Huberman Lab - Female Hormone Health, Fertility & Vitality | Dr. Natalie Crawford

Starting point is 00:00:00 Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Natalie Crawford. Dr. Natalie Crawford is a medical doctor specializing in obstetrics in gynecology, reproductive endocrinology, and infertility. She also holds a degree in nutrition science. Dr. Crawford runs a clinical practice, seeing patients daily, as well as being active in gynaecology, involved in public education, both through social media and through her popular podcast entitled As a Woman. Today, Dr. Crawford teaches us about all aspects of female hormones and hormone health

Starting point is 00:00:43 and fertility, beginning as far back as in utero when we were still in our mother's womb and extending as far forward as menopause. We discuss topics such as the timing of puberty and what the timing of puberty in girls means for their fertility, and we discuss birth control, both hormonal and non-hormonal forms of birth control and how birth control may or may not relate to long-term fertility and different aspects of female health. We also talk extensively about measuring fertility, that is egg count. We also talk about egg retrieval, aka freezing one's eggs, as well as in vitro fertilization. And we also take a deep dive into the popular and important topics of nutrition and supplementation as they relate to fertility, as they relate to pregnancy, but also how they

Starting point is 00:01:26 relate to female hormone health generally. Indeed, Dr. Crawford provides us, with a masterclass on female hormones and fertility, one that I know that all women ought to benefit from and that men would benefit from listening to as well. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information

Starting point is 00:01:49 about science and science-related tools to the general public. And now for my discussion with Dr. Natalie Crawford. Dr. Crawford, welcome. Thank you so much for having me. I'm honored to be here. I've been paying attention to your content for a long time, and I find it to be incredibly clear, informative, and for many people, actionable. So today, I'd like to talk about both fertility and, of course, hormones. But as we both know, fertility is not limited to a discussion

Starting point is 00:02:18 about hormones. And actually relates to things like behaviors, sex behaviors, and other behaviors, nutrition, supplementation. So we'll get into all of it. But if we could just back up developmentally and talk a little bit about female puberty because I think pretty much everything we'll talk about today is related to what happens puberty forward, mostly in females, but we will also discuss male fertility and hormones a bit. And the question I have is, is there anything about a woman's timing or, let's just say, patterns of puberty, right? how frequently they menstruate early on, what the timing of menstruation is in terms of their age, etc. That provides hints or maybe even facts or directives about her future fertility or how long

Starting point is 00:03:11 her fertility might last. This is a great question. And I think defining some terminology before we begin is helpful. So if we go all the way back to when you're a fetus inside your mom, So when there's a female fetus inside her mom, you have the most eggs you're ever going to have at about 20 weeks gestation. You have about 6 to 7 million eggs. By the time you're born, you've already lost more than half of those. And you continually lose eggs all the time. So the analogy that I always use and you do too is imagining that there's a vault inside the ovary where all your eggs are kept. And every single month, since the moment you have an ovary, you lose a group of these eggs.

Starting point is 00:03:51 And when there's more inside, you're losing more. So you're losing all of these eggs throughout early fetal development and then up until the time period, even of puberty. When you reach puberty, you have a lessening of the number of eggs in your ovary to the point where it can start to respond to the signals from the brain. So we think about puberty onset and females. First, we have really thylarchy, which is the development of breasts. So that happens about two years on average before you have minarchy, which is your period. starting. So what happens is the brain, as we know from the hypothalamus sends out GNRH, and then we have FSAH coming out, which really starts to stimulate those follicles. So FSAH or follicles stimulating

Starting point is 00:04:35 hormone, well-named hormone for the female. Of course, men have it too, and it's less well-named for them. But it starts to get those follicles, which house the eggs, to grow and make estrogen. Women have about two years of estrogen exposure alone, so unopposed estrogen, with no progesterone because they're not yet ovulating. And that's when you start to see breast budding and you start to see the development of some of those secondary sex characteristics before you actually have a period. What are some of the other secondary sex characteristics that precede menorchy? So you said breast bud development and then breast development on average about two years before.

Starting point is 00:05:12 About two years before, you have sexual hair development. So actually adrenarchy is one of the first, usually comes right before at the same time with breast buds. So two to three years before you'll see your period. So genital hair, underarm hair typically. Genital hair usually first and then underarm hair. And we're getting right down into the weeds here, which is good. You know, a goal of this podcast is to normalize all aspects of health, including sexual health and reproductive health. Is that commensurate also with the development of body odor?

Starting point is 00:05:43 You know, because as a young boy who eventually hit puberty and became a young man and now, I suppose I'm in middle age, I'm 48, I can tell you that the locker room smelled a lot different before and after middle school, right? Right. Like in other words, boys start to smell stinky. They do, yes. And that's usually around that same time of sexual hair development is when you start to have those glands around the hair making some of those odors that start to produce stinky. Do they reflect hormones themselves? Not this, like the smell, the actual smell, doesn't actually reflect levels of hormones or anything like that. It is just that your body, your gonads, whether it is testes or ovaries, are now starting to respond to those brain signals.

Starting point is 00:06:30 The brain is turned on. They're starting to respond. And your body is starting to mature in a way to get to the point where it can support reproduction. The reason I ask that question is not to get people thinking about stinky smells. And by the way, some people love the musty smell of their own armpits or others. You know, you're referring to adults, by the way. But the reason I ask is that there's a wealth of data in animal models, including non-human primates, suggesting that exposure to the odors of others can either stimulate or accelerate puberty.

Starting point is 00:07:06 Is there any evidence for that in humans? So there's mild evidence, and it's murky because we also know that anything that could be an endocrine disruptor, which a lot of scents or fragrances are also, can accelerate the onset of puberty by disrupting part of this system. And so we know that toxins and, you know, scents and a lot of the world that we're exposed to is part of the reason why we're seeing puberty happening at such a younger age now in females, specifically, but in both, but in females. than we have before. We have young girls seeing their onset of monarchy or their period at a much younger age. How much younger? I've seen the various graphs for different countries, but can we say that, you know, 10 years ago, on average, girls in the United States and Northern Europe were getting menorkey at about, what, 12 to 13 years old age? Yeah. So, you know, we'll use monarchy for the purpose of this. So having your period, you know, 10 to 20 years ago, you will see most data would say,

Starting point is 00:08:06 oh, 13 to 15 would have been kind of the average age. And now we're really seeing it shift to be starting at 10 to 11 and completing by 13, 14. So most girls are definitely going through the puberty change earlier. And the other thing to note is that most girls get their final height growth right before they start their period too. So not only are we seeing a change in this getting starting earlier, what we're also seeing is probably some reduction in height from having gone through puberty at an earlier process, because once you start actually menstruating, once the ovaries have really started to learn how to respond to that FSAH and grow the follicle, and it gets to the point where you can start ovulating. So about two years later, then that ovulatory period, those

Starting point is 00:08:56 high levels of estrogen, are going to go and they're going to close those growth plates. So you've really started to limit your final adult height as well when you go through puberty earlier. And that's definitely something that's a huge concern for precocious puberty or very young puberty, right? And we can use blockers when there are children who start to exhibit signs of puberty. And one of the main reasons people do that is to try to get them to a greater adult height if they're really starting to go through puberty at a very young age. Is that also true for males? That is happening earlier. that earlier puberty means that your growth spurt in terms of height is going to be truncated.

Starting point is 00:09:35 Not the same. And you probably, most men will say, oh, but I had my growth spurt, you know, kind of after I started having some of the puberty change that happened. But because it is this estrogen-related process and women that we see that growth-spurt, really your final height is within that year of when your period starts. Interesting. Yeah, this discussion is certainly not about me, but I was one of these what I thought was kind of an odd duck. I hit puberty about 13, 14. Let's just say I knew I did. But I didn't shave

Starting point is 00:10:06 until I was after college. My growth spurt between freshman and sophomore year. I grew a foot. Right. So I was like, you know, I grew a full foot, but I was the same weight. So I was like real tall, real skinny or pretty tall, you know, real skinny. And then it seems like, you know, some people in my life would argue that puberty is still occurring for me. But it feels like it's very long and protractive, which leads me to a very specific question. If puberty, you know, If puberty arrives, let's again define as menorkey for sake of our discussion right now, if puberty arrives early in a girl, does that mean that her fertility will shut down earlier as well? Great question. It does not. So the age of which you start the onset of your period does not impact

Starting point is 00:10:47 how long you're going to have a reproductive lifespan. And that's because you have the eggs inside that vault. You're losing them every month no matter what. So you lost them all those years. before your period started, no matter if your period came at 10 or at 15. It's just about when did they start allowing your body to ovulate, determined by being able to carry a baby. Your body now thinks you can be pregnant. I think this is so important to highlight because it puts together what you said earlier about the loss of eggs even as a fetus. I think most people sort of assume that the reduction in egg count is due to ovulation and the fact that, you know, one egg ovulation. You know, one egg ovulate, typically, but that other eggs are deployed in that ovulatory cycle. And then those basically

Starting point is 00:11:34 are taken out of the vault and out of the opportunity for fertilization. But what you're saying is that the eggs are constantly being culled from the vault starting from early embryonic development and that ovulation is a distinct step in some sense unrelated to the loss of eggs. I think this is going to be very important for our discussion later about potential egg. harvest. Yes. Because I think some people have it in mind. It's a lot of misconceptions that you're losing eggs from your fault. And that's not the case. You're just accessing the ones outside. Gosh, so you're not, so we can just answer this now, perhaps. It seems, if I understand correctly, that if one were to harvest eggs for IVF or for embryogenesis in addition to set them aside

Starting point is 00:12:18 later or freeze them for later, if they want to use them, eggs or fertilized embryos, that one is not reducing their total number. of eggs any more than they would, how they just let their cycles proceed naturally. Exactly. Oh, that's such an important point. I think there, I think a lot of people believe the opposite. It's probably the number one thing that patients fear when they come talk to me about egg freezing or going through IVF is I don't want to harm my future fertility. I don't want to cause myself to run out of eggs earlier or going to menopause earlier.

Starting point is 00:12:50 And it's explaining this process to them that your ovaries are on a pathway that you can't change. Those eggs are coming out of the vault, regardless of if you're on birth control. Pills, you're pregnant, we do IVF. What we're modifying is one's not going to ovulate and have the rest of them die. We're going to try to give you medication to get them all to grow so we can take all of the ones that have been released from the vault that month and give them a chance for later. And the next month, you'll have another group come out. So IVF is not about stimulating hyper-release or excessive release of eggs. It's about stimulating the growth of the ones that have been released so that they can be frozen-est,

Starting point is 00:13:29 either for later fertilization or fertilized in addition than frozen is embryos. Is that right? Exactly. And we just use the hormones that your body normally makes in a different way. The medications we use are FSH and LH to get the eggs to grow. So people will say, I don't want to take all these weird hormones or strange medications, but we're just manipulating that normal process that happens in the natural menstrual cycle in order to say, hey, this month, let's get all these eggs to grow. Let's try to improve the efficiency of finding which eggs are going to be normal or not and help you along this process. I think a good number of people are now going to head to the IVF clinic.

Starting point is 00:14:04 I think, again, I really want to highlight this. I think most people that I've spoken to assume that the process of harvesting eggs for freezing for fertilization then or later is going to diminish their fertility because they're basically pulling more out of the savings account, so to speak. Right. Okay. So we're making the withdrawal no matter what. Great.

Starting point is 00:14:25 Well, such an important point for people to know and propagate. Getting back to puberty, a little bit later on I wanted to get into endocrine disruptors and things of that sort. But since you brought it up, you know, I've heard things such as, okay, things like evening primrose oil. If mom is putting evening primrose oil on or has it in her shampoo that I've heard of young males getting precocious breastbud development. Keep in mind, folks, that some transient breastbud development is characteristic of some normal puberty in males, at some sometimes. times shows up and goes. I knew some kids like that in the neighborhood. They got teased a little bit, and then they stopped getting teased. Hopefully nowadays they don't tease those kids. But when I was growing up, those kids got teased, not by me, but by other people. But it was normal and it passed for some, right?

Starting point is 00:15:11 It occurred normally and then passed. But I've heard that things like exposure to evening primrose oil, maybe even just through contact with mom, can increase the frequency or degree of that male breastbud development, is it also true that young girls can undergo precocious puberty or, let's just say, accelerate or exacerbated puberty through contact with things like evening primrose oil, which is a, I think, has some pseudo estrogen-like properties? It's important to differentiate that the secondary sex characteristics we see like breastbud development are from estrogen, but it's not really puberty being initiated when it's from an endocrine-disrupting chemical. So taking, you know, being exposed to evening

Starting point is 00:15:53 primrose or lavender or tea tree oil in a male isn't going to cause him to start to go into puberty, but it is going to expose him to estrogen when his body is not and therefore stimulate some breastbed development. Same thing can happen in young girls, meaning they could show some of those secondary sex signs earlier than they normally would. And this is why, if that's happening at a really young age, kids should go to a pediatric endocrinologist who are going to check things like bone age and see if you've really started the puberty process or not, or is it an outside exposure, which is causing it. Interestingly, about the young child exposure and development, the other thing to say that's really interesting and relevant in my field is that when

Starting point is 00:16:40 we think about how many eggs are in the vault, and everybody's born with this different number, and I'm sure we'll talk about ovarian reserve, what we now know is that the vault, your ovaries are most susceptible to whatever your mother does when she's pregnant with you. And that that epigenetic, that programming, which is happening, is predisposing young women to probably having some of them low ovarian reserve, some of them having diseases we associate with infertility like PCOS or endometriosis. And we haven't yet characterized what all they are. But if we look at the incidence of some of these disease that we see now, what we do know is that the time period of which these people were pregnant, the 80s and 90s was not the healthiest time when it comes to

Starting point is 00:17:26 endocrine disruptors and plastic exposures and chemicals and all of this processed stuff. Let's just say that people have been exposed to that were really seeing that those, that are very insusceptibility to egg quality and quantity happens in that beetle development period. It's interesting because there's some parallels. to male fetal development, like the fact that you have these early organizing effects of hormones like dihydro testosterone, which essentially stimulate the growth of the penis, but also then establish a propensity for hormones during puberty to activate growth of the sex organs, but also activate the brain areas. They're responsible for a host of different things.

Starting point is 00:18:12 So I only mention that because what I'd like to kind of illustrate in the background here is that basically our reproductive health begins really prior to conception, really. It's dependent on mom and dad, but certainly to a great degree on mom. But then fetal development is going to be important. So sort of us being able to pick our parents. I do have a couple of questions about lavender, tea tree oil, and evening primrose oil. I was aware that evening primrose oil, excuse me, can somehow bind estrogen. receptors or mimic some of the estradile or something similar to it. I wasn't aware of tea tree

Starting point is 00:18:52 oil or lavender. Here are we talking about oils? What about aromas? And how concerned do people have to be about this stuff? Because, I mean, you'll go into a restaurant bathroom. There'll be potpourri. Some people wear perfume. I mean, we don't want to set a paranoia. But I think people should know about this stuff. Tea tree oil is in a lot of those natural shampoos. A lot of the shampoos. The ones that burn. Yes, the one that tingle your scouts. I don't like those. Some people love them, though. Constant exposure is very different than a one-time hand-washing in the bathroom.

Starting point is 00:19:24 And I think that's the big difference for everything when we talk about chemicals or toxins or exposures in the world. You can't live in a toxin-free world. But choosing what you put in and on your body on a regular basis does set the tone for certain physiologic changes. And so, you know, using unscented products, especially with, children is a really an important thing because we want to make sure that their lifetime exposure to some of these things, especially during critical times, is much less. And so you'll see people recommend things like your laundry detergent. You know, what sense are in your laundry detergent? The shampoo and conditioner are a big one and the soaps that you use on a day-to-day basis in

Starting point is 00:20:07 your house or the oils you put on your body. Lavender is huge because there's this whole community of people. They want to rub lavender oil on their baby's feet and help them sleep. But really, we can see, and if somebody goes and shadows a pediatric endocrinologist for a day, they'll see some kids come in, and this will be the reason why. What about cloth diapers versus non-cloth diapers? I've heard that you have your very strong cloth diaper proponents, right? And that because they seem to feel or believe that non-cloth diapers somehow contain things that can get into baby's skin. And maybe there's a bigger question here.

Starting point is 00:20:45 is baby skin more permeable than adult skin? I don't know that baby skin is more permeable or not. To me, it seems like it would be hard to imagine it is, but babies do seem to have this incredible skin, right? Their skin is so smooth. It's very soft. And you want to squeeze their cheeks and all this kind of stuff. But yeah, the idea they would be more permeable.

Starting point is 00:21:05 I think it's more that their development is this time is very important and setting the stage for a lot of what happens later. versus an adulthood, those stepwise developmental processes have already happened. So I think that's why we pay so much attention to what happens in the, you know, childhood period of time because we're now learning about those later consequences of what you're exposed to. It's not that, you know, regular diapers versus cloth, whatever we want to say, one's necessarily better than the other.

Starting point is 00:21:34 It's more honestly a personal preference. Babies are exposed to them a lot, and there's been a lot of attention to that. But similarly, somebody could use cloth and wash it with a detergent that then, you know, has certain chemicals in it. So there hasn't been a study shown that this one thing is an exposure for a baby that somebody needs to be worried about. There's definitely companies now which are promoting and talking about, you know, traditional diapers that they are making sure have less toxins in them. And I always think any time you can decrease toxin exposure to a child is going to be very important. Is there any evidence for, you know, breast milk versus formula in terms of impact on future reproductive development or reproductive status of a child?

Starting point is 00:22:22 That's a complicated question because breast milk exposure, at least for the first six months of a child's life, certainly helps with the immune system development. And we know that poor immune development can lead to higher risk of autoimmune disease later, what people call leaky gut, and some of those diseases certainly are correlated with fertility. So I wouldn't say we've gone so far to say that if you don't breastfeed your child, they're going to have fertility issues. But we do know that there's an in-between correlation with things that breastfeeding is protective against and how those diseases themselves may relate to fertility in the female later on.

Starting point is 00:23:01 Okay. So if we're thinking about a young girl slash woman because we're talking about puberty, Right. So I don't know what the exact nomenclature is there. You know, my experience is I'll offend and somebody no matter what. But a girl who undergoes puberty, right? So a young woman who's maybe 13 or so, so she's early teens, undergoes puberty and therefore is continuing to lose eggs from the vault. But now is undergoing presumably roughly every 28 days, manorchy. But let's talk about this 28 days thing because I think a lot of, people think that, quote unquote, normal menstruation is always 28 days. And we know that's not true. So what is the range of normal durations between menstruation cycles or duration of the menstruation cycle? And let's also define when the menstruation cycle starts, probably for the males mostly in the audience. Sure, sure. So let's think through the cycle. We'll do a quick one over and then answer the questions. So what we think of is cycle day one or when you're going to say this starts is going to be the day that you start bleeding. So that's actually shedding the endometrial lining from what grew the last time.

Starting point is 00:24:15 So any spotting even would be considered day one? Okay. So it is, we can get back to it. But there's problematic if you have a lot of spotting before that full flow starts. A day or so can be really normal just as the body is adjusting to the drop in progesterone. But let's just start at the beginning. Day one, you have a period, a mincease. This is when you're actually bleeding.

Starting point is 00:24:35 At this time period, we like to think about all of those new eggs being out of the vault, being susceptible to that FSA, which of course is that well-named hormone, because it stimulates a follicle to grow and each egg is in a follicle. That egg starts to grow and makes estrogen. That estrogen stimulates the proliferation of the lining of the uterus in preparation for potentially that pregnancy that may come. And also, that estrogen makes you feel really great, right? That's the follicular phase, name so because that follicle is growing and it's an FSA,

Starting point is 00:25:05 dominant phase where you have a lot of estrogen. And people feel great when they have a lot of estrogen. Yeah. Because women feel good with estrogen. Because of the relationship between estrogen and other neuromodulators like dopamine serotonin. And is that happening in parallel or are they somehow related? Like is estrogen controlling the release of serotonin somehow and vice versa?

Starting point is 00:25:25 Or are they just kind of coincidentally happening in parallel? We definitely think that there's more of a correlation causation than just coincidence because we know there's time periods of people are more depressed within your cycle, correlating with those low estrogen levels. And we know that when you go into menopause or you run out of eggs and you're now in a low estrogen phase, we see a lot more of a depressed mood. And, you know, anadonia, lack of response to things which would normally give you pleasure happens more frequently.

