was like 78 or something. The problem with stories like that is that they grab people's attention because they're high signal-to-noise, and they distract from the stuff that really matters to most everybody. Like freezing eggs is not going to take more eggs out of your reserve than you need. The NSAIDs, I mean, I'm just still wide-eyed about this NSAID thing. It's something to avoid-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... while trying to get pregnant.

Dr. Natalie Crawford:
Okay, let's do another one. Taking a biotin supplementation of 300 micrograms or more for seven days can actually influence your lab assays for sex hormones or for any steroid hormone, actually. So when I will sometimes see patients who are going through an IVF cycle and their estradiol levels are not matching what we're seeing for follicular development, if we go and talk to them and they're taking hair, skin, and nail supplements or something with a high dose of biotin because commercial supplementation-- There are certain very popular hair supplements that have 10 to 30 times that amount in them. This is binding to the lab test, so we're getting false reads on these labs. It's not changing in your body-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... but this is an REI board question, an oral board question, is that it binds to the steroid assay, so this can happen to estradiol, to progesterone, to HCG, to TSH, to testosterone. So if you are back where we started and you want to get data about your body, maybe you feel off or you're going through IVF, or you want to get a hormone panel done, if you're taking a supplement that has more than 300 micrograms of biotin, you're going to have results that are inaccurate and we cannot trust. So really making sure that you're looking at what's in your supplements, and biotin is that specific one that I want to make sure we're not taking excess amounts of.

Andrew Huberman:
Wow. As long as we're talking about things that people take or put on their body, the last time we sat down and spoke, we had a conversation about endocrine disruptors.

Dr. Natalie Crawford:
Oh, man. People really-

Andrew Huberman:
And that went-

Dr. Natalie Crawford:
... loved and hated us for that.

Andrew Huberman:
Well, I will say, because it's tricky with comments, again, signal to noise. I think many, many more, meaning millions of people, appreciated it as opposed to had issues with it. I mean, you can tell how frustrated I get with-- My frustration is not with medicine or with science. It's with the lack of open ears-

Dr. Natalie Crawford:
Hmm

Andrew Huberman:
... in a certain generation of physicians and scientists. My colleagues at Stanford are very open-minded, and by the way, many of them call me saying, like, "What should I take for this?" Or like-

Dr. Natalie Crawford:
I love that

Andrew Huberman:
... "What can I do that's not TRT for testosterone?" They're humans, too, and I think the issue around endocrine disruptors for the longest time was seen as kind of hippie science with no data. And then now, because the Environmental Working Group started getting-

Dr. Natalie Crawford:
Mm-hmm

Andrew Huberman:
... really vocal about this, and Shanna Swan, who's-

Dr. Natalie Crawford:
Yes, lovely

Andrew Huberman:
... a long-time researcher. Yeah. But then there was this sort of political backlash because somehow people decided to slot her and the Environmental Working Group as kind of anti-standard science.

Dr. Natalie Crawford:
I know.

Andrew Huberman:
But you sit down with her, that's the furthest thing from the truth. She's all about data. So I think as we tiptoe into this endocrine disruptor thing, I'll just say it for you, and then if you want to add, none of what we're about to talk about negates anything about standard medicine.

Dr. Natalie Crawford:
No.

Andrew Huberman:
It's just ways and places to be additionally cautious about things that you are around and might go into you.

Dr. Natalie Crawford:
You make decisions every day.

Andrew Huberman:
Yes.

Dr. Natalie Crawford:
You should be making it from a place of knowledge.

Andrew Huberman:
Yeah.

Dr. Natalie Crawford:
And the things that you're exposed to more frequently matter the most, right?

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
So a one-time exposure because you used hand soap and it had lavender or tea tree oil or whatever, I'm much less concerned about than the products you buy for your home that you're using every single day.

Andrew Huberman:
Mm.

