352 ‒ Female fertility: reproductive health, treating infertility & PCOS, and the IVF process

1. 0:00 – 1:15

   Intro

   1. PAPeter Attia0:00

      Getting this looked at now is a great way to get ahead of an infertility problem 10 years hence.

   2. PAPaula Amato0:06

      For sure. Women are born with a finite number of eggs. Actually, the most eggs you'll ever have is when you're in your mom's womb.

   3. PAPeter Attia0:13

      So let's just walk through how IVF works.

   4. PAPaula Amato0:15

      Usually about 70% of the eggs fertilize.

   5. PAPeter Attia0:17

      That's an important message for anybody listening.

   6. PAPaula Amato0:19

      Yeah.

   7. PAPeter Attia0:20

      If you're trying to get pregnant, you should not be on a GLP-1 agonist.

   8. PAPaula Amato0:23

      Right. You can be on it pre-pregnancy, just the recommendation is to stop for at least two months.

   9. PAPeter Attia0:27

      Okay.

   10. PAPaula Amato0:28

       Now, having said that, there have been lots of-- You may have read about Ozempic babies.

   11. PAPeter Attia0:32

       Do you caution women or do we know anything about too much exercise?

   12. PAPaula Amato0:37

       Extreme exercise can be associated, um, with fertility issues. We talked about semen analysis being kind of a marker of other health outcomes. Your periods are also a marker. Don't wait till you're ready to try to get pregnant to figure that out. You know, there may be something important you need to know way ahead of time.

   13. PAPeter Attia0:55

       If a woman came to you at 20 and said-

   14. PAPaula Amato0:57

       Yeah

   15. PAPeter Attia0:57

       ... I just want to double down on my career right now. Uh, I want to do X, Y, and Z. I think I want to have kids. I at least want the optionality. When should I freeze by? [upbeat music] Hey, everyone. Welcome to the Drive podcast. I'm your host, Peter Attia.

2. 1:15 – 3:48

   The finite nature of a woman’s egg reserve & the basic process of ovulation & fertilization

   1. PAPeter Attia1:16

      Hey, Paula. Thank you so much for, for coming to Austin and, um, sitting down to share some remarkable insights. Uh, you know, listeners last week will have heard us talk about all things that pertain to male fertility. Um, and as promised, we're gonna s- now talk about, uh, fertility, but from the female perspective. The physiology here is, is different, uh, but no less complex. Um, and there are some, some pretty unique things about it. One of them being that unlike sperm, which seem to be an infinite, uh, resource, uh, men are constantly generating literally billions of these things, uh, the exact opposite is the case with, with women. Tell, tell us a bit about that.

   2. PAPaula Amato1:55

      That's right. Well, first, thanks for having me. Thanks for inviting me. Uh, it is true that when an embryo or fetus develops, uh, the gonad differentiates into either a testes or an ovary, and the main difference, as you said, is that sperm is produced throughout a man's lifetime, whereas women are born with a finite number of eggs. Actually, the most eggs you'll ever have is when you're in your mom's womb as a fetus.

   3. PAPeter Attia2:22

      Hmm.

   4. PAPaula Amato2:22

      And by the time you're born, there's about two million or so eggs, and by the time you start menstruating, you're down to maybe four hundred thousand or so. And-

   5. PAPeter Attia2:31

      Wow.

   6. PAPaula Amato2:31

      Yeah.

   7. PAPeter Attia2:31

      Five-- So a fivefold reduction from birth to, say, a, a average age would be maybe fourteen when a-

   8. PAPaula Amato2:39

      Yeah.

   9. PAPeter Attia2:39

      Yeah.

   10. PAPaula Amato2:39

       Yeah, twelve to fourteen. And we don't know why exactly that happens, but most of the eggs in the ovaries actually undergo a process we call atresia. They, they basically die.

   11. PAPeter Attia2:49

       Hmm.