Starting point is 00:25:55 The female brain loves estrogen and it's protective against things like dementia. So this is a time period where women are going to be more energetic. they're going to have more energy, more focus. This is the estrogen dominant phase of the cycle. And when you have seen that estrogen at its high levels, which it's only made from a mature follicle, and it's very specific, 200 picograms per milliliter for 50 hours, that's the brain's clue. Okay, we must have a mature egg, and it can send out that surge of LH or lutonizing hormone. And now you ovulate. And when you ovulate, the follicle opens up, releases, closes back, and then it's the corpus luteum, and we've entered the luteinizing hormone. And we've entered the lute. luteal phase. And the corpus luteum, as the name suggests, a corpus, it's like a body that's basically the, it's basically the corpse of what essentially in she, yeah, insheed the egg before. And it, what I find so amazing, I mean, biology is so beautiful, right? Instead of just taking that tissue and saying,

Starting point is 00:26:53 okay, like, let's just discard this or that becomes the trigger for the next phase of the, it is essential for life, right? The corpus luteum, which makes progesterone, opens and close is the implantation window. It is what allows somebody to get pregnant and for our species to continue. So it's extremely fascinating. And that corpus luteum gets stimulated to produce progesterone impulses throughout the entire luteal phase because it's still controlled by the brain unless you get pregnant. And then in that luteal phase, progesterone is fascinating. It's trying to protect you from things which could potentially harm your baby. So suddenly now you have less energy. You want to sleep, more, you want to eat more, you maybe do not want to have sex as much because your body is

Starting point is 00:27:39 suddenly saying, let's just protect this potential implantation that you're going to have. If that pregnancy doesn't come, the corpus luteum can only live 12 to 14 days. It has a very distinct lifespan. And then it dies. Your estrogen and progesterone both drop. You bleed starting over the next cycle, and a new group of follicles comes out to be released. And the reason why walking through that very succinctly but is important when you're asking how long is the normal cycle.

Starting point is 00:28:09 Because the ludial phase is pretty set at 12 to 14 days. The follicular phase can vary in person to person. And what we know, though, is for one individual, if your menstrual cycle, your reproductive hormones are working right, it should be relatively constant for you. And so if your periods are every 24 days, but they've always been every, 24 to 25 days, then that's not concerning. And if your periods are every 33 days, but they've always been every 33 days,

Starting point is 00:28:40 then that's not concerning. But we do get concerned when there's a change in your period, or we get concerned when people have what I like to say is irregularly regular periods. Because what you'll see textbooks tell you is that your periods could be as short as 21 days, as long as 35 days, and that can all be normal. But people will hop between.

Starting point is 00:29:02 them. And they'll have one cycle that is 24 days in length from day one to the last day before the next day one. Then the next cycle is 32, and then it's 26, and then it's 34. And that's not normal. That's too irregular. And that can be a sign that something is not communicating correctly within your reproductive hormones. So what I tell patients is, in general, your period should be less than 35 days apart. And you should be able to look at a calendar. And with your finger, put a finger on the date, and within a couple days of accuracy, be able to predict when your period's coming. And if you can't, there could likely be something that is interfering with the hormonal signals between the brain and the ovary. And one of the biggest, really, one of the only things we

Starting point is 00:29:50 see as women start to have fewer eggs in the vault is a shortening of their cycles. So you have a regular period, and suddenly now you have less eggs in the vault, so less are coming out each month. And when the brain sends out that FSA signal, now there's fewer eggs, so it's not getting as dilute, and you have one starting to respond sooner. So suddenly, you're ovulating shorter, faster in your cycle. You're ovulating on cycle date 9 instead of 14. Your ludial phase is still set. But the person who comes to see me and says, my periods have always been 28 to 30 days, But now they're every 24. I just figure it's no big deal.

Starting point is 00:30:31 I have red flags going off everywhere because I'm now really concerned that potentially their ovarian reserve has dropped to a point where we are starting to see clinical changes. Now, of course, things like thyroid and prolactin and other hormones can also cause such changes. But that's why you'll hear most reproductive endocrinologists

Starting point is 00:30:50 say your period's a vital sign. And what we really mean is the regularity at which it comes and the predicament ability of it is telling us if your hormones are all communicating in a normal fashion or if something could potentially be off. I'd like to take a quick break and acknowledge one of our sponsors, Athletic Greens. Athletic Greens now called AG1 is a vitamin mineral probiotic drink that covers all of your foundational and nutritional needs. I've been taking Athletic Greens since 2012, so I'm delighted that they're sponsoring the podcast. The reason I started taking athletic greens and the reason

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Starting point is 00:32:21 We've got this thing that we call call the menstrual cycle or the ovulatory cycle. There's two phases, a follicular phase and a ludial phase. The ludicase the ludial phase tends to be, if I heard correctly, fairly fixed, about 14 days. The follicular phase can vary in duration, maybe 10 to 14 days, maybe even 10 to 18 days, depending on something about their brain to ovary communication. For those that aren't familiar with this, I always learned that estrogen primes progesterone, this kind of the really basic top contour description of the ovulatory cycle,

Starting point is 00:33:01 that estrogen is going to slowly climb toward the point of ovulation, and then there's a peak and then a drop, and then progesterone is going to dominate in the ludial phase, the second half. You said that estrogen is associated with a psychological level and a physiological level, more energy, feelings of vitality,

Starting point is 00:33:22 and some of that estrogen, increase is actually coming from the one egg that got stimulated the most, the one that got selected, right? So it picked for the team, potentially for the team, but got picked, potentially for fertilization. And that egg sheds its corpus luteum, which is this piece of the egg that then triggers the progesterone that dominates the luteal phase. Do I have that right? Mostly, mostly. Okay. Yeah, please correct me where I'm wrong. The follicle in which the egg grows, right? When you ovulate, it ruptures, the cyst burst. A follicle. A follicle. A follicle. A Focals a cyst, a cyst is a fluid-filled structure,

Starting point is 00:33:57 follicles of fluid-filled structure that holds an egg. So when you ovulate and you get that LH surge, the cyst bursts, it opens up, and the egg comes out of it, and then it reheals and becomes the corpus luteum. Got it. So just a little bit different in timing. And you're right with estrogen primes progesterone, but really we think about it the layer of the uterus, because estrogen stimulates the growth of that lining, and then progesterone stabilizes it and allows implantation to occur.

Starting point is 00:34:23 But the sequence of events of when you're estrogen dominant and progesterone deficient, which is the follicular phase, and people will come in having labs drawn randomly, and they're all concerned that they don't have progesterone. And when you talk to them about where they are in their cycle, you say, you're not supposed to have progesterone. That's your follicular phase. This is perfectly normal. Okay, great.

Starting point is 00:34:45 Thanks for that clarification. I get a lot of questions about birth control, but on my social media handles. Don't we all, don't we all? To be clear. It's a vast topic for exploration, but along the lines of what we're talking about now, I've heard, and I suspect it may not be true, but tell me, is there any evidence that taking birth control can disrupt the process that you just described? And when we talk about birth control, we should probably define what we're talking about.

Starting point is 00:35:17 So there are hormone-based birth controls, aka the pill. There are also hormone-based birth controls that are not in pill form. There are IUDs that are copper IUDs. There are other IUDs. Let's just talk about hormone-based contraception in females. Okay. Which many of them, as I understand, are estrogen mimics or estrogen themselves that suppress ovulation. Do they diminish or increase the number of eggs that are taken from the vault?

Starting point is 00:35:48 Fantastic question. Let's talk about what people say is, pill. So let's specifically talk about combined oral contraception, the pill which has ethanol esteridial and some type of progestin. No, contraception does not change the release of eggs out of the vault. They are occurring at the same process and the same pathway. You're not ovulating because that estrogen does prevent FSA from coming from the brain. So you have the group of eggs still come out of the vault. There's no FSAH. They just all die. The next group comes out. So when you are saying, are you going to run out of eggs faster? Is it going to harm your fertility? Does birth

Starting point is 00:36:26 control impair the process? The answer is no. But there's a couple important caveats. One is that the birth control pills, especially if you take them continuously or for a prolonged period of time, the body's smart and the ovaries start to say, well, we're not really doing anything. And one of those markers of ovarian reserve we have is AMH, and that's anti-Mularyin hormone. And AMH is made from the granulosis cells or the cells that serve. around every follicle. So in the shortest way possible, more eggs in the vault, more come out every month, higher AMH. Fewer eggs in the vault, fewer come out, lower AMH. If your AMH is being suppressed because of the birth control pill, because it's decreasing the activity of those granulosis cells,

Starting point is 00:37:10 you might get a low AMH value when you've been on the birth control pill for a long time. That is completely reversible. But it can be significant. So if somebody is wanting to, you know, to get an AMH level. Let's say somebody comes to my clinic, they're not trying to get pregnant, and they're on the pill, and they're considering freezing their eggs, so we're going to check their ovarian reserve. If we draw it, I always say this, AMH may be up to 30% lower in somebody who is on the birth control pill.

Starting point is 00:37:40 So we can still draw it, and if it comes back in the normal range, we feel good. But if it does come back low, we're going to have to make a decision. Are we going to stop the birth control pill for a period of something? some months, use alternative contraception if you don't want to be pregnant, and then repeat this test to see if this is a true low, because we do see that young women do have low ovarian reserves sometimes, or was this just suppressed because you were on the birth control pill? So we see it impact some of the hormone testing that we can do, and I think that's an important distinction, and we can see that the longer you take it, that potentially it might actually

Starting point is 00:38:20 improve your fertility if you had underlying endometriosis or some medical conditions that we see associated with infertility. So prolonged pill users can potentially improve their fertility versus people who are trying to get pregnant that same age who were not on the pill. Those studies are complicated, right, because of selection bias. Because if you've been on the pill for 10 years, you're a little bit older. So is it that they were preventing pregnancy and the other group potentially had some exposures, so they were inherently more infertile than the group that was on the pill. But we do know that the pill doesn't cause infertility. And I use it all the time. All the time in IVF cycles, we put people on the birth control pill because we can actually synchronize that

Starting point is 00:39:04 group of eggs that comes out of the vault to grow together because your body doesn't want to have 20 babies at one time. Right. And what we're trying to do with IVF, get 20 eggs to grow if that's what's out of the vault really goes against the check and balance of the human body to not have 20 babies at once. Why is it that males who take testosterone, synthetic testosterone, it shuts down their own testosterone production and sperm production, but females who take estrogen in the form of birth control pills, it doesn't shut down estrogen production by the ovaries? So I love this question.

Starting point is 00:39:38 You know the answer, so I like it extra because I know you're asking. spermatogenesis is a constant and ongoing process, right? So in women, you're born with all the eggs you're ever going to have. And what we're talking about is if we stop FSAH at that moment, we're just impacting the ability to ovulate at that time. But we're not changing this constant loss throughout the vault. Spirmatogenesis, right? The sperm is made every single day you're making brand new sperm. So 72 days for the sperm to be created in the testes and 18 days to find their way out the ejaculatory system.

Starting point is 00:40:11 And so exposures that you have that stop the production of FSH and LH inhibit the development, the creation of new sperm. So somebody who's been on testosterone will tell the brain, the brain doesn't know it's from you're taking it. It says, hey, we have plenty of sperm, we're good, we don't need anymore. So the brain then gets suppressed and doesn't make that FSH and LH, therefore not stimulating both further testosterone production because you don't need that. But testosterone production and sperm production go hand in hand.

Starting point is 00:40:43 So therefore, you're no longer making new sperm. And in fact, the longer you're on testosterone, the harder it may be to get sperm production to come back. And in 25% of people, they may not get it back if they've been on prolonged testosterone exposure. So it's really because of what women will sometimes say is unfair, which is the fact that you're born with all these eggs and you run out of them. They accumulate the wear and tear of your life, right? we see egg quality being a huge issue in female reproduction, yet men get to have new sperm every 90 days.

Starting point is 00:41:17 They get to wash away whatever bad deeds they did and can change their lifestyle and their exposures and have very different sperm. But because of that same process, things that shut off the production of FSHLH really impact sperm quite significantly. You mentioned bad deeds for sperm, not by sperm, I said, for sperm. And, you know, we know that heat is a, you know, a pretty dramatic insult to the to the spermatogenesis cycle, saunas and hot tubs and whatnot. I did receive the question as to whether or not heat exposure, saunas, hot tubs, et cetera. Are they detrimental to ovulation or egg production in any way? I mean, obviously things are more internal in females.

Starting point is 00:42:02 The ovaries are internal, but is there any evidence for that? I mean, the body does heat up. Yeah, there's no. it doesn't harm the ovulatory period or the ovaries. And just like we know, the reason why the testes are so susceptible is because they're supposed to be at a cooler temperature. That's why they're in the scrotum outside the body. That's why the testes are so susceptible to heat changes. But the ovaries being inside the body, they're not in the same way. Now, when somebody's pregnant, important distinction, right, we know that the development, especially organ development of an

Starting point is 00:42:32 embryo can be more sensitive to certain things and that heat exposure at that time, whether it's hot tub use or extreme fevers even can make a difference in development of a fetus. But when it's coming to the ovulatory cycle or hormone production, heat in the female doesn't make any difference. I want to be clear before I ask the next question that I don't want to be responsible for any unwanted pregnancies. But when I was in high school, they told us that women can get pregnant even while they have their period. Is that true? Seems like a lie based on everything you're saying,

Starting point is 00:43:07 but I don't want anyone to run out and test that hypothesis without having the facts first. So in general, if somebody has extremely regular cycles, then that's a complete lie. You can't get pregnant on your period. The reason why they tell us this

Starting point is 00:43:23 is one, especially when you're younger, your period cycles tend to be irregular. They're not, your body hasn't fully mature to have that regular. and that we know that sperm do live in the reproductive tract for much longer than the egg does. So sperm can live there for up to five days. So if somebody did have a shorter period window, let's say their normal periods are going to be 24 days, they're ovulating on cycle day 10.

Starting point is 00:43:50 If they have a regular period that's five or six days, they could potentially have intercourse that end part of that period. The sperm could live for five days and be right there when you... have the egg en route. So it's not the most fertile time for sure. And in most people that is considered a time when you're not going to get pregnant, but especially when you're younger and you have more irregularity or in people who have a short cycle window, that might not be the case. So by extension, can we conclude then that the most fertile time is going to be when sperm meets egg, let's save timing of intercourse for the time being, but because there can be a delay,

Starting point is 00:44:32 there, when sperm meets egg on obviously day of ovulation or day after? Day of. Day of. The egg lives for 24 hours. So the egg can only be fertilized for 24 hours while it's in the fallopian tube. Once the egg has entered the uterus, it can't be fertilized anymore. So it has this very short window of time where it will allow sperm to enter it. Now, sperm can live for five days.

Starting point is 00:44:59 So we'll say the fertile window is this five days? period ending on the day of ovulation. You will hear a lot of us, a lot of doctors say the day after ovulation, because do you really know exactly what time you ovulated on? And if the egg has 24 hours, then that extra day could potentially be helpful. But really, it's five days ending on the day of ovulation. And people with very regular cycles or who can track them and they know when that ovulation is happening, the day before and the day of ovulation, those are the two top-hitting days. So if you're kind of not in the mood to have lots of sex, those are going to be the days you target to have the highest chance of conceiving. And what is the relationship between estrogen, libido, and ovulation in females?

Starting point is 00:45:40 The higher your estrogen is, the increased libido that you're going to have. And, of course, you see those peak estrogen levels, which are going to trigger that LH surge. So the body is made to get pregnant. You're going to have that peak estrogen, that peak libido right before and right at that ovulatory time period. so that hopefully you also want to have intercourse and get pregnant. I've heard before, let's just say, that some people, to be careful here, can sense the, literally the deployment of the egg, the ovulation. They report that they can feel that, let's just say, the departure of the egg. Is that an imaginary thing?

Starting point is 00:46:24 No, no, that's very real. I always liked that image that people can know when that happens, right? It has a name. I mean, after all, men generally know when their sperm are leaving their body. Let's hope they do. But why wouldn't there be an internal sense for women also of what's going on? I mean, we have interoception. There's a ton of nerve innervation of that area.

Starting point is 00:46:47 It doesn't communicate to the brain. Excellent as far as tracking to where that sensation is. But you're right. I already said ovulation is the rupture of a cyst, right? It is rupturing and the egg is being. released and those follicular fluid is also exiting and going into the peritoneal cavity. And so there is a group of women who can feel that, especially people who are very in tune with their body. And it has a name. It's called middle schmerts. The pain almost feels like a crampy

Starting point is 00:47:16 pain that happens in the middle of the cycle. And that is your ovulatory pain. Oh, interesting. What is it called? Middle schmarts. Okay. We'll put that in the show note captions and whoever does it is going to have to get the spelling right, middle schmerts, amazing, amazing, and foreign to me, but for obvious reasons, but amazing. I'm always astonished in how incredibly well orchestrated this whole process is. It's just an incredible feat of biology. I mean, the number of things that have to be timed correctly and the use and, I don't want to say re-use, but the repurposing of tissues for different things. And like, it's what an incredible dance.

Starting point is 00:47:59 It's just amazing. It's beautiful. I mean, I'm so nerdy because I just love how everything has to communicate just perfectly. It makes you in awe of all the pregnancies that just happen just all the time because really things have to synchronize really at the wonderful time period. And even though this isn't what we're talking about, I've heard you say this. So I want to say this. People always ask every single day, well, how much sex should you have?

Starting point is 00:48:21 When should you have sex? Is there too much sex? And what we know is that you definitely should not decrease your sexual intercourse interval. So if you are in a relationship and you are sex everyday people, have sex every day. You will 100% hit intercourse throughout your entire fertile window on the day that you ovulate. You're depositing the same sperm there because you're not generating new sperm. It's whether the load went half and half and half and half or if it went in, you know, one big group. But if you're constantly putting more sperm out there, you have a higher chance.

Starting point is 00:48:56 And so studies go back and always say daily intercourse associated with the highest chance of fecundability, especially during the fertile window. However, for couples who are not sex everyday people, that idea can cause a lot of stress. Stress, of course, impacts the system in a lot of different ways. It can also cause sexual burnout where they no longer feel like being intimate or having sex. on the day they're actually ovulating because they've been doing it this whole time leading up. And that's where the time period of saying have sex every other day throughout the fertile window, so starting five or six days before you think you're going to ovulate,

Starting point is 00:49:35 and then try to target having intercourse on the day before and the day of ovulation. And the reason why people said every other day or a few days prior to kind of get some sperm exposure there in case you ovulated early, but really to try to prevent some of that increased stress that can happen when you're trying to conceive, especially if you have programmed or timed intercourse that needs to happen on an everyday interval. But the odds of getting pregnant by saving up sperm for two or three days, that's not higher. Curious then why if, let's just say hypothetically, someone is donating or freezing sperm or doing IVF, why they instruct the male to not ejaculate for 48 to 72 hours prior to, let's just say, depositing sperm.

Starting point is 00:50:23 It's such a funny word. It is. But it works. Two points. One, if we're doing a semen analysis, now we're trying to evaluate this sperm. And any test has certain normal parameters, and these are all based on a 48 to 72 hour abstinence period. So, yes, if you ejaculate more frequently, you're going to have less sperm. And that can be very normal.

Starting point is 00:50:46 but if we're looking at a test with set normal parameters that are based on two to three days of not having intercourse, that's why we want you to do it for that. If we're doing, let's say, IUI or entry uterine insemination, also known as artificial insemination, or where we take the sperm and put it in a catheter and put it in the uterus, we're trying to get more players further down the field. And in that case, I know when you ovulate because I'm timing it perfectly, and I am trying to get as many possible in this process because we're not just having them deposited in the vagina,

Starting point is 00:51:20 we're trying to get them further. So we want more because that's part of that treatment process. And similarly with IVF, I want to have as many sperm as possible to sort through and pick out the best looking, the most modal, the most normally shaped ones. So we're trying to get just a better sample. And by having these normal guidelines,

Starting point is 00:51:37 we're able to judge this is low for what it should be, which can also be a clue to other problems. I definitely want to talk about chemistry, both sort of interpersonal chemistry and literally ejaculate and vaginal chemistry. But before we do that, I'm curious whether or not we can just touch on a few of the things that a lot of people wonder about in terms of egg quality. And if they touch on sperm quality, maybe we can also just mention that. But for instance, does cannabis either by edible or by smoking can.