Dr. Natalie Crawford:
Because when it comes to endocrine disruptors, a lot of it is the quantity of exposure that really adds up, and this typically comes from frequency because typically it's low levels in a variety of different products. But they absolutely can disrupt hormone function. They cause longer time to pregnancy. There's now been robust data looking at one of the biggest cohort studies we have, and it's called the EARTH Study, where they're looking at different environmental compounds on reproductive health, and they're looking at cohorts of people trying to get pregnant naturally, and they did a sub-study looking at endocrine-disrupting chemicals specifically of those people who went on to do IVF and showed that those who had higher levels of endocrine-disrupting chemicals had a harder time getting pregnant, even with IVF, and their IVF markers, fewer eggs retrieved, fewer embryos, poorer sperm counts. So it's definitely not hippie science at this point.

Andrew Huberman:
Okay.

Dr. Natalie Crawford:
It's well demonstrated that it impacts our bodies in multiple ways.

Andrew Huberman:
And as I recall, the things to be cautious of are lavender, evening primrose, or basically anything with a scent-

Dr. Natalie Crawford:
Essential oils, for the most part, tend to be fine, but it is lavender, tea tree, and evening primrose that have more endocrine properties for them.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
When it comes to other products, scented products have a lot of phthalates in them, and then that's an endocrine-disrupting chemical. And an important note here, which is wild to me because we see so much greenwashing on products where they'll slap a label on it and they'll say "Unscented," but unscented is a scent to mask other scents.

Andrew Huberman:
Really?

Dr. Natalie Crawford:
So unscented just means you've masked a scent. What you really want to look for is fragrance-free.

Andrew Huberman:
Mm.

Dr. Natalie Crawford:
Because fragrance-free means we added no fragrance to it. To be called unscented, we could have added something to counter the fragrance that was in it.

Andrew Huberman:
Amazing. And Uber drivers, I'm not saying riding in your Uber with your terrible air freshener is going to prevent people from getting pregnant or conceiving with their partner, but take the freshener out of your Uber-

Dr. Natalie Crawford:
Please

Andrew Huberman:
... because you might not be able to have children.

Dr. Natalie Crawford:
But also for you. Like for your-

Andrew Huberman:
Yeah, no, I was saying for the drivers are the ones exposed to it the most.

Dr. Natalie Crawford:
Well, for these things, one of the top exposures of BPA right now is actually thermal paper, so receipts. So think about receipts-

Andrew Huberman:
Mm

Dr. Natalie Crawford:
... at the grocery store or the airline counter. So for getting it one time and touching it, it's probably not a big deal. But for the people who do that job and are exposed all the time to thermal paper, that actually can be such a high-level exposure. So that's a good example where I say you need to use gloves if that's your industry that you're going to be exposed to thermal paper a lot. So same thing for, let's say, the Uber driver. This is what you're spending your time doing. You don't need that fragrance for your own health.

Andrew Huberman:
Mm.

Dr. Natalie Crawford:
And certainly, we don't want to get in the Uber with, I know I'm so mean, if this smells, I'll star them lower. Because it's like I think-

Andrew Huberman:
No, that's fair

Dr. Natalie Crawford:
... you should know.

Andrew Huberman:
Yeah. You're paying for a service. I usually roll the window down and stick my head out the window. If they're coughing, I hate being sick, and I'm like-

Dr. Natalie Crawford:
I know

Andrew Huberman:
... "I didn't pay to get sick." So, I try to be polite about it, but there's just-

Dr. Natalie Crawford:
But again

Andrew Huberman:
... you got to take care of-

Dr. Natalie Crawford:
We control the things we can, right?

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
So let's control the fragrance in our home and in our products-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... because to your point, we can't control what's in the Uber. And so we're not going to stress about it. That's the argument I get, number one, is that you're causing people to be stressed about toxins that otherwise they wouldn't be. And again, that's paternalistic. Toxins are impactful to your health. I should give you the data so that you can cultivate the day-to-day life that is to the degree where you don't stress about it when you're on the plane or you're in an Uber or you're at a party because that one-off isn't such a big deal because you're not exposed to it every single day inside your home.

Andrew Huberman:
I like to think that people want information. I realize they can feel overwhelmed by too much information-

Dr. Natalie Crawford:
Mm-hmm

Andrew Huberman:
... but in the end, even though what we're talking about here seems like a lot of to-dos and not to-dos, there's a logic to it. I think the logical backbone is you do what you can. You do your best to control the key variables. The point about cannabis, I think, is really important that especially men hear, because I think most people don't know, and women don't know they should get their AMH checked. That's changing because of people like you being out there doing public education. But I like to think that people want knowledge. I really do.

