Dr. Natalie Crawford on Huberman Lab: Why AMH drops early

Tracking ovulation and testing AMH early flags fertility reserve loss; meiosis errors, luteal defects, and inflammation compound age effects on fertility.

Dr. Natalie CrawfordguestAndrew Hubermanhost

Apr 13, 20262h 36mWatch on YouTube ↗

EVERY SPOKEN WORD

150 min read · 30,252 words

0:00 – 2:26
Natalie Crawford
1. NCDr. 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 ch- of how many eggs you have, and that knowledge can be really impactful for how you view your future and your plan.
2. AHAndrew Huberman
  Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life. [guitar music] 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.
2:26 – 5:34
Fertility as a Health Marker, Infertility
1. AHAndrew Huberman
  Dr. Natalie Crawford, welcome back.
2. NCDr. Natalie Crawford
  Thank you so much for having me. I'm thrilled to be here.
3. AHAndrew Huberman
  And congratulations on your new book-
4. NCDr. Natalie Crawford
  Thank you
5. AHAndrew Huberman
  ... The Fertility Formula. It's no small feat to complete a book, and it's, and it's especially a big feat to complete a book that offers people so much advice, not just people who wanna get pregnant, but also looking at things through the lens of fertility as an important health metric.
6. NCDr. Natalie Crawford
  Yes.
7. AHAndrew Huberman
  So, yeah.
8. NCDr. 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-
9. AHAndrew Huberman
  Mm-hmm
10. NCDr. Natalie Crawford
  ... to work with editors, to try to refine within your word count. I w- you know, it 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.
11. AHAndrew Huberman
  Yeah. I am insisting as much as one can insist that various people in my life read this book, um, including family members and other people, because again, it's not just about people who wanna 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. Um, so if you don't mind, um, how should people think about fertility purely as a, a readout of health? I mean, w- just how do you, how do you frame this for... Like, if somebody comes to you and says, listen, uh, they have kids or they don't want kids-
12. NCDr. Natalie Crawford
  Mm-hmm
13. AHAndrew Huberman
  ... or they're not sure if they want kids, but, um, why use fertility as a lens on general health?
14. NCDr. 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 wanna 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 wanna be really specific, if you have infertility, you have increased rates of metabolic syndrome, cancer, heart attack, stroke, and dying early. Those, 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.
15. AHAndrew Huberman
  For women who are still of reproductive age-
16. NCDr. Natalie Crawford
  Yeah
17. AHAndrew Huberman
  ... and I realize there's no strict cutoff, um, we can and, and certainly will talk about what are the measures, direct and indirect, of fertility that, um, can give them a window into their kind of health span risk factors, lifespan risk factors.
5:34 – 11:01
Perimenopause, Menopause, Hormone Replacement Theory
1. AHAndrew Huberman
  For women that have already reached menopause or in perimenopause, um, how should they think about fertility as a health marker? Meaning if somebody is, has passed the point where they can safely, um, get pregnant-
2. NCDr. Natalie Crawford
  Mm-hmm
3. AHAndrew 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.
4. NCDr. 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 reliableCharacteristic 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 twelve months without a period. So menopause is one single day and time. Really, it means you've been in ovarian failure for twelve 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 twelve months, no estrogen, feel terrible before we'll allow them to have hormone replacement therapy.
5. AHAndrew Huberman
  Yeah, this is such an important theme and if, and if I may, um, I, I realize I have to be very careful, uh-
6. NCDr. Natalie Crawford
  [laughs]
7. AHAndrew Huberman
  ... 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 dif-
8. NCDr. Natalie Crawford
  Yeah
9. AHAndrew Huberman
  ... 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, you know, for many years now, um, for reasons that, uh, are unfair, um, hormone r-replacement therapy was sort of became widely available for men before it-
10. NCDr. Natalie Crawford
  Yeah
11. AHAndrew Huberman
  ... became widely available for women. Uh, there are reasons for this. We don't have to go into it, but they're th-the, they're the kind of obvious ones, [laughs] um, uh, that things were pushed to market more quickly and, and so forth. But there's been this idea, you know, should-- And, and there it's usually testosterone replacement therapy, right? Um, and there was this idea that unless somebody fell below three hundred nanograms per deciliter-
12. NCDr. Natalie Crawford
  Mm-hmm
13. AHAndrew Huberman
  ... for, for a male, that they weren't, um, uh, that they shouldn't get h- uh, testosterone r-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, of the range so that they can get their symptoms away-
14. NCDr. Natalie Crawford
  Optimal
15. AHAndrew Huberman
  ... and, and just feel-- Right, to optimize within the normal range. That sort of-- 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, like, no periods for a year, well, I mean, it could take a long time to reach that. I mean, what if it's, you know, two periods per year, right? Does that mean that that person-
16. NCDr. Natalie Crawford
  Exactly
17. AHAndrew Huberman
  ... doesn't deserve the therapy, which is what, essentially what-
18. NCDr. Natalie Crawford
  Yeah
19. AHAndrew 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.
20. NCDr. Natalie Crawford
  Exactly.
21. AHAndrew Huberman
  Okay, so for-- 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.
22. NCDr. 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 cardioprotective. 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.
11:01 – 13:35
Sponsors: David & BetterHelp
1. AHAndrew Huberman
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13:35 – 19:11
Hormone Therapy, Extending Ovarian Lifespan
1. AHAndrew Huberman
  that, uh, the medical profession, um, could agree on nomenclature that included hormone replacement, the R-
2. NCDr. Natalie Crawford
  Mm-hmm
3. AHAndrew Huberman
  ... replacement therapy for people that are out of range, you know, they're too, uh, too low, out of the normal reference range, hormone augmentation therapy, um, 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-
4. NCDr. Natalie Crawford
  Mm-hmm
5. AHAndrew Huberman
  ... and then estrogen's a steroid, you know, 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 mean, I think ten years ago, I think the medical profession was not open to the idea that a forty-year-old woman, for instance-
6. NCDr. Natalie Crawford
  Right
7. AHAndrew 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.
8. NCDr. Natalie Crawford
  Isn't it interesting? And, you know, by professional organizations, they would even call it menopausal hormone therapy, MHT-
9. AHAndrew Huberman
  Mm-hmm
10. NCDr. 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, right? I've been out of practice for over ten years, and what's so interesting is that we'll use premature ovarian failure. So going into ovarian failure before age forty, 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.
11. AHAndrew Huberman
  Mm-hmm.
12. NCDr. Natalie Crawford
  And so I think it's really important, you know, 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 perimenopaused or diminished ovarian reserve, like we call it in the fertility world, I mean, that can last five to ten 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.
13. AHAndrew Huberman
  Are all, um, now I want to call it hormone augmentation-
14. NCDr. Natalie Crawford
  [laughs]
15. AHAndrew Huberman
  Hormone re- let's just call it hormone replacement for, for sake of, of simplicity. Um, hormone therapies, uh, for women, do they always start with estrogen when it comes to trying to encourage fertility or push fertility or wellbeing out into, um, more years?
16. NCDr. Natalie Crawford
  That's an interesting question. I think when it comes to hormone replacement therapy in general, we've got estrogen, progesterone, testosterone.
17. AHAndrew Huberman
  Mm-hmm.
18. NCDr. 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, right? 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-
19. AHAndrew Huberman
  Mm-hmm
20. NCDr. Natalie Crawford
  ... but that's never one hundred percent of the time. I think greater to your question about how is there a way for us to extend the ovarian lifespan is a really good oneWe 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 have-- 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.
19:11 – 22:02
Plastics, Toxins & Fertility
1. AHAndrew Huberman
  I know these days people are very concerned about plastics-
2. NCDr. Natalie Crawford
  Yeah
3. AHAndrew Huberman
  ... and you mentioned toxins, so I was gonna get to this later, but I'll just ask now. How concerned are you about plastic water bottles and, um-- I mean, 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, um, because they're big, but the, some of them get into our cells. Are, are, are there any data that have you, or observational, um, data that have you genuinely concerned that plastics are becoming more of an issue vis-à-vis fertility?
4. NCDr. Natalie Crawford
  There definitely is concern. I, I always wanna frame this, and you did a nice job of it, so I'll, 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 wanna 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 wanna 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 controlled 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 gonna 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 is not gonna make it or break it, together they can add up to that inflammatory burden, or they can help decrease it. And that chronic inflammation does in fact matter to your fertility and does worry me.
22:02 – 29:02
Does Prior Pregnancy Make Conception Easier?, Secondary Infertility
1. AHAndrew Huberman
  I realize I'm jumping, jumping around here a bit-
2. NCDr. Natalie Crawford
  Hmm
3. AHAndrew Huberman
  ... but, um, in just thinking about what seems to be on a lot of people's mind, I took a informal poll o-of some people heading into this 'cause o-obviously I, I only know my own experience as, as a male. So, uh, to a number of w-women I asked the question, um, you know, "What, what are you wondering about?" And a common question was, um, it seems that for some women, if they've been pregnant once before, uh, 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? Um, and that fertility drops off with time. But there seems to be this, um, kind of belief, uh, 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.
4. NCDr. Natalie Crawford
  Yeah.
5. AHAndrew 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, it's not a perfect ex-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-
6. NCDr. Natalie Crawford
  Yeah
7. AHAndrew Huberman
  ... uh, it, it's not a good control group for an experiment. But for within the person, if they've been pregnant before, can they exhale a little bit that, yes, they can get pregnant?