Starting point is 00:52:13 cannabis impact quality in either direction. Alcohol would be the next. And then I'm going to assume, and I have to do this strictly because of what I understand about, you know, drugs of abuse like cocaine and amphetamine, methamphetamine, that none of those can be good for systems of the body because they create so much stress for the body. But let's just say alcohol and cannabis. I read a statistic when researching the episode on cannabis that shocked me, which is that 15, percent, one five percent, not one point five, 15 percent of American women, at least in this one study, a survey reported having consumed or smoked cannabis during known pregnancy, which is wild. Wild. Unless, of course, I'm just naive and THC is not harmful to the fetus, but I have a hard

Starting point is 00:53:08 time believing that. So what gives? I mean, here we're to, and there I actually just through in fetal development. So is cannabis, is alcohol bad for egg quality? So there's different things and they're the same thing in one. So let's answer them each individually. So we'll go with the one that everybody knows and has accepted now that they wouldn't have accepted 40 years ago, right? Smoking cigarettes. So that's obviously bad. Decreases the number of eggs you have in the vault. Smoking cigarettes actually gets into your vault decreases the number that you have. You have a higher chance of going into menopause earlier. And it increases the risk of having abnormal chromosomes, what we really think about when we think about egg quality, right, impacting those myotic spindles

Starting point is 00:53:49 inside the eggs, which hold the chromosomes in their perfect position, they are associated, they get wear and tear from things that cause inflammation or are toxic. So cigarette smoke, we know, decreases egg quality, egg quantity, increases miscarriage, and then, of course, has fetal impacts. Could I just ask you? When we talk about there's nicotine, which itself is not carcinogenic, and then there's the smoking process, which brings in a bunch of other things. The question I know is burning in everybody's mind is vaping. Yeah. Right?

Starting point is 00:54:19 Because vaping is – I'm very bullish on this. I mean, it's very clear that the chemicals associated with vaping are just, oh, so bad for everybody's health. But it's distinctly different from saying that nicotine is bad for one's health. And it can be. But without doing too much of a deep dive, are there any data that show that vaping is bad for egg quality? Of course, there's not as much data because it just hasn't been around as long. But yes, vaping definitely has chemicals that looks like it's associated with poor success rates and IVF cycles. And that's really kind of one of the most finite measures of egg quality we can see because we're really testing the egg at a level in a lab versus just are you getting pregnant naturally.

Starting point is 00:55:02 And sorry to interject again, but any time a conversation like this comes up, especially between two people in the health science space, there are these shout, because I'm not. I hear them, literally, where people say, well, listen, I vaped every day and I've had three healthy babies. And I think my response is always, okay, there's going to be a distribution of responses. And then, of course, how much healthier could your babies have been had you not vape during pregnancy or vaped prior to pregnancy? Well, sure. I mean, I think these are the key issues that, like, you can't rewind the clock as far as I

Starting point is 00:55:34 know, right? In the absence of a time machine, you can't rewind the clock. So, I mean, basically everything you're saying is that smoking, something. cigarettes or vaping nicotine, just can't be good for egg quality. We know that. We know that it's not good for getting pregnant. We know that it's not good for sperm. And therefore, we also know it's going to impact pregnancy rates. You know, things like cannabis, right? Decreases sperm production, decreases sperm motility, the shape of it, changes the DNA, increases the fragmentation of the DNA. If your partner uses cannabis and you get pregnant, you have a higher chance of

Starting point is 00:56:11 miscarriage because of the sperm association with the cannabis. Now, edible cannabis as well as smoke cannabis. I don't know, right? Because you can't study something that's illegal. So a lot of this data is just more new and a lot of it's going to be observational. And in states like Colorado and California where, you know, canvas is essentially legal. Yeah, I'm assuming there are more data. But okay, so smoking and or vaping nicotine, cannabis, either.

Starting point is 00:56:41 edible or smoked, very likely detrimental to egg quality and sperm quality, which is not to say that one can't conceive. It just means that the quality of your baby, your child, will not be as high as the quality of that baby if you didn't do that. Is that right? Yes. And I'm not trying to demonize anyone that did do this during pregnancy. A lot of people didn't know. But this is, this is really about people trying to make choices in anticipation of future pregnancy. Yeah, and when you're trying to set yourself up for success, because we know infertility is becoming more common, we don't always know who is going to have it, and when you find yourself in that position, specifically, you now want to optimize everything you can. So if there's something that is going to make the sperm quality worse and the egg quality worse and your success with treatment lower and your miscarriage rate higher, we're going to recommend that you not do it. If you're trying to get pregnant naturally, all these things correlate over. But of course, there's always going to be outliers and exceptions. I'm going to sit here and tell you that the odds of getting pregnant at age 43 are less than

Starting point is 00:57:45 3% per month. And every single person is going to be like, but my aunt Barbara or I know this person who did because three person's not zero. And you're talking about natural pregnancy there by intercourse. Old-fashioned way, yes. Okay. Right. But yes.

Starting point is 00:58:00 So people will get pregnant. People will have healthy children who do have exposures to nicotine to cannabis, even to alcohol, even though we know that alcohol can cause fetal alcohol syndrome, zero percent of alcohol should be the acceptable level in pregnancy. And then does alcohol impact fertility? Such a complicated question. And this is probably due to the amount you consume and the frequency of which you consume it. Alcohol is a toxin that your liver must filter out and we know it causes inflammation. Anybody who's had a fun night with alcohol knows they can wake up the next day and they feel different. their body is processing that alcohol.

Starting point is 00:58:39 And that inflammation, especially if it's chronic, chronic exposure, we know chronic inflammation is one of the things that we see impacting egg quality and sperm quality. So certainly if you enjoy alcohol, it should be something that is done in moderation, one or two drinks a week at the most, and you should not do it at all once you find out you're pregnant. When we were talking about birth control, I unfortunately moved us forward. and forgot to ask about IUDs. Oh, yeah.

Starting point is 00:59:08 So my understanding is that the copper IUD works by creating a sort of not actually electric, but a kind of an electric fence that kills sperm. Like, sperm don't like copper. Yeah, I love that one. Spirm don't like copper. Copper likes to kill sperm. There's some interesting history.

Starting point is 00:59:27 I've been reading a lot on the history of medicine of people who, you know, for whatever reason, were forced into or chose to be in the sex trade prostitutes using inserting copper coins into their vaginal tract to try and kill sperm, but to varying degrees of success. Obviously, there's a whole socioeconomic landscape around that. So I think it's obvious what I'm referring to, but very interesting. But that's just one form of IUD, right?

Starting point is 00:59:53 There are some other IUDs. And then there's, of course, the ring. We didn't talk about that. So maybe we just touch on a few of those within the context of whether or not it alters egg quality and or future fertility. when one takes the ring out, takes the IUD out. This is a great question because a lot of people don't know this. And I'll roll through a few of the top birth control methods and just thinking through.

Starting point is 01:00:14 Copper IUD, as you already said, no hormonal involvement. It causes inflammation in a toxic environment inside the uterus, isolated, does cause sometimes heavier periods, but they should still be regular. If they are irregular, that's a sign of a hormonal issue because you still ovulate with the copper IUD. Is it literally a copper wire woven into the tissue of the ears? Well, the IUD is a little. tea and the arms are have copper wires wrapped around them. And they and those are they grow into

Starting point is 01:00:42 the uterine lining. They don't grow into the uterine lining. IUD just sits in there and just the presence of that copper causes that inflammatory reaction and that toxic environment. And is it toxic to the environment in ways that are detrimental to the woman or just to sperm? Both. I mean implantation is not going to occur likely right. I mean no nothing has a hundred percent successful but it's much harder for an embryo to implant within that highly inflammatory environment. To me, amazing that people figured this out before the advent of like laboratories. Right. Let's just put some copper in some uteruses and see what happens.

Starting point is 01:01:16 You know, it really speaks to the urgency that must have existed to preventing pregnancy and just how costly, biologically, and financially pregnancy is. And pregnancy is not health neutral. So it is something that somebody needs to be of right health or it can be a deadly circumstance. When we get back to other IUDs, so IUDs that more people are more familiar with are the progesterone-based IUDs. This is going to be your Morena, Kyelina, Laileta. They have a bunch of different names based on the amount of progesterone and how long they last for.

Starting point is 01:01:50 These work mostly by thinning out the uterine lining. As we already said, progesterone compacts the uterine lining to prepare it for implantation in a normal cycle. but if you have constant exposure to progesterone, what is going to happen is it's going to prevent the uterine lining from growing, and it gets it very, very thin. Not all IUDs. In fact, most of them don't prevent ovulation. Only in about 50% of people do they actually prevent ovulation. So their main mechanism of action is this endometrial effect. When you remove the IUD, especially if you're already ovulating, no problem. The problem is the problem. we do see in some people with progesterone IUDs that maybe isn't talked about as much,

Starting point is 01:02:34 is that this prolonged progesterone exposure, because people are putting IUDs in for five to seven years and not having a period for that length of time because the endometrium has become so atrophic or non-existent that you're no longer bleeding despite the fact that you may be ovulating. It can take a while for that lining to grow back. And so it's not uncommon to have an IUD in place. And if you have no period, you're going to say this is great. I don't have a period. Wonderful. You get it removed.

Starting point is 01:03:06 And now your period hasn't come back. And that leads people to sometimes be concerned that the IUD is causing them not to ovulate or they have this. Infertility caused by the IUD. But really what it is is that the linings become so, so thin, that it can take many months of that unopposed estrogen exposure on the follicular phase to get it thick enough to finally bleed when you're ovulating. So I do tell people if they have a progesterone IUD to get it removed three to six months before they want to get pregnant, use some other form of contraception, but give their body time to make sure they have that regular period pattern back. Important distinction, if you're still ovulating and having a period on an IUD, then this is going to be less of a concern because if you're growing enough of aligning to then shed it, we're less worried about it. But if you are amenoreic or have absence of your periods with an IUD, we need to think about removing it for a period of time before you get pregnant so that your body can grow that lining again.

Starting point is 01:04:08 When it comes to some of the other things that you mentioned, one you didn't ask that I want to mention, is the depot-prevara shot. The depot-prevara shot is a high dose of progesterone, high enough to actually prevent ovulation. So in that circumstance, you are not ovulating, and therefore, if you don't ovulate, you're going to get pregnant. Debo Prevara is proven to prevent ovulation for three months. So when you take it, you need to get it every three months to have a proven contraceptive benefit. However, it can last in your system for 18 months and prevent ovulation for up to 18 months. So I will see people who liked that option for contraception and now they haven't had a period in a long time, but their last

Starting point is 01:04:51 Debo shot was six months ago. And they're all frustrated. by the fact when I tell them, well, you still may not have another period for a year plus because this high level of progesterone that you've already injected into your system can last a substantial amount of time. So that is a contraceptive option that I tell people to discontinue a year and a half to two years before they want to get pregnant, which sometimes people don't know that yet. And so that's something that can be a contraceptive option if you're very remote from wanting to have a child.

Starting point is 01:05:23 but in people who are in their child-bearing years, contemplating family building soon, that is not my favorite option. So you haven't mentioned, because I haven't asked, any negative consequences of birth control of any kind. And I'm not encouraging you to, if you don't believe in them, I know this is a very controversial topic. But, you know, one of the more popular studies discussed on social media is one that I've spent some time with the paper. and a few of the papers that stemmed from it. Not a huge study, but describing that how women rate the faces of men as either more, essentially what happens is there seems to be, at least in this study, there was a statistically significant bias for women to select particular male faces as attractive,

Starting point is 01:06:16 and those male faces tended to be of the more square jaw, aka masculine features, right? In air quotes, right? This is what the study found, but that when women were on oral contraception, presumably estrogen, progestin type oral contraception, that that effect was smeared. They had not a statistically significant tendency

Starting point is 01:06:41 to choose the quote-unquote more masculine phase. I have to be very careful with my language here because, you know, it's easy to get description of a study like this wrong. And that has led a lot of people to the things, that birth control is going to throw off their partner choice. Now, of course, it is a small study. Studies like it are not always so well controlled.

Starting point is 01:07:03 But is there any evidence that birth control, oral estrogen-progestin-based birth control, just to keep it specific, can increase rates of cancers, can decrease rates of cancers, can lead to any sorts of disruptions in bodily function or health, that's really like a rock-solid result. That's been seen by multiple studies, clinical trials,

Starting point is 01:07:27 or are we still just in the dark about a lot of this stuff? Okay, so nothing is without risk. Getting pregnant is not without risk. Taking the birth control pill is not without risk. We do see that there's been a lot of not informed consent in people who are taking the birth control pill, meaning maybe they weren't educated about what all of their options were, the positives and the negatives,

Starting point is 01:07:51 about each one of them. If we're going to reference the combo to the pill, estrogen progesterone pill, important to understand that neither the estrogen nor the progesterone are the same estrogen progesterone that your ovaries make, right? It's ethanol estradial, which your brain interprets as an estrogen, but other parts of your body may not. And then it's various types of progestins, some of which have even androgenic or male hormone-like properties, and some of which do not.

Starting point is 01:08:17 So there's a ton of variation, even the amount of ethanol-estradite. that each pill has, with your low, low and your low pills having less, and even with the modern-day average pill having a lot less estrogen than it used to. When you're on the birth control pill, your ovaries aren't making estrogen-yel. And that estrogenial is important in growing the uterine lining, but also for the genital structures. And so we think about vaginal health and both our health, we certainly see that especially with continuous use. So if we distinguish you take the pill for 21 days and you have a seven-day break where you might bleed or you take sugar pills and then you take them again, a lot of people now are taking continuously where you have exposure to these compounds every single day.

Starting point is 01:09:07 So in like the wheel, the little pouch with the wheel of different colored pills, may have seen these on the on the countertop in previous relationships. And then there's the ones that sometimes people just opt not to take because those are the placebo. There's sugar pills. There's no need to take estrogen during that phase. And then they repeat. Exactly.

Starting point is 01:09:29 Okay. But some people are taking estrogen all the way around the aisle. It's very common right now. So people, and they're not wrong. They say, oh, well, why have a period in these little breaks? It's not really a reflection of my hormone status, which is accurate. And so they're taking them continuously. You also have less pill failure pregnancies.

Starting point is 01:09:47 So if you're using the pill for contraception, that can be a great strategy. But the longer you take them, we do see some vaginal and vulvar changes, right? And so atrophic vaginitis, people who notice increased sensitivity, decrease elasticity, increase discomfort with intercourse, increase in yeast infections. That can sometimes be seen because that environment is different. Now, that's just one thing that can come from the pill. We also see the pill be life-saving for other people. They have terrible, you know, PMS or premenstrual dysporic syndrome where their mental health

Starting point is 01:10:23 when they change from high to low estrogen. It's always the change in estrogen that interferes can cause them people to really have mental health issues that are so severe that having that stable hormone level is helpful. And so the pill can be extremely beneficial. for some people when it comes to mental health, it can be beneficial for people who have issues with very heavy periods and anemia. Instead of getting blood transfusions, you know, taking the birth control pill might prevent the lining of the uterus from growing so much that they bleed so much. Same thing with fibroids. People with PCOS. PCOS is polycystic ovarian syndrome.

Starting point is 01:11:00 If we want to put it very simply, you have a lot of eggs in your vault. So you release a lot of eggs every month. And what this does is the FSH signal gets diluted. And so you're not responding to the normal signal and you don't ovulate. And because the ovary is a hormone-making factory, it gets really bored when it can't make estrogen because that egg's not growing. So it starts to make testosterone. So you start to see this androgen-dominate environment associated with lack of ovulation and having a lot of follicles inside the ovary that are not really responding.

Starting point is 01:11:32 And the endrogenization of other tissues like body hair, deepening of voice. where typically the level of testosterone made in PCOS isn't truly deepening voice. It can if there is an ovarian tumor making testosterone or certain other conditions. But typically with PCOS, you see increase in body hair, increase in acne. And you can see some even like male pattern balding, some temporal balding of women. So some hair loss. Temporal wise. So like the widow peaking?

Starting point is 01:12:03 Yeah, the widow peaking and then sitting out in these two areas. And then we see an increase in body. composition toward a male level. So if we think about a male body holding your fat in your abdominal region, and if we think about the traditional female body holding more fat in the hips and thighs area, we see that when this hormone shifts in PCOS, you tend to get more abdominal fat distribution, which then leads to further insulin resistance and metabolic syndrome. But in PCOS, because you're not ovulating, and those ovaries, each little follicle makes a tiny, amount of estrogen. We'll say each little follicle, when it's not responding, we'll make,

Starting point is 01:12:43 you know, one to two picograms of estrogen. But if you have 50 of them each month, you're having some constant estrogen exposure. So that lining of the uterus is being constantly stimulated to grow, and you're never getting the progesterone to stabilize or the progesterone withdrawal to bleed. So endometrial cancer is much higher in people with PCOS who don't ovulate, and the birth control pill can prevent that. Any unopposed estrogen situation, because the body, body is made to have both estrogen and progesterone. So we see an immense decrease in endometrial cancer, an immense drop in ovarian cancer. Ovarian cancer comes from the remodeling of the ovary. So every time you have a follicle grow and it ruptures and it makes the corpus luteum and then it

Starting point is 01:13:25 heals up, those are opportunities for those cancer cells to go away in that remodeling process and lead to ovarian cancer. And because you're not ovulating on the pill, your incidence of ovarian cancer drops dramatically. Ten years of pill use has dropped the chance you get ovarian cancer by more than 90%. And of course, ovarian cancer is super hard to diagnose because the innervation to the peritoneal system is poor, and you don't have any outward signs often to late-stage disease. That being said, could you potentially have an increase in breast cancer in some people? By taking the pill?

Starting point is 01:14:06 By taking the pill. That's a concern, especially. people who might be predisposed to this for some other reason. So you might have Bracca mutations or something like that. And then is there a situation where the pill certainly masks what's going on with your menstrual cycle? And I really think this is where women's health has a huge history in paternalism, meaning doctors will just tell people this is what you're going to do.

Starting point is 01:14:31 So your periods are irregular. Here is the birth control pill. And they're not explaining why or the pros and cons to it. And what happened is people are not being taught how their bodies work. And now they are because of your podcast amongst others. And now they're able to know that my period's a vital sign, and I don't know what it is, because the pill is producing a different environment. The pill's also been associated with potentially development of things like leaky gut or IBS.

Starting point is 01:14:59 And so there is a definite change in your environment when you're on the birth control pill. Increase risk of blood clots because of how it's. processed in the liver, increasing your clotting factors. Can I just interrupt there? You know, I'm aware that a fairly high percentage of people have mutations in Factor 5 Leiden, a clotting factor. Fewer people are, as we say, homozygous have two deficient copies, mutant copies, I should say.

Starting point is 01:15:29 But there are many people out there that have one mutant copy of Factor 5 Leiden. And my understanding is that oral contraception in females can really exacerbate the factor five Leiden mutation. Do you suggest that people get their factor five Leiden genetics analyzed? I mean, it's pretty inexpensive to do, right? I think on a standard blood test, you can just ask for the factor five analysis. And it's not like a really in-depth thing. You don't have to fly to somebody. Yeah, it's a blood test. Yeah, you don't have to fly to another country, you know, like you do for many things. It's important to say that's not the norm, right? Like, that's not the recommendation. When you're talking about putting somebody on the birth control pill, you want to

Starting point is 01:16:07 make sure they don't have high blood pressure because it can increase their blood pressure. You want to make sure they don't smoke cigarettes because the combination of the pill and cigarette smoking can increase the risk of a stroke. But the recommendation is not to screen them to see if they have any inherited clotting disorders. That said, if you ever have a blood clot on the birth control pill, because you're traveling on a plane or you're just on the pill or you're living your life, you're now going to get this extensive workup to find out if you do have that. It's by no means wrong, and specifically you should, if anybody in your family has ever had a DVT, so a deep vein thrombosis, so a blood clot in their leg, or a pulmonary embolism or a PE.