Dr. Natalie Crawford:
I actually think people do want knowledge, and I don't think they're the ones giving the counterargument, to be honest, right?

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
I think it's our colleagues who say, "Oh, people don't want to hear that," or they make assumptions. And again, in today's world where we have data, why are we talking about assumptions?

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
Let's give people data and let them make the choices they make.

Andrew Huberman:
Yeah. Ignorance is not bliss when you're running up against a health challenge.

Dr. Natalie Crawford:
Yeah. If you haven't had your own health challenge, maybe it's hard to understand what it is. And for infertility, for most people, this is their first time their health is really being challenged, usually because of the age range of which it hits. That was my story. A decade later, I got diagnosed with celiac disease despite having unexplained recurrent pregnancy loss. I can tell you that this collided with my fertility fellowship when I advocated for doing vitamin research and all this epidemiology. I saw the word inflammation in all of that text, yet we weren't talking about it with our patients. And I went on this journey to get rid of Teflon in our kitchen because I studied PFCs, and we changed the foods that we ate, changed how we exercised, and how we slept. And one of the things that I cut out learning to listen to my body was gluten at the time. Even though I would have never said I had GI symptoms from it, I just said I felt more inflamed, like-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... vague symptoms, kind of headache, kind of more fatigued. And when I conceived my children, before we ever had to do IVF, we got pregnant naturally in that time period when I didn't have gluten. So decade later, get the diagnosis that was actually contributing to why we had these different pregnancy losses. So it wasn't unexplained at all. And not that everybody needs to cut gluten out, but understanding how chronic inflammation impacts our bodies and learning to listen to our body is one of the most powerful tools that we have.

Andrew Huberman:
Mm.

Dr. Natalie Crawford:
And it starts with education and knowledge, learning how to advocate for ourself, right? When you know what's normal, you can sit in front of somebody and say, "This isn't normal," and mean it with your full heart. And then how do you optimize all the things at home? Because back to the other point, even if you need IVF, I can only work with the eggs and sperm you give me. And maybe if we're focusing on some of the stuff earlier, there's probably a subset of people who can get pregnant without IVF, or who can freeze eggs and have an easier journey because they had this information, and they made choices based off of it.

Andrew Huberman:
What I'm realizing hearing you today is that we need to listen to our bodies. Women need to listen to their bodies because we're mainly talking about women's health here. Men do too, but we're talking about women. But also learn to be scientists of our bodies.

Dr. Natalie Crawford:
Yes.

Andrew Huberman:
And when it comes to nutrition, I'm very curious because of your example Do you think there's any value to people experimenting with a "cleaner" diet, if for no other reason than to figure out which ingredients don't work for them? Meaning, if you have granola for breakfast and a side of eggs and some toast, or one day you have eggs and the next day you have toast, or both, whatever, and then for lunch you're having a sandwich-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... and then for dinner you're having some pasta with some sauce, and you don't feel well. You don't know what the problem is.

Dr. Natalie Crawford:
Exactly.

Andrew Huberman:
So I'm not advocating for a spartan diet where it's chicken breast next to rice next to broccoli with a tablespoon of olive oil next to it, although that sounds pretty okay. I'd prefer-

Dr. Natalie Crawford:
There's worse

Andrew Huberman:
... steak. There's worse. But when you eat that way for a short period of time, the sort of cleaner and more or less individual ingredients-

Dr. Natalie Crawford:
Mm-hmm

Andrew Huberman:
... I do think that you can get insight into what works for you and what doesn't, independent of all the other information out there. Like for instance, there's certain forms of fibrous foods, I definitely believe in fiber, that I just don't feel well.

Dr. Natalie Crawford:
Yeah.

Andrew Huberman:
And then my sister, who is not a scientist, she'll chuckle at that. But she had this intuition about histamine-

Dr. Natalie Crawford:
Mm-hmm

Andrew Huberman:
... that has now been confirmed by two guests on this podcast who are MD PhDs who work on these sorts of issues. In one case pain, in another case gut inflammation. And she was convinced that she had some histaminergic thing that she read about in some book. Suggested I take this histamine enzyme tablet before I eat, and it's opened up this whole array of other foods that I can eat.