8. NCDr. 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 zeroAnd 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 eighteen to twenty percent up till age thirty-seven.
9. AHAndrew Huberman
  Wow.
10. NCDr. 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?
11. AHAndrew Huberman
  Yeah.
12. NCDr. 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.
13. AHAndrew Huberman
  Oh my goodness.
14. NCDr. Natalie Crawford
  Right? Oh, I've had patients try for years, be dismissed by their doctor.
15. AHAndrew Huberman
  Because men and women mistakenly think that because there's semen, there's sperm.
16. NCDr. Natalie Crawford
  Exactly. There's ejaculate, so there must be sperm inside of it.
17. AHAndrew Huberman
  Mm-hmm.
18. NCDr. Natalie Crawford
  And then when we find out there's none, it's, 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 twelve 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 seventy-two percent of people will get pregnant in that first six months of trying, and only thirteen percent will get pregnant in the next six months of trying. That's why if you're thirty-five 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," force them to try longer and fail, and then to find out fallopian tubes were 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 l- 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 twelve months.
19. AHAndrew Huberman
  Mm-hmm.
20. NCDr. 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, you know, 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 dis- 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, I would say kind of at the longest, go and get an evaluation. And if you're a little bit older, maybe started your journey a little bit later, it's never too early to get an evaluation for anybody at any time 'cause you can't make decisions on data you don't know.
21. AHAndrew Huberman
  Mm-hmm.
22. NCDr. 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.
29:02 – 38:17
Testing Sperm; Pregnancy Loss & Conceiving Again, Fertility Testing
1. AHAndrew Huberman
  Yeah, all excellent points. And, um, with respect to the sperm testing, since clearly there are men who think they're making, uh, sperm and they're not, um, 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.
2. NCDr. Natalie Crawford
  There are some that are just telling you almost like a pregnancy test, plus/minus, are sperm present, are sperm not.
3. AHAndrew Huberman
  Mm-hmm.
4. NCDr. 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.
5. AHAndrew Huberman
  Mm-hmm.
6. NCDr. Natalie Crawford
  So it's a, 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.
7. AHAndrew Huberman
  Mm-hmm.
8. NCDr. 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 OB-GYN. They're getting dismissed and just, "Oh, just try first. It's probably fine."
9. AHAndrew Huberman
  Mm-hmm. You mentioned that if a woman has had a successful pregnancy that the probability of getting pregnant again is significantly higher-
10. NCDr. Natalie Crawford
  Mm-hmm
11. AHAndrew 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?
12. NCDr. Natalie Crawford
  It'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 gonna be random genetic abnormality.
13. AHAndrew Huberman
  Mm-hmm.
14. NCDr. 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-
15. AHAndrew Huberman
  Mm-hmm
16. NCDr. Natalie Crawford
  ... that it's probably going to be a little bit easier because certain-
17. AHAndrew Huberman
  Mm
18. NCDr. Natalie Crawford
  ... boxes are checked. I think it's also really important to say, I mean, I had four pregnancy losses myself. I don't know if you know this. So I had four pregnancy losses-
19. AHAndrew Huberman
  From your book
20. NCDr. Natalie Crawford
  ... yeah
21. AHAndrew Huberman
  Yeah. I mean, and, and by the way, c- I really appreciate the, the personal story sh- uh, sharing in the book because it, um, it really clearly was in service to your patients and to the, to the reader. And e- even as a male who-
22. NCDr. Natalie Crawford
  Mm
23. AHAndrew Huberman
  ... can't relate certainly to certain aspects of all this, um, it was, it was not only very moving, but it was, 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, the other information because otherwise, I mean, it would sort of be like if I'm talking about ovarian health, right? [laughs]
24. NCDr. Natalie Crawford
  [laughs]
25. AHAndrew Huberman
  Which I've, I've talked about on podcasts, but-
26. NCDr. Natalie Crawford
  Which we're talking about [laughs]
27. AHAndrew Huberman
  Yeah, right. With all the caveats, you know, that, that how... But of course, how could I possibly know? So the, your personal experience, well, well, the reader and I, you'll feel f- feel and felt for you in, in reading it. It is, it is super impactful because people-- There's a level of trust that just comes from somebody who's been through that-
28. NCDr. Natalie Crawford
  Mm
29. AHAndrew Huberman
  ... whole jungle.
30. NCDr. Natalie Crawford
  Thank you. I'll try not to cry on this show about it, which is funny 'cause 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 I was-- This was the end of OBGYN and then the beginning of my reproductive endocrinology fellowship. So I felt like, "How am I gonna 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? We... Especially in an era where you separate your personal and professional life, which is, you know, what was 100% accepted back then. You know, my last pregnancy loss was an ectopic pregnancy. My fertility nurse had to give me my methotrexate shot. I mean-
38:17 – 39:40
Sponsor: AG1
1. AHAndrew 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.
39:40 – 48:17
Menstrual Cycle, Egg Number & Quality, AMH Test
1. AHAndrew Huberman
  One theme that I heard, uh, over and over again, um, was, um, 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-
2. NCDr. Natalie Crawford
  Yeah
3. AHAndrew Huberman
  ... and that their mom had want either them or a sibling, um, let's say at, like, age forty-two or forty-three, and they're in good health themselves. Um, and so they had it-- have in mind that there's time. I think this is not uncommon.
4. NCDr. Natalie Crawford
  Mm-hmm.
5. AHAndrew Huberman
  Um, and given that, uh, life is very expensive, um, most people in the world seem to be underpaid nowadays. [chuckles]
6. NCDr. Natalie Crawford
  Yeah.
7. AHAndrew Huberman
  Um, and, uh, people are waiting longer to get married and have children. Um, and the other common narrative that I was hearing was that there are people that want kids, but they-- 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."
8. NCDr. Natalie Crawford
  Yeah.
9. AHAndrew Huberman
  That's not always the case, but it's, it's pretty-
10. NCDr. Natalie Crawford
  It's a true statement.
11. AHAndrew Huberman
  It's, it's a, it's a common theme, right? So for those women, which I think is, uh, quite a few, whether or not they're in their twenties or their thirties or their forties, um, what sorts of things do you recommend they would add to that, uh, rather just kind of real-life analysis? Those are not meaningless metrics, like how one's mother had a child-
12. NCDr. Natalie Crawford
  Yeah
13. AHAndrew Huberman
  ... or for instance, but things have changed. Microplastics, maybe certain things have gotten better, right? We're no longer eating margarine. I'm, I'm not trying to be facetious here. I think that-
14. NCDr. Natalie Crawford
  No, no
15. AHAndrew Huberman
  ... there's so many variables. People are living longer, yet there are more environmental toxins perhaps. I mean, we-- people are smoking less. So it-- the-
16. NCDr. Natalie Crawford
  Are they, though?
17. AHAndrew Huberman
  Are they? [chuckles] We'll talk about nicotine for sure. Um, so for those women, um, in their, let's say twenties, thirties, and early forties-
18. NCDr. Natalie Crawford
  Yeah
19. AHAndrew 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, um, they'll say that they're having regular periods.
20. NCDr. Natalie Crawford
  I'd love to answer it, and I'm going to, but for the person who's maybe coming to this discussion, l-let me-- let's explain egg quality really quickly-
21. AHAndrew Huberman
  Mm-hmm
22. NCDr. Natalie Crawford
  ... 'cause it really is gonna tie into what we can test and what we cannot. As you know well, w-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, two hundred picograms for fifty hoursAnd 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 twenty-four 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 and 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 s- 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 gonna call that ovarian failure and not menopause for the sake of our discussion. But so everybody will go into ovarian failure. Now, the timeline once you have-- your, 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 s- 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. Oh, those first few days are one hundred percent 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 two 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 twenty-three X. The other part goes into a polar body. Okay, this means that when you're twenty-five, your eggs have only been held in metaphase for twenty-five 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 forty, forty 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 forty years, like, somebody's gonna 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 forty-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?
23. AHAndrew Huberman
  I mean, to me
48:17 – 53:13
Tool: AMH Test; Fertility Education & Patient Choices
1. AHAndrew Huberman
  as well. I mean, it just seems like, like th-this failure criteria-
2. NCDr. Natalie Crawford
  Again
3. AHAndrew Huberman
  ... it just seems so-- it s- seems just very extreme and unnecessary. U-unless there's some, uh, hidden agenda to try and prevent people from maintaining fertility or-
4. NCDr. Natalie Crawford
  Which doesn't even make sense
5. AHAndrew Huberman
  ... or having children because-- And that doesn't square with at least my assumptions.
6. NCDr. 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 re-- I have two thirty-year-olds. One has twenty 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 eggThey have the same chance of getting pregnant, right? 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 gonna sit here and say, "Okay, well, you can still get pregnant, no worries." I'm gonna 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, right? To your point, the woman who's twenty, thirty, forty 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, like, "Let's do the investigation and see if we can find out why." Probably fifty percent of the time we find an autoimmune disease. I can't reverse the clock, but I can slow down the rate of inflammation, right?
7. SPSpeaker
  Mm-hmm.
8. NCDr. Natalie Crawford
  If, 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?" You know, 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 do-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, right? 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." I mean, that was the longest discussion to say everybody should get an AMH.
9. SPSpeaker
  Mm-hmm.