Starting point is 01:16:45 So anybody in your family has had one of those, you should 100% get worked up for clotting disorders. And if you have something like you carry factor five, you should no longer take the birth control pill. And specifically the pill, because it's an oral pill and how it's metabolized in the liver is actually what is causing the change in those clotting factors because that's where they're made as well. So it doesn't mean you can't take any form of contraception, but we do want to make sure that we counsel you appropriately. I never think it's wrong to be an advocate for your own health or to ask questions. It's important to know that screening, I mean, I'll get on my soapbox because we'll talk about screening for ovarian reserve and it is 100% not recommended even though I think

Starting point is 01:17:29 it should be. Yeah, my next question was going to be about testing AMH level. and we'll return to that for those that hear that and it sounds cryptic as well as getting an ultrasound, just seeing basically how many eggs are likely to be in the vault on both sides. Okay. So we have to remember that screening recommendations come from at what point in the population does it make sense to spend the money to test for a disease based on the likelihood of finding it. So if we think about, right, that's what your PAP smear guidelines and your colonoscopy and your mammograms, everything is all based on when are you going to find enough cases at some age to make it worthwhile testing, which is a crazy principle, especially in the U.S., because the government's not

Starting point is 01:18:15 paying for our health care. So why should these guidelines be based on when is it cost effective to do testing? Well, I'll put in a, this is going to sound a little bit conspiratorial, but it's not. I mean, I think that given that for people who have insurance, private paid insurance or through their work, that there's a cost to doing these tests of any kind colonoscopy, AMH, et cetera, and they must have figured out the optimal point on the graph with which they can reduce their payout to people who, for instance, get colon cancer if they didn't get the colonoscopy at 45, as opposed to 50, as opposed to 60, as opposed to 25. I mean, the reality we know is that the more information you have, the better choices you can

Starting point is 01:18:56 make. I mean, the only caveat to that would be that. For some, not all, but for some people, sort of the hypochondriatic type, sometimes more information leads to more anxiety, which leads to more problems. But that's a rare instance. I always think that in general, data is always good. I agree. Having the information at hand about your body and being able to make educated choices versus being in a position where you say, I had no idea that I had Factor 5 Light in, and I had this terrible blood clot because pulmonary amylums can kill people. We all know that, right?

Starting point is 01:19:30 So we talk about this rare thing, but it can happen. But this is really where it can be tough. It can be tough to find even a doctor who may, like we said, factor five is a blood test and relatively inexpensive. So that one is not hard. But physicians live in a weird world where, you know, they have recommendations based on screening, based on the likelihood of finding disease that they follow. And when they go off of those, they start introducing themselves to why are you not following medical guidelines. But for an individual, this is really tough to advocate for yourself.

Starting point is 01:20:06 And the one thing that I'll say, too, this is why paying attention to your body is so important, right? Understanding your stool habits and what's normal and what's not so that you can catch early signs of things and present for that colonoscopy earlier. The current screening guideline for should you get your ovarian reserve checked is that you should not. ACOG, the American College of OBGYN, has an entire practice bulletin situation saying there's no utility and screening for AMH. Okay. I mean, I totally disagree. But I'm glad you disagree.

Starting point is 01:20:40 I mean, to me, it just seems nuts. Okay. Or ovaries, rather. I mean, the AMH is a blood draw. AMH is a blood test. It's a blood draw. It, one could opt to do the ultrasound as well, which is, of course, more invasive. but but women who are seeing their OBGYN are probably familiar with with with

Starting point is 01:21:01 pelvic exams yeah I mean it's a fastional ultrasound but it's not painful not painful but different than a blood draw just just for in full disclosure so and you know I've heard of women in their early 30s going in getting their AMH levels checked getting their ultrasound and then going oh my goodness they're down to like you know I don't want to throw out numbers because this actually can get tricky. You know, they'll say, oh, you have whatever, you know, four follicles. And then someone in their early 40s will have 20 follicles. And then people start to sort of becomes a scorekeeping thing.

Starting point is 01:21:36 And of course, follicle quality. There are a bunch of other things. And then you can tell us more about those. But let's say someone did not have insurance or insurance permission to get this pay for. What is the approximate cost of getting one's AMH levels analyze? $79. $79 to find out essentially where your ovarian reserve is at. So let's talk about this. I already said this in my soapbox. So A-clock says you shouldn't screen it because AMH does not predict your fecundability, right? Your body's ability to get pregnant in that month is independent of your AMH. And for the most part, that's true, right? Because let's say you have a person and they're both 30, you have two people. One has low ovarian reserves. They have five eggs coming out of. of the vault. And this one has normal ovarian reserve and they have 20 eggs coming out of the vault. And we should probably clarify that the number of it, because you said this earlier,

Starting point is 01:22:31 but the number of eggs coming out of the vault is an indirect measure of how many eggs is in the vault. When that number is going down, it means the number of eggs in the vault is likely going down as well. It's also down. Correct. So like your body starts to take smaller withdrawals as you start to run out of. Yes. The vault wants to be at like equilibrium, right? It really wants to be in this middle ground. So when you have too many, it shoots out more every month. It's too crowded, it doesn't want that. And then when it starts to get low, it gets scared about being empty and sends out fewer per month. So what you see outside the vault, and that is called an antral follicle counter, an AFC, it's an ultrasound-based measurement of how many eggs you have

Starting point is 01:23:06 outside the vault at one point in time. And on the ultrasound, if one looks, this is going to show up as to what look like little hollow spaces, like so not gray stuff, but hollow bodies. I say chocolate chips and the chocolate chip cookie. If we can imagine the ovary, yeah, like looks like a chocolate chip cookie, the chocolate chips, small, little dark fluid-filled follicles, each one of those houses an egg. Some bigger than others because they're more mature than others. Based on when you check in the cycle. So if you're looking in that early follicular phase when somebody's on their period, they all

Starting point is 01:23:35 should be small because nothing's been stimulated. If I'm looking periobulatory, I'll see that dominant follicle that's about to ovulate, and then everything else will be small. And is there a graph that people can look at or that we could link to that says, okay, the average with a distribution of, you know, standard error on either side for, let's say, a 28-year-old woman or a 37-year-old woman or a 45-year-old woman of the number of follicles on the right and left side, and as I understand, asymmetries are common, tends to be, you know, like if someone goes in and you've got six follicles on the left side

Starting point is 01:24:09 and 12 on the other side, are they, how do people gauge what they're at? Fantastic points. One, because their doctor should tell them, but that doesn't always happen. But yes, we add these counts together to get your antral follicle count because there is often asymmetry. But what we should expect, let's say, in somebody who's 30, is you should have in the 16 to 20 range of total follicles per month. Right and left side. Combined. Okay. Okay.

Starting point is 01:24:35 When you're 35, that number is closer to like 14 to 16. So starting to drop, it's still pretty good. When you're 40, it's 8 to 10. When you're 44, 2 to 4. Right? So you start to have this immense drop that exponentially starts to increase really around age 37. So things start to kind of get into this severe zone really after age 37. And we didn't really talk about ages 18 to 25, but there are people who get pregnant in that age bracket. Are, is the follicle count very, very high? Is there sort of an ace, is a nonlinear drop off? Yeah, their follicle count would be higher. And I mean, I occasionally have patients who are very young, but have infertility or want to freeze their eggs. I also had patients in that age range who are in premature ovarian failure, right?

Starting point is 01:25:23 Because there can be things that go wrong even early. But we should probably highlight again something that you said earlier. But gosh, you know, this contradicts so much of what's out there, which is that even if you have low follicle count, if you collect eggs, you're not changing what's in the vault. You're not pulling from the vault. You can't. Right. Those eggs are spent. you now have the opportunity to turn them into potential pregnancies.

Starting point is 01:25:45 Correct. I mean, side note, right? We haven't even dove into IVF, but that's the next wave of technology is what we call IVM in vitro maturation. People are trying to figure out how can you get eggs from the vault and get them to grow in the lab because that would open up possibilities for people who have fewer eggs to have a higher efficiency of this process. Because one of the limiting factors when you're doing fertility, when you're doing

Starting point is 01:26:08 egg freezing or IVF is how many eggs can you get per month? And that's why some people have to do cycle after cycle because they can only get five eggs or five eggs. But if we circle back to what we were saying when we got off on this beautiful tangent, is that no matter if you have five or you have 20 eggs outside the vault, you're ovulating one. So you're trying to get pregnant naturally. That's what fecundability is, probability of getting pregnant per month naturally. You have the same chance if you're the same age, regardless of if you have five eggs or you have 20 eggs. And that's why ACOG came in and said, well, AMH doesn't impact fecundability. It doesn't predict your ability to get pregnant or who's going to have infertility and who's not going to have infertility.

Starting point is 01:26:49 So there's no utility and screening for it in people. Now. For one, some speechless. I mean, that argument makes sense through the lens of just probabilities of pregnancy through natural conception. but it completely erases the very, very, very real situation where people are making choices about, for instance, whether or not to stay with a given partner, whether not to leave a given partner, whether or not to accelerate the process of building a family. She raised my eggs.

Starting point is 01:27:21 Should I have a baby now? Oh, my goodness. There's so many factors that this American College of whoever, whoever is like completely – OB2.I.N. They're a big deal. But they're crazy. And that's what I say. They argue in their statement that –

Starting point is 01:27:35 finding that you have, sorry, I'm like, I'm reeling it in. I mean, I'm trying to think of an analogy that doesn't fail, but it's like if you can, it's like saying, okay, if you can walk now, great, there's no reason to test for this inevitable paralysis that's going to happen at different rates in different people. And there are things that you can do to offset. In other words, you could like take a little bit of some tissue that will allow you to walk in the future, but we're not going to do that because if you can walk now, you can walk now. It's good now. That's absurd. And that's really what it is. And they say, well, finding out that you have low ovarian reserve at a young age is going to cause undue stress that is unwarranted because most people

Starting point is 01:28:11 don't have infertility. And so they're purely putting it through the lens of your likelihood to get pregnant. But it's actionable stress. Exactly. If it were just stress like, hey, guess what? And, you know, I know people who have family members with Huntington's mutations and some opt to not know whether or not they themselves have the Huntington's mutation. And it's a very personal choice, right? But here, whereas, unfortunately, there still isn't a cure for Huntington's, hopefully someday there will be, Malcolm Wood. But in the meantime, there is essentially a cure for this situation, which is the harvest and potential fertilization. There's at least an opportunity. And this is what I say.

Starting point is 01:28:48 And of course, you and I feel similarly. Education and data, like being the one to make the choice is an extremely important distinction versus having it happened to you. So if you're young and you find out you have low ovarian results. Is that going to make a difference and it very well might? You might now freeze your eggs when you wouldn't have otherwise. You might now start to try to get pregnant if you're partnered when you otherwise were just waiting. But now you know. It might change the conversation with your partner too, right?

Starting point is 01:29:15 Because a lot of people think they can just wait because of age, right? We're in our 30s. I can totally wait. But if you have a low ovarian reserve, then that you may lose the opportunity for parenthood. And for a lot of people, this is a life goal. And this is what's wild to me. When on earth, besides reproduction, do we have life goals that we take the approach? I'll just wait and see if it's a problem later.

Starting point is 01:29:38 Never, right? If you want to become a doctor, you want to become an athlete, you are constantly working towards that goal or understanding what it's going to take to get there. But why does the goal of parenthood, the attitude is completely, I'm not going to think about it until later. And then I'll deal with it if it becomes a problem. because you can make choices. You could freeze your eggs. You could try to get pregnant sooner. You could evaluate for reasons of low ovarian reserve.

Starting point is 01:30:09 Do you have a genetic mutation or an autoimmune disease? Why is it low? It's not just always a big unknown. There can be some actual things that potentially might be impactful for your health long term. So I think it's wild that this is the current conversation. And I will say, I know personally a lot of OBGYNs, who 100% will draw an AMH blood task if you're at your annual and you ask. And I recommend all of my OB friends because I see people at a different stage, right?

Starting point is 01:30:41 When they see me, they're struggling to get pregnant or they want to freeze their eggs. But when we talk about this, I say, hey, just like you say, are you trying to get pregnant now? And if somebody says no, and your follow-up question is, well, do you want to be on birth control? The same question should be, well, do you want to be pregnant at some point? point. And if so, should you consider freezing your eggs or getting this blood test checked? And very often, people will make a different decision with that information. I'm so glad that you're highlighting this because my understanding is, at least in the state of California, I don't know about other states, or if it even varies by state, that the opportunity to harvest eggs and freeze them,

Starting point is 01:31:23 there's a hard cutoff at age, I think it is 42. Prior to age 42, they'll do it. After 42, they'll do it if and only if you're willing to do in vitro fertilization to actually fertilize and then they'll freeze embryos. But they're far more reluctant to collect eggs after age 42. Yes and no. So when you think about egg freezing and IVF are really the same process, right? When you're going through the exact same thing, you're taking the eggs out of the body,

Starting point is 01:31:52 and then you're either just freezing them as an egg or you're fertilizing them in the lab, and that's IVF and making an embryo right away. Egg freezing has changed dynamically over the past 10 years, whereas 10 years ago, survival rate of eggs in the lab was 40%. Really terrible. And so we really didn't offer it to many people. It wasn't something that was talked about,

Starting point is 01:32:15 and now it feels trendy almost, but it's really just the tech has gotten so much better. And cheaper. Yeah, 90% of eggs now survive. freeze thaw. So 90% is not a low number by any means. Embryos are much stronger, right? An egg is a single cell. It's a single cell. An embryo, when we freeze an embryo that's day five or six, is 300 plus cells. So it's so much stronger. And those embryos survive the freeze thaw, 99% of the time. So yes, there's a 9% difference. That being said, making embryos is a lot more

Starting point is 01:32:48 expensive. Eggs is cheaper. You could do two rounds of eggs and have just as many eggs or have more eggs than if you'd made them into embryos right away. So I never recommend that somebody commits to a sperm source that they don't want to have a child with unless that's the sperm source they want to have a child. And this has changed because when embryo survival was so much greater than egg survival, especially if you had few eggs or you were older, making embryos was the only option. What we do know is that egg quality decreases immensely as we get older.

Starting point is 01:33:23 And we've touched on this, but we haven't really mentioned it. So not only do you have fewer eggs as you get older, the chromosomes inside start to lose their positioning. And so we think about egg quality, we think about genetic normalcy,

Starting point is 01:33:37 and we know that the rates of aneuploity or abnormal chromosomes increases proportionally to your age. Which for people that aren't aware are going to predispose, not always, to miscarriages if they're implanted or potentially even the formation of a fetus that carries, for instance, trisomies. So chromosome repeats or lack of, lack of certain chromosomes. These could be deadly or they could be capable of carrying to term and then but have undetectable to mild to severe developmental abnormalities, correct? Correct. And this is why you have a lower probability of pregnancy per month as you

Starting point is 01:34:15 you get older. So if we look at your natural fecundability, it's not because you have fewer eggs, because we already said your egg count per month that doesn't impact your probability of getting pregnant. It's because the normalcy of those chromosomes has changed so dramatically that the odds that your body's randomly choosing the good one to ovulate become so low. And that's why those natural fertility rates are so low because most genetically abnormal eggs do not fertilize or implant. But if they do, they have a significantly higher chance of miscarriage. It's 40% at age 40, right? So you have a much lower chance of seeing the positive pregnancy test.

Starting point is 01:34:53 But then your chance of losing that pregnancy is significantly higher as well. So when we are counseling somebody about egg freezing, what we know is that not every egg is going to fertilize with sperm, going to make an embryo, going to be genetically normal, or even implant when it is genetically normal. There is huge loss in human reproduction, meaning the more eggs you have at a younger age, the better the ROI on this process is going to be. It doesn't mean you don't do it when people get older, but every clinic does have a cutoff and every clinic's going to be a little bit different.

Starting point is 01:35:29 A lot of different reasons why we actually probably have an older cutoff, so we will let somebody go through IVF or freeze their eggs up to age 45. And it's a lot about informed consent and having the approach that you're smart. smart enough that if I give you the odds and I walk you through how many eggs you are and the likelihood of them making into embryos, you can say, yeah, but four eggs or 10 eggs is way more than zero based on my circumstance. And that is worth it to me because it gives me the opportunity to potentially have a child when otherwise my opportunity is going to be zero. So a lot of this is rooted in paternalism that people can't, as a patient, understand these odds. And, you know,

Starting point is 01:36:13 and they have unrealistic expectations. I think there's a huge shift in reproductive medicine to really counseling patients and giving them autonomy and some of these decisions. But there does become a point where there's the likelihood of finding a normal egg is so, so low that the money or the expense of the process doesn't make sense. And people should utilize egg donation or other opportunities for conception. This drop in both the number of eggs and the egg quality, they really start. to become so profound at age 37 and on. And that's when we really start to see both these things are overlapping at the same time. So if you're waiting until age 35, 36 for your first kid, but you want two or three, we've got to really look forward about is that strategy makes sense.

Starting point is 01:37:03 Well, what is your AMH? One, are you going to run out of eggs before then? Two, how, what other issues could be going on? Is the sperm fine or the tubes open? because we are seeing that when people start families later, when people have more chronic illness and autoimmune disease and obesity, that it's much harder to get pregnant. And so the birth rates, right, are for the first time and a long time across the board are dropping, and infertility is rising because of all of these factors combined. So based on everything you just said, and yes, I'm going to say it a fifth time, because the misconception about this is one of the primary reasons why people avoid.

Starting point is 01:37:43 harvesting eggs. It's not the only reason, but when you harvest eggs, freeze them. Now, sounds like the viability of those eggs is quite, quite strong compared to a few years ago. So that's great, 90% recovery when they thaw them, is not going to diminish the number of eggs in the vault. Such a critical point. And post-age 37, there's a, sounds like a non-linear drop-off in egg quality for most, and these are averages. Of course. Right. So the people that got pregnant with healthy kids in their late 30s and 40s, you know,

Starting point is 01:38:18 yes, we hear you. Congratulations. We're happy. But this speaks to the logic anyway. We're not putting any emotion or circumstances on this, but the logic of somebody in their, let's say, late 20s, early 30s, getting their AMH levels through a roughly $80 blood draw. And then perhaps based on their. life goals and circumstances doing either one or several rounds of egg collection and freezing,

Starting point is 01:38:48 especially since it sounds like you don't need to fertilize those eggs. So if one doesn't have a partner or is concerned about what they're going to do, who's going to be, who's going to provide the sperm, you know, because of course some people choose to raise kids on their own. But parenting is a whole other issue. But they could do that later. So that raises the questions of what are the, health risks, if any, pain levels, if any, and that includes psychological pain of egg harvest. I love it. So going back to what you said earlier, this is going to be injecting synthetic mimics of FSAH and LH, follicle stimulating hormone and lounizing hormone, maybe some growth hormone.

Starting point is 01:39:31 I hear nowadays there's also the practice of injecting these are essentially platelet-rich plasma, PRP, platelet-rich plasma, excuse me, PRP, and perhaps even into the ovarian vault, we can get back to that. So there's a bunch of stuff that's being done to someone. There's low-stem where people are getting, like, low doses of these drugs. There's high-stem where it's like a full blast. Maybe you could walk us through that procedure and just sort of general contour because it, you know, it would require a lot of time to go through it all in detail. But is this a horrible thing to go through?

Starting point is 01:40:02 Is it mild to go through? Is it like a walk in the park? Let's walk through it all. So I love this, and this is my bread and better, and this is what I do every day. Studies tell us that if you are not ready to have a family by age 32 to 33, that that is the optimal time for the average person to intervene and freeze their eggs. It's not up for debate. It's when you have both the intersection of still a good egg quality and good egg quantity on average. And so that is younger than a lot of people are thinking about having families.

Starting point is 01:40:33 And the reason why is when we really think about what happens to the egg afterward, that's what's really critically important. So I'm going to answer the question about what you go through, but just thinking, we already said you freeze your eggs, 90% of them are going to survive the free saw. About 75% will be fertilized by sperm, and about 50% of those will even make it to an implantation stage embryo or a blast acid. We're assuming healthy sperm. So sperm, no DNA, excessive DNA fragmentation.

Starting point is 01:41:00 You've already hit the nail in the head. One of the biggest issues with egg freezing is I don't know the future. I don't know if this sperm is going to be great or not. It could be from a pot smoker. Just kidding, pot smokers. Not kidding, pot smokers. We're not. But we don't know, right?