   12. PAPaula Amato2:49

       So once, uh, a woman goes through puberty or a girl goes through puberty, every month, if she's not on hormonal contraception, one of those eggs grows. Actually, probably a group of eggs every month starts to grow, but then one kinda takes over and is released from the ovary and usually finds its way into the fallopian tubes. That's the tube connecting the ovary and the uterus. And then normally, if there's not sperm around, the egg is-- just reabsorbs, and there's no pregnancy, and the lining of the uterus sheds, and, uh, a girl or a woman has a period every month. If there's sperm around, there's a chance that that egg might fertilize, and that fertilization usually happens in the fallopian tube, actually. And then that now zygote or embryo travels down the tube into the uterus and some of the time implants into the wall of the uterus or the lining of the uterus and establishes

3. 3:48 – 15:52

   How hormones influence egg selection, & how chromosomal errors lead to most miscarriages

   1. PAPaula Amato3:48

      a pregnancy.

   2. PAPeter Attia3:49

      Okay. So let's now talk about a woman in the prime of her reproductive age. She's twenty years old, um, as, as an example. And, um, let's, let's talk through the cycle of, um, what is happening and the role that hormones are playing. Um, one of the things that to me has always been fascinating about this is the selection, right? So with, with males, we don't have to think about that problem. The selection tends to be maybe more metabolic or stochastic. In other words, which sperm is the sperm that makes it isn't really predetermined. Uh, how is it that, let's say, from day zero when a woman begins her menstrual cycle and all of a sudden everything starts to turn towards the next cycle, she's about fourteen days out from ovulation-

   3. PAPaula Amato4:39

      Mm-hmm

   4. PAPeter Attia4:39

      ... we start to see the interplay of luteinizing hormone and follicle stimulating hormone, particularly FSH. Walk me through what's happening in that period of time that ultimately leads to one and only one egg being the chosen one.

   5. PAPaula Amato4:52

      Yeah. Yeah. It's a little random in women as well, actually.

   6. PAPeter Attia4:55

      Okay.

   7. PAPaula Amato4:55

      But it's true that the pituitary hormones, namely FSH or follicle stimulating hormone and LH, luteinizing hormone, are what drives growth of the, we call them follicles. The eggs are inside the follicles. And as I said, usually a cohort of eggs starts to grow, and then one-

   8. PAPeter Attia5:15

      And tell me what grow means.

   9. PAPaula Amato5:17

      The follicles start to, um, get bigger and the cells surrounding the eggs start to divide.

   10. PAPeter Attia5:25

       And what do they look like prior to all of that happening? These are cells that-

   11. PAPaula Amato5:29

       Mm-hmm

   12. PAPeter Attia5:29

       ... only have fifty percent of the genetic material, right? They've already undergone meiosis.

   13. PAPaula Amato5:35

       Yes. It-- Meiosis-- They're kind of arrested in meiosis-

   14. PAPeter Attia5:39

       Yeah

   15. PAPaula Amato5:39

       ... and meiosis not completed until they actually ovulate-

   16. PAPeter Attia5:44

       Okay

   17. PAPaula Amato5:44

       ... and then in some cases are fertilized. Yes.

   18. PAPeter Attia5:47

       So we have an arrested cell-

   19. PAPaula Amato5:49

       Right

   20. PAPeter Attia5:50

       ... that has, uh, one of each of the mother's chromosomes, including one X chromosome by definition, one of her two sex hormones, and I don't know if this question makes sense, but it's, is it still in its young phenotype? In other words, if the, if the woman is 20 years old and all of the cells in her body are functionally 20 years old, is this egg prior to, uh, ovulation still basically an infant cell?

   21. PAPaula Amato6:21

       As far as we know, although there's some data recently to suggest that, um, perhaps the cells surrounding the egg are, um, metabolically active-

   22. PAPeter Attia6:34

       Mm-hmm

   23. PAPaula Amato6:34

       ... and may be aging.

   24. PAPeter Attia6:36

       Mm-hmm.

   25. PAPaula Amato6:36

       Certainly, we do know that the quality of the eggs decreases, right, as women get older.

   26. PAPeter Attia6:43

       Yeah.

