Andrew Huberman interviews Natalie Crawford on women's fertility and hormone health
Andrew Huberman speaks with reproductive endocrinologist Natalie Crawford about optimizing female fertility and hormonal health.
Summary
Andrew Huberman hosts Natalie Crawford, a double board-certified physician specializing in obstetrics, gynecology, fertility, and reproductive endocrinology, to discuss her new book The Fertility Formula: Take Control of Your Reproductive Future. Crawford argues that fertility is not merely the ability to get pregnant but a broad marker of metabolic, hormonal, and cellular health — and that poor fertility is associated with increased rates of metabolic syndrome, cancer, heart attack, stroke, and early death. A central claim of the episode is that the American College of OB/GYN's recommendation against routine AMH testing is actively harmful, depriving women of a $79 blood test that could dramatically alter their reproductive decisions. Crawford also presents clinical observations — not yet fully supported by published trials — that GLP-1 agonists at low doses may reduce inflammation in patients with endometriosis or unexplained infertility, improving IVF outcomes. Throughout, she draws on her own experience of four pregnancy losses and a later celiac disease diagnosis to illustrate how systemic inflammation and delayed diagnosis damage both patients and the field.
Key Takeaways
FULL TRANSCRIPT
Fertility as a Marker of Overall Health
Andrew Huberman: Natalie Crawford, welcome back.
Natalie Crawford: Thank you so much for having me. I'm thrilled to be here.
Andrew Huberman: Congratulations on your new book, The Fertility Formula. It's no small feat to complete a book, and it's especially a big feat to complete one that offers people so much advice — not just people who want to get pregnant, but also looking at things through the lens of fertility as an important health metric.
Dr. Crawford: Thank you so much. You know what goes into writing a book, and it's always been this aspirational goal of mine. 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 than I expected — going through it, working with editors, trying to refine within your word count. I was 20,000 words over and had to bring it back in. So thank you for having me, and for holding it up and reading it early and sharing your endorsement. That means so much.
Andrew Huberman: I am insisting, as much as one can insist, that various people in my life read this book — including family members — because again, it's not just about people who want to have children or who already have children, but fertility as a way of knowing where one is in their health arc, in their life arc. So if you don't mind, how should people think about fertility purely as a readout of health? How do you frame this for someone who comes to you and says they have kids, or they don't want kids, or they're not sure — why use fertility as a lens on general health?
Dr. Crawford: Fertility is a health marker. I love that you bring that up at the top of the episode because so often patients — women specifically — think fertility is only the ability to get pregnant. We really simplify it into this one phase of life. But if we want to zoom out, your fertility is a sign that you have good hormonal health, good cellular health, 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. Your hormonal health and ovarian function is also going to impact your entire life and how you feel on a day-to-day basis as a woman.
But if we want to be really specific: if you have infertility, you have increased rates of metabolic syndrome, cancer, heart attack, stroke, and dying early. Those are extremely scary statistics. 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 — that there are higher levels of chronic inflammation or insulin resistance that we know can impact long-term health outcomes.
Andrew Huberman: For women who are still of reproductive age — and I realize there's no strict cutoff — we can talk about what are the measures, direct and indirect, of fertility that can give them a window into their health span and lifespan risk factors. For women who have already reached menopause or are in perimenopause, how should they think about fertility as a health marker? If someone has passed the point where they can safely get pregnant, does that mean their periods are no longer informative?
Dr. 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 and the eventual lower egg count — you will start to see some cycle changes, but you can still get pregnant. And in fact, I see a fair amount of patients who said they thought they were past that stage of their life based on their 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. We can look at the distinct phases of the cycle — the follicular phase and the luteal phase.
When we're a little bit past this, menopause by definition — which I hate — is 12 months without a period. So menopause is one single day in time. Really, it means you've been in ovarian failure for 12 months before you'll magically get this diagnosis. But menopause at its purest is ovarian failure. The ovaries no longer have the capability to respond to the brain signals. You're not going to make estrogen or progesterone anymore. At that time, a woman's metabolic health completely changes. But the age at which you went through menopause can really impact your long-term health outcomes. And some of the characteristics you might have had in your cycle, when we look backwards, can inform us 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. 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. For a long time we felt really comfortable starting it right at the time of menopause, but we're starting to see benefits from starting it in the perimenopausal period. I think it's a disservice to women to make them have no period, ovarian failure for 12 months, no estrogen, feel terrible — before we'll allow them to have hormone replacement therapy.
Andrew Huberman: This is such an important theme. I realize I have to be very careful not to draw parallels to men's hormonal health when talking about women's hormonal health, because it's not a one-for-one — they're very distinct processes. On the other hand, I think thematically what I'm about to say holds. For many years, hormone replacement therapy was sort of made widely available for men before it became widely available for women, for reasons that are unfair and obvious. There was this idea that unless somebody fell below 300 nanograms per deciliter for a male, they shouldn't get testosterone replacement therapy. Now it's kind of understood that if somebody chooses, they can usually find a doctor who will push them from the low end of normal to the high end of normal so they can get their symptoms away and just feel right — to optimize within the normal range. I'm relieved to hear you're saying the same is true for women. I'm relieved because having these strict cutoffs — like no periods for a year — seems very extreme and unnecessary. What if it's two periods per year? Does that mean that person doesn't deserve the therapy?
Dr. Crawford: The R in hormone replacement is the dangerous letter in my opinion, because there is this notion of augmenting hormones.
Andrew Huberman: Exactly. So forgive me for going long, but I think the two situations would be great if both women and men could augment their hormones to be at the high end of normal, or wherever puts them in a place where they're not experiencing symptoms.
Dr. 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. 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 these harsh cutoffs — especially for something that can be so protective long term. 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. I think it's really important for women to know their body, know what's normal so they can advocate for what's not normal, and really feel like they have their own agency over their health and their own future.
Hormone Augmentation and Extending Ovarian Lifespan
Andrew Huberman: I wish the medical profession could agree on nomenclature that included "hormone replacement therapy" for people that are out of range, "hormone augmentation therapy" for people that want to push within the normal range, and then of course there's supraphysiological stuff — and that's kind of how all of this got here, with mainly guys taking tons of anabolic steroids. Estrogen's a steroid, testosterone is a steroid, and then it became a long road to get to this point where people like you are able to even talk about this. I think 10 years ago the medical profession was not open to the idea that a 40-year-old woman who had not yet undergone menopause by the strict definition would take estrogen. It was seen as a risk as opposed to a benefit.
Dr. Crawford: Isn't it interesting? Professional organizations would even call it menopausal hormone therapy — MHT — not even just hormone replacement therapy. I talk about this a lot with my patients: the difference between replacing a hormone versus supplementing. Your body's making some and we're supplementing that, or augmenting it, to get it to the appropriate level or to make sure we have enough.
I've been in practice for over 10 years. What's so interesting is that we'll use premature ovarian failure — going into ovarian failure before age 40 — as a case where it's well accepted that these women need hormone replacement even when they still have low-end hormonal function. 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.
I'm really glad to see the tide is turning and we're really allowing people to stand up for themselves — to know what's normal within their body. Many women have been dismissed and gaslit for so long. If you go to your doctor and talk about your painful periods, your irregular cycles, your bloating with your period, the spotting — these red flag warning signs — and it gets pushed to the side, then when you start to go through actual hormonal change later, it's really hard to believe yourself. 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. That's going to help you stand up for yourself later when you're in this transitional period. Perimenopause or diminished ovarian reserve — as we call it in the fertility world — can last 5 to 10 years. That can be a really long transitional period, and women deserve support if they're not feeling their best.
Andrew Huberman: Are all hormone therapies for women — let's just call it hormone replacement for simplicity — do they always start with estrogen when it comes to trying to encourage fertility or well-being out into more years?
Dr. Crawford: That's an interesting question. When it comes to hormone replacement therapy in general, we've got estrogen, progesterone, and testosterone. Most women, when they start not reliably making estrogen, that's when they really start to feel bad. So typically some type of estrogen replacement — and there are many different ways: patches, pills, vaginal inserts, 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, but I have some perimenopausal patients who feel great on just progesterone.
To me, testosterone is 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, they tend not to need testosterone, but that's never 100% of the time.
Greater to your question about whether there's a way to extend the ovarian lifespan — that's a really good one. We know that women who go into ovarian failure early have ovaries with more inflammatory markers, 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 something to be said — despite not having the perfect paper to sit here and say definitively — that 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. Paying attention to these factors earlier in your life — whether it's controlling an autoimmune disease, earlier diagnosis of Hashimoto's, treating your endometriosis, or cultivating a lifestyle that decreases inflammation, avoiding certain toxins, eating anti-inflammatory foods, the type of exercise, how we deal with stress — that likely has the capability to extend our ovarian lifespan to the degree that it can.
Plastics, Toxins, and Fertility
Andrew Huberman: I know these days people are very concerned about plastics. You mentioned toxins, so I'll ask now. How concerned are you about plastic water bottles? We can't avoid exposure to plastics. Dr. Rhonda Patrick has done a nice job highlighting that the really small microplastics are the ones we worry about most because they can get into so many tissues. Are there any data that have you genuinely concerned that plastics are becoming more of an issue vis-à-vis fertility?
Dr. Crawford: There definitely is concern. The goal when we talk about toxin avoidance is that you can't avoid everything. You cannot avoid every toxin in this world, nor should we try to have an all-or-nothing mentality — which is what so many people do. "Oh, if I can't avoid it, I'll just totally ignore it."
When we want to think about toxins, there are many different mechanisms by which plastics can be harmful. When it comes to microplastics, we know they can accumulate in the ovary. If we want to be really transparent and simple: your ovaries must function in order for you to make estrogen and progesterone, in order for you to ovulate, in order for you to get pregnant. So if microplastics can accumulate inside the ovary, that's obviously detrimental towards fertility or ovarian function.
On a greater scale, we know that some of the endocrine-disrupting chemicals in plastics have been associated with worse IVF outcomes, lower live birth rates, and longer time to pregnancy. These are population-based cohort studies, so there's no randomized control trial, and we have to acknowledge that people who might be more exposed to plastics may have other lifestyle factors — we know plastics can also be in food wrappers, 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. 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? How much sleep am I going to get? What foods am I going to eat? How do I deal with stress? These choices, even though one single one's not going to make it or break it, together they can add up to that inflammatory burden — or they can help decrease it. And that chronic inflammation does in fact matter to your fertility.