Starting point is 01:41:16 So we have this future yet undetermined sperm source. So I am going to assume you're going to fall average on these data points that we're going to walk through. But the reality is you buffer the risk by having more eggs frozen. And that's why people are going through multiple rounds or cycles because we don't know. don't know how that fertilization will be. If you have 20 eggs and 18 survive the freeze thaw and 14 fertilize and seven make it to the blastocy stage, if you're age 30, we would anticipate around 60 to 70 percent of them are going to be genetically normal. You're young, so that's

Starting point is 01:41:49 already kind of a big hit at that age. So let's say of the seven, four of them are genetically normal. When I go to transfer them, I have at best a 65 percent chance of live birth per embryo, which is really good when you put in the lens of fecundability and peak success tends to be closer to 20%. And you're going to implant one embryo at a time? 100% we're going to implant one embryo at a time now. Does anyone ask for two? People ask for two. Doctors will do two.

Starting point is 01:42:15 It is, it lowers live birth rates. If we're looking at giving each embryo the healthiest opportunity at becoming a baby, number one, embryos with IVF have a slightly higher chance of monozygotic twinning, right? So twinning, fraternal twinning comes. If you ovulate two eggs, they both get fertilized. So each baby is completely different genetically, own egg, own sperm. Monozygotic is from an embryo split. Because of the IVF process, likely putting the embryo in the catheter,

Starting point is 01:42:47 maybe having that outer surface touched, predisposes it to splitting after you put it into the body. So more identical twins, monozygotic. Two to three percent chance of monozygotic twins with IVF. and the natural chance is 0.03%. So it's significantly higher, even though ultimately not a probable outcome, I'm going to have a couple patients a year who are going to have monozygotic twins. And if I put two embryos in, I've now one taken this from a potential twin pregnancy to a triplet or even a quad if they both split.

Starting point is 01:43:21 So hence presumably like the octomom cases and things like that. Well, that one they just literally put eight embryos inside, but that's a whole set. I mean, that's medical malpractice, right? But really most of the time, when we're talking about embryos, we're talking about people with infertility or people who spend a significant amount of money, a huge portion of fertility as embryo quality, right? The competency of the embryo, the genetics of the embryo, it's expensive to go through egg freezing and IVF. Yet the uterine environment is another component. It doesn't make sense to waste multiple embryos in the same uteran environment. Statistically doesn't make sense.

Starting point is 01:43:55 It also doesn't make sense to make your embryos compete against each other. So will people put one embryo into, let's just say, DNA mom, right? And one into surrogate mom and try and get two siblings simultaneously? I've definitely done that and had patients do that. It's not common because surrogacy using a gestational carrier is so expensive and there's such limited supply. It's very hard to find somebody who wants to go through the act of carrying a child for somebody else. But that definitely is a strategy that some people utilize, especially if they're older or

Starting point is 01:44:30 they're concerned that they might have a lower chance of implantation, but they want to give themselves a try. But if we look at one embryo, 65% chance of success, cumulative probability after the second is 88%. Okay. Almost everybody's pregnant after two, and these are you ployed genetically normal embryos, okay? And then if you go to the third, so, So cumulatively after three uploid embryo transfers, each one being a single embryo, 95% of people have a baby in their arms, meaning the incidence of recurrent implantation failure is actually pretty low, 5%. But how many normal embryos do you need for what family size if you're freezing your eggs? Because you got 20 eggs at age 30, and the example I gave, and you just made four normal embryos, right? So that's really unlikely to make three or four kids.

Starting point is 01:45:25 It has a really good chance of making one, gives you the opportunity for a second. But that's also presuming that everything happened perfectly, that the sperm is not pot-smoking sperm. But you know what I mean? Not bad-quality sperm. There's not other environmental issues when it comes to your own health when you're trying to get pregnant or other diseases you may have. So we really need a higher number of eggs, specifically when we don't know what the equation is. will truly look like for one individual person when they go through the process. And one of the only added benefits of embryos, especially if you are partnered, if you're with somebody who you do

Starting point is 01:46:03 want to have children with, you just don't want to have them yet, is that I know the downstream, I know the number, I know how many embryos I have, and if it's not enough to give you a high chance of what you want your family to be, you can intervene now, right? Because by definition with egg freezing, we're not wanting to be pregnant for years. So if you're doing this with a partner and you're making embryos, and now I say we only got one genetically normal embryo, you have the opportunity to choose to either go through more cycles and store more embryos for later to maybe try to get pregnant sooner because there's some underlying issue with your fertility. You can make a choice because you're falling off the curve there. Could I ask you a question. So this, you

Starting point is 01:46:50 mentioned age about 32, 33, in an ideal circumstance with the finances there, et cetera, one would harvest eggs, unless they're already starting a family through natural means. What about for sperm? I mean, we've all heard the studies that with increased age of the sperm, that there's a higher, although still statistically pretty small incidence of things like spectrum conditions. So do you recommend to young gyr males men in their late 20s, early 30s, to free sperm? I mean, it's never going to be wrong to save your gametes because we don't have crystal balls for the future, right? So your gametes are your eggs and your sperm.

Starting point is 01:47:32 That increase in, we'll just say negative outcome from advanced paternal age, really starts to be seen at age 50. So most men are not looking at primarily starting their family. after that age. However, what I run into all the time is maybe you're working on a second family or maybe life has gone down a different pathway and now you're with a partner who potentially is younger and wants to conceive and you now have older sperm. Having sperm in the bank is so cheap and easy to free sperm. Eggs, I haven't even answered your primary question. And the process of collecting sperm while not entirely without its issues is far simpler. It's embarrassing at best, but it's much simpler.

Starting point is 01:48:14 Yeah, it's much simpler. It generally doesn't require hormone injections, although, you know, maybe for rare instances where people are hypogonadal or something. If you're going to freeze your sperm, you're right. Typically, you're going to get some blood work done because most places that store sperm per FDA guidelines have to make sure that if you carried an infectious disease, it's stored in a special tank. So you'll have to get blood work done.

Starting point is 01:48:34 Then you have to abstain for your two to three days, collect into a cup, you're done. Which, by the way, guys, you can do at home and bring it in. Sperm are so stable. Yes. If you've ever done this, you just bring it in. It's pretty – Just carry it in the little bag. A little bit of – I think I'm not going to feign that my friend did this and told me.

Starting point is 01:48:50 But, you know, it's kind of outrageously easy in the sense that you just bring it in, and they'll, like, take it out in the lobby and be like, is that your name? And they'll do – like, very different than the egg collection procedure. Yeah. So here's what I'll say about sperm and what I wish more men knew slash more men did. If you're going to get a vasectomy because you are choosing that you don't want to have kids. And we see many men who do this. They say they don't want to have kids. They want to go get a vasectomy. Yet later on in life, you don't have a crystal ball about life is dynamic and things can change. If you're going to get a vasectomy, go free sperm first.

Starting point is 01:49:23 Why are so many men getting vasectomies? I don't have the answer to that. I hadn't heard this. Yeah, a lot of men are getting vasectomies even, I think, to just take control over not having a child out there when they don't want to. Maybe this explains the drop in birth rates. I'm just kidding. It's multifactorial. But so many people, even if you're in your family, let's say you have two kids and you all decided you're going to get the vasectomy so that you don't have any more children. Things happen. Terrible things happen. Life changes. There might be a circumstance where you potentially would have another kid if something really bad happened or you just changed your mind.

Starting point is 01:50:03 Freezing sperm is so easy and so much easier than if you don't, not all vasectomy reversals work, especially the long. that it's been reversed, the lower the likelihood that it's actually going to work. And very often if it does, you don't get sperm insufficient levels for timed intercourse and you're seeing me in the office. And freezing sperm is cheap. I mean, it's relatively cheap. It's like $400, right? So it's much, much cheaper all in than the entire egg freezing process.

Starting point is 01:50:31 So to answer the original question, when you go through egg freezing, most people do fantastic. And we'll just use egg freezing and IVF interchangeably here because what you as a person is going through to harvest your eggs or to take them out of your body is exactly the same, right? The distinction between egg freezing and IVF is all about what happens on the lab end of it after they've come out of your body. So if we have this group of eggs that comes out of the vault, your body doesn't want to allow them all to grow, even if it's a low number, right? That's the check and balance to not have so many kids. So we need to override that process. And what we tend to do with this is to use a combination of hormonal medications.

Starting point is 01:51:11 And very often, I describe it to patients as suppressing your body and then stimulating it. So if I can temporarily stop the production of FSAH and you have a group of eggs come out of the vault and we can imagine that FSA is their food and there is no food because you're taking the birth control pill for three weeks. These eggs are going to synchronize, be very small, be very hungry. For lack of a better word, their FSAH receptors are going to open all up. It's like a nest of baby birds that are all now starving instead of the hungry bird gets the worm. So now we go with this suppression period for a few weeks.

Starting point is 01:51:47 We can come in and give gonadotropins, which is fsh and LH. FSH is now synthetically made in a lab. It's very easy. It's a synthetic compound that mimics the structure of the brain FSAH. We actually can't synthetically make LH very interesting. We don't have a way to make it yet. And so we use the purified urine of menopausal women because when you're in menopause, your FSA and LH levels are naturally so high because they're trying to get that egg to make some estrogen.

Starting point is 01:52:19 So here are some that we've covered male hormone health before. And there's been a discussion of HCG, human corionic gonadotropin, which is essentially mimics LH. In the receptor it does, yes. All right. So is pregnal human corionic gonadotropin? Is it purified from postmenopausal women's urine? No. It's synthetic. HCG is synthetic. And so why can't... What's talking about? It's called Minipur. Minipure. Minopure is a combination of FSA and LH.

Starting point is 01:52:50 The reason why we give HCG to men to try to stimulate the spermatogenesis process, which, of course, if we could just give LH, we'd give LH. It's the same reason why we give HCG for a trigger. If we're going to good. through fertility treatments, and we're trying to mimic that LH surge, which naturally would cause ovulation, we actually are giving HCG because it does mimic LH when it comes to the receptor action of it. But when it comes to really, especially in getting follicular development and the relationship between LH and FSA, meaning LH is really providing some of the hormone substrate that we need to be able to make estrogen.

Starting point is 01:53:29 And so you really need some LH in a lot of people, depending on your protocol, or if you're older and you're naturally making less. The example or the offshoot would be like the PCOS patient who has some naturally high LH. Sometimes they don't actually need LH in their protocol. So who are these postmenopausal women that are supplying their urine? They're paid? Right, right? Yeah, I sort of imagine them on some island someplace. Yeah, yeah.

Starting point is 01:53:57 Go to the menopause. Getting paid to urinate. And it's called menopure. Like it's purified menopausal urine, right? It's wild. I did not know that. They know now. Now they know.

Starting point is 01:54:07 So we use FSA and LH. We'll just say, in lack of better terms, those are the two primary compounds that we're giving over the course of, on average, a 12-day period to get the follicles to grow and the eggs to mature. So you can measure egg maturity by blood levels of estradiol and by transvaginal ultrasounds. So when you're going through egg freezes, you. our IVF, you're taking these hormone shots of F-SH and LH, and they are getting those follicles to start to grow, the eggs are starting to mature, we're monitoring them along the way, trying to determine the time period where we think most of the eggs will be in the mature range. These eggs have gotten to maturity. You then are going to take a trigger shot, which allows that final stage

Starting point is 01:54:55 of myosis so those chromosomes can separate, right? We think about the egg. We remember that normal female genetics 46XX, and I always think about in the egg that these chromosomes are lined up. Your eggs are frozen inside your body. When you're born, your eggs are in metaphase of meiosis. So that's when, right, metaphase, chromosomes meet in the middle, and they're held apart by these myiotic spindles. And this is why eggs are so stinking fragile because they're held like this.

Starting point is 01:55:23 And those myotic spindles just absorb the wear and tear of your life. but when you use that trigger shot, that LH search naturally or that HCG in a cycle, that's when you're going to get that final separation into half the eggs, you know, half those chromosomes into the egg. So for people listening, think about like a zipper. Oh, I love that. And you're pulling apart of a zipper that then you now have the chromosomes, just one, you now have half the chromosomes because why?

Starting point is 01:55:52 Because in successful fertilization, the other chromosomes are going to come from sperm. The sperm. And that's why this process has more error, the older you are, and the longer your chromosomes have been sitting there because those spindles are going to break down. And we're going to have that increase in aneuploidy, like we already said, purely because of this impact. Can I ask a question about that specifically? I think now would be the right time to ask, which is that my understanding is that a lot of the dynamics of pulling apart of this zipper-like thing, these chromosomes, and then is related to mitochondrial DNA. Because there are a lot of mechanics. We're literally talking. about an egg splitting itself, you know, in half. It's powerhouse. Yeah, and the mitochondrial. And so mitochondrial health is a big topic these days. And so we were sure to touch on nutrition, supplementation, and prescription drugs that

Starting point is 01:56:38 impact mitochondrial health. But I've heard of a new procedure called three-parent IVF where they're taking basically the DNA from the intended mom, the DNA from intended dad, and then putting it into a, you a surrogate, like a donor egg that is where the DNA has been sucked out and then, you know, because it has healthier, younger mitochondrial DNA. So you're essentially, let's say you've got a couple in there, like let's say late 30s, early 40s, and they're not getting successful embryos or implantations or whatever. Things aren't working. They'll take the DNA from mom and dad and they'll merge it with a third parent encapsulation. There are clinics that do this. I know that,

Starting point is 01:57:26 a lot of this was actually being done in Eastern Europe until recently. Mexico offers, there are places in Mexico that do this. In England, it's been used to solve mitochondrial dysfunction, but in the U.S. this is still not legal. Is that right? Yes. So the purpose of what you're talking about, essentially, when we think about utilizing a donor mitochondrial or a donor egg, the point of that technology existed to help cure mitochondrial. diseases, which are 100% fatal. And so you would have this subset of people who would, because if you're the mom, you always pass on your mitochondria to all of the offspring. So if there's disease inherent in your mitochondria, everybody's going to get it. And these are very severe

Starting point is 01:58:16 diseases. So the idea of this was first to say, hey, can we overcome this mitochondria disease and give up people the opportunity, which has done that, right? And so. So it works when done properly? When done properly, especially for that purpose. Now, that purpose is distinct because those people aren't infertile, right? There's something else going on within their mitochondrial disease. Utilizing that technology to overcome age-related changes in the eggs has not been successful yet. Are we hopeful that it can?

Starting point is 01:58:50 Will people charge you money for it in certain places, yes. But you're hitting on a really important topic is that the political environment of embryo research in the United States makes it extremely hard for us to be the pioneers of new technology in this space. And that is because a lot of views about an embryo or when does life begin that happens here in the U.S. that results in limiting the availability and the possibility of doing research in a meaningful way on human embryos. Right, because it would require the destruction of a lot of, and it would also, and, you know, I looked into this a little bit as a, from an academic perspective, to be clear, it would also require that the abortions be performed differently because suction abortions destroy embryos

Starting point is 01:59:43 in ways that extraction abortions don't. So there's a very controversial topic. I mean, it's something that maybe we'll return to in an episode about stem cells in the future. Yeah, it's fascinating because especially if you look at IVF, the whole separate issue is that there's millions of embryos that people are no longer using because they have had success. They had extra embryos in the bank. They got divorced, a variety of reasons. And a lot of people would like to donate their embryos to science feel like, hey, I don't want to have this embryos. implanted. I don't want to carry this child, but potentially could something good or could it help

Starting point is 02:00:21 advance the field? But that's not really a tangible option. When people do that, what is actually happening is their embryos are being utilized to train embryologists, which is valid, right, to teach them how to thaw and freeze and biopsy and do different things. So it's still useful, but it's not in a meaningful way like we'd really love to be able to utilize to advance the science, especially for these embryos that have been created, yet people no longer need them for family growth. So what happens to all the embryos that people don't use? Oh, it's a fantastic question. Right now they sit in storage.

Starting point is 02:00:58 Forever? Well, this is a new problem. Okay, IVF is only 40-ish years old. Embryo freezing alone, right? The first IVF, we haven't even gone through the whole process, but the first IVF baby, there's no FSSHLH to stimulate more of the eggs outside the vault to grow. so they followed the single follicle, and they didn't have the procedure, which we do now, which is a minimally invasive procedure to extract eggs. We go vaginally with a needle attached to the

Starting point is 02:01:24 ultrasound, and we enter into each follicle, and we drain it. The very first IVF, you followed one follicle, and you went in abdominally with a surgery to put that needle into the follicle and drain it out and give that just one egg a chance. And then, of course, there was no embryo freezing originally. So the field is still rather young to understand some of this. And as technology rapidly improves, we see things like better success rates with freezing and thawing embryos, better process of getting more embryos to grow. But now we have a lot of embryos in storage that may or may not be used. I personally tell people, you should keep your embryos, you should pay the storage fee,

Starting point is 02:02:08 until no matter what the worst thing on planet Earth happens to you, you're done having children. Because sadly, I live in a spectrum with my field where I see a lot of sadness. And people who maybe have lost a child, something else has happened, and they have maybe a sibling who they feel like they really want to give this sibling child the chance to be a sibling again. And often you're much older when you're experiencing this. And if you had had embryos frozen that you could have used, but you got rid of them, them, you're going to be really upset if you find yourself in that circumstance. So I always say you should save them until you know that you are not going to need them.

Starting point is 02:02:47 And then what do you do with them? Most people just discard them. Some people will donate them to labs, which is called for research, but mostly it's for embryologist training. To get better at doing IVF. Which is also important. Okay. But embryo donation is a new thing.

Starting point is 02:03:03 So being able to, just like we have people who donate sperm and donate eggs, Embryo donation is the next evolution of an opportunity to allow more people to become parents. It's a little bit of the Wild West. People finding people in Facebook groups and connecting. It's this whole other dynamic when it comes to what we call third-party reproduction or, you know, what do you do with known donors and things like that. But it's a very interesting concept. So this problem is emerging as a.

Starting point is 02:03:38 technology is getting better. I'm realizing now, remembering rather, that when I was in college and graduate school, you would see these ads in the student paper for egg donors and sperm donors. Sperm are generated throughout the lifespan, so that's a kind of less controversial issue, but this is now not allowed most places to advertise for egg donors on college campuses. That's my understanding. egg donors were often paid whatever they were paid. I'm not going to say it was reasonable amounts or not because I don't recall what they were

Starting point is 02:04:13 paid and everyone's circumstances are different. But the argument that most people use against this is, oh, well, these people are giving up eggs that they could otherwise use, but we now know that's not true. So do you have any knowledge that's like what was the rationale for kind of limiting the recruitment of egg donors. Anyway, I'm not arguing for or against. I just, it's no longer supported based on what you've said by the argument that they're losing eggs they would otherwise be able to keep. Some of it's about proper informed consent, especially at an age where the financial incentive can be very persuasive without understanding. That makes sense. Not that it harms your

Starting point is 02:05:00 fertility later, but that you're going to have genetic children out there. And you might potentially, and we are seeing this now, we don't know if you individually will have infertility for a variety of reasons because you're not trying to have a family until much later. But the same concern doesn't seem to exist for men who are donating sperm. I mean, it should. There's this whole donor-conceived community where people are really talking about putting new restrictions on, will you sperm donation, For example, there are sperm donors who have hundreds of children, hundreds, right? There are these sibling pods because it's been so unlimited and sperm banks are a business that work to make money and they make money by selling more sperm. But that's not healthy, one for a population, you need genetic diversity.

Starting point is 02:05:48 But also, it's not healthy necessarily for one person to have all these have siblings and to just not know when you're going to run into somebody who could potentially. be your sibling. Is it this guy at the bar that you like? Do you have to worry about that if your donor conceived? So we're starting to see sperm banks finally start to reel back and put limitations on how many families. Total children's tough, right? Because one family might have a child and you want them to be able to have sibling children, but at least for how many families that that donor can contribute to. And we're seeing sperm donors deal with the fact that now there's no anonymous donation. We can act like anonymous donation exists, meaning it is not identified at the time that somebody's utilizing the sperm. But with, you know, direct-to-consumer testing for genetics, like 23 and me

Starting point is 02:06:39 and ancestry, people are being connected with their sperm donors, with their egg donors, with their sibling pods. And we have to believe that technology is only going to improve over time. So what people do for money, especially when they're young, I think without understanding the potential ramifications. And I don't want to act like sperm donation or egg donation are bad. They give people the opportunity to become parents that otherwise might not be able to. And that is a lovely and a beautiful gift. But you need to understand what that might mean and how that might impact your own potential children later too to know that there have genetic half siblings out there. Egg donation, people do get compensated much better than sperm donation.