   27. PAPaula Amato6:43

       So that affects how the eggs and the chromosomes ultimately divide. That's part of the reason it's harder to get pregnant as you get older. Even though you're ovulating, you may be releasing an egg every month, but that egg could be abnormal. And if it's abnormal, it likely won't fertilize, and you kinda don't want it to fertilize if it's abnormal and establish a pregnancy. Uh, but you're right. It's, they're pretty much arrested in time [chuckles] during, um, certainly, you know, before puberty, and then every month, a few start to develop, and then one-- We don't really know how that one egg is selected.

   28. PAPeter Attia7:21

       Hmm.

   29. PAPaula Amato7:22

       Okay? It's definitely hormonal factors play a role, um, but it's somewhat random. One kinda grows, and then eventually is released.

   30. PAPeter Attia7:32

       Now, n- not to anthropomorphize this too much, but one would sort of assume that natural selection runs strong. And if a woman, by the time she begins her, uh, fertility stage of life, has four hundred thousand eggs-
4. 15:52 – 25:40

   The full journey of conception & early pregnancy risks

   1. PAPeter Attia15:52

      this process.

   2. PAPaula Amato15:53

      Mm-hmm.

   3. PAPeter Attia15:54

      So it's day zero.

   4. PAPaula Amato15:55

      Mm-hmm.

   5. PAPeter Attia15:55

      So a woman just begins her period. We're just getting ready to embark on her next fertility cycle.

   6. PAPaula Amato16:00

      Mm-hmm.

   7. PAPeter Attia16:01

      The pituitary g- gland is secreting luteinizing, uh, hormone and follicle-stimulating hormone. Walk me through what is happening in the next 14 days that leads to that ovulation. Um...

   8. PAPaula Amato16:13

      Right. So a group of eggs or follicles are starting to grow. One gets selected. We don't really understand-

   9. PAPeter Attia16:18

      We still don't know how?

   10. PAPaula Amato16:19

       We don't understand why. [laughs] It's random.

   11. PAPeter Attia16:21

       Wow.

   12. PAPaula Amato16:21

       Um, and that follicle, that's egg is in a follicle. Follicle's kind of a fluid-filled cyst-like structure that surrounds each egg. So that continues to grow, and then eventually, uh, what's happening hormonally, so those cells surrounding the eggs are producing estrogen. That estrogen is preparing, acting on the uterine lining to build up the lining to potentially support a pregnancy. And then what happens just before ovulation is there's, um, a surge in a hormone called LH, luteinizing hormone, and that's what we think triggers ovulation or release of an egg. So all that has to happen before an egg is released. So it kind of busts out of the ovary, finds its way to the tube.

   13. PAPeter Attia17:10

       How energetically demanding is that? We learned last week in talking with Paul that the ATP requirement for those sperm to travel all that distance is unbelievable.

   14. PAPaula Amato17:23

       Yeah.

   15. PAPeter Attia17:24

       Uh, what, how passive versus active is the movement of that egg? How metabolically demanding is it?

   16. PAPaula Amato17:30

       I don't know that we understand it completely, but you would imagine that their energy is required for, for that to, to happen, certainly other-

   17. PAPeter Attia17:38

       So it's not passive. It's not just-

   18. PAPaula Amato17:40

       No

   19. PAPeter Attia17:40

       ... sort of a diffusion-

   20. PAPaula Amato17:41

       No

   21. PAPeter Attia17:41

       ... down the fallopian tube.

   22. PAPaula Amato17:43

       Right. Prostaglandins are involved and a lot, calcium, all kinds of things have to happen for, for that process to occur.

   23. PAPeter Attia17:51

       Okay. How long, approximately, just give people a, a sense of how long a fallopian tube is.

   24. PAPaula Amato17:57

       Probably a few centimeters, like five to 10.

   25. PAPeter Attia18:00

       Okay.

   26. PAPaula Amato18:00

       Mm-hmm.

   27. PAPeter Attia18:01

       And, um, you know, everyone's probably used to seeing the image of ovaries being these little eggs and fallopian tubes having these little fingers that hug up on the eggs.

   28. PAPaula Amato18:09

       Yeah, yeah.

   29. PAPeter Attia18:10

       What, what is actually in between that space? How does the, how does the egg get from an ovary into a fallopian tube? Is there an actual connection there?