Age, Prior Pregnancy, and Secondary Infertility
Andrew Huberman: I took an informal poll of some people heading into this episode. A common question was: it seems that for some women, if they've been pregnant once before, they have it in mind that it's going to be easy for them to get pregnant again later. They understand the logic that they were younger before by definition, even if it's a year, and that fertility drops off with time. But there seems to be this belief that if one was pregnant before, it's going to be possible to get pregnant again within the normal biological windows. Is there any evidence that having been pregnant before makes it easier to get pregnant again?
Dr. Crawford: I did fellowship research with the primary investigator on a large cohort study — one of the biggest ones we have on natural fertility. This study was called Time to Conceive. It was looking at women who did not have a history of infertility, who were trying to get pregnant, who were 30 and older. One of the most startling pieces of data is that there's a huge age-related impact on fertility. This data set set the standards for the numbers that we quote.
If you're trying to get pregnant with your first child and you're 30, you'll have a 20% chance per month. 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, none of those numbers are zero. By no means do we mean you can't get pregnant.
But in the group who had a child before and were trying to conceive with the same partner, that number stayed between 18 to 20% up till age 37 and then it dropped. So we do see that there is this protective benefit for a multitude of reasons. You conceived with that person, so they had sperm. Sometimes I find out some patients' male partners have no sperm, and we didn't know all that time they were trying.
Andrew Huberman: Oh my goodness.
Dr. Crawford: Right. I've had patients try for years, be dismissed by their doctor, because men and women mistakenly think that because there's semen, there's sperm.
Andrew Huberman: There's ejaculate, so there must be sperm inside of it.
Dr. Crawford: Exactly. And then when we find out there's none, it's heartbreaking. It's a big reason why I 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. The definition of infertility is trying to get pregnant for 12 months, and then once you've reached that point, well, now we'll check a semen analysis, now we'll do an anatomical investigation, now we'll check your ovarian reserve, now we will discuss if you're ovulating. So we're making you go through this period of time where you're trying, and yes, maybe the majority of people will get pregnant, but most people who do will get pregnant in the first six months. 72% of people will get pregnant in that first six months of trying, and only 13% will get pregnant in the next six months. That's why if you're 35 and older, we will shorten that testing interval down to six months.
But sitting across from so many people who've tried and tried, went to their doctor, their doctor said, "Oh, you're fine, you're young," forced 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 have intervened differently back at time period A had they had that data. It really makes me feel like we have to switch how we approach infertility in a world where infertility rates are rising and women are waiting later to get pregnant. It doesn't really make sense to make people fail first before we'll even do an investigation. We should test things, and if it's all normal, maybe you do just go try your six or 12 months. We would capture people who don't get pregnant and be able to help them sooner, which is so valuable.
So to your original 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 come into it assuming it will be as easy. They watch their children have a bigger age gap than they wanted. But also, they don't really fit into the community — there's a really robust infertility community, and so many patients who have secondary infertility say they feel caught in between: feeling guilty that their child isn't enough for wanting more, not really fitting into that infertility category, yet also simultaneously feeling left behind their friend group or family group.
Even in women who've had a prior child, age does become impactful. Sperm counts change with age, so your partner's sperm count will change. 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 — simply, you've had more time, so there's a higher probability that these diseases could be present. So I think it's important to say yes, you can probably take a sigh of relief that most likely you won't have trouble again. But if you've been trying those six months and you're not pregnant, go and get an evaluation. And if you're a little bit older, it's never too early to get an evaluation for anybody at any time, because you can't make decisions on data you don't know.
Andrew Huberman: 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.
Dr. Crawford: Yeah. And with respect to sperm testing — since clearly there are men who think they're making sperm and they're not — there are at-home tests as well. Some are just telling you almost like a pregnancy test, plus or minus, are sperm present or not. 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. It's called a CLIA-certified lab — C-L-I-A — for somebody listening. You can find some of these online mail-in sperm tests, collect a sample, they send you the whole kit, you mail it off. It's very valid and you get all the sperm parameters that we would look for. That's a great way to get data yourself without having to have your doctor tell you no or go to a fertility clinic. Most clinics will do a semen analysis for anybody who calls. It's usually earlier that patients are getting roadblocked — whether it's their PCP or their regular OB/GYN — getting dismissed with, "Oh, just try first, it's probably fine."
Pregnancy Loss and What It Tells Us
Andrew Huberman: You mentioned that if a woman has had a successful pregnancy, the probability of getting pregnant again is significantly higher, with the caveats you mentioned. Is there any data about whether having been pregnant and either terminated or lost the pregnancy is related to ability to get pregnant again later?
Dr. Crawford: It's a good question. Most of the data that exists is looking at prior live birth. But I think there are a couple of 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. 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. And we know your body could accept an embryo implanting at least to some degree. The top cause of pregnancy loss is going to be random genetic abnormality — this wasn't the right embryo, or the embryo didn't have the right capacity to truly implant. So I think that should give you some sigh of relief that it's probably going to be a little bit easier because certain boxes are checked.
I think it's also really important to say — I had four pregnancy losses myself. I don't know if you know this.
Andrew Huberman: I really appreciate the personal story sharing in the book, because it clearly was in service to your patients and to the reader. Even as a male who can't relate to certain aspects of all this, it was not only very moving, but it was really a testament to just how that sort of thing lands — and then the process of trying to sort out what's real. It made me even more grateful for the other information, because otherwise it would sort of be like if I'm talking about ovarian health — how could I possibly know? Your personal experience, while the reader and I felt for you in reading it, is super impactful because there's a level of trust that just comes from somebody who's been through that whole jungle.
Dr. Crawford: Thank you. I'll try not to cry on the show about it, which is funny because it's so long ago. 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 roller coaster. I started to have a lot of self-blame. I felt like it was my own body, something was wrong. And professionally, what I was unprepared for is that this was the end of OB/GYN and the beginning of my reproductive endocrinology fellowship. So I felt like, how am I going to be a fertility doctor if I can't even get myself pregnant? The professional impact of how it made me view myself in my space — I was so unprepared for that.
We especially in an era where you separate your personal and professional life — which was 100% accepted back then. My last pregnancy loss was an ectopic pregnancy. My fertility nurse had to give me my methotrexate shot. Everybody knew about it and I felt like a really big failure. And when I sought help, to be told, "It'll happen, just relax, there's nothing you can do" — or even just "do IVF" — felt so dismissive of what I felt like was true as the patient experience. I would say, "Well, what about this symptom or this question?" and just really, really be pushed aside.
I'll be honest — it made my whole career different, which isn't that interesting? How sometimes things happen to us that are not ideal and can be really terrible. I have the two kids I'm meant to have, but I have forever viewed fertility differently. In fact, all my fellowship research was on natural fertility because of it. I said, at the core, I want to know why some people get pregnant naturally and why other people don't. I wanted to do epidemiologic research. I got a master's in clinical research because that research is very complicated to understand, and most fellows do an IVF lab project. And then I've been so passionate about talking about it since then.
What I wanted to say though is: if you've gone through pregnancy loss, I don't want to ever dismiss how terrible that experience is. And sometimes it can feel that way when I sit here as a professional and say, "Oh, you had a pregnancy loss, so that could be a good sign for the future." I don't want anybody to ever feel dismissed hearing that. But it does tell us that certain systems are intact.
On the other hand, after two pregnancy losses, you need an evaluation. The evaluation is for certain blood tests, a semen analysis, a sperm fragmentation test, and a uterine and tubal evaluation. That can be moved up to one loss if you had heavy blood loss, needed a D&C procedure, if your periods have changed afterward, if anything was really off. We never want to be in the world where we used to make women go through three pregnancy losses before they would get an evaluation. I fell into that camp after two. I said, "Shouldn't we do tests? I'm starting to fall off the curve here. Isn't something wrong?" And I was told, "You need to have another pregnancy loss before we'll do those tests." It was the worst feeling — that I had to fail again and lose a pregnancy before they would even investigate why.
Andrew Huberman: This theme — it's only menopause when you haven't had a period for a year, you have to have two pregnancy losses before you can be put into a category amenable for treatment — there's something really backwards about all of that. I imagine with your book and you being public-facing with health information, and hopefully others with you in your field, that eventually this will change. If I were to draw the parallel to psychiatry — should someone really have to be waking up at 3:00 in the morning for an entire year and be near suicidal before they get adequate treatment? It doesn't make sense. It doesn't serve us.
Dr. Crawford: We're starting to see a change. My big lofty hope for the book is that it changes the entire field of fertility. I understand why OB/GYN used to take care of this, and then at some point they said some people have infertility, let's draw a line in the sand and have some people specialize in this — and I did three years of training in that after OB/GYN. But at the same point, it doesn't make sense to practice that way. It doesn't make sense to force people to fail.
I might tell you the greatest likelihood is all the tests will come back normal, but we should do them because sometimes they don't. If I look across somebody who has recurrent pregnancy loss and I say 80% of the time every test will come back normal — but 20% is a big number. That's a lot of people where maybe it's a simple medication, maybe it's a procedure, something can markedly change what they're going through. And in the same breath, the 80% really need specialized care because what's really going on if we don't have an easy test for it.
I think the whole field needs to change. We need to change how we define terms, how we address women, how we approach reproductive health and hormones and fertility — really in a more proactive, patient-centric approach. Women and men are driving this by talking about it. Ten years ago when I started on social media, nobody talked about fertility. Patients who did had nameless, faceless accounts. Now you see celebrities talking about IVF, talking about endometriosis, talking about their termination for genetic reasons or whatever happened. Those stories are so powerful to drop the stigma, but also highlight how wrong it is that we force women to fail before we'll even evaluate what's going on, let alone treat.