Dr. Natalie Crawford:
Oh, fantastic.

Andrew Huberman:
But for years, I would get super sleepy after I would eat certain foods. I'm like, "This makes no sense. I like starches, I like fiber." Turns out I have a sort of mild histamine sensitivity to four different foods. I don't think you can figure that out unless you separate out the ingredients.

Dr. Natalie Crawford:
Absolutely. It's like I planted this question for you, even though I didn't, because I advocate, especially if you are falling off the curve. I think if you're trying to learn to listen to your body, you say, "I want to optimize my own health," for a very temporary but restrictive clean eating pattern where you're having lots of fruits and vegetables and fiber, and you're cutting down some of the things that more commonly cause certain reactions.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
Cutting out gluten, cutting out dairy, cutting back on red meat, and then you add them back in and start to listen to how your body is functioning. But you have to really eliminate first, and then you can add back and see, oh, I feel better, worse, the same. Okay, well, if it's worse, that's maybe not something you should have.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
And then learn to listen for it. The tenets of a fertility diet are really not eye-opening. Fiber is hugely important for the gut microbiome and hormone health and inflammation and insulin resistance. So high fruits and vegetables, high-fiber diet, whole grain carbohydrates over your refined carbohydrates. Ultra-processed foods don't have a place in the modern diet. Added artificial sugars, those non-nutritive sweeteners, they don't have a place in this. We want to have quality of our protein. Most people could benefit from some increased plant protein due to the increased fiber than they actually get in the standard American diet. But meat is not universally bad nor necessarily good. It's the quality of the meat that probably matters a lot. The meat data to notice is that for every serving of plant-based protein over animal, people tended to ovulate better and had higher fertility rates.

Andrew Huberman:
Hmm.

Dr. Natalie Crawford:
Probably more suggestive of an overall healthier fiber-first dietary pattern on the population-based level, because ultra-processed foods don't have a lot of fiber in them or any fiber in them. Animal-based products don't have fiber in them, so we want to be mindful of that ratio. Red meat's the really controversial one, and increased servings of red meat, of course, dietary studies quartile it, lowest exposure, highest exposure. Highest exposure groups had poor embryos develop, worse outcomes with IVF, and an increase in staging of endometriosis when they went to surgery. That doesn't mean to me that all red meat is bad, but it probably is for a subset of people, more inflammatory, causes more IGF-1. We want to be mindful of it. The question I always get is does source matter. Probably, but we weren't looking at it in any of those studies. So I think being very mindful of where your animal-based protein is coming from is really important in today's kind of food world.

Andrew Huberman:
Mm-hmm.

Dr. Natalie Crawford:
Not all foods are created equal, even when they fall into the same category. And it's worth saying that healthy fats are really, really important. Cholesterol is the backbone for steroid hormones, so you need cholesterol in your body. So we really want to encourage those monounsaturated, polyunsaturated fatty acids. So the nuts, olive oil, fish, algae, chia seeds, flax, those things have so many benefits when it comes to the omega-3 fatty acids they have. But also, they're great healthy sources of cholesterol, which your body needs. And in fact, if you don't intake enough, you're not going to make progesterone as well. We want to be really minute. Need progesterone for implantation, don't have enough unsaturated fat in your diet, you're not going to make as much progesterone. So there's some nuance there, but to the heart of your question, I'm a huge advocate for that, especially if you're struggling with something, you're not feeling your best. If you say you kind of hit the marker on a lot of these inflammatory symptoms and you don't know what's going on, it can be a really helpful tool once you're controlling the other ones to try to leverage. But again, sleep, stress, building muscle, avoiding those excess toxins, those are a huge piece of the puzzle, too. And a lot of them go hand in hand. A lot of times we eat a food that's also wrapped in something that has toxic chemicals in it. So we really want to think about the fact that when you work from home, when you have access, whole foods is really important. As always, leveraging processed or ultra-processed versions.

Andrew Huberman:
Would you say that what you just described, in fact, everything we talked about, also pertains to perimenopause and menopause?