   30. PAPaula Amato18:17

       There is, actually.
5. 25:40 – 32:21

   How infertility is defined & diagnosed, & the rising infertility rates

   1. PAPeter Attia25:40

      Got it. Okay. So let's talk about a patient that comes to you and they're, and they're, they're gonna say, "You know, we're, we're having difficulty conceiving." Um, what are the questions you have to, to render the diagnosis of infertility, meaning we need some intervention, versus, hmm, you just need to make a few adjustments in something, and I, I'm not willing to put the label of infertility on. So how, how do you s- is that-

   2. PAPaula Amato26:13

      Yeah

   3. PAPeter Attia26:13

      ... would that be the first bifurcation in thinking?

   4. PAPaula Amato26:16

      Yeah. We wanna take a full medical history of both partners if it's a couple, and that includes, you know, medical history, reproductive history, psychosocial history, sexual history. All those things are important. Lifestyle factors. We ask about all those things. And the definition of infertility is, is trying for about a year. So unprotected intercourse for about a year without success. That's the sort of medical definition of infertility. But we start our testing, uh, after a year in women who are less than 35, and after six months if a woman is older than 35. Even though it may take longer to get pregnant if you're older, if there's something wrong, you kinda wanna know about it sooner rather than later. So if a couple, uh, and the female partner's over 35 and she's-- they've been trying, having timed intercourse at the right time and still not pregnant, then we would initiate some preliminary investigations. Um, on the female side, what's most important usually is we wanna ask about the woman's menstrual cycles. You know, are they regular? Is she tracking ovulation? You know, do, does it look like she's ovulating, et cetera. On the male side, you know, we wanna ask about sexual function. Have they had a semen analysis? If not, we usually order one because we're interested in the sperm concentration, the motility of the sperm, the shape of the sperm, those types of things.

   5. PAPeter Attia27:41

      Yeah, one of, one of the things I was very surprised by in the podcast that we did last week on male fertility was how infrequently men are getting evaluated-

   6. PAPaula Amato27:50

      Mm-hmm

   7. PAPeter Attia27:50

      ... and how many missed opportunities.

   8. PAPaula Amato27:53

      Yes.

   9. PAPeter Attia27:53

      In other words, how much, how much-

   10. PAPaula Amato27:54

       Yeah

   11. PAPeter Attia27:54

       ... wasted time is being generated because infertility is being assumed to be-

   12. PAPaula Amato28:01

       Right

   13. PAPeter Attia28:01

       ... the, the responsibility of the female. Responsibility might be the wrong word, but it's just assumed that, well, that's more likely where it is.

   14. PAPaula Amato28:07

       Cause, yeah.

   15. PAPeter Attia28:07

       And so th- through no bad intention, the guy is not getting evaluated-

   16. PAPaula Amato28:11

       That's true

   17. PAPeter Attia28:12

       ... when in reality, the issue could have been with him all along, and-

   18. PAPaula Amato28:14

       That's right. Right

   19. PAPeter Attia28:15

       ... time is, time is wasted.

   20. PAPaula Amato28:16

       Right. When you look at the data, it's about a third of the time it's a female factor, a third of the time it's a male factor, and another third of the time it's some combination of male and female factors. So yes, definitely one of the first things that we do is a semen analysis on the male partner.

   21. PAPeter Attia28:32

       And do you guys do that yourselves as well? Or do you re-

   22. PAPaula Amato28:34

       We do. At the fertility clinic.

   23. PAPeter Attia28:35

       You do? Okay, great.

   24. PAPaula Amato28:35

       Yeah. If, if there is an abnormality, we usually refer that, um, male partner to a reproductive urologist, uh, for further evaluation. Um, but these days it's recommended actually that men, even if they're not trying to get pregnant, sometimes assess their sh- their semen analysis, and because it can be a marker of other health problems, just like a woman's menstrual cycle can be a marker of other health problems. So I should qualify that one-year timeframe. If you have some reason to believe that you have a fertility problem, I wouldn't necessarily wait-

   25. PAPeter Attia29:06

       Yeah

   26. PAPaula Amato29:06

       ... a whole year and then go see a f- you know, a provider. If your cycles are irregular, if you think you might have polycystic ovary syndrome or something, then you, you definitely wanna see somebody sooner than a year.