Understanding Egg Quality and Ovarian Reserve
Andrew Huberman: One theme I heard over and over again was women saying, "Okay, they thought they might have been pregnant before, or they knew they had been pregnant once before, and their mom had them or a sibling at like age 42 or 43, and they're in good health themselves." So they had it in mind that there's time. This is not uncommon. Life is very expensive, most people seem to be underpaid nowadays, people are waiting longer to get married and have children. The other common narrative was people who want kids but are waiting for the right person. So for those women — whether they're in their 20s, 30s, or early 40s — what sorts of things do you recommend? And what's the level of urgency that they get certain things checked out, and what should they get checked out?
Dr. Crawford: I'd love to answer it, but for the person who's maybe coming to this discussion, let me explain egg quality really quickly because it's going to tie into what we can test and what we cannot.
As you know well, women are born with all the eggs they're ever going to have. The eggs are kept — I like to think about it as in a vault inside your ovary. They're stored there. You have the most eggs when you're five months old inside your mom — six to seven million eggs. By the time 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 that every single month you are losing eggs. I like to imagine and describe to my patients that a group of eggs is coming out of the vault. Each egg grows inside a small fluid-filled structure called a follicle. The brain sends out follicle-stimulating hormone — or FSH, well named — gets a follicle to grow. As the follicle grows, it makes estrogen. This is called the follicular phase. Estrogen levels talk back to the brain. Remember that the brain does not see what's happening anywhere in the body — it is simply waiting for the hormone signal. That's what hormones are: they're communication signals. I like to think about it like text messages between friends.
When estrogen is high enough for long enough — 200 picograms for 50 hours — that level will tell the brain it's time to ovulate. The brain will send out a surge of LH. A follicle will then rupture. The egg will be released. It only has 24 hours to be fertilized. But that follicle will actually reform and become the corpus luteum. Now we're entering the back half of the cycle called the luteal phase. The corpus luteum makes progesterone, stimulated from LH pulses from the brain. It 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, the corpus luteum will die, progesterone will drop, and you'll get a period.
Also, back to the vault: you have a different number of eggs that come out every month, and that is proportional to how many remain. So when you are younger and have more eggs, more eggs come out of the vault every month. As you get older and 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. We're going to call that ovarian failure. Everybody will go into ovarian failure. 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. Those women can get pregnant with donor eggs or donor embryos. They can still carry a pregnancy. That's sometimes a myth 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 — they absorb the wear and tear of your life. 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 as 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. Those first few days are 100% maternal.
The egg also has to hold the chromosomes in correct position. An interesting fact is that inside the egg, it is frozen in metaphase of meiosis 2 for whatever reason. The chromosomes have met in the middle and they're held apart by those meiotic spindles, and they do not separate until you ovulate. So then you get your egg that has what we think about as your 23X, and the other part goes into a polar body.
This means that when you're 25, your eggs have only been held in metaphase for 25 years. Your chromosomes are for the most part still in the right position. Your proteins are strong. Most people have better generalized metabolic health. Their mitochondria are stronger. When you are 40, 40 years have passed. We've asked those chromosomes to hold there longer. I always say if I have a line of kindergarteners and I ask them to stand for 40 years, somebody's going to get out of line. So tincture of time adds up.
But the other thing that happens as we get older is that as a population we get more metabolically unhealthy. We see more chronic inflammation, more insulin resistance, more obesity. All of those factors influence oxidative stress, mitochondrial health, and 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.
We don't have a direct test for egg quality — that's what we call egg quality: genetic normality and egg competency. How good are the mitochondria? Can it do its job? We approximate it to age, which has some fault because not all 40-year-olds are created equal.
When we think about ovarian reserve, this is how many eggs you have remaining — how many eggs are inside the vault. 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. 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.
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 we have outside the vault. 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 OB/GYN says that women should not get an AMH checked unless they have infertility.
Andrew Huberman: I mean, to me as well. It just seems like this failure criteria. It seems very extreme and unnecessary. Unless there's some hidden agenda to try and prevent people from maintaining fertility or having children — and that doesn't square with at least my assumptions.
Dr. Crawford: The idea here is that it can be really stressful. This is what they say in their document. 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 it realistically. I have two 30-year-olds: one has 20 eggs outside the vault, which would be age-related norm, and one has five eggs outside the vault. If every single other factor is the same and they each are ovulating one egg, they have the same chance of getting pregnant. So that's not a faulty statement.
However, the person who has five eggs will not have as long to grow her family. She will not get as many eggs if we're doing advanced treatment like egg freezing or IVF, because I can only get the eggs outside the vault to grow. So it's hugely impactful for what your journey may look like in treatment.
But more so than that, so many of the causes of a low AMH directly contribute to infertility — things like autoimmune disease, insulin resistance, endometriosis, smoking cigarettes. So if there are factors, some of which you can control, some of which you can treat — if I have a woman who has a low AMH, I'm not going to sit here and say, "Okay, well, you can still get pregnant, no worries." I'm going to say I don't know that you'll have infertility, but some of the reasons your AMH is low can cause infertility. You will get fewer eggs if we're freezing your eggs or doing IVF. You will go into menopause earlier. So we need not wait.
To your point, the woman who's 20, 30, 40, thinking about this — she might make a very different decision when she knows she's really faced with a timeline that is less than ideal. And why should we allow time to be making that decision for us instead of at least playing an active role?
I sit across from women every day who find out they have a low AMH. I say, "Let's do the investigation to see if we can find out why." Probably 50% of the time we find an autoimmune disease. I can't reverse the clock, but I can slow down the rate of inflammation. If it's Hashimoto's, suddenly we can do thyroid replacement. We can work on decreasing inflammation. And if inflammation harms our ovary, maybe we can slow down that rate of egg loss. At least she's being treated, probably feeling better, and we'll have improved fertility outcomes because her Hashimoto's is treated.
We also might say, what should we do about this? I have a lot of couples who are partnered but just waiting for the right time to get pregnant — they're in medical training, law school, 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. There's no one right answer. We might choose to try to get pregnant now. If we don't have a partner, we might buy donor sperm and try to get pregnant. Maybe we freeze eggs. Maybe we freeze embryos. Maybe we do none of those things. But we made the active choice.
Sitting here saying, "I chose not to pursue treatment knowing my AMH was low, and that I might be in ovarian failure at the point when I was planning to have a family" — 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, I might have done something different."
That was the longest discussion to say: everybody should get an AMH. I think it's a very important marker. It's a newerish test — we've only been checking it for about the past 10 years. It's not a perfect test. I don't have the nomogram for exactly how it should drop over time. 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.
It is not a test of egg quality — again, we talked about what egg quality is: genetics and egg competency. But it is a check of how many eggs you have. And that knowledge can be really impactful for how you view your future and your plan.
I think we've also got to learn to track our cycle. 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, because tracking ovulation is going to allow us to know how long is your luteal phase and how long is your follicular phase. Ovulation disorders progress through a very predictable pattern.
The first stage of an ovulation disorder is a luteal phase defect — a shortening of your luteal phase. So you're ovulating, but the brain and ovary have a miscommunication and we don't make progesterone long enough to sustain the luteal phase. Less than 11 days is a short luteal phase, but you'll still have regular cycles. So if I sit across from somebody and I just say, "Are your cycles regular?" and they say yes and we carry on, I've missed the fact that they actually have a shortened luteal phase — and that warrants further investigation: prolactin, thyroid, AMH, PCOS, looking at different causes.
The second stage of ovulation disorder is a long follicular phase — it takes the ovary longer to actually respond to the FSH stimulus from the brain. And then from there, we'll progress into irregularity and true amenorrhea, or absence of periods. But those first stages, you might miss the little red flag warning sign that something's wrong inside your body because you're just tracking when you bleed and it's every 34 days, so you think it's normal. But if we were looking at when you actually ovulated, we have more data. So learning to track ovulation as opposed to just cycle tracking is one of the most important skills a woman can have for learning to listen to her own hormonal cues.
Andrew Huberman: Amazing. And I don't say that lightly — you just explained egg quality, the biology of the ovulation cycle, and how it links to the actionables. Some practical questions: some people will have insurance, some won't. What's the cost of an AMH test, let's assume insurance doesn't cover it and they have to go completely out of pocket?
Dr. Crawford: $79.
Andrew Huberman: $79.
Dr. Crawford: Yeah. We're withholding a $79 test. 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. Your insurance doesn't cover it — you can make the decision if $79 is worth it to you. But in the age of information, where that's an easy test to do, every lab runs it, and it's relatively inexpensive compared to freezing your eggs or IVF — multitudes. $79. We're throwing a fit over a $79 test.
Andrew Huberman: Wow. I thought you were going to say maybe in the high hundreds or thousands, which for some people is going to be prohibitively expensive. So get AMH checked.
IVF, Egg Freezing, and Ovarian Reserve Myths
Andrew Huberman: How many women out there know whether doing an egg harvest cycle decreases their ovarian reserve or not?
Dr. Crawford: The majority of patients that I sit across from will tell me they're afraid to freeze their eggs or do IVF because they don't want to go into menopause earlier. The myth that doing that is going to tap into the vault and pull out eggs is inaccurate and a fear that really does need to be busted, because it doesn't. It's a limitation of the science that I can only get the eggs outside the vault to grow. If I could tap into the vault, it would change the game. But right now, I am limited by the eggs you give me — the number of them controlled by whatever's outside the vault.
In IVF, we just give FSH — the same hormone your brain makes — trying to stimulate more than one egg to grow. Your body doesn't want to have five kids or 12 kids or 20 kids, so it has checks and balances to prevent that from happening. I, however, would like every egg outside the vault to grow, because in nature, you will ovulate one and everything else will die. You are constantly losing eggs no matter what — when you're pregnant, when you're breastfeeding, when you're on birth control, before you start your first period. Constantly losing them. I cannot change that right now. So doing IVF or egg freezing is not going to decrease your ovarian reserve. It is simply going to influence one month in time, trying to not have all those eggs die.
Andrew Huberman: The myth is that by doing a cycle of egg freezing, you're taking more eggs from your reserve. But as you pointed out, women are losing the same number of eggs each month regardless. You're maximizing on that process by maturing more and taking them as opposed to letting them die.
Dr. Crawford: Exactly. We are not running out of eggs early. Nobody understands basic biology, so we think we're just losing that one egg since we're ovulating. We're not thinking about all of the ones that were sent out of the vault who weren't chosen.