10. NCDr. Natalie Crawford
  I think it's a very important marker. It's a newer-ish test. We've only been checking it for about the past ten 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 request. Many of the online platforms like Function Health, you can have an AMH checked 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-
11. SPSpeaker
  Yeah
12. NCDr. Natalie Crawford
  ... an important marker. 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 ch- 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.
53:13 – 55:11
Tool: Tracking Ovulation; Ovulation Disorders
1. NCDr. Natalie Crawford
  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 eleven 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 will 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're just tracking when your bleed is, and it's every thirty, forty 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.
55:11 – 1:01:13
AMH Test Cost; Genetic Testing & Patient Choice
1. AHAndrew Huberman
  Amazing. Um, just, uh, uh, and I don't say that lightly. You just explained egg quality, the biology of the, of the, uh, ovulation cycle, and how it links to the actionables, and, um, I'm just struck. It's, uh, awesome. Um, and it has me asking a couple of practical questions.
2. NCDr. Natalie Crawford
  Yeah.
3. AHAndrew Huberman
  Um, some people will have insurance, some won't.
4. NCDr. Natalie Crawford
  Mm-hmm.
5. AHAndrew Huberman
  Uh, what's the cost of an AMH test? Let's assume insurance d- doesn't cover it-
6. NCDr. Natalie Crawford
  Yeah
7. AHAndrew Huberman
  ... um, and they just have to go completely out of pocket. Uh, and before you answer, I will say, uh, whatever it is, I think, uh, should probably be compared against what it would be to try and, um, uh, I don't wanna say rescue, but, but to not take the test and then, you know, three years later you're trying to harvest eggs. It could be multiple cycles-
8. NCDr. Natalie Crawford
  Yeah. Exactly
9. AHAndrew Huberman
  ... because you, you realize it was only five eggs per, uh, you know, uh, per month as opposed to-
10. NCDr. Natalie Crawford
  And what could have been three years ago
11. AHAndrew Huberman
  ... age, age match, right? F- fifteen, right? Exactly. So, um, so are we talking hundreds of dollars? Thousands?
12. NCDr. Natalie Crawford
  Seventy-nine.
13. AHAndrew Huberman
  Seventy-nine dollars.
14. NCDr. Natalie Crawford
  Yeah. We're withholding a seventy-nine dollar test, and I, 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 seventy-nine dollars is worth it to you.
15. AHAndrew Huberman
  Mm-hmm.
16. NCDr. 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 I- IVF. I mean, right, multitudes. Seventy-nine dollars. We're throwing a fit over a seventy-nine dollar test.
17. AHAndrew Huberman
  Wow. Um, I, I'm gonna make sure that message goes far and wide-
18. NCDr. Natalie Crawford
  [chuckles]
19. AHAndrew Huberman
  ... um, because I, you know, I thought you were gonna say maybe in the high hundreds-
20. NCDr. Natalie Crawford
  Yeah
21. AHAndrew Huberman
  ... or thousands, which for some people is going to be, you know, prohibitively expensive.
22. NCDr. Natalie Crawford
  Would be cost-prohibitive.
23. AHAndrew Huberman
  Yes. I-- So get AMH checked. I think I'll avoid going into too much editorializing here because I'm really just interested in, in how you view this. But how you describe the, the sort of the, the way your field has, uh, originated and where it's headed-
24. NCDr. Natalie Crawford
  Mm-hmm
25. AHAndrew Huberman
  ... reminds me a little bit of... I remember in the '80s, there was a ge- a... 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, like, Huntington's disease-
26. NCDr. Natalie Crawford
  Yeah
27. AHAndrew Huberman
  ... which is-- can be a devastating disease. Um, and the idea was people don't wanna know. People don't wanna know. I think everything I've ob- I've observed, I can't speak for everyone, but everything I've observed about people's interest in their own health and genetics and what genetics does and doesn't-
28. NCDr. Natalie Crawford
  Mm-hmm
29. AHAndrew 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.
30. NCDr. Natalie Crawford
  A hundred percent.
1:01:13 – 1:05:29
Does Egg Freezing Cause Early Menopause?, In Vitro Fertilization (IVF)
1. AHAndrew Huberman
  thing that-- Well, I'll just pose this as a question. How many women out there, um, do you think know if... I have to be careful how I word this. If doing a egg harvest cycle, um, decreases their ovarian reserve or not?
2. NCDr. Natalie Crawford
  [sighs] 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, that 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, same hormone your brain makes, trying to stimulate more than one egg to grow. Your body doesn't wanna have five kids or twelve kids or twenty 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.
3. AHAndrew Huberman
  And I think the myth is that, um, by doing a cycle of, of egg freezing, that you're taking more eggs-
4. NCDr. Natalie Crawford
  Mm-hmm
5. AHAndrew Huberman
  ... from your reserve. Um, 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-
6. NCDr. Natalie Crawford
  Exactly
7. AHAndrew Huberman
  ... as opposed to letting them die.
8. NCDr. Natalie Crawford
  Exactly.
9. AHAndrew Huberman
  Yeah.
10. NCDr. 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.
11. AHAndrew Huberman
  Yeah, and I think people also assume, um, because they haven't been told that if you do an egg-
12. NCDr. Natalie Crawford
  Mm-hmm
13. AHAndrew Huberman
  ... you know, if you stimulate for more to mature-
14. NCDr. Natalie Crawford
  Mm-hmm
15. AHAndrew Huberman
  ... that you're somehow, um, taking away from eggs that you would've had, you know-
16. NCDr. Natalie Crawford
  Yeah
17. AHAndrew Huberman
  ... stuck around somehow. Uh, so we're, we're hitting, we're a- we're saying the same thing three different ways.
18. NCDr. Natalie Crawford
  Yeah. So you're giving-
19. AHAndrew Huberman
  But-
20. NCDr. Natalie Crawford
  I mean, 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, right? 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. You know, early IVF days, I mean, IVF's not that old. It's only been around like forty-six years. I think the oldest IVF babies-- We didn't have gonadotropins. We didn't have FSH, um, that was, you know, 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 when-- 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 in the 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 sort of 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 is such an amazing advancement in science that we can leverage that physiology for egg freezing or IVF.
1:05:29 – 1:15:21
Egg Freezing, IVF, Ethical Concerns; Embryo Banking
1. AHAndrew Huberman
  A very practical, uh, question. Um, it's clear that the younger that a woman is, the, the more eggs-
2. NCDr. Natalie Crawford
  Yeah
3. AHAndrew Huberman
  ... that, uh, could be, uh, 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, um, are, are waiting.
4. NCDr. Natalie Crawford
  Right.
5. AHAndrew Huberman
  They're just waiting. What stands between, um, us now in the United States and egg freezing being covered by insurance one hundred percent? I don't hold any superpowers, but there are, you know, there are pretty powerful ways to lobby, um, all the administrations, regardless of who happens-
6. NCDr. Natalie Crawford
  Yeah
7. AHAndrew Huberman
  ... to be in office when that actually happens. I mean, it is possible, right? The, the, the p- the phone is a powerful tool. Advocacy is a powerful tool. I do think that, um, things can happen, um, if there's a lot of advocacy. So, um, first question is, you know, what would that require?
8. NCDr. Natalie Crawford
  [chuckles]
9. AHAndrew Huberman
  And, um, is that a good idea?
10. NCDr. Natalie Crawford
  I am a fan of knowledge and options, and egg freezing is not a guarantee. So you know how I pose it to patients is, we are gonna keep the door of opportunity open longer for you, and that is our goal. If we wanna 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 'cause an insurance policy always pays off, but it's an investment in my fertility.
11. AHAndrew Huberman
  Mm-hmm.
12. NCDr. Natalie Crawford
  Like investing in the stock market, like probably will pay off, but depends on external factors that we don't have yet, right? 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, you know, 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 wanna 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.
13. AHAndrew Huberman
  Embryo disposition?
14. NCDr. Natalie Crawford
  Yeah, like the personhood of an embryo. Is an embryo a person?
15. AHAndrew 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, ah, k- killing a baby.
16. NCDr. Natalie Crawford
  Correct.
17. AHAndrew Huberman
  Right. That's their, that's their view.
18. NCDr. Natalie Crawford
  Yeah.
19. AHAndrew Huberman
  Yeah.
20. NCDr. Natalie Crawford
  And, and we should acknowledge that I have many patients right now who are donating embryos-
21. AHAndrew Huberman
  Mm-hmm
22. NCDr. Natalie Crawford
  ... you know, when they are done with their family, which is an amazing way to kind of pass forward the-
23. AHAndrew Huberman
  Mm-hmm
24. NCDr. Natalie Crawford
  ... opportunity and for other couples to have a family. And I also just wanna say at the top of this is that IVF's incredible. 17 million babies have been born in this world because of IVF. So I- 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, um, they're really pushing something called restorative reproductive medicine, and they're opposing a lot of the American Society for Reproductive Medicine's, um, t- 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.
25. AHAndrew Huberman
  But these people are ostensibly pro-child, so that-
26. NCDr. Natalie Crawford
  I, I agree with you
27. AHAndrew Huberman
  ... I'm not p- my political stance-
28. NCDr. Natalie Crawford
  Yeah
29. AHAndrew Huberman
  ... I- people often speculate. Like, I'll be really honest, I don't like politics.
30. NCDr. Natalie Crawford
  Yeah.
1:15:21 – 1:16:39
Sponsor: Eight Sleep
1. AHAndrew Huberman
  I'd like to take a quick break and acknowledge our sponsor, Eight Sleep. Eight Sleep makes smart mattress covers with cooling, heating, and sleep tracking capacity. One of the best ways to ensure you get a great night's sleep is to make sure that the temperature of your sleeping environment is correct. And that's because in order to fall asleep and stay deeply asleep, your body temperature actually has to drop by about one to three degrees. And in order to wake up feeling refreshed and energized, your body temperature actually has to increase by about one to three degrees. Eight Sleep automatically regulates the temperature of your bed throughout the night according to your unique needs. I've been sleeping on an Eight Sleep mattress cover for nearly five years now, and it has completely transformed and improved the quality of my sleep. The latest Eight Sleep model is the Pod 5. This is what I'm now sleeping on, and I absolutely love it. It has so many incredible features. For instance, the Pod 5 has a feature called Autopilot, which is an AI engine that learns your sleep patterns and then adjusts the temperature of your sleeping environment across different sleep stages. It'll even elevate your head if you're snoring, and it makes other shifts to optimize your sleep. If you'd like to try Eight Sleep, go to eightsleep.com/huberman to get up to $350 off the new Pod 5. Eight Sleep ships to many countries worldwide, including Mexico and the UAE. Again, that's eightsleep.com/huberman to save up to $350. So