Dr. Natalie Crawford:
Absolutely. It's so fascinating because when I sit with a lot of people who just do menopause, we have the same recommendations for lifestyle and decreasing inflammation because it's going to improve ovarian response. It's going to improve how your body feels, decreasing inflammation. We know that when you go into menopause, estrogen has such profound anti-inflammatory benefits that one of the biggest problems is a baseline increase in your inflammation. So don't wait till you're in perimenopause or menopause to start to learn these things. Learn them whatever point you are at now is the perfect time-

Andrew Huberman:
Mm-hmm

Dr. Natalie Crawford:
... where we can start to make a difference, both for hormonal health now, fertility now or later, but also your ovarian function long term.

Andrew Huberman:
Amazing. Dr. Natalie Crawford, thank you so, so much. I can't tell you how much I learn every time you speak on this podcast and elsewhere. People should definitely get your book. Again, I've read it. I read it cover to cover. "The Fertility Formula: Take Control of Your Reproductive Future." Natalie Crawford, MD, did all the training, runs a clinic, is out there doing public education amidst everything else, co-managing a family, and just really expanding the field. You're taking it in new directions, which is really, to me, the most important thing, that you're out there teaching people, but you're also going back to the clinic and you're paying attention to the science and evolving the science, because this field is just going to improve over time. But you've given people so many actionable things to contemplate, to definitely do-

Dr. Natalie Crawford:
Yeah

Andrew Huberman:
... if I may insert my own beliefs there, and just a lot to think about in terms of the general landscape of how we think about reproductive health, both our own and societally. So thank you so much for coming back. We will do it again, if you're willing, and I'm just grateful to you.

Dr. Natalie Crawford:
Always. Thank you so much for having me and holding space for this discussion. I appreciate it.

Andrew Huberman:
Absolutely. Thank you for joining me for today's discussion with Dr. Natalie Crawford. To find links to her podcast and her new book, "The Fertility Formula," please see the links in the show note captions. If you're learning from and/or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zero-cost way to support us. In addition, please follow the podcast by clicking the follow button on both Spotify and Apple. And on both Spotify and Apple, you can leave us up to a five-star review, and you can now leave us comments at both Spotify and Apple. Please also check out the sponsors mentioned at the beginning and throughout today's episode. That's the best way to support this podcast. If you have questions for me or comments about the podcast or guests or topics that you'd like me to consider for the Huberman Lab Podcast, please put those in the comments section on YouTube. I do read all the comments. For those of you that haven't heard, I have a new book coming out. It's my very first book. It's entitled "Protocols: An Operating Manual for the Human Body." This is a book that I've been working on for more than five years, and that's based on more than 30 years of research and experience. And it covers protocols for everything from sleep to exercise to stress control, protocols related to focus and motivation, and of course, I provide the scientific substantiation for the protocols that are included. The book is now available by presale at protocolsbook.com. There you can find links to various vendors. You can pick the one that you like best. Again, the book is called "Protocols: An Operating Manual for the Human Body." And if you're not already following me on social media, I am hubermanlab on all social media platforms. So that's Instagram, X, Threads, Facebook, and LinkedIn. And on all those platforms, I discuss science and science-related tools, some of which overlaps with the content of the Huberman Lab Podcast, but much of which is distinct from the information on the Huberman Lab Podcast. Again, it's hubermanlab on all social media platforms. And if you haven't already subscribed to our Neural Network Newsletter, the Neural Network Newsletter is a zero-cost monthly newsletter that includes podcast summaries as well as what we call protocols in the form of one- to three-page PDFs that cover everything from how to optimize your sleep, how to optimize dopamine, deliberate cold exposure. We have a foundational fitness protocol that covers cardiovascular training and resistance training. All of that is available completely zero cost. You simply go to hubermanlab.com, go to the menu tab in the top right corner, scroll down to Newsletter, and enter your email. And I should emphasize that we do not share your email with anybody. Thank you once again for joining me for today's discussion with Dr. Natalie Crawford. And last but certainly not least, thank you for your interest in science.

Speaker 4:
"I didn't like what you said." Odin pauses. "About the future." This is the love story of real Hinge couple Odin and Edward, written and read by me, Curtis Garner. Listen to the free audiobook now.