So you're giving — if you think about it — the possibility for you to have children in your family that likely you would not have, right? Because if you were to get pregnant naturally that month, the greatest probability is it would just be one that you would ovulate. 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 of children for you from this one exact cohort.
IVF's not that old — it's only been around about 46 years. In the early IVF days, we didn't have gonadotropins. We didn't have FSH that was synthetic or purified, so we couldn't get multiple eggs to grow. 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 estradiol was rising and when they were getting closer to ovulation. In those days, they went and did abdominal surgery to aspirate the egg. Now we do a vaginal egg retrieval where we take a needle attached to a vaginal ultrasound — just a minimally invasive procedure. But back in the origin IVF studies, they had to 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.
But the advent of gonadotropins — the ability to purify FSH and LH and give that to people to stimulate more than one egg — and understanding this concept that there are so many more eggs outside the vault every month, that has changed the game. It's such an amazing advancement in science that we can leverage that physiology for egg freezing or IVF.
Access to Egg Freezing and Insurance Coverage
Andrew Huberman: It's clear that the younger a woman is, the more eggs that could be frozen in a given cycle. But many people, either because of finances or life circumstances, are waiting. What stands between us now in the United States and egg freezing being covered by insurance 100%? Is that a good idea? What would that require?
Dr. Crawford: I am a fan of knowledge and options, and egg freezing is not a guarantee. I pose it to patients as: we are going to keep the door of opportunity open longer for you — that is our goal. Some people will falsely sit across from me and say, "Oh, egg freezing is an insurance policy for my fertility," and it's not, because an insurance policy always pays off. But it's an investment in my fertility — like investing in the stock market. It probably will pay off, but it depends on external factors that we don't have yet. The ROI is yet to be determined, but in general it's considered to be a good thing.
I think it would be absolutely incredible to be in a place where egg freezing could be covered. There are definitely countries where it is — they've said the birth rate is dropping, we want to keep the reproductive lifespan open for some patients, we want to offer this. To be honest and transparent, the number one restriction against that that we see as a field right now is the camp of people who are ethically or morally opposed to IVF for reasons of embryo disposition.
Andrew Huberman: Like the personhood of an embryo. Is an embryo a person?
Dr. Crawford: Yes. Because embryos that are not used are going to be either kept frozen or discarded. And to those people, that's seen as essentially killing a baby.
Andrew Huberman: That's their view.
Dr. Crawford: Yeah. And we should acknowledge that I have many patients right now who are donating embryos when they are done with their family, which is an amazing way to pass forward the opportunity for other couples to have a family. I also just want to say that IVF is incredible — 17 million babies have been born in this world because of IVF. 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 are 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. 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 that's really pushing something called restorative reproductive medicine, and they're opposing a lot of the American Society for Reproductive Medicine's attempt to get fertility treatment and fertility preservation covered. Their rationale — even though a lot of restorative reproductive medicine 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 — but bullet point 10 on their list is that IVF is unethical. These people are ostensibly pro-child. So that doesn't square with me.
Andrew Huberman: I try to go issue by issue, and I realize that's itself a controversial statement. But I think that as a biologist, I look at certain things and I go, "All right," and I look at other things and I go, "What stone age are we living in?" The whole notion of freezing eggs and creating embryos seems very pro-child to me. So it doesn't square with number 10 on this list.
Dr. Crawford: I agree with you. And I think a lot of the people who are fans of restorative reproductive medicine might actually agree with you and me, but there are definitely people who are very adamantly opposed to IVF who put number 10 in there because they have a different agenda.
I'm a fertility doctor. I want as many people to have a family as they desire. I want to do everything I can to help you have that. I am not here to sell IVF or force IVF. At the end of the day, it impacts me zero what you individually choose to do. But I believe that across the board, people deserve the tools in the toolbox. They deserve to be presented with all the choices — we could try Clomid, we could try IUI, we could try surgery, we could try IVF. Oh, you're getting older — we could freeze your eggs. They're just more tools, more opportunities. And based on your circumstance, your financial situation, your beliefs, you should be allowed to choose.
I feel very adamantly that one's own beliefs should not be the beliefs that we enforce on everybody — especially when we know that IVF can be so powerful to help so many people have a family. It should be something that is offered to you if indicated, and you get the choice.
Back to the origin: it would be incredible to live in a world or a country where egg freezing was offered to women, as we do see people are waiting longer to start their families. It would allow more people to feel less pressure — less pressure with a partnership and on their relationship, not to feel like, "This better work out because my clock is ticking." And be able to really feel like they could chase one dream not at the expense of another.
I think we're further in this country than we want to admit from that. We can't even get fertility treatments covered for patients with cancer when we know that chemotherapy is going to deplete their ovarian reserve. We have some states where we can't even get egg freezing covered for them.
Andrew Huberman: So this is state by state.
Dr. Crawford: This is state by state right now. We would love federal protection for everybody. To me, that's my litmus — what your state or your country would do for patients who have cancer who are in this position. And if we're not even willing to move to help them, the idea that we could cover it for everybody — we're still ages away from that, I think.
Andrew Huberman: Because none of what we're talking about is forcing anyone to do anything. Nor is it necessarily the destruction of an embryo. There is a world where the embryos are created and kept frozen.
Dr. Crawford: They call that embryo banking. To specify for somebody who doesn't understand: egg freezing is getting those eggs outside the vault to grow, taking them out of your body, and freezing them right there at the egg state. Making an embryo is going to be thawing that egg, fertilizing it with sperm, letting it grow out to the implantation stage, which is day five or six. Not every egg will survive, fertilize, or grow — there's a ton of attrition in culture. 90% of eggs survive the freeze-thaw, 75% will fertilize, 50% will make it to the implantation stage, and then not everyone will be genetically normal based on your age and other factors. And then even a genetically normal embryo only has a 65% chance of live birth. The science has come far, but we're not all the way there.
With that being said, some patients do morally really feel like an embryo could be a potential life, and they do struggle with what to do if they have leftover embryos. I have some patients who've told me every embryo we make, we're going to transfer. Well, we want to be really mindful of what we do in that circumstance. I have a patient right now with four children and one embryo in the freezer, because we froze five knowing that everyone shouldn't implant based on that 65% number — but we've gone four for four.
So we have to know that if that's what we're doing, we're prepared for how the data may fall. Data just helps us guide decisions, especially when it comes to live birth — it's zero or 100. It happens or it doesn't.
Now, if I freeze them as eggs, for some patients who have really strong beliefs and are afraid of that number five, we might take more time or more money, but we might say, "Let's thaw them and only fertilize two. Let's leave everything else frozen, and then whatever makes it to embryo we can transfer." Yes, that's not a cost-effective way to go through the process, because we might be having to pay for thawing and the fertilization and the transfer more times because there may be nothing to transfer based on that attrition. But it can let some patients say, "Okay, I feel better with that process."
So just freezing eggs is not making embryos. There are different things we can choose along the way to make an individual person feel comfortable, but we shouldn't be dictating how the field has to function. I think it would be incredible if we could encourage egg freezing earlier. It would open the door of opportunity, and not everybody who freezes eggs will need them — but the peace of mind knowing that there's a chance is really impactful on the human mind.
Andrew Huberman: In the Bay Area, where there are a lot of tech companies, my understanding is there's an opportunity at many of these companies for female employees to freeze their eggs. That landed much more controversially than I thought it would.
Dr. Crawford: Isn't it crazy? Because the tacit message to some people was: don't have kids now, work like crazy, and then have them later.
Andrew Huberman: But having known some people who worked there and froze their eggs in their late 20s or early 30s, the ones I know would say, "Yeah, I'm really grateful that I did that and that the company I worked for paid for it." So there's that. Anyway, we're getting kind of sociological here, but I think it's important.
Dr. Crawford: 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. They feel more comfortable exploring bigger opportunities and they are grateful to the company. They stay with the company longer because that is an investment in your employees.
In Austin, a lot of these tech companies have second homes, so we see a lot of these patients also. And I do think that has changed the game for so many people to be able to have access, because for many it's not ethical or moral — it's financial. 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 impactful. I wish more companies would do that.
Birth Control and Its Effects on Fertility
Andrew Huberman: You mentioned that birth control can reduce AMH levels on a month-to-month basis. Is there any evidence that taking hormonal birth control can lower chances of pregnancy when somebody comes off birth control? I know a number of people who were on birth control, came off birth control, and got pregnant right away. But are there any good examples of how certain forms of birth control can actually suppress fertility in women long after they come off?
Dr. Crawford: Excellent question. Let's break the data down from big to little. Number one: big studies looking at all different types of contraception show no higher rate of infertility — again, defined as failure to get pregnant at 12 months. So you come off your contraception, and at 12 months later when we look, there's no higher rate of infertility than we would have on the population-based level. That data leads us to comfortably say birth control is not causing infertility.
Now if we go and look more nuanced at different types of contraception — the birth control pill is a combination of synthetic estrogen, ethinyl estradiol, and a type of progesterone or progestogen. These work by telling the brain, essentially tricking it, so the brain doesn't send out FSH or LH. As we described earlier, those are important in getting you to ovulate. So you don't ovulate when you're taking the birth control pill, and that's why it's a very effective contraceptive choice. However, the half-life of the birth control pill is only 28 hours. It's actually quite short. So you can miss even just one pill and you could ovulate. When you stop the birth control pill, your period should come back that next month — immediately you should have resumption of ovulation.
A couple of problems with this: the birth control pill has some valid medical uses, but very often — especially in the generation of women we see right now — they were given the pill potentially for a valid medical reason without any investigation of what it was. So maybe a woman had irregular cycles or some acne and her doctor said, "Well, here, take the birth control pill. It will help." And it did help. But just based on that history, I would sit here and say, "I bet she has PCOS." The woman though was never 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 are lifestyle things we can do to decrease insulin resistance." She never had that discussion. So in her mind, she had some symptoms, started the pill, those symptoms resolved. Now she stops the pill and she's not getting pregnant and she has irregular cycles, and she starts 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, with the idea, "I'm going to stop the pill and get pregnant right away."