   27. PAPeter Attia29:18

       Is it possible to say anything about fertility rates changing over the past 50 years? Uh, c- is there any statement you can, you can make on that?

   28. PAPaula Amato29:26

       Yeah, there's some data that seems to suggest that infertility rates are increasing over the last several years. Uh, it's pretty common. I don't know if your listeners know, but about, you know, the lifetime risk of infertility for each person is about one in six, so that's close to twenty percent. Uh, in the last few years in the United States seems to be kind of a plateau of the prevalence, but-

   29. PAPeter Attia29:49

       Let me, let me just ask a clarifying question-

   30. PAPaula Amato29:51

       Yeah
6. 32:21 – 42:56

   Fallopian tube damage: how STDs & scarring impact fertility & raise ectopic pregnancy risk

   1. PAPaula Amato32:21

      ago.

   2. PAPeter Attia32:21

      Well, and then the question of course would be if this is an environmental reason-

   3. PAPaula Amato32:26

      Mm-hmm

   4. PAPeter Attia32:26

      ... what are the environmental triggers?

   5. PAPaula Amato32:28

      Right.

   6. PAPeter Attia32:28

      Now, you mentioned STDs a minute ago.

   7. PAPaula Amato32:30

      Mm-hmm.

   8. PAPeter Attia32:30

      So how do STDs and which STDs play a role in fertility?

   9. PAPaula Amato32:35

      The ones most well understood are probably gonorrhea and chlamydia, which are very common sexually transmitted diseases. And on the female side, those particular infections can ascend to the fallopian tubes and cause scarring in the fallopian tubes, which then interfere with that process that we talked about earlier, the egg and the sperm meeting, and can lead to infertility.

   10. PAPeter Attia32:57

       And is that something that happens if it is left untreated, or is that something that's easy to address with antibiotics if caught early?

   11. PAPaula Amato33:04

       I mean, if it's caught early, then it's usually treatable with antibiotics, or there's some issues with antibiotic resistance, especially with gonorrhea. But usually if you catch it early, it's treatable. Um, but if it's late stage or it's unrecognized or untreated, then it has more likely, more likely to ascend to the fallopian tubes where it usually cause fertility problems.

   12. PAPeter Attia33:25

       How prevalent is gonorrhea today in the U.S.?

   13. PAPaula Amato33:28

       I think it's pretty common. I don't know.

   14. PAPeter Attia33:29

       Really?

   15. PAPaula Amato33:30

       Yeah. Yeah. In certain populations it's more common than others, but, um, yeah, unfortunately. And there's a number of reasons for that. Uh, some of it is just lack of awareness and education arou- about safe sex practices. Um, maybe less testing as well, especially we saw that during the pandemic for sure.

   16. PAPeter Attia33:50

       How does it present?

   17. PAPaula Amato33:52

       In women usually with, um, pelvic pain, fever, vaginal discharge. Those are the most common symptoms.

   18. PAPeter Attia34:01

       And is it equally transmissible from male to female and female to male?

   19. PAPaula Amato34:06

       It's probably more transmissible from male to female.

   20. PAPeter Attia34:11

       Okay. And is it a, is it an STD where the person who has it knows they... Like if a male has it, does he know he has it?

   21. PAPaula Amato34:19

       Not always.

   22. PAPeter Attia34:19

       Presumably not if it's being-

   23. PAPaula Amato34:20

       Not always

   24. PAPeter Attia34:20

       ... transmitted this readily.

   25. PAPaula Amato34:22

       Yeah. Yeah. Not always.

   26. PAPeter Attia34:23

       Okay.

   27. PAPaula Amato34:24

       Yeah.

   28. PAPeter Attia34:24

       Uh, what about HSV? Does that factor into fertility at all?

   29. PAPaula Amato34:28

       Uh, not as much, no. Yeah.