Starting point is 02:07:27 there's certain characteristics that are hard to find that get compensated even more so, and certain, you know, ethnicities, doctor degrees and things like that where somebody can really pay for their education by donating their eggs. It's a dilemma because what you'd love to say is like, freeze some eggs for you, too. If you're going to do that, you're at the perfect age to freeze your own eggs. And there's been strategies to try to mitigate this. And I don't want to get off too much on a tangent, but it's a really fine line that you walk with what people understand. So there is a company, and I won't name them, but they are promoting that young women donate their eggs, and they will freeze half of them for you.

Starting point is 02:08:14 And half of them will go and become donor eggs. Interesting business model, but I could see the potential ethical concerns. So I think ethically, this sounds good because you get to freeze some. eggs. But I think more people will donate eggs than otherwise would have for some of the reasons we previously stated. And I also think you would get more money by simply donating your eggs and then turning around and paying for us round of freezing your own eggs. You would get paid more and you'd have more eggs because one of the issues is do you now falsely believe that you have enough eggs in the bank because you did this split? But you don't really have enough because we

Starting point is 02:08:54 already walked through the math at 20 eggs doesn't really result in such a high probability of having a multi-child family. So, you know, there's a lot of ethical debate in gamete and embryo donation. It definitely is the Wild West, and there's uncharted territory, even an embryo donation. There's places who are very unethical about it, who will only allow people to have embryos if they are heterosexual, been married for three years, make a certain. certain income, submit to a home study, yet they let the people have no say over the embryos that are transferred, be it how many, what stage, what quality. And they are taking evil's money and putting terrible embryos inside of them and really wasting their resources, which

Starting point is 02:09:42 could have been used in another way. Yeah, the dangers of prophetization of biology. Right. And tech entering spaces is amazing, but also technology starts to advance before studies. Right. Tech is going to become, has more finance backing than we see scientific studies get. I feel like one of the major questions out there is whether or not IVF babies, we'll just call them that, have a higher incidence of things like spectrum conditions or other developmental trajectories, let's call them. And I'm not trying to be politically correct here, but, you know, I think nowadays the word disorder, It has to be like really carefully examined when considering any neurologic and psychiatric situation.

Starting point is 02:10:32 You know, we've had discussions about this on this podcast before, but a lot of people are wondering, just to be to be direct, a lot of people are wondering, do more IVF babies have autism than non-IV babies? Is this a good question? And it's changed over time in a couple different ways. And I think this is important to understand. So if we just think about the hormonal environment with natural conception, and, you know, you have a peak estrogen, let's say you have 200-something, you have progesterone being made, the placenta is implanting. And what is the main difference with IVF babies? And a lot of it has been tied back to the uterine environment, especially in what we call fresh embryo transfers, which is really not a common practice anymore.

Starting point is 02:11:19 So in a fresh embryo transfer, I'm going to take the exit. out of your body, fertilize them in the lab and grow out embryos. And then I'm going to put the best embryo back in your body five days later at the natural time of implantation. And if we rewind the clock, that's how IVF was done, right? When you couldn't freeze embryos very well and they didn't survive. And you'd put lots of embryos inside because they wouldn't survive. And that's the early days of IVF when you saw a lot of multiples, a lot of high order multiples. And of course, multiples have their own distinct issues that put them at higher risk for developmental disorders and issues with development and birth risks in general, right?

Starting point is 02:11:59 They're common, to be fair, they're commonly referred to as disorders. I just think around autism in particular, there's a camp, a growing camp out there that one, it referred to differently. We've covered this. Anytime this comes up, I bring up both just to highlight the fact that, yes, we are aware and sensitive to that emerging issue. Right now, unfortunately, for sake of conversation. There's no new nomenclature.

Starting point is 02:12:22 So we could easily get caught down in the attempt to try and like, you know, smooth over everything with everybody and as a consequence confuse everybody. So I think we'll go for clarity forward with the understanding that the nomenclature is changing. Can't even say alcoholism anymore because it's alcohol use disorder. And I don't have a problem with that. But a lot of people wonder if those are two different things. It's just confusing. And we want to simplify science for people.

Starting point is 02:12:45 Right. Exactly. So feel free. Okay. So when we first were doing IVF, we're putting embryos. back in an extremely unnatural environment. If you have 20 eggs growing and each egg makes 200 picagrams of estrogen, suddenly now you have these extremely high superphysiologic estrogen levels, higher progesterone levels because there's more corpus luteums. And this environment is not

Starting point is 02:13:08 the normal for how the placenta would invade into that maternal blood circulature. And a lot of these issues that are commonly associated became so because of placental issues. So, a lot of things like growth restriction, small for gestational age, preterm birth, which further puts you at risk for other developmental disorders, were associated with these fresh transfers. The field has changed. We do a lot of frozen embryo transfers, and a lot of it for this reason, we see huge improvement in neonatal outcomes when you bleed off that high hormonal uterine environment and then regrow the lining of the uterus and a hormonal level that's more natural and then transfer the embryo, and we see completely different fetal outcomes.

Starting point is 02:13:54 So that's fantastic as far as looking at the change over the field. But of course, if you take all IVF babies over all time, it's a little murky because you have modern practice and old practice. We also know that infertility people, if you get diagnosed with infertility, so you're under age 35 and you try to get pregnant with regular periods for one year and have not. not had success or you're 35 and older and you've tried for six months and you've not had success, you meet the medical definition for infertility. When that happens, you now statistically, regardless if you get pregnant naturally in the next month or you do IVF, you have a 1% higher

Starting point is 02:14:36 chance of birth defects and you have a slightly higher chance of developmental disorders. So is it more population-based versus procedure-based? And there's probably something to that to underlying a lot of potentially what goes in or what can cause infertility when it comes to, you know, quality of eggs or sperm or uterine environment or things that we're still learning about. When it comes to autism specifically, the number one strongest association we have is advanced paternal age. So when you look at the people and the male sperm comes from an ejaculation after age 50, that one does have the highest significance associated with autism. And also, with some other very interesting autosomal dominant disorders. So we don't want to take advanced

Starting point is 02:15:23 paternal age likely, although it does get so much less attention than what we call advanced maternal age or being over age 35 and a woman. And that is purely because of the differences in the sperm and the egg environment and how their quality is impactful. Thank you for that answer. I think it's really important for people to hear that because, you know, the lore out there is that IVF, higher incidence of autism and IVF babies, but it sounds like a good percentage of those could be because of age-related factors as well as technology-related factors

Starting point is 02:16:00 and that the technology is getting better all the time, if I understood correctly. We didn't complete the discussion of IVF, and I want to do that, talk about Ixie and a few other things. I know that's definitely your wheelhouse. Before we do that, can we inject a little sub-conversation around this because I neglected to bring this up earlier. And I know there's a lot of curiosity about this.

Starting point is 02:16:23 And then we'll finish off IVF. Can we do that? Let's do it. Sort of a pause in the IVF. So the eggs are out. They're frozen. Spirms out. It's frozen.

Starting point is 02:16:32 Or maybe they're going to put live sperm on a non-frozen, excuse me, sperm directly onto those unfrozen eggs. We'll pause there, intermission for those potential embryos. And talk about something that you've been, very open about, which is, and a lot of people are not, frankly, in your profession. So I really appreciate this, which is nutrition and supplementation to optimize the health of egg quality and not just for people who want to get pregnant, but for people who believe that fertility is a proxy for overall health. So, I mean, are there things that people should

Starting point is 02:17:11 eat and not eat, things that people should supplement and not supplement in order to optimize their fertility? I mean, this is definitely an interest of mine, right? All my fellowship research cycles around fecundability and natural fertility. And I think we really do a disservice by how medicine really is categorized by organ systems because we act like things in one place don't impact the other. As if. Right?

Starting point is 02:17:35 But you have a body and your body and especially your hormones change and fluctuate and they're meant to. They are meant to be a dynamic system. but the world and the environment of which you are subjecting your body to has proven changes on both hormonal function and also when it comes to egg and sperm quality. And so if you are somebody who just wants to live your healthiest life and have your most regular periods and have your hormones as well balanced as they can be for a lack of a better word, we'll just say that that means that they're functioning normally.

Starting point is 02:18:10 then paying attention to the things that you do are really important. And so I know this is a big one for you. Sleep is probably the number one thing that people don't do that does impact their reproductive hormone system and therefore can impact egg and sperm quality because sleep is when you have cellular repair and when you can drop your inflammation levels. We know that inflammation is just toxic to eggs and sperm. It is. The inflammatory environment is not ideal for conception.

Starting point is 02:18:38 And then for a female, you have to deal with the fact that you have your egg quality, but you also have how inflammation or what you're exposed to impacts your uterine environment. So you have a two-fold situation here. So none of this should be shocking news when it comes to nutrition, but it is not talked about enough. You're right. Decreasing inflammation by the foods that we put in our body is consistently shown with an improvement in fecundability, an improvement in ovulation, an improvement in success with IVF, and a decrease in miscarriage. Right?

Starting point is 02:19:15 Huge studies have looked at these. Now, the big caveat is that nutrition studies are super hard because people who consume flax, for example, tend to have other good health behaviors that sometimes make it hard to identify what flax did versus their general health versus somebody who eats fast food every day. So nutrition studies tend to be observational, and fertility studies are really hard too, because what end point are you using? Is it getting pregnant? Is it live birth? Are you looking at IVF? Are you looking at natural fertility? And we have a lot of different overlap that makes both of these a little bit difficult. And so they're all cohort-based or population-based studies where you analyze how people perform when it comes to fertility treatments or getting pregnant naturally based on their exposures to certain. certain things. Diet's high in fruits and vegetables are good for you, right? Fiber, antioxidants. Fruit is not bad. Fruit got this really bad reputation. Really? I love fruit. I love fruit, too, but people think that it has sugar and that it's bad for you. It has fructose. But it is, no, it's not, that type of sugar is not bad for you. If we can just agree on the fact that fruit has a lot of nutritional benefit, especially when it comes to vitamins and antioxidants,

Starting point is 02:20:31 that can be extremely beneficial in decreasing inflammation. Grain. So whole grains, especially that your body, you know, provide a lot of great fiber. So, of course, if you have celiac or your gluten intolerant, you're a different category. But there was so much focus on keto and people eliminating grains as a food group overall. And even though that might be utilized in a dietary strategy to lose weight and losing weight can improve fertility, likely because of inflammation being the primary driver, because we know that even in studies where I take donor eggs and I transfer that embryo, into somebody who's overweight, they have lower odds of success than if they were a normal BMI. So we can't act like that causation is just on egg quality from obesity, right?

Starting point is 02:21:19 There's also some inflammation, some inflammatory changes that impact the body's ability or desire to allow an embryo to implant. So fruits, veggies, whole grains are all good. Interestingly, you know, dairy, dairy tends to be, okay. in most studies, but what we do see is that if you're going to have dairy, have the real thing, the processed dairy, the skim milk, that actually decreases your fertility. And likely because the processing, to make it still look like milk when you take out the fat, is adding in things that are unnatural, potentially impacting your fertility.

Starting point is 02:21:59 I don't drink milk anymore, but when I was a teenager, I drank half and half. I'm not recommending anyone did that. Remember I was a skiing teenager. You were trying to book up. Well, no, I just could afford to. I wasn't trying. At that age, I wasn't trying to at all. But it was just delicious.

Starting point is 02:22:13 But so cheeses, full fat milk, half and half, yogurt. Yeah. But don't choose the skin one. Choose the actual one that comes with some of the milk fat. Fat is not bad for you. There's also this, right, hopefully we're getting away from it, but there's been such a low-fat craze or this real attention that fat is so bad. but fat comes in so many important forms,

Starting point is 02:22:39 avocados and oils and nuts, dairy, meat, fat and cholesterol are the backbone for all hormones, right? So you need that in order for your body to make the estrogen and progesterone that it needs to allow this whole process to happen. And so there's this idea that those are bad for you. That's just really not.

Starting point is 02:23:00 So healthy fats, whole grains, fruits, veggies. And what about proteins and meats? because I think within those categories, you know, I'm a big fan of sustainably, you know, like raised meats if possible. Some people choose not to eat meat, but fish eggs. Love it all. Okay, so let's just go through the meats and the myth and the facts. So we'll do tofu. So there's this big issue that tofu has soy and that too much soy can be bad because soy can be a phytoestrogen. Tofu does not negatively impact fertility, even in men. In fact, it can improve it because it does have some antioxidant, like,

Starting point is 02:23:34 properties, lots of iron. When it comes to fish, fish are fantastic sources of healthy fats and omega-3 fatty acids, which are very crucial in the reproductive process. We do worry about if you're pregnant having too much fish and overexposure to mercury and how that can impact fetal brain development. So the general recommendation is three servings per week. Let me guess a serving is like four to six ounces as opposed to like a real human that eats, You know. Oh, real human. Yeah.

Starting point is 02:24:03 That eats, you know, six to eight ounces of things. Yeah. And I think it's important to say, even though people will tell you that when you're trying to get pregnant with the idea of we don't know when you're going to be pregnant, if you're going through things like egg freezing or IVF and you know when you're going to be pregnant, I wouldn't feel like you have to restrict yourself on the consumption of seafood during those time periods when you know you're not pregnant yet. Because really the concern is about that mercury and what it could potentially do,

Starting point is 02:24:31 to a fetal brain. And raw seafood, correct? No sushi, no sashimi. Well, when you're pregnant, correct. And that's mostly because of the risk of infectious disease that can cause, you know, severe brain development and other issues. What are they do in Japan? I don't know.

Starting point is 02:24:44 I don't live there. They probably laugh at this. They probably do laugh at us. They probably do laugh at us. Someone who's been pregnant in Japan. Yeah, reach out. Tell us. Or conceived in Japan.

Starting point is 02:24:55 Don't tell us the story of the conception. But tell us, tell us. Oh, did you have sashimi? Overall, meat is a really broad category, and studies study it differently. Like, is it all meat? Are you distinguishing out red meat and chicken? Are you putting it all together? I mean, obviously, I think we can all come to the agreement that processed meats are not good for a variety of different reasons.

Starting point is 02:25:19 In addition to being carcinogenic, those toxins do negatively impact fertility. Now— So, deli meat, no bueno. So, yeah, but in specifically those things like the best. bacon and the, like, the things that are really highly prosely hot dogs. Sorry, the Fourth of July hot dog picnic. But those things really do not provide nutritional advantages and only harm. Especially then when we have red meat, for the most part, red meat when isolated individually, and most circumstances in moderation tends to be fine. I usually tell my patients, I want them to

Starting point is 02:25:56 eat a plant forward diet. But it doesn't mean no meat, but I say, look at your meat servings. I don't want it red meat every single day because there was a study looking at IVF and looking at embryos. And the more servings, a lot of nutritional studies based things on quartile. So who eats the lowest and the second most and the third most and the topmost. And people who ate in that top quartile of red meat had lower progression of embryos through the culture, so less embryos that developed. less normal embryos and lower success rates. And do we know anything about how that meat was arriving?

Starting point is 02:26:33 No, unfortunately we don't. Like hoagy sandwiches? We don't know. We don't know. We don't know. Like grass-fed steaks. Right. These studies are not wonderful, but that doesn't mean that they don't hold merit in helping

Starting point is 02:26:42 us guide counseling. But, no, that one was how many servings of red meat do you eat in a week, right? So we don't really know, does the really ethically source, the grass-fed, you know, this environment, which we feel like. is much less toxic than potentially, let's say, like a cattle factory where the cows are injected with all sorts of things. Is there a difference in how those impact your reproduction? Probably, right? If this cow is getting injected with a lot of hormones, why are we thinking that it's not impacting the meat that you're then ingesting into your body?

Starting point is 02:27:14 I think our audience will certainly subscribe to that idea. I think most of them will. I mean, the notion that like the pollutants you breathe in the air somehow are not, the air that you breathe into your lungs is just like completely naive. But people feel that way and they hold strongly to this idea that it can't be this thing that I love that is causing this problem, right? The denial of the association between what we put in and on our body and how it impacts our body's function is really strong in some people. And I think it's really just lack of education and awareness because the medical community,

Starting point is 02:27:55 for so long did not address these factors, right? Your doctor never talked to you about nutrition. And so it just became this idea that it must not matter, otherwise your doctor would talk to you about it. I think sugar is the last thing I just didn't mention, but added sugar and artificial sugars are bad for you. Artificial sugars. Artificial sugars, too. Including stevia, so plant-based, low-calorie sweeteners. Stevia itself hasn't been studied as much as the other ones, things like sweet and low and all of those. But what we do know is that they interfere, they cause inflammation inside the body. And then they also can cause a stress reaction and they can cause higher rates of miscarriage

Starting point is 02:28:40 when you intake more sugar and artificial sugar. So that's a lot to wrap your head around. And I say the same thing to every patient. One cake, one this, one hot dog. I mean, those things individually are not going to make a difference. Right? It's the choices that you make every single day that are going to set you up to be your healthy self or not. And so you should make choices in line with how you want to treat yourself. You want to be in your best health. You want your hormones functioning the best. And if that added

Starting point is 02:29:11 helps you get pregnant when you want to, helps you have a better chance of success with IVF. Oh my gosh, what a fantastic benefit. But that doesn't mean you can't enjoy some of these bad things here and there. as long as you've set yourself up on the day to day where you're giving your body lots of nutritious food that it needs to make hormones. Similarly, being, you know, very underweight and calorie restricting, we all know, is really terrible for your reproductive system and can cause the brain to totally shut down ovulation because it senses that you can't have a pregnancy. If people miscarry, excuse me, by virtue of being underweight, does the body, like I learned

Starting point is 02:29:53 some years ago, I think this is still true, that one of the signals for the onset of puberty and females is that leptin hormone is secreted from body fat. That then signals to the brain, to the hypothalamus, like, okay, there's enough reserves to create environment. It's a signal about environmental. Yeah, there's enough extra fat to have a baby. Yeah, and there's presumably enough food around to sustain that baby. Right. Are miscarriages and lack of body fat correlated? On both ends of the spectrum, yes. Right. So lack of body fat and being overweight, we see decrease in getting pregnant per month, and we see increase in losing pregnancies. So certainly there is a healthy medium where your body has what it needs. And that makes sense because if you have, I like to even say, hypothalemic dysfunction. So maybe your brain's not totally shut off where it's sending out no hormones and you're not ovulating because you're not getting pregnant in that circumstance. circumstance. But certainly, ovulation disorders are on a spectrum where you go from a perfectly synchronized cycle to one that prolongs it, you know, gets shorter together than prolongs and then

Starting point is 02:31:02 you have nothing. There's this spectrum of dysfunction, which is representing your hormones not being necessarily perfect, and that can have impacts on the placenta trying to grow into that uterus. I mean, the placenta is fascinating, right? An entire talk just on the placenta. but it does this incredible job where your body has to not reject it, yet allow it to eat away at the side of your uterus and grow into your blood vessels. But that requires a very specific hormonal environment for it to be done and to be done right. I think in the same breath of all this, what you're also asking is, okay, so that's eating healthy. None of that's really new news for most people.

Starting point is 02:31:40 A lot of those things I just said. Well, I think so, but I do want to thank you because I think rarely, if ever, do we hear somebody, so physician, be really direct. about like, hey, listen, some red meat, yes, not excessive amounts of red meat, ideally from sustainable sources, whole fat milk products, grains, fruits, vegetables. I mean, those kind of straight, what, like, do you seem like straightforward directives are actually pretty rare in the landscape of public health discussion because more often than not people talk about nutrition in these kind of elimination diet type things, like, you know, eliminate all the grains or eliminate all the meat or, you know, eliminate all the milk fats.

Starting point is 02:32:18 when in reality, I think people forget that, like, most people out there are omnivores. And they can make better choices about not deli meat, you know, less bacon, if any bacon, right? Have some veggies with your lunch, right? Like, you can make better choices on the day-to-day. I think that is a great point. I think there's a place for supplements. I think the big disclaimer that everybody's going to say with supplements is that they are not regulated like the way medications are, right? And I will say supplements and herbs are different things, right?