What I like to say is: you're not ovulating on the pill. If ovulation and knowing when you ovulate is one of your most sensitive health markers and really essential information in trying to get pregnant — the egg only lives for 24 hours. The fertile window is the five days before and the day of ovulation. Sperm can live in the reproductive tract for up to five days, most will stay around for two days. That's why the two days before and the day of ovulation have a 20 to 30% chance of getting pregnant, compared to zero the day after ovulation. It's a very defined fertile window. So if you know when you're ovulating and you target intercourse, you're going to have 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 I recommend that you stop the pill three to six months before you're really wanting to start your family, so you can track your cycle, learn to detect ovulation. And if you do have an abnormality, you're not now six months of trying or one year of trying before it's evaluated. You can say, "Oh, I can't detect ovulation, or my cycles are irregular. Let me go get that investigated now." So we're not behind in our own timeline.
The progesterone IUD is another one that we talk about a lot. The progesterone IUD is local progesterone placed inside the uterus. There are 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. That can be great if you don't like having a period — it 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 for at least six months after it's been removed. It can take time to build that lining back up. So I always recommend that a progesterone IUD is removed at least six months before you want to get pregnant. Give the endometrium time to rebuild and regrow, and then you'll have better odds of conceiving. We do see a little bit of lower pregnancy rates in those first six months after coming off the IUD, with more of them getting pregnant in the back six months. So kind of shift your own timeline.
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. This is a high-dose intramuscular progesterone shot that can prevent ovulation for three months on population-based levels. But one single dose can prevent ovulation for 18 months. So this is that one exception where if you want to get pregnant potentially in the next two years, please don't get Depo-Provera.
Andrew Huberman: Great. Incredibly thorough and clear. Is there any evidence one way or the other that intentional termination of a pregnancy can disrupt chances of getting pregnant again later?
Dr. 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. That could be having an IUD, 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 and are 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. She went through IVF and had a baby that had no brain development. They made the decision that they wanted to terminate that pregnancy since it'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 cancelled, so they had to make another one in a different state. It took them much longer than they wanted. They had the procedure much later. And then she had residual scar tissue inside her uterus — because it was done at a later term — that we then had to fix before she could get pregnant again.
So I think it's just important to say that across the board, any intrauterine procedure poses a little bit of a risk. No matter what it is, if your periods are different afterward, the hallmark sign is going to be a lighter cycle. So no matter what thing on that list you had done, if your cycle is now lighter afterward, I am worried there could be scarring inside the uterus. 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.
Lifestyle, Inflammation, and the Five Non-Negotiables
Andrew Huberman: Some practical questions about metabolic health, mitochondrial health, and egg quality. When you think about the things that can really help support egg quality aside from age — at any age — what are the top contours of those? You mentioned inflammation is the enemy, but inflammation happens all the time and we can't avoid it. What are the things that people can do, not do, and take?
Dr. Crawford: 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. 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 — we need our acute inflammatory response to allow that to happen. To the degree that if women take NSAIDs around the time of ovulation — Advil, ibuprofen, Aleve — they'll prevent the follicle from rupturing.
Andrew Huberman: Really?
Dr. Crawford: Yes. So they will go through the hormonal changes of ovulation, but the egg will not be released. That's why we recommend — and this is an important thing to know if you're trying to get pregnant — you can take those medications only when you're on your period. Period cramping, fine. But we don't want you taking them for the rest of the cycle because you can prevent ovulation from occurring.
Andrew Huberman: How many people in your experience do you think know that?
Dr. Crawford: I don't think very many, honestly.
Andrew Huberman: Which is why it seems like it should be banner across the sky — like the fact that you're not going to lose eggs by doing a collecting cycle. Basic facts about our biology that we were never taught. So if somebody's trying to get pregnant, NSAIDs can be problematic.
Dr. Crawford: They can prevent the egg from being released with ovulation. I will sometimes have patients say, "Well, if inflammation is bad, can I just take medicine for it?" That brain might make sense. But I always want to say your immune system is essential for ovulation and also for implantation. I don't want to turn off your immune system. What I want to do is not have it be so burdened with what we call chronic inflammation — that constant activation — that it can't even do the job that we need it to do.
So I like to think about this as that inflammatory burden. We're all exposed to some, but how do we make it better? How do we add to it and make it worse? And really framing ourselves so that we can cultivate resilience within your body. You're going to be exposed to inflammation. Life is going to throw things at you. But you want to cultivate these best practices so that you are reducing inflammation to the degree that you can.
I usually divide it into what I call my five non-negotiables: sleep, stress, muscle, food, and toxins. Thinking about how we leverage these to our benefit — by giving people the knowledge that if they understand their bodies, they can be empowered to make choices that are in line with their goals.
I really also just want to say: I hate the narrative that there's nothing you can do for your fertility, or that it's all luck. The truth is, even if we can't control everything, we have a huge amount of control over our metabolic and cellular health, which plays a huge role in our ability to get pregnant for both men and women. 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 have made a different decision." Why do we make people go through a failed IVF cycle, 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 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 the 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.
Sleep and Circadian Rhythm
Dr. Crawford: Number one for me is sleep. When you sleep, this is when your body is going to get rid of some excess chronic inflammation — it lowers our inflammatory markers. When we get less sleep, it causes us to have more cellular stress, more oxidative stress. Your gonadotropins — FSH and LH — are released from the brain in the early morning hours. So when you don't sleep long enough, you're not going to have the same hormonal response.
We know really directly: men who get less sleep have lower testosterone levels and lower sperm counts. Women who get less sleep get fewer eggs at an IVF cycle. And we see that if you say you have poor sleep, you have double the rate of infertility — just subjectively saying, "Yeah, I have poor sleep." You have double the rate. And people who are not sleeping well, either partner, will take longer to get pregnant. They have lower fecundability — that month-to-month pregnancy rate.
It's not just me sitting over here saying, "Oh yeah, you need to sleep better." Your physiology is meant to sleep. It is a sign to your brain. If we go back and 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 — 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 — dark room, sound machine, a sleep mask, a cooler temperature. It 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 the same time. You need to have similar sleep practices. And we know that day-to-day consistency is also impactful in fertility. 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. Doses of one to three milligrams 30 minutes before you go to bed can improve your odds of getting pregnant as well and can influence egg quality. We know that naturally you make more melatonin when you ovulate to kind of counter some of the oxidative stress to the ovary. You really have to be careful though — a lot of over-the-counter products have like 10 times the amount of melatonin. I always want to tread lightly with that one and recommending it to patients. Often a pediatric dose is like one milligram, and that's the perfect amount just to augment. Again, we're not trying to replace your body's melatonin — we want to augment it and kind of help your body.
Andrew Huberman: I don't want to disrupt your flow, but if a woman is already sleeping well, should she take melatonin?
Dr. Crawford: I would say for the average person, probably don't need to. The exception to the rule would be 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 we've ever been told we have quote "bad egg quality" — then the anti-inflammatory properties of it might be advantageous.
NSAIDs, Cold Plunges, and Anti-Inflammatory Cautions
Andrew Huberman: Since NSAIDs can disrupt the inflammation requirement for ovulation, I'm curious about other things that are known to potently reduce inflammation. Cold plunges — we know that one shouldn't do them after resistance training or any kind of exercise where you want the inflammation to get the adaptation. We know that, and it's a pretty potent inhibitor of inflammation. So is there any reason to think that in the time where somebody's trying to conceive, perhaps they should avoid the cold plunge?
Dr. Crawford: I usually recommend against them for reasons stated here. I think there are very few things we have that are going to really turn off that acute inflammatory response to the degree that NSAIDs do, but we should proceed with caution in doing those things. Most everything else is trying to just get rid of the excess inflammation we have. But if something is dampening down into that acute inflammatory response, then I think we have to be a lot more judicious. So I'm not a fan of cold plunges when trying to get pregnant.
Andrew Huberman: I hate a cold plunge. I tried it one time. That was one time too many.
Dr. Crawford: I always say if you like it, great. If you think you benefit, great. But otherwise, don't worry about it.
Andrew Huberman: One thing that's commonly used is curcumin, and it's a pretty potent anti-inflammatory. Do you recommend people stay away from — not cooking with curcumin, but the high-dose curcumin that comes in a lot of supplements?
Dr. Crawford: Yeah, I don't usually recommend it in supplement form. I never recommend it. I think if you have a doctor who's giving it for a very specific purpose, you might be a unique person who has excess inflammation they're trying to target. But that's not something that I recommend. Cooking with it is fine.
Andrew Huberman: NAD and NR — I get asked about them thousands of times per week. I'm more or less a fan of NR or NMN if one is trying to increase energy. NR in particular, there are data that it can be very anti-inflammatory. So if a woman is trying to conceive, should she stay away from NMN, NAD, and NR? Because I often see it listed in infertility protocols.
Dr. Crawford: Animal data looks like NAD and NMN can be advantageous, especially for unexplained infertility — which to be clear is different than just wanting to get pregnant. In unexplained infertility, you're not conceiving, you do the basic tests — anatomy, ovulation, ovarian reserve, semen analysis — and they're all fine. So I view that as chronic inflammation unless proven otherwise. That's a unique situation where 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. There might be utility in certain subgroups who are really falling off the curve and we think there's excess inflammation. I don't ever say no, and I sometimes use it. But on the flip hand, we could say CoQ10, which has robust human data that is advantageous without a negative benefit. That's an easier place to leverage your supplement dollars if you're going to spend, because most of us don't want to spend endless amounts on all the things we can craft for our supplement list. The human data is yet to be out, although animal data looks promising for the right patients.
Andrew Huberman: I'm glad you mentioned coenzyme Q10. CoQ10 and L-carnitine are the two I'm aware of with some decent data on supporting sperm and egg quality. Do you encourage patients to start taking that 60 days before trying to conceive and then continuing through pregnancy?
Dr. Crawford: We usually stop CoQ10 in pregnancy just because of lack of data. We're very cautious in pregnancy about not exposing you to anything additional you may not need. But I think it's in my "everybody should take before you get pregnant" list. In your trimester zero — hey, we want to get pregnant soon — we should take a prenatal vitamin that has folic acid, we should take CoQ10, we should take omega-3 fatty acids, we should take vitamin D. These are all going to optimize and give you the nutrients you need for a pregnancy, helping support good mitochondrial health, which is important for egg quality, without risk of harm. Those are the universal "we're trying" supplements.