1:16:39 – 1:21:22
Egg Freezing, Cost & Patient Choices
1. AHAndrew Huberman
  in- insurance, I would think would want to do this because, um, covering all the other stuff is expensive, too.
2. NCDr. Natalie Crawford
  Most insurance doesn't cover IVF. You're not wrong, right? In principle, if I freeze a twenty-five-year-old's eggs, I will have three times as many eggs to work with, you know, than I would if she's going through IVF when she's thirty-seven. So if I'm gonna pay for her to do IVF at thirty-seven, 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's incredible. As somebody who has an IVF lab, as somebody who keeps embryos on site, it's-- I mean, it's outrageously expensive. I mean, our generator alone is a million dollars, right? Because if the power goes out, like, what do we have to keep going? We always say, "If there's zombies coming, like, come to the clinic." The technology to keep up with all the advancements, to have trained embryologists, I mean, 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, like, I shouldn't be the one sitting here making assumptions again on what you're gonna 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? 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 gonna 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-
3. AHAndrew Huberman
  Mm-hmm
4. NCDr. 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, like, I, 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 gonna do about it? Again, like, 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.
5. AHAndrew Huberman
  In the Bay Area, where there are a lot of tech companies-
6. NCDr. Natalie Crawford
  Mm-hmm
7. AHAndrew Huberman
  ... um, there's aMy understanding is there's a, an opportunity at many of these companies for female employees to freeze their eggs. That landed much more controversial than I thought it would.
8. NCDr. Natalie Crawford
  Isn't it crazy?
9. AHAndrew Huberman
  Um, because the, the assumption, the sort of, uh, to some people, uh, the tacit message there is, "Don't have kids now-
10. NCDr. Natalie Crawford
  Yeah, don't have kids now, work for us
11. AHAndrew Huberman
  ... work, work, work like crazy, and then have them later," right?
12. NCDr. Natalie Crawford
  Yeah.
13. AHAndrew Huberman
  But having known some people that worked there and froze their eggs in their, um, late 20s or early 30s, I think they would say, the ones I know would say, "Yeah, I'm really grateful that I did that, um, 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.
14. NCDr. Natalie Crawford
  Yes.
15. AHAndrew Huberman
  So there's that. But it was kind of interesting. So anyway-
16. NCDr. Natalie Crawford
  Yeah, I mean-
17. AHAndrew Huberman
  ... we're, we're getting kind of-
18. NCDr. Natalie Crawford
  We are
19. AHAndrew Huberman
  ... um, sociological here.
20. NCDr. Natalie Crawford
  But what, what we can say is-
21. AHAndrew Huberman
  But I think it's important
22. NCDr. 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-
23. AHAndrew Huberman
  Mm-hmm
24. NCDr. Natalie Crawford
  ... because that is an investment in your employees. I think it's incredible. In Austin, right, a lot of these tech companies have second homes, so we see a lot of these patients also.
25. AHAndrew Huberman
  Mm-hmm.
26. NCDr. Natalie Crawford
  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.
27. AHAndrew Huberman
  Mm-hmm.
28. NCDr. Natalie Crawford
  The 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.
29. AHAndrew Huberman
  I tend to get pretty loud and pretty consistently loud about the things that, uh, I believe in once I understand the landscape. So I, I plan to be vocal about it, um, for what it's
1:21:22 – 1:27:17
Concieving After Hormonal Birth Control, IUD or Depo-Provera
1. AHAndrew Huberman
  worth. Uh, you mentioned that birth control can reduce AMH levels-
2. NCDr. Natalie Crawford
  Mm-hmm
3. AHAndrew Huberman
  ... um, on a month-to-month basis. Is there-- and we should define birth control-
4. NCDr. Natalie Crawford
  Mm-hmm
5. AHAndrew Huberman
  ... 'cause it's such a broad category. Um, 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, uh, my, um, and this isn't I have a friend, I just-- I know a number of people who have kids now-
6. NCDr. Natalie Crawford
  Mm-hmm
7. AHAndrew Huberman
  ... who, um, were on birth control, came off birth control, and got pregnant right away.
8. NCDr. Natalie Crawford
  Right.
9. AHAndrew Huberman
  So I think a lot of people assume that's how it works, but are there any, uh, good examples of how certain forms of birth control can actually suppress fertility in women long after women come off birth control?
10. NCDr. 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 twenty-eight 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 po- 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 gonna 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 twenty-four 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 twenty to thirty percent chance of getting pregnant compared to a zero day the day after ovulation, zero percent. So very defined fertile window. So if you know when you're ovulating and you target intercourse, you're gonna 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 in, 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.
11. AHAndrew Huberman
  Hmm.
12. NCDr. 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 wanna 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 wanna get pregnant potentially in the next two years, please don't get Depo-Provera.
1:27:17 – 1:29:28
Pregnancy Termination & Concieving Again
1. AHAndrew Huberman
  Great. Uh, 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?
2. NCDr. 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, it could be having a fibroid removed, it could be a prior C-section, it can be a prior D&C 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 gonna 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.
1:29:28 – 1:34:03
Support Egg Quality, Tools: Ovulation & Avoiding NSAIDs; 5 Lifestyle Non-Negotiables
1. AHAndrew Huberman
  Thank you. Um, some practical questions-
2. NCDr. Natalie Crawford
  Yeah
3. AHAndrew Huberman
  ... about metabolic health-
4. NCDr. Natalie Crawford
  Yeah
5. AHAndrew Huberman
  ... mitochondrial health, and egg quality.
6. NCDr. Natalie Crawford
  Let's do it.
7. AHAndrew Huberman
  Um, in your book, you go into this in some degree of detail, but, um, when you think about the things that can really, um, help support egg quality aside from age-
8. NCDr. Natalie Crawford
  Yeah
9. AHAndrew Huberman
  ... um, in fact, I should say at any age, uh, what are the, you know, sort of top contour of those? Um, you mentioned inflammation is the enemy.
10. NCDr. Natalie Crawford
  Mm.
11. AHAndrew Huberman
  But inflammation happens all the time-
12. NCDr. Natalie Crawford
  Yeah
13. AHAndrew Huberman
  ... and we can't avoid it. Um, but we can certainly avoid exacerbating it. So what are the things that people can do, not do, and take? We can do that-
14. NCDr. Natalie Crawford
  Okay. I love it
15. AHAndrew Huberman
  ... those three things. Do, not do, and take. Yeah.
16. NCDr. 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.
17. AHAndrew Huberman
  Really?
18. NCDr. Natalie Crawford
  Yeah. 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.
19. AHAndrew Huberman
  How many people, in your experience, do you think know that?
20. NCDr. Natalie Crawford
  I don't think very many-
21. AHAndrew Huberman
  Okay
22. NCDr. Natalie Crawford
  ... honestly, right? Which is, which is why-
23. AHAndrew Huberman
  I mean, I feel like it's sort of like banner across the sky, like these, you're not gonna lose eggs by doing a, a freeze cycle, a collect and freeze cycle. The, uh, um, I mean...
24. NCDr. Natalie Crawford
  Basic facts about our biology that we are never taught.
25. AHAndrew Huberman
  So if somebody's trying to get pregnant, NSAIDs can be problematic.
26. NCDr. Natalie Crawford
  They can be problematic. They can prevent the egg from being released with ovulation. So I think 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, you know, 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. I mean, you're gonna be exposed to inflammation. Life is gonna throw things at you.
27. AHAndrew Huberman
  Mm-hmm.
28. NCDr. Natalie Crawford
  But you wanna 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, like, what I call my five non-negotiables of s- sleep, stress, muscle, food, and toxins, and thinking about how we leverage these to our benefit by giving people the knowledge that they can-- 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 wanna 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 y- one person can take with that and make the choices they wanna make.
29. AHAndrew Huberman
  Mm-hmm.
30. NCDr. Natalie Crawford
  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 in diving into them?
1:34:03 – 1:38:41
Sleep, Melatonin; Cold Plunge
1. NCDr. Natalie Crawford
  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 gonna take much to convince you. When you sleep, this is when your body's gonna get s- 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 gonna 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." Like, your physiology is meant to sleep.
2. AHAndrew Huberman
  Mm-hmm.
3. NCDr. 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. You know, 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.
4. AHAndrew Huberman
  Interesting.
5. NCDr. Natalie Crawford
  Can influence egg quality. And we know that naturally you make more melatonin when you ovulate to kinda counter some of the oxidative stress to the ovary. Really have to be careful, though. A lot of over-the-counter products have, like, 10 times the amount of melatonin-
6. AHAndrew Huberman
  Yeah. Right
7. NCDr. Natalie Crawford
  ... so I always wanna tread lightly with that one in recommending it to patients.
8. AHAndrew Huberman
  Mm-hmm.
9. NCDr. Natalie Crawford
  Often a pediatric dose is, like, one milligram, and that's the perfect amount-
10. AHAndrew Huberman
  Mm-hmm
11. NCDr. Natalie Crawford
  ... just to augment. Again-
12. AHAndrew Huberman
  Mm-hmm
13. NCDr. Natalie Crawford
  ... we're not trying to replace your body's melatonin.
14. AHAndrew Huberman
  Mm-hmm.
15. NCDr. Natalie Crawford
  We wanna augment it and to kinda 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.
16. AHAndrew Huberman
  I don't wanna disrupt your flow-
17. NCDr. Natalie Crawford
  You're fine
18. AHAndrew Huberman
  ... but if a woman is already sleeping well-
19. NCDr. Natalie Crawford
  Yeah
20. AHAndrew Huberman
  ... should she take melatonin?
21. NCDr. Natalie Crawford
  I would say for the average person, probably don't need to.
22. AHAndrew Huberman
  Mm-hmm.
23. NCDr. 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.