Starting point is 02:32:47 a supplement, but many companies are adding herbs to their supplements, and that can get into really murky territory, especially when it comes to how some of these herbs do have estrogen and progestin like properties and can impact reproduction and hormones. And perhaps even endrogenic properties too. So we can't act like everything's created equal. So I always tell people, if I recommend you take a supplement or your doctor does, your due diligence is to look at what is also included and make sure it doesn't have the, you know, these extra added things that they're unaware of because sometimes they can have negative impact

Starting point is 02:33:23 at one stage of your life or another depending on where you are. Certainly, you know, a prenatal vitamin which has folic acid. We all know that folic acid is really important to prevent neural tube defects, but it's also important in cell division and how the ovary is growing follicles and growing eggs. So should people, women, but also men, be taking a vitamin with folic acid even when they're not trying to conceive. There's no harm in having it, but very often pregnancies occur when you're not trying to conceive. And that is a store that needs to be built up three months ahead of time. So we really need you to be taking that ahead of getting pregnant. So not just let's get pregnant right now. I'm going to start this prenatal vitamin. So I recommend anybody

Starting point is 02:34:09 who's in their reproductive years, take a prenatal vitamin. We also know that, Many, many people are vitamin D deficient, and vitamin D does impact reproduction. And so I usually say a thousand international units of vitamin D is not going to be harmful in anybody. It's going to be helpful for most people. Some people definitely need higher levels. So we screen everybody with a vitamin D to see who needs to have extra. But, you know, a blanket statement that extra vitamin D is going to be helpful. Omega-3 fatty acids also extremely important.

Starting point is 02:34:44 in one being anti-inflammatory, but two, brain development of a fetus. So most prenatals now actually do have those omega-3 fatty acids in them. But if they don't, I recommend a patient, take those. Just a brief question slash insertion there. There's a laboratory up at the University of California, Santa Barbara that's published some really interesting data showing that, you know, essentially brain weight, which is just but one indirect measure of brain health, but brain weight at birth, seems to be correlated, at least in some positive way, with the amount of essential fatty acids that mom consumed during pregnancy. Does that sound, does that hold? Yeah, I mean, that does hold? And there's, like, there's my studies about that mice are smarter when they have diets,

Starting point is 02:35:31 you know, with omega-3 fatty acids when they are in utero, right? So the exposure and the time period is really important. And omega-3s have a lot of help benefits when it comes to their antioxidant properties, especially in like endometriosis, diseases that are very highly inflammatory. They can be very beneficial. We're definitely going to talk about your work about after baby has arrived and impact of essential fatty acids. But what would you say is the dosage cut off on this podcast before? I've sort of thrown out numbers like one to two grams per day of the EPA form of essential

Starting point is 02:36:06 fatty acids. And then we could have a whole discussion about omega-3-Omega-6 ratios. But do you think there? there's a upper limit. Is it truly that, you know, let's say up to four grams per day of EPA, would that be advantageous? Is it better than one gram? I tell people a gram. A gram. Okay. That's in alignment with pretty much what we've talked about before. So that's what I recommend, you know, when I give my handout to my patients and they're trying to get

Starting point is 02:36:29 pregnant, it's going to have a prenatal, a thousand I use of vitamin D, a gram of omega-3s, and then co-cutin. So co-cutin, which, you know, essentially in general, is trying to help the mitochondria. That's the whole idea here that it is helping provide support across the body in a lot of different ways, right? Like CO-Q-10 is used in a lot of different areas of the body, but when it comes to reproduction, when it comes to meiosis and cell division and ovulation and egg quality and even sperm quality, there's a place for CO-10 showing benefit without harm, right? And so no, as we said earlier, nothing's without any harm or any risk of harm, but very, very little. So I usually recommend

Starting point is 02:37:11 if you're trying to get pregnant and you take CoQ10, a dose of 200 milligrams three times a day. So there's kind of a higher dose than sometimes people are on. Often prenatals now have just like 200 total in it. And so we- The expensive ingredients are usually the lower concentrations in blends. They're going to use just enough so they can put it on the label. Right. It includes Co-Q10.

Starting point is 02:37:34 Does the form of Co-Q10 matter because you'll find them in gel capsules? You'll also find them in powdered capsules. I always say, I mean, there might be for the individual person. I mean, absorption of medication is really depending on a lot on gut health and other factors. But the number one issue with supplementation is that people don't stick to it. So I always say, whichever one you're going to consistently take is going to be the better form. Great. A question about al-carnatine.

Starting point is 02:37:59 Yeah. And researching a little bit for this episode and others. Oral al-carnatine has been associated with some improvements in forward motility and sperm, maybe egg quality. But we know that a very small percentage of the oral al-carnatine that one ingests is actually utilized. So some people actually purchase and use injectable l-carotene, which is kind of painful because it's in an alcohol-based suspension. So not comfortable.

Starting point is 02:38:23 It's got to be done intramuscularly. But my read of the data is kind of impressive. I wouldn't say super impressive. Are you ever injecting patients or having them inject themselves with al-carnatine? This would be both female or male patients or both. using oral l-carnatine, or do the data just not impress you enough to motivate that? We use a gram of l-carnatine with a gram of vitamin C for our male patients who have any abnormal sperm parameter.

Starting point is 02:38:51 And so that is kind of what we consider the sperm enhancement protocol. And so just that. That with a multivitamin. So those two with a multivitamin and CO-10. So that's kind of like the male protocol. Of course, there's different specifics for one individual person. I don't tend to recommend it for most females. That being said, those who have endometriosis fall into a unique category where inflammation

Starting point is 02:39:13 is so high that usually it's a different environment where we recommend L-carnatine, Nacetyl-sistine, vitamin C and E. They kind of fall into a different category because they have a known inflammatory disease. But if we're just talking about the person at whole who maybe wants to take some supplements for their reproductive health that have very little side effects and for the most part can potentially be helpful, it's going to be, you know, know, Kocutan, Elkarnatine, vitamin C can be helpful, especially for the male, for the female partner.

Starting point is 02:39:45 We're going to be looking at that extra vitamin D in addition to the prenatal with folic acid. And what about women with PCOS? I get so many questions about PCOS. Inocetal. And there are we talking myoanositol or the, what is it, the De Chiro? Do I have that right? You do have that right. Myonocetal is the main driver of anastol and how it can be helpful.

Starting point is 02:40:05 If you, most blends are going to have a combination of both of them, but a much higher ratio of myoanacetal to decyro. And so myoanostal is probably the one that really is doing the work in PCOS. What is it doing? It is definitely helping the body when it comes to insulin and sugar, helping the body be more sensitive to insulin or less resistant to it, essentially helping you respond to what you eat in a better way. And it also looks like it does potentially decrease some of that inflammation pathway in PCOS. In PCOS, this insulin resistance correlates with this testosterone production from the ovary, meaning even metformin alone can decrease testosterone levels based on some of the change that it has in the ovary.

Starting point is 02:40:55 Take note, men, so many guys taking metformin or berberine thinking, oh, this is great, I'm going to lower my blood sugar, mimic fasting, and live longer. and then these are also the same people who are writing to me go, how come when I take metformin, I either have headaches because I'm, you know, essentially hypoglycemic. Yeah, your teeth is low, too. But also their testosterone levels are getting crushed. Not in every case, but it happens.

Starting point is 02:41:18 And I think those are things people just don't think about. They read that a supplement might be beneficial for this one thing that doesn't apply to them, and they start taking it. Also, the evidence on metformin extending life, we had Peter T on here to talk about this, like the evidence for that is like, oh, so. poor. It's just not really that convincing. It may change. But then now all the excitement is about rapamycin. And so, you know, extending your life while plummeting your testosterone, you know, I mean, that's a, actually that strategy has been tried in the longevity community. There's a,

Starting point is 02:41:46 there was this whole castration idea. Oh, I don't know this. Oh, yeah. This was like the Heaven's Gate cult where they castrated themselves. Did they live longer? Well, they ended up committing mass suicide. So, you know, they ended the experiment early. Rightfully. You know, yeah. So in any event, um, going back to, to supplements, sorry, I couldn't help myself, supplements that women can potentially take, just to increase their fertility, even if they don't want to get pregnant, as just kind of creating a milieu of health. You talked about the nutrition, you talked about CO-10, maybe al-carnatine, vitamin C,

Starting point is 02:42:20 the essential fatty acids getting at least one gram of EPA, so that might require taking two grams of fish oil to get the EPA, myonostitol. So how much are you talking about? I've seen some pretty high dosages thrown out there. For my own osteal? 2,000 milligrams. Okay. Taken before sleep or does it matter?

Starting point is 02:42:39 That one doesn't matter. That one doesn't matter. Thank you for covering the topic of supplements and supplementation. This is probably a good point to return back to those harvested eggs. So eggs are out and there's a collection of them frozen. Maybe, just maybe, they're always alive, sorry. Fresh sperm. They're not always alive.

Starting point is 02:43:02 Fresh sperm. They're not always alive. Some portion of the ejaculate is going to be dead sperm, right? Some live, some form motile, some non-forward motile. The twitchers, I read it is the name. I hate those twitchers. Right. And so, okay, they're going to wash the sperm.

Starting point is 02:43:18 Why? Because, yeah, most of what people see as ejaculate or no, excuse me, as ejaculate, is not actually the sperm. Yeah. Okay. So, but sperm are washed. They're in one compartment. You get the eggs out. you or your embryologist at your clinic is then going to at some point decide to combine them.

Starting point is 02:43:38 So is it kind of, is it a sperm race or you maybe could explain Ixie? Yeah. And why would one want, why would one opt for Ixie? And are there any risks with Ixie? Because there you're really, at some level, this is the only place where I kind of sit back and okay, as somebody you know, say neural development, like at some level you're saying, hey, that sperm looks good. Whereas when you run a sperm race, nature is saying, hey, they're saying, hey, they're

Starting point is 02:44:01 this sperm really did beat all the other sperm. So let's segue first, because I think this is nice, because the question I get asked all the time, when we talk about nutrition and supplements and all of that, is to now you're doing IVF or you're freezing your eggs. And what if, what behaviors are good or bad? Of course, all of those same ones are, but about how long do you need to do them?

Starting point is 02:44:23 And this is why if you live healthy most of the days, it doesn't really matter because that's how you're living. But we already know the sperm cycle is about 90 days, And the eggs, I like to say, even though they're in the vault, they become, they start lining up, getting ready to exit the vault and become more susceptible to the things you're doing in that 90-day window. And we know that to be true as well. So they start to be pre-selected for who's coming out the next month. They start to line up. And so making these changes as you start thinking about getting pregnant, doing fertility treatments, is still extremely beneficial.

Starting point is 02:44:57 People will often say, well, I haven't been doing that. So why start now? It's not going to make a difference. But truly, it can. Or I'll drink up until the week. Until the day up, right? I'll just get it in the entire time. Like, I'm going to have my two glasses of wine, which actually equates to about six

Starting point is 02:45:14 glasses of wine when you measure out by the volume. Right, right up until the week before getting pregnant or something like that. Yeah. But no. So people always ask, what should I be doing? Is these healthy behaviors and you should be doing, you know, this whole time. When we do IVF, and I'm going to get to all the things you just asked, but earlier you said, well, how tolerable is it? The truth is you're taking shots.

Starting point is 02:45:36 These are subcutaneous shots during the egg growth process. So next to the belly button? Yeah, next to the belly button, like how a diabetic gives insulin a very small needle. I mean, nobody loves shots, but they're not a big intramuscular shot. It's not like a flu shot or something like that. Listen, I've been to Austin, the Texan mosquitoes. They're way worse. They hurt way worse than one of these needles.

Starting point is 02:45:55 Exactly. So you're going to use those medications for about 12 to 14 days. You're going to have your follicles grow. You're going to feel that. So you're going to have pelvic pressure. As your estrogen rises, you're also going to third space your fluid, which means your fluid, your water component of your blood is going to start to just eke out a little bit. And you're going to get more bloated. You're going to have more water, weight. You're going to feel puffier. And that is very common just because of getting the eggs to grow. You're going to mentally, be fine because the female brain loves high estrogen. So you're doing fine. And that's one of the main concerns is how emotional will I be. And during this phase of the process, people do great. When we take the eggs out of the body, it's about a 20-minute procedure. It is usually done under IV sedation, like propofal and fentanyl. And we are watching while we drain those follicles and get test tubes full of the eggs. Do some people opt to not use any, you know, say, I hear the word fentanyl. And I'm sure a lot of people are like, wait, fentanyl crisis.

Starting point is 02:46:56 And, you know, obviously fentanyl is a drug that has its uses, valid uses in the medical community. Does anyone just kind of opt for, you know, just? I mean, we have an anesthesiologist who is really talking to the patients. I mean, propopal is the base of it. Certainly there's some patients who may want to avoid narcotic usage and they use different strategies. I mean, there was this huge, right? The Retrievals podcast came out from, like, the New York Times doing a deep dive into a fertility clinic. Yale where a nurse was siphoning off fentanyl for herself.

Starting point is 02:47:26 For herself and replacing it with saline and giving patient saline, this clinic did not do anesthesia-based propofal. So they were supposed to just get fentanyl and have kind of a less pain environment, not a no-pane environment. And not just a few. Hundreds of women reported extreme pain, extreme pain through the procedure really speaks largely to pain not being taken seriously when they went and found this out. Whoa.

Starting point is 02:47:54 What happened to, I can't help but ask. What happened to this technician? Well, I mean. Yeah. They're, they're trying to find fun and all behind bars. Yeah. I mean, and, but it's huge as far as to like, I mean, I can't imagine, I can't imagine doing, I do this procedure like all the time, right?

Starting point is 02:48:10 I've done thousands and thousands in my career. And I can't imagine having people be in pain during it. So it's, but it's important to know that some clinics don't use. IV sedation or they don't use propofol, they don't put you to sleep. Understanding what your clinic is using is really, really important to set the expectations or to know, am I going to be awake or am I going to be asleep? Can a patient ask you to what specific drugs are you going to give me to kill pain? For sure. And I mean, some clinics only do one. Like, I am not going to do a retrieval under no sedation. Now, some clinics would allow that. Some clinics, that's all that they do.

Starting point is 02:48:47 but you, that's a huge piece of the puzzle that you need to know if you're a patient. Are you going to be feeling pain, not feeling pain? What's it going to be like? I'll see most clinics use propofol and put patients to sleep. And so you take a nice little nap for 15 to 20 minutes. The eggs are retrieved from the follicles under direct visualization. They're in test tubes. You wake up and you're going to feel crampy.

Starting point is 02:49:12 And you'll get a period 10-ish days later. But this is when you'll feel your worst. And this is just the one thing I want to say about tolerability of it. Can you get pregnant in that time? Yeah, yeah, yeah. And there's a case report of an egg donor who was donating her eggs, and she had sex with her boyfriend. And because not every egg is always retrieved from the follicles or some small ones could ovulate too. And she got pregnant with quintuplets.

Starting point is 02:49:37 Whoa. Okay. So you have to really tell people not to have intercourse, one, from an infectious standpoint, because we really are poking, you know, a pretty large-gauge needle through the vaginal mucosa into the paratum. cavity. So we don't want to introduce infection, but also for pregnancy in that time period. And if you got pregnant, your risk of what we call ovarian hyperstimulation syndrome, or OHSS, is very profound. So what is normally happening is after the retrieval, your estrogen and progesterone are going to drop. You're going to feel a severe PMS, for lack of a better word. It's when you'll be more emotional.

Starting point is 02:50:11 You're still pretty bloated until this all heals. If you get OHSS, which is very uncommon. in modern practice. But when you did fresh embryo transfers or people who don't utilize some of the modern protocols, this means that HCG continues to encourage all those follicles to make estrogen and progesterone. And if you are pregnant, you're just going to have a constant yet exponential increase in HCG. And so this is going to get worse and worse. So we really don't want people to get pregnant in that time period. So when during that time period, should they avoid sex. So is it in the few days before the extraction? So typically, I usually say it's from like day five of your stimulation. Okay. So usually the earliest egg retrievals are kind of around cycle day

Starting point is 02:51:00 nine or ten if somebody goes fast until your next period comes. So that's usually about a three week time period where we want you to abstain from intercourse. So for the most part, though, the more eggs you have, the more you're going to feel both this hormonal and physical shift than the fewer eggs that you have. So if you have a low egg count and you need to do IVF or freeze your eggs and you might do multiple cycles or rounds, you're going to tolerate it actually pretty fine because you're not going to have these huge shifts. Physically, you're going to feel fine. And that's always a big concern. When you mentioned earlier about different stimulation types, people have this idea that things that are more natural are better, right? It's just like this human thought

Starting point is 02:51:43 that natural is good and synthetic is bad. Naturally, you ovulate one egg a month. When we're trying to get eggs out of your body, the success is determined by how many eggs I can get and how young you are. So it doesn't make sense in most circumstances to do a minimal stimulation protocol, meaning purposefully under-stimulating somebody by saving the money and medication cost in order to purposely get fewer eggs because their odds of getting the ultimate success of what they want is going to be so much lower. Is there, I don't want you to be in the position of, I don't want to put you rather in the position of kind of like having to demonize your colleagues in your profession.

Starting point is 02:52:31 But I could see how there's a pretty significant financial incentive for people who are really desperate to have children or who just simply might want to have children down the road to hear low stem is better. We're talking multiple low stem cycles. They might be even a fraction of the cost of a full stem cycle, but then there are many, many more low stem cycles. You got it. You can make a lot more money by doing things that are not in the best interest of the patient.

Starting point is 02:52:55 And I mean, that's not uncommon in my field, which is very sad. But it does mean that because reproduction and IVF are so foreign and unknown, so many people walk in blind, not knowing if what they're being told really makes sense for their situation. There are a couple situations where minimal stimulation makes sense. If you're only going to make three eggs, you're only going to make three eggs. I don't need all the drugs in the world to tell your body to make three eggs because there's only three. And so that is a scenario where minimal stimulation does make sense. And then there's the scenario where there's something called InvoCell. Has your researched exposed you to this? No. Invo Cell is a little.

Starting point is 02:53:34 is a way to try to take IVF into making it more financially accessible for certain patient populations, mainly people who don't ovulate, like your very refractory PCOS patient who doesn't respond to medication or who have tubal factor in fertility, right? So your fallopian tubes are blocked because of chlamydia or endometriosis. And we just have a problem here that egg and sperm can't get together because you're not ovulating or your tubes are blocked. And, and In Invocell, it's a device that is plastic. And you can fit up to 10 eggs in it. And there's a little middle chamber where the sperm can go.

Starting point is 02:54:15 And so you go through this IVF process with the goal to only get 8 to 10 eggs because that's what fits in the device. And then you put the sperm in the middle of it. And then you put it inside your vagina and you hold it in place it with a diaphragm. And the vagina is the right temperature to incubate. And so you incubate your embryos in this little invocell container inside your vagina. And then five days later, you come in and we take it out and we take the best embryo and we transfer it. And you can do a fresh transfer because you didn't make so many eggs so your hormones weren't so high. Do people like this procedure?

Starting point is 02:54:52 There's something that seems like staying in proximity to the sperm and egg. Like you're taking it home. Okay. So I love this procedure in some circumstances. and I see it applied often in the wrong case, and that can be frustrating, right? Because it's still not cheap. Even if it's cheaper than IVF, it is still not inexpensive in any means. And so patient selection, like most things in this field are so important.

Starting point is 02:55:16 So let's just say, if you've had no, like if the sperm's the problem, then it's probably not smart to just presume that the sperm and egg will be fine in there, right? Like that might be a case where you really do need help with it. assisted fertilization, or if you have unexplained infertility. If we don't know why you haven't been able to get pregnant, because everything looks good on paper, what if fertilization is the issue? And these are circumstances where you pull out an invo cell and there's no embryos, and you don't really know where it went wrong. Was it the fertilization step? Was it the growth step of the embryos in culture? So you do have less data. Notably, I like data. You can't do genetic testing.