And then for sperm health, L-carnitine we like a lot. And then zinc and selenium can have benefits as well.
Supplements, Red Light Therapy, and Emerging Research
Andrew Huberman: How much conversation is there at the various meetings and in the journals about things like coenzyme Q10 and L-carnitine? Is there a consensus or is there sort of a distribution of old school versus new school?
Dr. Crawford: Over the past 10 years, we've seen a huge change in how we talk about fertility even at meetings. The first ASRM — the American Society for Reproductive Medicine — meeting that I went to was probably 15 or 16 years ago, and it was so IVF-heavy. Now, to be fair, the science was rapidly evolving — genetic testing was just introduced for embryos. But as we also see more patients and the general public really curious about what they can do, that public curiosity drives research to a degree, because if you're hearing it from your patients, that's the formation of research questions.
When we do randomized control trials in the IVF subset, because we can look at more distinct criteria — how many eggs were mature, how many embryos formed, how many were genetically normal, the pregnancy rate per embryo transfer — we definitely see robust data that certain supplementation, CoQ10, vitamin D, omega-3 fatty acids, are clearly associated with improved reproductive outcomes. And we're starting to see more interest in the nuance — inositol for PCOS decreasing insulin resistance, N-acetylcysteine for endometriosis or chronic inflammatory disease.
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. At the end of the day, my job is not to say just do IVF. My job is to explain what's going on, what the options are, and help you make that decision. 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 — say, "What about CoQ10?" or any merit of the other lifestyle factors.
The plethora of research that exists — which is more and more now — is that these lifestyle factors matter a lot. That decreasing inflammation can influence your fertility from how your hormones function, how your ovaries respond, how many eggs you pull out, how many embryos you form. And supplementation is one piece of the puzzle. It's not the end-all be-all. We should probably always focus first on where we can move the needle the biggest — those more core lifestyle practices should be tenant 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.
One thing that I really encourage is allowing ourselves space in each patient to be their own n-of-one experiment — 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. Learning to trust that instinct about what's working for you is really important when it comes to optimizing your own health.
Andrew Huberman: If we'd been sitting here 15 years ago and I said red light therapy can be useful for skin and for offsetting age-related vision loss, any reasonable physician would have said that's nonsense. I spoke to an ophthalmologist recently — there's been a clinical trial using red light and infrared light for dry AMD, dry macular degeneration, to offset age-related vision loss. This looks promising. It doesn't reverse age-related vision loss completely, but it seems to help the mitochondria and the photoreceptors. There was a cover of what I'm told is the premier dermatology journal exploring the recent studies on red light and infrared light. So it's a common practice now. In the field that you're in, how are things like red light and infrared light therapy looked at currently?
Dr. Crawford: 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. If you have chronic inflammation, it's going to interfere with hypothalamic receptivity — 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 egg quality. So the bigger answer of what type of therapy matters maybe depends on the outcome that we're looking at.
In short, data is inconclusive but all appears to be beneficial. Whether it is to improve ovulation patterns — which we've seen signs showing is more the systemic effect, sitting in front of your red light panel, that's going to decrease some whole-body inflammation, which is the inflammation 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 through the abdomen. And there is now — we don't have definitive data — but there's even a vaginal ultrasound wand that's got red light therapy. Seeing intravaginally, you're much closer to the ovaries. This is 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 potentially benefit egg quality more. I think most people are going to say we don't have definitive data yet, yet everything's pointing to likely benefit.
Andrew Huberman: I don't know if this study could be done, but one thing I'd love to see the experiment done is either maintaining or doing fertilization of eggs under red light, because so much of the proper chromosomal arrangement seems to be dependent on mitochondrial health. The more I learn about the different wavelengths of light and how they impact mitochondria, and I think about the horrible lab lighting that I lived under for many years of my life, I think — these such precious embryos, is there a way to put them under beneficial lighting as opposed to neutral or potentially detrimental lighting? It would be a fun study to fund if there's a way to do it. Could it be done?
Dr. Crawford: I think it definitely could be done. We have incubators. That could definitely be done. And where you fertilize, too. Off topic — my daughter did her science fair project on chicken eggs. They looked at blue light, green light, and natural light to see if their hatchability was different. And the group that was exposed to blue light actually had the highest hatchability, and UV light was actually the lowest. But in their research, what's so fascinating is that red light is really detrimental to chicken eggs. So I think — well, that's why science is fun.
Andrew Huberman: Oh, congratulations to her. She should write it up. She'll be published. And that's what's so cool about science — sometimes we think the red light is going to be the beneficial one, the blue light is going to be the bad one. But then vitamin D production is dependent on blue and UV. Nature's mysterious.
Dr. Crawford: It keeps it interesting for us.
Andrew Huberman: Is she going to become a scientist?
Dr. Crawford: She's 11, but she's a scientist right now.
Andrew Huberman: I love it. Red light and infrared comes from sunlight, and of course there are circadian benefits of getting sunlight.
Dr. Crawford: All circadian benefits of getting sunlight are pro-fertility, pro-hormonal health. Yes.
Andrew Huberman: I don't want to give people the impression that they have to purchase a panel. There's no hidden agenda here.
Cannabis, Nicotine, and Behavioral Toxins
Andrew Huberman: The do-nots — I think broadly: don't smoke, don't drink. I was shocked to learn that 15% of women in the United States report having used cannabis in some form or another while pregnant. Does that concern you?
Dr. Crawford: Cannabis use is probably the most concerning thing that I see in clinical practice. If that many are using it in pregnancy, let's extrapolate to how many are using it beforehand. And ultimately, something that we are just now getting robust data on because it's hard to study something when it's illegal.
All cannabis use is hugely detrimental to sperm for sure across the board — both production, the quantity of sperm, testosterone production, and 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 ten times he is using cannabis that he previously denied.
So it is one of the most movable factors right now in this country for improving fertility outcomes for women. Cannabis use in the prior year can decrease the eggs you get at egg retrieval by 25% and can decrease fertilization rates by 28%, and can increase miscarriage rates, therefore decreasing live birth rates. So huge numbers in science — we get excited when something's a few percentage points different, but these numbers are really high. To the degree that it's really easy to sit here and say: if you're trying to get pregnant the fastest, if you want to have the best pregnancy outcomes, or even if you want to have the best hormones, longevity of your ovaries, or the best sperm counts or the most testosterone, cannabis use should not be a part of that.
And THC crosses the placenta directly. THC levels in edibles are usually the highest. So I think it's really important that sometimes people say, "Oh, 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 is meant to function.
Andrew Huberman: Critical message. Thank you so much. I've been put through the ringer around this cannabis thing because I've hosted people that said it does increase the risk of psychosis in certain typically young males. I've been accused of all sorts of things related to that, then had someone on who confirmed that, someone who refuted it. Cannabis has recently been rescheduled at the federal level from Schedule 1 — which assigned it no medical application — to Schedule 3. So there's going to be a lot more cannabis use going forward. It's so critical that people hear this. The argument I always hear — and it's always dudes, typically on X — is that they smoked a lot of weed and they got their wife or girlfriend pregnant x number of times, and it sort of becomes this point of boasting. And I'll make the comment now: yeah, but you're talking about brain development in your kid. They could be a lot healthier. So I think to me, it just seems like anything that one could do — since it's ostensibly a short-term decision, certainly for the man — the outcome is so important.
Dr. Crawford: The outcome is so important. And when we want to think about even just male cannabis use — yes, sperm count decreases, sperm quality decreases. That sperm quality is important for programming of the embryo, for how the placenta develops. If the placenta is not as good, there's an association with earlier birth. It's just not worth the risk when the outcome is so important. We're all weighing risk every day with different decisions. To me, there are a lot harder decisions you have to make. But nicotine use, cannabis use, alcohol use — the data here shows none of that is advantageous for your health, especially if we're looking primarily through a fertility lens, a hormone lens, or specifically a pregnancy lens. There's no place for it. You can choose to do what you want with that data. And people will always say, "I know someone 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 is even stronger if you are having infertility, if you are older, depending on your scenario — because you want to control what you can, because you can't control everything.
Andrew Huberman: For whatever reason, nicotine has become kind of a right-wing associated thing. I recently spoke to about 4,000 young men and women, and I would say about 30 to 40% of them raised their hand that they're using oral nicotine every single day — anywhere from probably 12 to 70 milligrams of nicotine a day. So for women in particular, is oral nicotine use detrimental to either egg quality or probability of successful pregnancy?
Dr. Crawford: It's definitely correlated because of how it works in the brain — ovulation, getting pregnant, hormone response. So it should not be something that we're adding to our day-to-day life in any form if we're trying to get pregnant. Most of the egg quality data from nicotine comes from cigarette smoking. I think it's a little bit more nuanced because smoking directly — I always say it's one of the few things that gets into the vault and decreases our egg count. Nicotine, cigarette smoking definitely does. You go into menopause early, you'll get fewer eggs, the egg quality is detrimental. It makes sense based on what nicotine does to your body and how it changes your cellular response that it probably is impacting your egg quality. Also, even with these oral nicotine pouches that we're seeing everybody utilize — it's tanking sperm counts. That one's really clear.
Andrew Huberman: And then of course everyone's talking about the reduction in population growth. When I was growing up, we were told the Earth is going to be overcrowded. Now we're told there's not going to be enough people. I don't think either extreme is true. But these are vitally important things for people to think about because these are easy decisions to make and they can be short-term decisions.
Dr. Crawford: They are. You know, we make decisions every day and you don't have to be perfect and you don't have to be all or nothing and it doesn't have to be forever. A lot of these things, once you really start making a bunch of them and decreasing inflammation, you will tangibly feel better. Humans by nature adjust to the environment we put our body into. So even things like sleep — chronic stress is directly associated with insulin resistance. Building skeletal muscle is one of the top ways you can reverse insulin resistance. It's the best mechanism for hormonal health we have — to build more skeletal muscle. These things can impact your fertility and your health long term. And so once we start to make these little decisions — eating more fiber, anti-inflammatory foods, cutting down the ultra-processed foods, removing the toxins, changing the toxic behaviors, sleeping more, really trying to manage stress in a more productive way — together, when your inflammatory burden lowers, people feel better. And then they get it. Then they say, "Oh, like this running on just caffeine and eating whatever food I could on the go and not getting enough sleep and then using nicotine — 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?" 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.