   30. PAPeter Attia34:30

       And chlamydia, again, I apologize for my ignorance, I just don't remember any of this [laughs] this stuff-
7. 42:56 – 46:11

   Unexplained infertility: how doctors evaluate ovulation & cycles

   1. PAPeter Attia42:56

      back to our hypothetical case here. So woman comes in, um, let's just assume for the sake of simplicity, the workup on her male partner, totally fine.

   2. PAPaula Amato43:05

      Okay.

   3. PAPeter Attia43:06

      His, his sperm are fine. Um, the, uh, radiograph shows that she has at least to the, to the eye normal fallopian tubes. Um, what's the next step in the workup?

   4. PAPaula Amato43:18

      So we wanna assess her cycles and ovulation. So if she's ovulating regularly, then, you know, we call that sort of unexplained.

   5. PAPeter Attia43:27

      And how do you know that she is? Let's say she-

   6. PAPaula Amato43:29

      Mm-hmm.

   7. PAPeter Attia43:29

      Is that determined by the fact that she has a regular period? Does that alone tell you that?

   8. PAPaula Amato43:33

      Usually. Usually. It would be unusual to have regular periods and not be ovulating, um, but it could happen.

   9. PAPeter Attia43:40

      How stringent is your definition for a regular period? It's not 28 days necessarily, is it?

   10. PAPaula Amato43:45

       Not necessarily, yeah. There's a range. You know, it could be anywhere from like 21 to 35 days or so.

   11. PAPeter Attia43:52

       Wow.

   12. PAPaula Amato43:52

       Yeah.

   13. PAPeter Attia43:52

       That's a pretty big range.

   14. PAPaula Amato43:54

       Right.

   15. PAPeter Attia43:54

       Are you more... So it's-- Are you less concerned with the number of days of the cycle and more concerned with the fact that whatever the days are, it's just repeating over and over again?

   16. PAPaula Amato44:03

       Yes. If you mean duration of the period-

   17. PAPeter Attia44:05

       Correct

   18. PAPaula Amato44:06

       ... yeah, that's not as important as how frequently the, the period is happening.

   19. PAPeter Attia44:10

       So you'd, you'd be happy e-even if it was 21 days, but it was always 21 days, that's better than it's 24, 28, 31, vacillating back-

   20. PAPaula Amato44:19

       Well, no, there's v- very, there is some normal variation.

   21. PAPeter Attia44:21

       Okay.

   22. PAPaula Amato44:21

       So sometimes I'll, I'll see a patient, she'll say, "My periods are very irregular. Sometimes they're 26 days, sometimes they're 32." I consider that normal. Yeah. It's not-

   23. PAPeter Attia44:29

       Okay

   24. PAPaula Amato44:30

       ... usually always 28 days or always 21 days. There's some normal variation. Um, irregular would be you're skipping months, or maybe you're getting a period every three months or four months.

   25. PAPeter Attia44:42

       And what's happening in that situation in a young woman?

   26. PAPaula Amato44:46

       Yeah. There, there are a number of different causes. Probably the most common is something called polycystic ovary syndrome. It's a very common hormonal condition. We don't know exactly what causes it. I feel like I'm saying that a lot about women's health, right? We don't know exactly what causes it because we're not investing enough in women's research.

   27. PAPeter Attia45:03

       Why do you think that is? This, this, this came up on another podcast-

   28. PAPaula Amato45:07

       [chuckles]

   29. PAPeter Attia45:08

       ... um, on HRT, which is another one of my big, uh-

   30. PAPaula Amato45:11

       Yep
8. 46:11 – 48:27

   The defining symptoms of polycystic ovary syndrome (PCOS), its hormonal characteristics, & its relationship with insulin resistance

   1. PAPeter Attia46:11

      talk about polycystic, um-

   2. PAPaula Amato46:12

      Yep

   3. PAPeter Attia46:13

      ... ovarian syndrome. So, uh, what's the prevalence of it in, in let's say women aged, uh, call it 15 to 30?

   4. PAPaula Amato46:20

      Yeah, super common. About six to eight percent of women will have polycystic ovary syndrome. Most common symptoms are irregular periods, um, also evidence of high androgen levels, and that could usually present with acne or excess hair growth. We call that hirsutism. Um, obesity or being overweight, that's also part of the syndrome. Not everybody who has PCOS-

   5. PAPeter Attia46:42

      And the androgens are specifically testos-- Could it be just testosterone, just DHEA, DHT?