24. AHAndrew Huberman
  Since NSAIDs can disrupt the inflammation requirement for ovulation-
25. NCDr. Natalie Crawford
  Yeah
26. AHAndrew Huberman
  ... um, I'm curious about other things that are known to potently reduce inflammation. Um, I, I think enough terrible things have been said about cold plunges, um, that we don't need to add any more, but we're seeking reality here, uh, and I don't have-- 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, um, or any kind of exercise where you want the inflammation to get the adaptation to the exercise.
27. NCDr. Natalie Crawford
  Mm-hmm.
28. AHAndrew Huberman
  We know that, and it's a pretty potent inhibitor of inflammation. SoIs there any reason to think that in the time where somebody's trying to conceive that perhaps they should avoid the cold plunge?
29. NCDr. Natalie Crawford
  I usually recommend against them for reasons stated here.
30. AHAndrew Huberman
  Mm-hmm.
1:38:41 – 1:42:05
Curcumin, NAD/NR, CoQ10, Supplements for Prenatal Care & Sperm Health
1. AHAndrew Huberman
  Um, one thing that's commonly used is, um, curcumin.
2. NCDr. Natalie Crawford
  Yeah.
3. AHAndrew Huberman
  Um, and it's a pretty potent anti-inflammatory. Do you recommend people stay away from-- Uh, let's-- not cooking with curcumin, but the high-dose curcumin that comes in a lot of, uh, of supplements.
4. NCDr. Natalie Crawford
  Yeah, I don't usually recommend it in a supplement form.
5. AHAndrew Huberman
  Mm-hmm.
6. NCDr. Natalie Crawford
  Like I, I, I never recommend it.
7. AHAndrew Huberman
  Mm-hmm.
8. NCDr. Natalie Crawford
  I think if you have a doctor who's giving it for very specific purpose, you might be a unique person who has excess inflammation they're trying to target.
9. AHAndrew Huberman
  Mm-hmm.
10. NCDr. Natalie Crawford
  But that's not something that I recommend. But cooking with it is fine.
11. AHAndrew Huberman
  NAD and NR-
12. NCDr. Natalie Crawford
  Yeah
13. AHAndrew Huberman
  ... uh, are-- I get asked about them thousands of times-
14. NCDr. Natalie Crawford
  Oh, same
15. AHAndrew Huberman
  ... per week. Um, 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. Um, 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? 'Cause I often see it listed in c- in fertility protocols.
16. NCDr. Natalie Crawford
  I know animal data looks like NAD and NNM can be advantageous-
17. AHAndrew Huberman
  Mm-hmm
18. NCDr. Natalie Crawford
  ... especially for unexplained infertility, which to be clear is different than I just wanna 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.
19. AHAndrew Huberman
  Mm-hmm.
20. NCDr. 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, I don't ever say no, and I sometimes use it, but on like 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-
21. AHAndrew Huberman
  Mm-hmm
22. NCDr. Natalie Crawford
  ... if you're going to spend-
23. AHAndrew Huberman
  Mm-hmm
24. NCDr. Natalie Crawford
  ... because most of us don't wanna spend endless amounts on all the things that we can-
25. AHAndrew Huberman
  Sure
26. NCDr. Natalie Crawford
  ... craft for our supplement list. But the human data is yet, yet to be out, although an-animal data looks promising for the right patients.
27. AHAndrew Huberman
  I'm glad you mentioned coenzyme Q10. CoQ10 and L-carnitine-
28. NCDr. Natalie Crawford
  Mm-hmm
29. AHAndrew Huberman
  ... are the two, uh, at least I'm aware of, uh, there's some decent data on s-supporting sperm and-
30. NCDr. Natalie Crawford
  Yeah
1:42:05 – 1:43:16
Sponsor: Function
1. AHAndrew Huberman
  I'd like to take a quick break and acknowledge our sponsor, Function. Function provides over one hundred and sixty 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 a hundred and sixty 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 fifty dollar credit towards your membership.
1:43:16 – 1:48:21
Fertility Research into Supplements & Lifestyle Factors
1. AHAndrew Huberman
  I'm sure there are, um, sort of standards and a lot of communication in your field about, you know, how many, uh, follicles to try and mature, um, if one does IVF or n- and, and-- or is pulling eggs. I don't know if that's the right term.
2. NCDr. Natalie Crawford
  [laughs]
3. AHAndrew Huberman
  Forgive me. There it is again. [laughs] I think, you know, and so, pulling eggs. Um, taking eggs out carefully and, uh, for sake of, of freezing or, or fertilization. Um, 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. Uh, my friends joke when people ask me, "Which supplements do you take?" They just shout-
4. NCDr. Natalie Crawford
  You're like, "All of it"
5. AHAndrew 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, um, they're not the be all end all, but some work. So how much conversation is there about things like coenzyme Q10, L-carnitine? Um, is there a consensus or is there sort of a distribution-
6. NCDr. Natalie Crawford
  Mm-hmm
7. AHAndrew Huberman
  ... of old school, new school? Um, and I am very curious, um, not trying to be political or politically correct, whether or not this divides on male/female, um, fertility docs or, um, like the, the culture within a field often tells us a lot. So I'm, I'm not asking you to throw any of your colleagues under the bus-
8. NCDr. Natalie Crawford
  Oh
9. AHAndrew Huberman
  ... but if you have to [laughs]
10. NCDr. Natalie Crawford
  No.
11. AHAndrew Huberman
  No.
12. NCDr. 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. You know, the first ASRM, which is the American Society for Reproductive meeting that I went to was probably 15, 16 years ago, and it's, it was so IVF heavy. Now to be fair, like the science was rapidly evolving, like 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 that's 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." Right? Control all of these variables. That public curiosity drives research to a degree.
13. AHAndrew Huberman
  Mm-hmm.
14. NCDr. Natalie Crawford
  Because if you're hearing it from your patients, that's the formation of research questions, right? That we're looking at. Now, granted, all data that exists is, is limited in its own form, right? 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 controlled trials though, which we often do in the IVF subset because we can look at more distinct criteria, I can say, well, how many, 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 s- robust data that certain supplementation, CoQ10, vitamin D, omega-3 fatty acids, those are clearly associated with improved reproductive outcomes. And I-- we're starting to see more, I don't want to say fringe, but of the specifics, right? 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. I think at the end of the day, my job's not to say, "Just do IVF."
15. AHAndrew Huberman
  Mm-hmm.
16. NCDr. 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, any merit of the other lifestyle factors that we talk about. You know, 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 a, how your hormones function, how your ovaries respond when you're-- how many eggs you pull out to the-
17. AHAndrew Huberman
  Mm-hmm
18. NCDr. Natalie Crawford
  ... what you say, how, how many embryos you form, and that supplementation is one piece of the puzzle.
19. AHAndrew Huberman
  Mm-hmm.
20. NCDr. Natalie Crawford
  It's not the end all be all. I think we can probably should always, you know, focus first on where we can move the needle the biggest.
21. AHAndrew Huberman
  Mm-hmm.
22. NCDr. Natalie Crawford
  So those more core lifestyle practices is, 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.
23. AHAndrew Huberman
  Mm-hmm.
24. NCDr. 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.
1:48:21 – 1:53:12
Inflammation, Red Light
1. AHAndrew Huberman
  If we'd been sitting here 15 years ago and I said, uh, you know, red light therapy can be useful for skin and for, um, offsetting-
2. NCDr. Natalie Crawford
  Mm-hmm
3. AHAndrew Huberman
  ... age-related vision loss, um, any reasonable physician would be like, "That's nonsense."
4. NCDr. Natalie Crawford
  That's bogus.
5. AHAndrew Huberman
  Um, I spoke to an ophthalmologist yesterday. There's been a clinical trial using red light and infrared light, uh, for what's called dry AMD, uh, dry, uh, macular degeneration, um, to offset age-related vision loss.
6. NCDr. Natalie Crawford
  Mm.
7. AHAndrew Huberman
  And it is, looks promising. I mean, it doesn't reverse age-related vision loss completely, but seems to help the mitochondria and the photoreceptors.
8. NCDr. Natalie Crawford
  Makes sense.
9. AHAndrew Huberman
  People are holding on to some vision that they would lose. There was a cover of what I am told, um, is the premier dermatology journal exploring the recent studies on red light and infrared light, so it's a common practice now.
10. NCDr. Natalie Crawford
  Yeah.
11. AHAndrew 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, um, red light, infrared light therapy, um, looked at currently, and if they are used, um, where is it directed?
12. NCDr. Natalie Crawford
  Mm.
13. AHAndrew Huberman
  Is, is it actually on top of the ovaries? Is that the idea, or that it's a more of a systemic effect?
14. NCDr. 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?
15. AHAndrew Huberman
  Mm-hmm.
16. NCDr. Natalie Crawford
  So if you have chronic inflammation, it's going to interfere with hypothalamic re- 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 like w- 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, um, signs showing thatThat's more the systemic probably.
17. AHAndrew Huberman
  Mm-hmm.
18. NCDr. Natalie Crawford
  Are you just sitting in front of your red light panel-
19. AHAndrew Huberman
  Mm-hmm
20. NCDr. Natalie Crawford
  ... that's gonna 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 therapy-
21. AHAndrew Huberman
  Mm-hmm
22. NCDr. Natalie Crawford
  ... so through the abdomen. But there is now... I mean, 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.
23. AHAndrew Huberman
  Mm-hmm.
24. NCDr. 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-
25. AHAndrew Huberman
  Mm-hmm
26. NCDr. Natalie Crawford
  ... potentially benefit egg quality more. I think most people are gonna say, you know, we don't have definitive data yet.
27. AHAndrew Huberman
  Mm-hmm.
28. NCDr. Natalie Crawford
  Yet everything's pointing to likely benefit.
29. AHAndrew Huberman
  Mm-hmm. I don't know if this study could be done, but, um, the one arm of this, uh, my podcast company funds research, and the one thing I'd love to see the experiment done is, um, either maintaining or doing fertilization of, of eggs under red light because so much of the proper chromosomal arrangements seem to be dependent on mitochondrial health.
30. NCDr. Natalie Crawford
  Mm-hmm.
1:53:12 – 1:58:57
Cannabis & Detriments to Egg & Sperm Health
1. AHAndrew Huberman
  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, um, 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.
2. NCDr. Natalie Crawford
  Yeah.
3. AHAndrew Huberman
  Does that concern you?
4. NCDr. 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.
5. AHAndrew Huberman
  Mm-hmm.
6. NCDr. Natalie Crawford
  And ultimately something that we are just now getting robust data on, 'cause it's hard to study something when it's illegal.
7. AHAndrew Huberman
  Mm-hmm.