Clinical Intuition and Emerging Treatments
Andrew Huberman: In your experience — your clinical and scientific experience — is there something that you've heard from your patients and then observed in terms of outcomes that is intriguing to you, that you would like to see more science on?
Dr. Crawford: I love that question. One thing I want most people to take away is that you can make tangible improvement in your fertility by looking at these lifestyle factors and coming up with a plan to try to decrease your inflammatory burden. You can have a different outcome. And I think that conversation is even more important if you're waiting longer to get pregnant, or if you're at an older age, or you have lower ovarian reserve — because knowing that you are controlling all these variables to put the best egg and sperm forward is really important.
The most intriguing part of the conversation for me right now is GLP-1s and their use for potential chronic inflammatory disease like endometriosis. As a field, we quickly accepted that they are hugely powerful for PCOS and states of obvious insulin resistance, for reasons that make sense to everybody. They also help 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 — 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 agonists can be a very powerful tool.
Where I see it right now are patients who have known endometriosis or what I call probable endo. They have unexplained infertility — 50% of those patients will end up having endometriosis. One of the problems with endo is that the 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 at low dose for three months. We have to stop them and then go through a cycle. We will see more embryos in the lab. We don't have a study to say that, but talking to colleagues across the country, we know that GLP-1s can be very anti-inflammatory and can kind of target what appears to be that inflammatory burden. And I think there will be utility there within the context of these chronic inflammatory diseases that might be able to help a patient population that we've struggled with — with difficulty getting to a diagnosis or limited data points on what to do with it. So the data is not out yet, but it is a tool I add to the box, especially if we're not getting outcomes we would expect and we don't have another reason why.
Andrew Huberman: Do you think there could be direct effects of the GLP-1s on reducing inflammation that are independent of less adipose tissue?
Dr. Crawford: I do, because some of these patients do not have much adipose tissue. So I think obviously that person's going to get even more benefit if they have adipose tissue to lose that's causing inflammation. But I think especially if we think about autoimmune disease — where people's immune system, their inflammatory response, is mistrigger — I think there's benefit for the GLP-1s in that population specifically that is giving them an added benefit to decrease inflammation in a really profound way.
Andrew Huberman: It's really interesting because I would have thought GLP-1s reducing body fat for a woman who isn't carrying excess body fat might actually be detrimental to getting pregnant.
Dr. Crawford: It's a fair point that we have to be really careful when it comes to skinny culture. We are seeing societal norms shift again to be very thin after being more body positive. We definitely know that at both extremes of body weight, the hypothalamus is your checkpoint. If you don't have enough body fat, we are worried that you cannot maintain a pregnancy. So it can stop how it's sending off hormones. And again, we can see a luteal phase defect as that first warning sign before you're in true hypothalamic amenorrhea. So they have to be really careful in that patient group, and it has to be done with the right person who has a lot of experience with GLP-1s. There are super low doses. The goal is not weight loss — it's really a different goal. And again, I don't have a paper to prove it, but we are seeing that clinical experience to say there's merit in trying to decrease inflammation, especially in people who we suspect it is contributing to the circumstance they are in.
Andrew Huberman: And you said low-dose GLP. Are these available in generic form now, or are they still under patent?
Dr. Crawford: I don't know the answer to that one. I know compounding pharmacies are making them. I know today the gray market for peptides in this country was shut down — you can no longer buy that just for research purposes. But compounding pharmacies seem to be protected. The GLPs at least in their full dosage — my understanding is that they can be rather expensive. But the lower dosages from compounding pharmacies perhaps are more affordable, one would think.
Dr. Crawford: And I think these add-ons — there's a lot of kitchen-sink approach we do in fertility medicine. I've used human growth hormone for years and years, right? There's not an FDA approval to use HGH for egg quality. Yet we see that it can improve egg quality in the right patient in the lab. So if somebody has a cycle and they don't get as many mature eggs or their embryos don't do as well, my partner actually did a study where she put them through the same protocol in a subsequent cycle and the only change was adding human growth hormone — and had improved embryo development and maturity effects.
Andrew Huberman: So this is like an IU a night or something like that — some low dose of HGH during the stim?
Dr. Crawford: Yeah. Just during the stim. So it's like two weeks of use. And so then that's starting to be extrapolated and people are starting to look at it longer or before stim. I love the fact that my field has always viewed cutting-edge research. It's a double-edged sword — there's some good and there's some bad — but we really want to think about mechanistically if it could potentially help. Having a low threshold to attempt it in patients who are getting at the end of their journey specifically — when they've done all the basics, they're controlling the lifestyle factors.
One thing I dislike is this "just do IVF" mentality — meaning nothing you can do can impact your egg quality, let's just do IVF. And then we're compounding dollars and dollars and dollars, yet we're not eating anti-inflammatory food and we're drinking wine every night and we're not getting enough sleep. So I think we've got to really look at these five non-negotiable areas and optimize them to the degree we can, knowing each day will be different, but building our body the resilience to be able to respond as it's appropriate to. Because sometimes you'll fly to Texas and get less sleep, or you'll go out to eat and eat differently. And your body's meant to handle those challenges, but it can't when it's constantly challenged every single day, all the moments of the day.
There's a ton of experimental stuff that we do that's really cool, and some of it will be introduced into practice in 10 years. Probably 15 years ago if I had said human growth hormone, people would have scoffed, and now it's commonly added on when we're not getting the outcome we want. And that's how medicine should be. We should not be afraid to say that the perfect study doesn't have to exist. If the physiology makes sense, if there are suggestive studies, if we explain it to the patients, we help have shared decision-making with them — because if we're always waiting for the perfect RCT, there will be thousands of patients we could have helped in the interim that we didn't.
PRP, Paternal Age, and Sperm Quality
Andrew Huberman: What are your thoughts on platelet-rich plasma?
Dr. Crawford: Such a good question. PRP has two potential different mechanisms by which it can be used, and it's different. 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. Small catheter, not invasive, just kind of goes through the cervix right into the uterus. The other is looking at ovarian PRP, which is a more invasive procedure. This is using the same needle like we do for IVF, yet instead of extracting the follicular fluid and the eggs, I'm putting the PRP into the ovaries.
We're looking at it for two different reasons: implantation failure or potential Asherman's scarring of the uterus in the uterine PRP group, and looking at it for low ovarian reserve or age-related fertility in the PRP of the ovary group.
Where it shows the most promise is intrauterine PRP, which is nice because it's less invasive. That's the minority of people who are having recurrent implantation failure. Most people don't have success because they don't make enough embryos — that's the rate-limiting step for most people with IVF. Meaning if you have three genetically normal embryos, almost 95% of people will have a live birth. So we're talking about a very small subset of the population here, but showing the most promise, though not universally accepted and not 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 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. It could potentially be something to consider if you're really approaching that endgame — you're really not getting the outcome you want, you are older, you have low ovarian reserve. There are people who have some success stories. So I think it's again the exception, not the rule — has potential benefit, but yet to be determined.
Andrew Huberman: A few years back there was more discussion about the age of the sperm and the probability of autism. Could you update me on the data?
Dr. Crawford: After age 50, we see a few different increases for sperm specifically. 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-based increased risk of autism, of autosomal dominant new mutations, specifically certain types of dwarfism or very specific diseases that are ultimately overall rare. And then you also can see an increase in some other mental health diseases like schizophrenia.
That data is scary, not the end-all be-all. At the end of the day, when you have an opportunity to bank sperm younger, it would make sense to utilize that preferentially. If somebody came to me and let's say they had banked sperm and it's gone now and I have a 52-year-old man across from me — this is who we want to have children with, then this is who we want to have children with. And we accept that risk because on a population level it's still very low. A small percentage point increase means still the most probable chance is you're going to have a very healthy baby.
It plays more into the idea that nobody's fertility is finite — that age-related impacts impact everybody. I would say the same thing is that if the mechanism is the DNA essentially, or the quality of the sperm, then those lifestyle tenants in the 90 days prior to getting sperm, or banking it, or using an IVF cycle, probably matter the most. I would want to be controlling all of those factors so I wasn't adding to risk.
Andrew Huberman: No cannabis, reduced heat, all the things that mutate DNA. Nicotine out, that kind of thing. Yeah, it's interesting. I think about the sort of high-signal-to-noise anecdotes — things like, "Oh, so and so smoked weed every day and has eight kids," or "so and so had another kid when he was like 78 or something." The problem with stories like that is that they grab people's attention because they're high signal to noise, and they distract from the stuff that really matters to most everybody. Like: freezing eggs is not going to take more eggs out of your reserve than you need. The NSAIDs thing — I'm still wide-eyed about that.
Dr. Crawford: Here, let's do another one. Biotin levels — taking 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 supplements like certain popular hair supplements have 10 to 30 times that amount in them — this is binding to the lab test. So we're getting false reads on these labs. It's not changing in your body, but it actually — this is an REI oral board question — it binds to the steroid assay. So this can happen to estradiol, to progesterone, to hCG, to TSH, to testosterone. So if you are back where we started and you want to get data about your body — maybe you feel off, or you're going through IVF, or you want to get a hormone panel done — if you're taking a supplement that has more than 300 micrograms of biotin, you're going to have results that are inaccurate and we cannot trust. So really making sure that you're looking at what's in your supplements, and biotin is that specific one that I want to make sure we're not taking excess amounts of.
Endocrine Disruptors and Everyday Toxin Exposure
Andrew Huberman: As long as we're talking about things that people take or put on their body — the last time we sat down and spoke, we had a conversation about endocrine disruptors.
Dr. Crawford: Oh man, people really loved and hated us for that.
Andrew Huberman: I think many many more — meaning millions of people — appreciated it as opposed to had issues with it. The issue around endocrine disruptors for the longest time was seen as kind of hippie science with no data. And then because the Environmental Working Group started getting really vocal about this, and Shanna Swan, who's a longtime researcher — 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. If you sit down with her, that's the furthest thing from the truth. She's all about data. So I'll just say it for you: none of what we're about to talk about negates anything about standard medicine. It's just ways and places to be additionally cautious about things that you are around.