Starting point is 02:55:55 and this isn't really a strategy that allows you to freeze embryos for future family growth. That being said, the young patient who's got great-ed quality who might have really bad PCOS or tubal disease, it can certainly allow them the opportunity for a child at a lower price point when they still have many reproductive years to finalize their family. It also is a lovely option for people who need donor sperm to conceive because the success rates with this are so much higher than an IUI, which is what a lot of people use an intra-uterine insemination or putting the sperm in the uterus. So now we're able to improve this outcome. So like our same-sex couples or our single parents by choice, if it's a single woman who's trying to become a parent, then they need to buy donor sperm and go through the process anyway.

Starting point is 02:56:45 This often can improve that efficacy through the process pending their age and other factors. There was a study that was just really neat. There was a lesbian couple and one of them the eggs came out of, and the other one incubated the embryos. And then the other one had the embryo transfer. But it gave both partners a way to feel a little more involved in the process, which I just think is always a really cool way when you have these different options with reproduction. It seems also that it's more of a three-dimensional environment. I always imagine that the petri dish approach is so two-dimensional compared to the bottom. body and all these things, having done cell culture before and, you know, cultured neurons and

Starting point is 02:57:28 and things of that. So, like, there's all these concerns about, like, the concentration of CO2 and the thing, or, you know, God forbid, if there's a fluctuation in, you know, you have backup generators and things, but in the electrical flow to the incubators, that's disruptive. Whereas the natural environment of the body, even though it fluctuates in temperature, it's, I mean, this has evolved over, you know, tens of thousands, if not, you know, hundreds of thousands of years to be the process by which embryos are created. So here's where I sort of default in my mind anyway to the kind of like, oh, like it seems more natural.

Starting point is 02:57:58 You're incubating in the quote unquote more natural environment. Yeah. But at the same breath, why are you having infertility if you're an infertility patient, right? So if you need donor sperm, you maybe don't have infertility. Or if you have tubal disease, you have a very defined reason why we don't think that there's this huge inflammatory issue in your body or something unnecessary. known. So again, I'll see it apply to people who really are bad candidates for it based on their age or based on their diagnosis. And so it's not always better, but for the right patient, I mean, I've had patients have babies that way who otherwise may not be able to. So it can really open up the door. So that's the most minimal of the minimal stimulation, right? Then we have minimal

Starting point is 02:58:44 stimulation because you don't have many eggs, so we don't really need that. But for the vast majority, of people who go through egg freezing or IVF. We are really trying to get as many eggs as you potentially have. Everybody has a different number. But whatever you have, whatever that antropholical count is for you, is what we're trying to get. And that's what these combination of medications is trying to do. When the eggs come into the lab, if you have egg freezing, very important to know is before we get into the Ixie discussion, the eggs are stripped of their outer cells, which is called the cumulus.

Starting point is 02:59:16 That's what the sperm has to attach to in order to fertilize. In order to freeze the eggs, those cumulus cells are stripped off, the eggs are frozen, you have to do Ixie. So if we're going to lead into this Ixie conversation, if you're freezing your eggs, you're having XI when you fertilize them. So I don't want somebody to ever not know that if that is what they are choosing. And IXY is, you can tell us. Yes, XSI. It's ICSI or intracidoplasmic sperm injection. It is taking a sperm that under the microscope looks normal in shape and move.

Starting point is 02:59:49 moves well, and you're pulling it up into a little needle, and you're essentially using a little laser on the side of the egg or the zona pellucid of the egg, and you're injecting that one sperm into that egg cytoplasm. And you're picking that sperm on the basis of shape, motility. You're picking what you think is the best sperm in the batch, obviously. Yeah, you're picking. I mean, there's going to be one sperm per egg, so there's multiple sperm that are chosen, but you're picking sperm that look like they have the highest potential.

Starting point is 03:00:18 My understanding is that there's a range from very low to potentially high, but hopefully not high, of DNA fragmentation in pretty much every cell to buy. Like, the cell is always repairing its DNA. So when visually selecting a sperm for XI, it's based on morphology, shape, and motility. Right. You can't see the DNA damage inside the head of the sperm or the DNA itself. Are we soon to have a technology where you could actually, like, get a dye that could label DNA fragmentation and select? because I feel like so much, like when we talk about embryology, not to get too far down in the weeds, but like the methods of selecting eggs and selecting sperm, I mean, these are the same methods

Starting point is 03:00:59 that have been used in embryology for like since the 1930s. Like, oh, this one looks good, that one looks good. And the skilled embryologist can really develop a real talent over time of like knowing what correlated with healthy pregnancy and an offspring. But I do like technology. You would think that by now, 2023, that someone would have some dye that you would, you could drop on the sperm and go, well, like, that one has a lot of DNA fragmentation and that one doesn't. I know, right? There should be better ways to choose which sperm. There's definitely people are trying

Starting point is 03:01:27 things. Nothing has proven to be helpful so far. There's definitely some interest in this because we're starting to get more insight as we have become better at embryo culture, getting embryos to grow, doing genetic testing on embryos to understand that that male genome kicks in at day three. And there's a subset of people who have beautiful fertilization and embryo growth day zero to three. And that's all on the egg. And then as soon as that male genome kicks in, you have this huge drop off in your embryo number. And even some of this is in the context of normal sperm parameters, right? So things aren't really normal, though, or there's something underlying it.

Starting point is 03:02:07 Does that mean that every embryo failure on day three post-fertilization is sperm-based? No, of course not. but it definitely means that none of the ones before that can be blamed on the sperm, and once after that, there's definitely still maternal and sperm contributions. We don't want to create any, you know, a couple disputes around this. But it can be an insight when you're trying to look through somebody's IVF cycle about potentially modifiable factors, right? Can you improve sperm quality by some of these lifestyle measures?

Starting point is 03:02:37 I mean, the debatable thing about a DNA sperm fragmentation, so what is that? It is not a normal semen analysis, but it is like that as far as it's a sperm sample that is then sent off to be evaluated how much fragmentation or abnormal DNA is in the heads of those sperm. The studies have shown that people who have abnormal DNA sperm fragmentation should do Ixie. Okay, that's like the point of the study. Now, Ixie has become very commonplace. So Ixie, choosing the sperm to put into the egg, originally didn't exist. Right. So what's the alternative conventional fertilization? This is having your petri dish, your eggs are on it, you scorch your sperm, you cover it up, you put it in the incubator. She didn't mean you squirt your sperm. She meant the embryologist squirts the sperm on top. Just to be clear. And then pulls it out and the next day sees by which eggs and sperm fertilized. Well, it's really devastating to pull out the dish and have no fertilization. And it definitely is a cause.

Starting point is 03:03:41 of infertility, and it can be very hard to know that because fertilization is not challenged on a cellular level until you challenge it. So ICSI used to be an add-on cost. It used to be a separate thing because it was harder to find embryologists who could do it. It's so standard that a lot of clinics do it the majority of the time, purely because you often don't know all the variables that are impacting fertilization, and you're trying to give somebody as many opportunities as possible. Ixie has, in a lot of those original IVF studies, got some of the bad reputation of being the problem with why you might see that 1% rise of birth effects. And so Ixie took the brunt from a lot of that. We really don't see that when we're growing out and we're doing freezing the embryos, doing frozen transfers.

Starting point is 03:04:33 And I mean, I do Ixie in almost every patient. I'm not going to say in everyone. Well, higher probability of success, right? probability of success. And when you get to this point, and so few people have insurance coverage, so they're spending their money, they're getting second mortgages, they're taking out loans, if there's one decision that you say, well, I don't know, you could have zero eggs fertilize, or I could have the embryologists pick the best firm and put them inside the egg, and we expect a 75% chance of fertilization. That makes sense for the majority of people. Yeah, that makes sense to me.

Starting point is 03:05:06 I because I'm obsessed with data and you know the blood work fairly regularly not not obsessively but twice a year or so now I didn't always do that and I actually did one of these DNA fragmentation tests that they're pretty expensive you know they're in the are more than a semen analysis yeah they're they're in the you know low you know there's sort $1,500 or so at least the one that I did it was very informative like I was relieved to see not abnormal levels of DNA fragmentation but I will say that based on everything you just said it seems like it might be the lower cost option because, you know, the alternative is to go through repeated cycles of IVF and it's failing, and that's certainly much more expensive.

Starting point is 03:05:46 It is. And I mean, I will say that there is some current thought by my urology colleagues, right? So I'm not a urologist, but definitely when I have a male who, you know, needs a sperm extraction, maybe he's had a prior bisectomy, maybe he's got very low sperm counts, and we're going and we're doing a sperm extraction procedure that potentially, if you have a sperm extraction procedure, that potentially, if you have a patient who has an abnormal DNA sperm fragmentation, and even with Ixie, has this drop-off in embryo growth after day three, because the sperm are still being made the same way, right? Are they still fragmented?

Starting point is 03:06:18 That potentially the ejaculatory process could cause some of that fragmentation in certain men, and by going in and doing a sperm extraction and not subjecting those sperm to the rigors of ejaculation, for lack of a better word, could potentially lessen the fragmentation and improve outcomes. And I have some patients who we've gone down that road and that has helped them, clear to say there's not a study. That's not the point of DNA sperm frag. It's to try to distinguish if potentially ICSI could be a helpful technology.

Starting point is 03:06:50 But a lot of doctors are offering or doing ICSI because we want you to fertilize your eggs. When they grow out in culture, as we talk about IVF changing, the metabolic needs of the embryo you know, change throughout the process. And so embryo culture has become so much more successful. But even in those best case scenarios, we're looking at 50% progression. So you're going to have loss throughout that culture process no matter what. And you said 50% progression. So half of the fertilized embryos that make it past a let's say day seven, then their screen for chromosomal abnormalities. So then, okay, then you've got, let's say two or three of those, maybe four, depending on how many eggs were harvested. And your age. And then and age, yes, thank you. And then,

Starting point is 03:07:31 And then you said of those that are implanted into, let's say, a woman, 45 or younger, you're looking at about anywhere from 30 to 65 percent successful implantation and pregnancy, like healthy baby. It's usually a 65 percent chance of life birth if it's a genetically tested embryo. That asterisk is the if, and that's why you're going to see such varying IVF success rates. Because if you don't do genetic testing of embryos, let's use the 40-year-old who makes four embryos. and I send them off for genetic testing. I anticipate she has one normal embryo.

Starting point is 03:08:05 If I do genetic testing, which takes, it's called PGT, pre-implantation genetic testing. I am testing for anuploity as the traditional testing, meaning does it have the right number of chromosomes? You can also importantly test for single gene disorders like cystic fibrosis or Huntington's. But if we're just doing PGT for aneuploidy, I expect an age-related proportion of your eggs to be normal or abnormal. So at age 40, I expect 20 to 25% normal. So I can choose that one and put it in you and have a 65% chance that you have a baby. I could not do it.

Starting point is 03:08:38 I still have the same four. That one is in there. But if I go and transfer them each independently, I'm now going to have closer to a 20 to 30% chance of success. Right. So it is not that I'm changing the embryo by testing it, but I'm allowing myself to have higher utility of success, higher efficiency, putting somebody through less failed transfers, which is extremely important and less miscarriages because those also take time. And one of the most important things is that you have the opportunity to understand how many potential normal embryos you have in batch cycles. So you could go and do

Starting point is 03:09:14 another cycle because I'm 40. I just met my person. I really want to have two kids because my sibling is really important in my life. Yet naturally, by the age I would be for that second child, it's going to be very hard to conceive. I can go through IVF and batch some embryos. So I could save two or three for that second baby that I'm not going to transfer for a few years. And that's called embryo banking. And that is changing the ways that people can potentially grow their family

Starting point is 03:09:44 at later ages. But you don't know that unless you know what's normal or not. And it also gives you the chance to go and intervene right now. Because right now, especially if you're older, I'm going to have a higher chance of success than if I am four transfers down the road, and maybe there was one miscarriage in there too, we're suddenly now eight months down the road before I can go do another cycle and get more eggs versus if I found out that none of those were genetically normal.

Starting point is 03:10:13 The average 40-year-old might have zero to one if they have average ovarian reserve per cycle. So they're going to need multiple cycles. It's not that it's impossible, but it's just setting that road of expectation for them. But if I don't get any normal embryos, I can turn right around and go get more. So I am using what's left in that ovarian vault each month to try to get to that opportunity of a pregnancy for you in a much more efficient way by utilizing genetic testing of these embryos. This is where we can put an ellipse in and sort of like dot, dot, dot, healthy baby, right? And maybe in the future, if we're lucky, you'll come back and talk to us about healthy pregnancy.

Starting point is 03:10:52 I love to. and healthy baby onward. That would be a fun and an important set of discussions. I would like to touch on the, I don't want to call it the issue, but the topic of menopause, which I assume is defined as the cessation of mencies. But there I'm guessing, and I'm guessing it's a constellation of things that happen. And I have a very straightforward question, which is, is there an acceleration of the onset of menopause?

Starting point is 03:11:19 Are we seeing that nowadays? are there good data on that? Should people try to delay menopause? What are some of the things that you talk to patients about in terms of their considerations of ways to ease that transition or maybe even offset that transition with hormone replacement therapy or other approaches? These are great questions. And I do think this is going to be a huge interest in upcoming years, as we have learned

Starting point is 03:11:46 more about the menopausal transition and the health risks really associated with being hypoestrogenic or having low estrogen. Menopause if we define it as ovarian failure. So your ovaries now have no eggs or so few eggs that they are refractory to the brain sending out FSAH. So your brain is sending out all the FSAH and LH that it can. Your ovary is done and not making any estradiol or progesterone anymore. In this time period, what we know is one.

Starting point is 03:12:19 Are we seeing a population-based increase in earlier menopause? There's not been a study to say that. Observational and clinically, I would say yes, because I see so many younger women having low ovarian reserve or having premature ovarian failure or premature ovarian insufficiency, which is the more politically correct way of saying it. But when we think about what this is, is there are modifiable factors, right? If running out of eggs is a variable, and we already said certain things like smoking cigarettes and exposure to toxins and likely chronic inflammation and untreated disease, we know that having

Starting point is 03:12:54 diabetes, those things increase your risk of going into menopause earlier. So paying attention to the lifestyle that you have when you're not concerned about your fertility, right? When you're in your younger years and maybe you're not worried about getting pregnant yet or you're not worried about menopause, but those choices that you're making in those time periods, at least for women, your eggs are going to hold on to them. So they have an influence later. Similarly, trying to live a lower inflammatory life and getting sleep and avoiding toxins of which you can is some of the best that you can do to try to naturally prolong when you'll go through

Starting point is 03:13:37 menopause with a huge caveat that everybody is truly born with a different number, and you do not control that. You don't. And so you might have been born. with a lower number, and you can't change that trajectory. And you might have cancer and be exposed to chemotherapy, which also will deplete your ovarian reserve. But so do things like endometriosis, especially if it's not being treated in any fashion. So that's where we think the birth control pill or progestin exposure or surgery,

Starting point is 03:14:09 ways to go and decrease the inflammation. It's that inflammation associated with endometriosis that's really causing these women to have, have low ovarian reserve and go into menopause early. So not only is that impacting, you know, fertility and how many eggs you get and how long do you have to grow your family, but when you go into menopause earlier, you have lower life expectancy than people who go into menopause later. And that's why you even said it earlier, fertility is this variable kind of reflecting longevity and like health overall. So what we do know about menopause is that having that low estrogen,

Starting point is 03:14:45 whether that happens at the average age of menopause at 5152 or at an earlier time period. It's not good for the brain, you know, higher risks of dementia, increased risks of osteoporosis, increased risk of heart disease and stroke, and essentially higher risks of death. And that's not even to talk about the impact on your life, what it can be like to have hot flashes, heat and cold, and sensitivity, to have profound vulvar and vaginal atrophy to the point that you no longer want to have intercourse. and the changes that it can even have on your gut and your immune system. So we as a community, you know, of doctors, especially OBGYNs, really recommend hormone replacement therapy in women who are going through menopause. And the key here is to initiate it right at the beginning.

Starting point is 03:15:33 That big women's health initiative study, which came out forever ago and showed all this harm with hormone replacement therapy, the big issue there was that these people were hypoestheto for 10 plus years in one group and then started back on the hormones. And in that circumstance, they'd already been put into this higher risk category and their body had adjusted to not having the hormones. And when re-exposed, they had more adverse events. But if you are starting on estrogen replacement, and it can be various, but honestly, the estrogen that we try to replace in this time period much more mimics estrogen. We have estrogenial pills. You can have vascular. You can have vascular. You can have vaginal inserts, you know, patches. So it depends on what's going to work for your life.

Starting point is 03:16:18 But it is not the birth control pill most oftenly. In some people, it might be that's what they choose, but we really are trying to pick an estrogen that is estradiol, or mimics that natural structure. And you can't have unopposed estrogen without reaching the risk of endometrial cancer. And so that's why we need to have some progestin. So some people will choose a daily progestin. Some will choose a cyclic progestin and still have periods. Some will put in an IUD at this time period and then take their daily estrogen. There's a lot of different options. We're trying to find the lowest dose of hormones that relieves your symptoms to provide you relief from some of these lifestyle issues, but also helps you not just live longer.

Starting point is 03:17:01 We're not just trying to live longer. We want to be healthy longer. We want to have a better quality of life. And certainly, women's health has for long. at this menopausal period. And then it's been, you're on your own kid. And this is when we're really starting to see that intervening at that place, especially for women who go into ovarian failure early. So those people who have low ovarian reserve, who I diagnose, I tell all of them, hey, if you don't freeze your eggs or I never see you again, you're going to go through

Starting point is 03:17:30 menopause early. And when you do, I want you to go see somebody. I don't want you to just ignore it and suffer with these symptoms, which is something that does commonly happen. So just making sure that women are empowered to know that these symptoms are what happens. It's what happens naturally, but by giving their bodies more estrogen and not crazy high doses, but just these physiologic levels can really improve both the quality and the longevity of their life. Is it just the presence of these symptoms that signals the onset of menopause or are there additional cues? Like, for instance, if their cycle is getting shorter or longer? Yeah, you certainly will have cycle changed.

Starting point is 03:18:10 And we consider that the perimenopausal period where you're starting to really start seeing a spacing out of your period. So they're no longer coming at that perfect ovulatory pattern. When you get into the low ovarian reserve, but you're still ovulating regularly, they first shorten, as we said earlier. But then when they start lengthening or you start skipping months, that's a real big clue that things are not going in the right direction. And if you find out you have very, very low ovarian reserve or you're approaching that perimenopause period, you're going to start to have more prolonged periods of low estrogen and you'll feel mentally cloudy, fatigued, more headaches, more hot flashes, lack of libido, those vulvar vaginal symptoms, overall, more likelihood to have depressed mood, and that's a lot.

Starting point is 03:18:58 There's a lot. Well, Natalie, Dr. Crawford, I want to extend a huge thank you on behalf of myself. I've learned so much from you today about fertility, about hormones, hormone health for women. And you've also touched on a number of important issues about hormone health and fertility for men along the way. So it's truly been a masterclass in fertility and hormones and really touched on topics that are so essential to everybody, even if people aren't seeking to conceive or maybe think they don't want to. I mean, there's so many considerations that really extend back to one's teens. And if one is beyond their teens, like whatever age people are,

Starting point is 03:19:36 essentially, they need to think about these issues and make important decisions. And you've really also clarified a lot of the, what I think are quite destructive myths that are prominent out there about, for instance, egg harvest and what that does to one's fertility. So, first of all, thank you for joining us today. I know you're extremely busy. You run a clinic. You have a, you manage a family as well, co-manage a family, I believe. But, you know, this is the sort of knowledge that is so challenging to find in one place. And yet you also have a number of really spectacular avenues that you deliver information, Instagram, podcasts, books, and things of that. So we will refer everyone to those links. I've learned so much from you over the years, really,

Starting point is 03:20:17 in following your content. And today you've just far exceeded already high expectations. So thank you ever so much. Thank you for having me. And just thank you for giving a space to talk about women's health and fertility and reproductive medicine. It means a lot to me. And it means a lot to the people who really are trying to do their best every day. So we appreciate it. We appreciate you. And with some luck, we'll commit you to come back and talk to us about pregnancy

Starting point is 03:20:44 and a bit more on some of the topics that we move through quickly. Thank you. Thank you. Thank you for joining me for today's discussion about female hormones and fertility with Dr. Natalie Crawford. You can find links to her clinical practice

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Huberman Lab - Female Hormone Health, Fertility & Vitality | Dr. Natalie Crawford

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