8. NCDr. Natalie Crawford
  All cannabis use is hugely detrimental to sperm, for sure, across the board, right? Both production, the quantity of sperm, uh, 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, you know, 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? I mean, like, we get excited when something's a few, you know, 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, you know, 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.
9. AHAndrew Huberman
  Critical message. Thank you so much. I, I've been, uh, put through the wringer around this cannabis thing 'cause I've hosted people that said it does increase the risk of psychosis in certain, typically young males-
10. NCDr. Natalie Crawford
  Mm-hmm
11. AHAndrew Huberman
  ... um, 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, um, cannabis, I believe, is recently rescheduled from Schedule 1, no, um, at the federal level, it's assigned a no, um, medical application, um, to Schedule 3, so there's gonna 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, um, typically on X, they'll say, um, that they smoked a lot of weed, and they got theirOr took edibles and they got their wife or girlfriend pregnant-
12. NCDr. Natalie Crawford
  Oh, yeah
13. AHAndrew Huberman
  ... X number of times, and it, it sort of becomes this sort of point of boasting. And then I never wanna make the comment, but I'll make it now. It's like, yeah, but you're talking about brain development in your kid.
14. NCDr. Natalie Crawford
  Yeah.
15. AHAndrew 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, um, healthy as they could be. I'll just say that 'cause I'm talking to the guys out there, and that's h- how we talk to one another.
16. NCDr. Natalie Crawford
  Yeah.
17. AHAndrew 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 a ostensibly a short-term decision, certainly for the man, right? The woman who's gonna breastfeed should probably avoid cannabis-
18. NCDr. Natalie Crawford
  Yeah
19. AHAndrew Huberman
  ... during breastfeeding too. You see where I'm going with this.
20. NCDr. Natalie Crawford
  Look, the outcome is so important, right?
21. AHAndrew Huberman
  Mm-hmm.
22. NCDr. Natalie Crawford
  And when we wanna 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, you know, association with earlier birth. I mean, it's just not worth the risk-
23. AHAndrew Huberman
  Mm-hmm
24. NCDr. Natalie Crawford
  ... when the outcome is so important, right?
25. AHAndrew Huberman
  Mm-hmm.
26. NCDr. Natalie Crawford
  We're all weighing risk every day with different decisions. To me, there's a lot harder decisions you have to make, but, you know, nicotine use, cannabis use, alcohol use, like 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 even-- or specifically a pregnancy lens. Like there's, there's no place for it. You can choose to do what you want with that data, right?
27. AHAndrew Huberman
  Mm-hmm.
28. NCDr. 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 wanna control what you can because you can't control everything.
29. AHAndrew Huberman
  Mm-hmm.
30. NCDr. Natalie Crawford
  So I call those the behavioral toxins.
1:58:57 – 2:02:21
Nicotine, Smoking, Egg Health & Sperm Count; Healthy Lifestyle Practices
1. AHAndrew Huberman
  along those lines, for whatever reason, nicotine has become kind of this right-wing associated thing.
2. NCDr. Natalie Crawford
  I know.
3. AHAndrew Huberman
  I recently spoke to about four thousand young, uh, men and women, um, and I would say about thirty to forty percent of them raised their hand that they're using, um, oral nicotine every single day. Anywhere from probably... I did, I did sort of crude analysis by hand, um, so these aren't, you know, uh, hard data, but it was somewhere between twelve and seventy milligrams of nicotine a day.
4. NCDr. Natalie Crawford
  That's wild.
5. AHAndrew Huberman
  So for women in particular, um, is oral nicotine use detrimental to e- either egg quality or probability of, of successful pregnancy?
6. NCDr. Natalie Crawford
  It's definitely correlated because of how it works in the brain to-
7. AHAndrew Huberman
  Mm-hmm
8. NCDr. Natalie Crawford
  ... you know, ovulation, getting pregnant, hormone response. So it should not be something that we're adding to, you know, our day-to-day life-
9. AHAndrew Huberman
  Mm-hmm
10. NCDr. Natalie Crawford
  ... in any form if we're trying to get pregnant. Most the egg quality data from nicotine comes from cigarette smoking.
11. AHAndrew Huberman
  Mm-hmm.
12. NCDr. Natalie Crawford
  So I think it's a little bit more nuanced-
13. AHAndrew Huberman
  Mm-hmm
14. NCDr. Natalie Crawford
  ... because smoking directly, if we wanna look at that, you know, 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, you know, s- nicotine, cigarette smoking definitely does. You go into menopause early, you'll get fewer eggs. The egg quality is de- detrimental. It makes sense based on what nicotine does to your body and how it kinda changes your cellular response, that it probably is impacting your egg quality also, even with these oral nicotine pouches, you know, that we're seeing everybody utilize. And it's tanking sperm counts. I mean, that one's really clear.
15. AHAndrew Huberman
  Uh, and then it, of course, everyone's talking about the reduction in, in, uh, in just population growth, which when I was growing up, we were told that, like, the earth is gonna be overcrowded. Now we're told that-
16. NCDr. Natalie Crawford
  Yeah
17. AHAndrew Huberman
  ... there's not gonna be enough people.
18. NCDr. Natalie Crawford
  It's not gonna be enough.
19. AHAndrew Huberman
  Everyone's gonna be alone on their phones. I don't think either extreme is true. Um, but these are, these are vitally important things for people to think about, 'cause these are easy decisions to make, and they can be short-term decisions.
20. NCDr. Natalie Crawford
  They are.
21. AHAndrew Huberman
  Yeah.
22. NCDr. Natalie Crawford
  You know, we make decisions every day, and, 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.
23. AHAndrew Huberman
  Mm-hmm.
24. NCDr. 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, you know, 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.
25. AHAndrew Huberman
  Mm-hmm.
26. NCDr. Natalie Crawford
  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.
27. AHAndrew Huberman
  Mm-hmm.
28. NCDr. Natalie Crawford
  Then they say, "Oh, like this running on just caffeine and eating whatever food I could on the go and not getting enough sleep, and then using a hundred nicotine pa-" Like that was my body giving me a hundred 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.
2:02:21 – 2:10:58
GLP-1s, PCOS, Endometriosis; Human Growth Hormone
1. AHAndrew 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 if-- that you would like to see more science on?
2. NCDr. Natalie Crawford
  Oh, yes. Yes, absolutely.
3. AHAndrew Huberman
  Um, and the reason I ask this is, is there's this, um, incredible intuition that comes from just being in regular contact with a certain process. For instance, anytime I've spoken to an embryologist who does the kind of work that they do in your clinic, they, they read journals, and there's a process. They learn protocols, but they also l-- they develop an intuition to pick that sperm, to wait just a-
4. NCDr. Natalie Crawford
  I know
5. AHAndrew Huberman
  ... little bit longer, maybe even, maybe even fertilizing that egg at the end of the day-
6. NCDr. Natalie Crawford
  No, I know
7. AHAndrew Huberman
  ... even though it looks more mature than the-
8. NCDr. Natalie Crawford
  Like just a couple hours. It's a little small. It's a little gray.
9. AHAndrew Huberman
  I mean, this, this is the, this is the art, not the-
10. NCDr. Natalie Crawford
  It's like the je ne sais quoi of medicine.
11. AHAndrew Huberman
  Right. The-- Right. The art, not the science of it. The same way a, you know, cooking is chemistry, but there's an art to it, too.
12. NCDr. Natalie Crawford
  Mm-hmm.
13. AHAndrew 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. Um, is there something that intrigues you and that you'd like to see more science on?
14. NCDr. 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 y-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 where 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. Fifty percent of those patients will end up having endometriosis. Maybe, you know, 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 take-- stop them and then go through a cycle of different IVF outcomes. We will see more embryos in the lab.
15. AHAndrew Huberman
  Hmm.
16. NCDr. Natalie Crawford
  And we don't have the study to say that, but-
17. AHAndrew Huberman
  Mm-hmm
18. NCDr. Natalie Crawford
  ... talking to colleagues across the country, we know that GLP-1s can be very anti-inflammatory and the way to kinda target that, 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.
19. AHAndrew Huberman
  So do you think there could be direct effects of the GLP-1s on reducing inflammation that are independent of less, uh, adipose fat tissue?
20. NCDr. Natalie Crawford
  I do because some of these patients do not have much adipose tissue.
21. AHAndrew Huberman
  Mm-hmm.
22. NCDr. Natalie Crawford
  So I think obviously that person's gonna 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-
23. AHAndrew Huberman
  Mm-hmm
24. NCDr. Natalie Crawford
  ... where people's immune system, their inflammatory response is mistriggering-
25. AHAndrew Huberman
  Mm-hmm
26. NCDr. 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.
27. AHAndrew Huberman
  It's really interesting 'cause I would have thought GLP-1s reducing body fat for a woman who doesn't-- isn't carrying excess body fat-
28. NCDr. Natalie Crawford
  Could be-
29. AHAndrew Huberman
  ... that might actually be detrimental to getting pregnant.
30. NCDr. Natalie Crawford
  It's a fair point that we have to be really careful when it comes to skinny culture. I mean, we are-
2:10:58 – 2:17:27
Platelet-Rich Plasma; Paternal Age & Sperm Quality; Biotin
1. AHAndrew Huberman
  What are your thoughts on platelet-rich plasma?
2. NCDr. Natalie Crawford
  Oh, such a good question.
3. AHAndrew Huberman
  Which is not stem cells, by the way.
4. NCDr. Natalie Crawford
  No.
5. AHAndrew Huberman
  Sorry to, 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, so now they just p-- but PRP is not stem cells.
6. NCDr. Natalie Crawford
  Okay.
7. AHAndrew Huberman
  Forgive, forgive me for interrupting.
8. NCDr. 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, just 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 ex-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, you know, low ovarian reserve or age-related fertility in the PRP of the ovary group. Where it shows the most promise is intrauterine PRP, so which is nice because it's less invasive. That's the minority of people who are having recurrent implantation failure. You know, 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 ninety-five percent 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, you know, 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 know, 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.
9. AHAndrew Huberman
  A few years back, uh, there was more discussion about the age of the sperm and the probability of autism.