Dr. Crawford: Decisions every day should be made from a place of knowledge. The things that you're exposed to more frequently matter the most. A one-time exposure because you used hand soap and it had lavender or tea tree oil — I'm much less concerned about that than the products you buy for your home that you're using every single day. Because when it comes to endocrine disruptors, a lot of it is the quantity of exposure that really adds up, and this typically comes from frequency because typically it's low levels in a variety of different products.
But they absolutely can disrupt hormone function. They cause longer time to pregnancy. There's now been robust data looking at one of the biggest cohort studies we have — called the EARTH study — where they're looking at different environmental compounds on reproductive health. They looked 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 they showed that those who had higher levels of endocrine-disrupting chemicals had a harder time getting pregnant even with IVF — their IVF markers showed fewer eggs retrieved, fewer embryos, poorer sperm counts. So it's definitely not hippie science at this point. It's well demonstrated that it impacts our bodies in multiple ways.
Andrew Huberman: And as I recall, the things to be cautious of are lavender, evening primrose, or basically anything with a scent.
Dr. 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. When it comes to other products, scented products have a lot of phthalates in them, and that's an endocrine-disrupting chemical. And an important note here — which is wild to me because we see so much greenwashing on products — they'll slap a label on it and say "unscented." But unscented is a scent to mask other scents.
Andrew Huberman: Really.
Dr. Crawford: So unscented just means you've masked a scent. What you really want to look for is "fragrance free," because fragrance free means we added no fragrance to it. To be called unscented, we could have added something to counter the fragrance that was in it.
Andrew Huberman: Amazing. And Uber drivers — I'm not saying riding in your Uber with your terrible air freshener is going to prevent people from getting pregnant, but take the freshener out of your Uber. The drivers are the ones exposed to it the most.
Dr. Crawford: Well, for these things — another one of the top exposures of BPA right now is actually thermal paper. Receipts. Think about receipts at the grocery store or the airline counter. For a one-time exposure, touching it once, it's probably not a big deal. But for the people who do that job and are exposed all the time to thermal paper, that actually can be such a high level of exposure. So that's a good example where I say you need to use gloves if that's your industry and you're going to be exposed to thermal paper a lot. Same thing for the Uber driver — this is what you're spending your time doing. You don't need that fragrance for your own health.
But again, we control the things we can. So let's control the fragrance in our home and in our products, because to your point, we can't control what's in the Uber. And so we're not going to stress about it. That's the argument I get number one — that you're causing people to be stressed about toxins that otherwise they wouldn't be. And again, that's paternalistic. Toxins are impactful to your health. I should give you the data so that you can cultivate the day-to-day life that is, to the degree where you don't stress about it when you're on the plane or you're in an Uber or you're at a party — because that one-off isn't such a big deal because you're not exposed to it every single day inside your home.
Andrew Huberman: I like to think that people want information. I realize they can feel overwhelmed by too much information, but in the end, even though what we're talking about here seems like a lot of to-dos and not-to-dos, there's a logic to it. The logical backbone is: you do what you can. You do your best to control the key variables. The point about cannabis I think is really important, especially for men. Women don't know they should get their AMH checked. That's changing because of people like you being out there doing public education. But I like to think that people want knowledge. I really do.
Dr. Crawford: I actually think people do want knowledge, and I don't think they're the ones giving the counterargument, to be honest. I think it's our colleagues who say, "Oh, people don't want to hear that," or they make assumptions. And again, in today's world where we have data, why are we talking about assumptions? Let's give people data and let them make the choices they make.
Andrew Huberman: Ignorance is not bliss when you're running up against a health challenge.
Dr. Crawford: Yeah. If you haven't had your own health challenged, 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 at 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 collided with my fertility fellowship when I advocated for doing vitamin research and all this epidemiology. I saw the word inflammation in all of that text, yet we weren't talking about it with our patients.
And I went on this journey to get rid of Teflon in our kitchen because I studied PFCs, and we changed the foods that we ate, changed how we exercise and how we slept. And one of the things that I cut out — learning to listen to my body — was gluten at the time. Even though I would have never said I had GI symptoms from it, I just said, "Oh, I felt more inflamed, vague symptoms, kind of headache, kind of more fatigued." And when I conceived my children, before we ever had to do IVF, we got pregnant naturally in that time period when I didn't have gluten. So a decade later I 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. It starts with education and knowledge. Learning how to advocate for ourselves — when you know what's normal, you can sit in front of somebody and say, "This isn't normal," and mean it with your full heart. And then how do you optimize all the things at home? Because back to the other point, even if you need IVF, I can only work with the eggs and sperm you give me. And maybe if we're focusing on some of the stuff earlier, there's probably a subset of people who can get pregnant without IVF, or who can freeze eggs and have an easier journey, because they had this information and they made choices based off of it.
Nutrition, Diet, and Listening to Your Body
Andrew Huberman: What I'm realizing hearing you today is that we need to listen to our bodies. Women need to listen to their bodies — we're mainly talking about women's health here. But also learn to be scientists of our bodies. When it comes to nutrition, 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, and for lunch you're having a sandwich, and for dinner you're having some pasta with some sauce, and you don't feel well — you don't know what the problem is. I'm not advocating for a Spartan diet where it's chicken breast next to rice next to broccoli with a tablespoon of olive oil. But when you eat that way for a short period of time — the sort of cleaner and more individual ingredients — I do think that you can get insight into what works for you and what doesn't.
For instance, there are certain forms of fibrous foods that I just don't feel well with. And my sister had this intuition about histamine that has now been confirmed by two guests on this podcast who are MD PhDs who work on these sorts of issues — in one case pain and in another case gut inflammation. She was convinced she had some histaminergic thing 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. But for years I would get super sleepy after eating certain foods. Turns out I have a sort of mild histamine sensitivity to about four different foods. I don't think you can figure that out unless you separate out the ingredients.
Dr. Crawford: Absolutely. I advocate especially if you are falling off the curve, or if you're trying to learn to listen to your body and you want to optimize your own health — for a very temporary but restrictive clean eating pattern where you're having lots of fruits and vegetables and fiber, and you're cutting down some of the things that more commonly cause certain reactions: 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 tenants of a fertility diet are really not eye-opening. Fiber is hugely important for the gut microbiome and hormone health and inflammation and insulin resistance. So high fruits and vegetables, high fiber diet, whole grain carbohydrates over refined carbohydrates. Ultra-processed foods don't have a place in the modern diet. Added artificial sugars, those non-nutritive sweeteners — they don't have a place in this. We want to have quality of our protein. Most people could benefit from some increased plant protein due to the increased fiber than they actually get in the standard American diet. But meat is not universally bad nor necessarily good — it's the quality of the meat that probably matters a lot.
The meat data to notice is that for every serving of plant-based protein over animal, people tended to ovulate better and had higher fertility rates — 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, and animal-based products don't have fiber in them. So we want to be mindful of that ratio.
Red meat is the really controversial one. Increased servings of red meat — of course, dietary studies quartile it from lowest exposure to highest exposure. Highest exposure groups had poorer embryo development, worse outcomes with IVF, and an increase in staging of endometriosis when they went to surgery. That doesn't mean to me that all red meat is bad, but it probably is for a subset of people. More inflammatory, causes more IGF-1. We want to be mindful of it. The question I always get is, does source matter? Probably, but we weren't looking at it in any of those studies. So I think being very mindful of where your animal-based protein is coming from is really important in today's food world.
Not all foods are created equal, even when they fall into the same category. And healthy fats are really, really important. Cholesterol is the backbone for steroid hormones. So you need cholesterol in your body. We really want to encourage those monounsaturated and polyunsaturated fatty acids — the nuts, olive oil, fish, algae, chia seeds, flax. Those things have so many benefits when it comes to the omega-3 fatty acids they have, but also that they're great healthy sources of cholesterol, which your body needs. And in fact, if you don't intake enough, you're not going to make progesterone as well. You need progesterone for implantation. If you don't have enough saturated fat in your diet, you're not going to make as much progesterone. So there's some nuance there.
But to the heart of your question, I'm a huge advocate for that. Especially if you're struggling with something, you're not feeling your best. If you say you kind of hit the marker on a lot of these inflammatory symptoms and you don't know what's going on, it can be a really helpful tool once you're controlling the other ones to try to leverage. But again, sleep, stress, building muscle, avoiding those excess toxins — those are a huge piece of the puzzle too. And a lot of them go hand in hand. A lot of times we eat a food that's also wrapped in something that has toxic chemicals in it. So we really want to think about the fact that when you work from home and have access to whole foods, that is really important — as always leveraging processed or ultra-processed versions.
Andrew Huberman: Would you say that what you just described — in fact everything we talked about — also pertains to perimenopause and menopause?
Dr. Crawford: Absolutely. It's so fascinating because when I sit with a lot of people who just do menopause, we have the same recommendations for lifestyle and decreasing inflammation, because it's going to improve ovarian response and improve how your body feels. We know that when you go into menopause, estrogen has such profound anti-inflammatory benefits that one of the biggest problems is a baseline increase in your inflammation. So don't wait till you're in perimenopause or menopause to start to learn these things. Learn them. Whatever play point you are now is the perfect time where we can start to make a difference — both for hormonal health now, fertility now or later, but also your ovarian function long term.
Andrew Huberman: Amazing. Natalie Crawford, thank you so so much. I can't tell you how much I learn every time you speak on this podcast and elsewhere. People should definitely get your book — again, I've read it cover to cover — The Fertility Formula: Take Control of Your Reproductive Future. Natalie Crawford, MD, did all the training, runs a clinic, is out there doing public education amidst everything else, managing a family, and just really expanding the field. You're taking it in new directions, which to me is the most important thing. You're out there teaching people, but you're also going back to the clinic and paying attention to the science and evolving the science, because this field is just going to improve over time. But you've given people so many actionable things to contemplate, to definitely do, and just a lot to think about in terms of the general landscape of how we think about reproductive health — both our own and society's. So thank you so much for coming back. We will do it again if you're willing, and just grateful to you.
Dr. Crawford: Always. Thank you so much for having me and holding space for this discussion. I appreciate it.