10. NCDr. Natalie Crawford
  Yes.
11. AHAndrew Huberman
  Could you update me on the, the, uh, the data?
12. NCDr. Natalie Crawford
  Yeah. After age fifty, 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, like, dwarfism or very specific, um, diseases that are ultimately overall rare that can-
13. AHAndrew Huberman
  Mm-hmm
14. NCDr. Natalie Crawford
  ... can happen. And then you also can see an increase in some other mental health diseases like schizophrenia.
15. AHAndrew Huberman
  Hmm.
16. NCDr. Natalie Crawford
  That data's scary, not the end-all be-all. At the end of the day, when youHave an opportunity to bank sperm younger, it would make sense, and utilize that preferentially. You know, 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 wanna have children with, then this is who we wanna have children with, and we accept that risk 'cause on a population it's still very low, right?
17. AHAndrew Huberman
  Mm-hmm.
18. NCDr. Natalie Crawford
  A small percentage point increase means still the most probable chance is you're gonna have a very healthy baby. It plays more into, though, the idea that nobody's fertility is finite, that, you know, age-related impacts impact everybody. I would say the same thing is that if the mechanism is the, 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 wanna be controlling all of those factors I was so I wasn't adding to risk.
19. AHAndrew Huberman
  No cannabis-
20. NCDr. Natalie Crawford
  Yeah
21. AHAndrew Huberman
  ... reduced heat, um, all the things that mutate DNA.
22. NCDr. Natalie Crawford
  Exactly.
23. AHAndrew Huberman
  Yeah. Nicotine out, that kind of thing. Um, yeah, it's interesting. I, I think about the, the sort of high signal-to-noise anecdotes, um, things like, "Oh, you know, um, so-and-so smoked weed every day and has eight kids," or, uh, you know-
24. NCDr. Natalie Crawford
  Ugh
25. AHAndrew Huberman
  ... or, or, um, you know, "So-and-so had kids when he... had another kid when he was," whatever. I'm thinking of some actors or something that I don't follow this stuff closely. It was when he was, like, 78 or something. The, the problem with stories like that is that they, they grab people's attention 'cause they're high signal to noise, and they distract from the stuff that, like, 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, I'm just, like, still wide-eyed about this NSAID thing.
26. NCDr. Natalie Crawford
  Yeah.
27. AHAndrew Huberman
  It's something to avoid while trying to get pregnant.
28. NCDr. Natalie Crawford
  Okay, let's do another one. Uh, biotin levels of 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 supplementat- like, you know, there are certain very popular hair supplements that have, you know, 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-
29. AHAndrew Huberman
  Mm-hmm
30. NCDr. Natalie Crawford
  ... but it actually-- This is an REI board question, 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 wanna get data about your body, maybe you feel off or you're going through IVF or you wanna get a hormone panel done, if you're taking a supplement that has more than 300 micrograms of biotin, you're gonna 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 wanna make sure we're not taking excess amounts of.
2:17:27 – 2:22:48
Endocrine Disruptors, Fragrances, Receipts, Tool: Fragrance-Free
1. AHAndrew Huberman
  Wow. Um, 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.
2. NCDr. Natalie Crawford
  Oh man, people really-
3. AHAndrew Huberman
  Um, and that went-
4. NCDr. Natalie Crawford
  ... loved and hated us for that.
5. AHAndrew Huberman
  Well, I will say, 'cause 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, it is... You can tell how frustrated I get with, with it-- My frustration is not with medicine or with science. It's with the, um, lack of open ears-
6. NCDr. Natalie Crawford
  Mm
7. AHAndrew Huberman
  ... in a certain generation of, of physicians and scientists. I mean, 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-
8. NCDr. Natalie Crawford
  I love that
9. AHAndrew Huberman
  ... "What can I do that's not TRT for testosterone?" And like, I mean, it's-- They're humans, too, and I think the issue around endocrine disruptors for the longest time was seen as kinda hippie science with no data. And then now, because the Environmental Working Group started getting-
10. NCDr. Natalie Crawford
  Mm-hmm
11. AHAndrew Huberman
  ... really vocal about this, and Shanna Swan, who's-
12. NCDr. Natalie Crawford
  Yes, lovely
13. AHAndrew Huberman
  ... a longtime researcher. Yeah. Um, 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.
14. NCDr. Natalie Crawford
  I know.
15. AHAndrew Huberman
  But you sit down with her, that's the furthest thing from the truth. Like, she's all about data. So I think as we tiptoe into this, uh, you know, endocrine disruptor thing, I mean, I'll just say it for you, and then if you, if you wanna add, like, none of what we're about to talk about negates anything about standard medicine.
16. NCDr. Natalie Crawford
  No.
17. AHAndrew Huberman
  It's just way- ways and places to be, uh, additionally cautious about things that you are around and might go into you.
18. NCDr. Natalie Crawford
  You make decisions every day.
19. AHAndrew Huberman
  Yes.
20. NCDr. Natalie Crawford
  You should be making it from a place of knowledge.
21. AHAndrew Huberman
  Yeah.
22. NCDr. Natalie Crawford
  And the things that you're exposed to more frequently matter the most, right?
23. AHAndrew Huberman
  Mm-hmm.
24. NCDr. Natalie Crawford
  So a one-time exposure 'cause 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.
25. AHAndrew Huberman
  Mm.
26. NCDr. 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, you know, one of the biggest cohort studies we have, and it's, you know, 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 show 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.
27. AHAndrew Huberman
  Mm-hmm.
28. NCDr. Natalie Crawford
  It's well demonstrated that it impacts our bodies in multiple ways.
29. AHAndrew Huberman
  And as I recall, the things to be cautious of are lavender, evening primrose, or basically anything with a scent.
30. NCDr. 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.
2:22:48 – 2:25:40
Patient Education & Empowerment; Inflammation, Celiac Disease
1. AHAndrew Huberman
  I like to think that people want information. Um, I realize they can feel overwhelmed by too much information.
2. NCDr. Natalie Crawford
  Mm-hmm.
3. AHAndrew Huberman
  But in the end, even though what we're talking about here seems like a lot of to-dos and not to-dos, it, there's a logic to it. I think the logical backbone is you do what you can. Um, you do your best to control the, the key variables. Um, I mean, the point about cannabis, I think, is really important that especially men hear, um, because I think most people don't know, and women don't know they should get their AMH checked. I mean, 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.
4. NCDr. 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?
5. AHAndrew Huberman
  Yeah.
6. NCDr. Natalie Crawford
  I think it's our colleagues who say, "Oh, people don't wanna hear that," or they make assumptions. And again, in today's world where we have data, like, why are we talking about assumptions?
7. AHAndrew Huberman
  Yeah.
8. NCDr. Natalie Crawford
  Let's give people data and let them make the choices they make.
9. AHAndrew Huberman
  Yeah. Ignorance is not bliss when you're running up against a health challenge.
10. NCDr. 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 is. I mean, 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 con- you know, 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 'cause 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, like, GI symptoms from it, I just said, oh, I felt more inflamed.
11. AHAndrew Huberman
  Mm-hmm.
12. NCDr. Natalie Crawford
  Like, vague symptoms, kinda headache, kinda 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.
13. AHAndrew Huberman
  Hmm.
14. NCDr. Natalie Crawford
  And it starts with, you know, 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? 'Cause 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
2:25:40 – 2:33:25
Anti-Inflammatory Diet, Protein, Fiber, Red Meat
1. NCDr. Natalie Crawford
  off of it.
2. AHAndrew Huberman
  What I'm realizing hearing you today is that we need to listen to our bodies. Women need to listen to their bodies 'cause 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.
3. NCDr. Natalie Crawford
  Yes.
4. AHAndrew Huberman
  And when it comes to nutrition, I'm very curious, uh, because of your example, do you think there's any value to people experimenting with a, quote-unquote, "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-
5. NCDr. Natalie Crawford
  Yeah
6. AHAndrew 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.
7. NCDr. Natalie Crawford
  Exactly.
8. AHAndrew Huberman
  So I'm not advocating for, you know, a Spartan diet where it's like, you know, chicken breast next to rice next to broccoli with a tablespoon of olive oil next to it, although that sounds pretty okay. I prefer-
9. NCDr. Natalie Crawford
  There's worse
10. AHAndrew Huberman
  ... steak. There's worse. But when you eat that way for a short period of time, the sort of cleaner and s- more or less individual ingredients-
11. NCDr. Natalie Crawford
  Mm-hmm
12. AHAndrew 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.
13. NCDr. Natalie Crawford
  Yeah.
14. AHAndrew Huberman
  And then my sister, who is not a scientist, um, she'll chuckle at that.
15. NCDr. Natalie Crawford
  [laughs]
16. AHAndrew Huberman
  But she had this intuition about histamine-
17. NCDr. Natalie Crawford
  Mm-hmm
18. AHAndrew Huberman
  ... that has now been confirmed by two guests on this podcast who areMD PhDs who work on these sorts of issues, um, in one case pain, in other 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.
19. NCDr. Natalie Crawford
  Oh, fantastic.
20. AHAndrew 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, like, four different foods. I don't think you can figure that out unless you separate out the ingredients.
21. NCDr. 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, right?
22. AHAndrew Huberman
  Mm-hmm.
23. NCDr. Natalie Crawford
  I think if you're trying to learn to listen to your body, you say, "I wanna 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 cause, more commonly cause certain reactions.
24. AHAndrew Huberman
  Mm-hmm.
25. NCDr. 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 kind of 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. And then learn to listen for it. The tenets of a fertility diet are really not eye-opening, right? 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 wanna 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.
26. AHAndrew Huberman
  Mm.
27. NCDr. 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 wanna 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 wanna be mindful of it. The question I always get is does source matter? I mean, probably-
28. AHAndrew Huberman
  Yeah
29. NCDr. Natalie Crawford
  ... 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.
30. AHAndrew Huberman
  Mm.

Episode duration: 2:36:02

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Natalie Crawford

Fertility as a Health Marker, Infertility

Perimenopause, Menopause, Hormone Replacement Theory

Sponsors: David & BetterHelp

Hormone Therapy, Extending Ovarian Lifespan

Plastics, Toxins & Fertility

Does Prior Pregnancy Make Conception Easier?, Secondary Infertility

Testing Sperm; Pregnancy Loss & Conceiving Again, Fertility Testing

Sponsor: AG1

Menstrual Cycle, Egg Number & Quality, AMH Test

Tool: AMH Test; Fertility Education & Patient Choices

Tool: Tracking Ovulation; Ovulation Disorders

AMH Test Cost; Genetic Testing & Patient Choice

Does Egg Freezing Cause Early Menopause?, In Vitro Fertilization (IVF)

Egg Freezing, IVF, Ethical Concerns; Embryo Banking

Sponsor: Eight Sleep

Egg Freezing, Cost & Patient Choices

Concieving After Hormonal Birth Control, IUD or Depo-Provera

Pregnancy Termination & Concieving Again

Support Egg Quality, Tools: Ovulation & Avoiding NSAIDs; 5 Lifestyle Non-Negotiables

Sleep, Melatonin; Cold Plunge

Curcumin, NAD/NR, CoQ10, Supplements for Prenatal Care & Sperm Health

Sponsor: Function

Fertility Research into Supplements & Lifestyle Factors

Inflammation, Red Light

Cannabis & Detriments to Egg & Sperm Health

Nicotine, Smoking, Egg Health & Sperm Count; Healthy Lifestyle Practices

GLP-1s, PCOS, Endometriosis; Human Growth Hormone

Platelet-Rich Plasma; Paternal Age & Sperm Quality; Biotin

Endocrine Disruptors, Fragrances, Receipts, Tool: Fragrance-Free

Patient Education & Empowerment; Inflammation, Celiac Disease

Anti-Inflammatory Diet, Protein, Fiber, Red Meat

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