   6. PAPaula Amato46:48

      Both.

   7. PAPeter Attia46:48

      All of the above?

   8. PAPaula Amato46:48

      Yeah, both, but typically elevated testosterone from the ovaries. Yeah.

   9. PAPeter Attia46:54

      Okay. So is that the cause or the effect?

   10. PAPaula Amato46:57

       We don't know. [chuckles] We don't know, but it's definitely seen in almost all women with PCOS that they have higher androgen levels.

   11. PAPeter Attia47:06

       And why is PCOS, uh, seemingly also highly associated with insulin resistance?

   12. PAPaula Amato47:12

       Again, we don't know exactly, but we think the androgens, um, play a role. We think there might be some genetic factors that play a role. I don't know that we understand why, but we certainly have recognized in the last several decades that most women with PCOS also happen to be insulin resistant.

   13. PAPeter Attia47:35

       But we don't know the direction of causality?

   14. PAPaula Amato47:39

       No. We know that not everybody who's insulin resistant has PCOS, of course-

   15. PAPeter Attia47:44

       Yes

   16. PAPaula Amato47:44

       ... because not all diabetics are insulin resistant.

   17. PAPeter Attia47:46

       But we also know that some women with PCOS are not insulin resistant, correct?

   18. PAPaula Amato47:49

       Probably on some level they are.

   19. PAPeter Attia47:51

       Okay.

   20. PAPaula Amato47:52

       But, um, they're, they're able to compensate, and certainly it's more likely if they tend to be overweight as well. So it's definitely multifactorial, and my guess it's like we're treating PCOS now more like other complex diseases like obesity or hypertension, et cetera. There's like lots of things going on.

   21. PAPeter Attia48:10

       But based on what you just said, if there is any causality between them, it's more likely that the PCOS is driving the insulin resistance than the other way around, given the number of women that are insulin resistant who do not have PCOS.

   22. PAPaula Amato48:24

       Yeah, that's probably true. Um.

9. 48:27 – 52:32

   Managing PCOS without pregnancy: cycle regulation, androgen suppression, & insulin resistance treatment

   1. PAPeter Attia48:27

      So then the question is what do we need, what do we need to do to treat PCOS?

   2. PAPaula Amato48:33

      Right. So depends on the goal of the patient, right? So if they're trying to get pregnant There's one set of treatments. If they're not trying to get pregnant, but they have PCOS, then we usually focus on their cycles 'cause it's generally not a good idea to go too long in between cycles because what can happen is the lining of the uterus can overgrow. If it overgrows too much, it can become what we call hyperplastic, worst case scenario cancer, so you definitely don't want that. So it's important to be shedding that lining or to be on hormonal suppression so that that doesn't happen. Um, if the goal is to treat the hyperandrogenic symptoms like the acne and the hirsutism, again, hormonal treatment's usually effective for that.

   3. PAPeter Attia49:18

      When you say hormonal treatments, you mean like spironolactone and things like that?

   4. PAPaula Amato49:21

      We usually start with birth control pills.

   5. PAPeter Attia49:23

      Okay.

   6. PAPaula Amato49:23

      Birth control pills, very effective for, for most sy- symptoms of PCOS. It'll regulate the cycles, decrease androgen levels, help with hirsutism and acne, et cetera.

   7. PAPeter Attia49:32

      So let's talk about why. So, so a birth control pill is a high dose of a synthetic estrogen and progestin-

   8. PAPaula Amato49:40

      Correct

   9. PAPeter Attia49:41

      ... that's given 21 days and then paused for a week. I mean, meaning you take it every day, but the last week is a, is a placebo. Um, so is the reason that that helps with the hyperandrogenism because it raises sex hormone binding globulin so much that it mops up all the excess testosterone?

   10. PAPaula Amato50:01

       Part of the reason. I'm impressed by your [laughs] endocrinology knowledge. Um, yes, that's part of the reason. And, and by the way, you don't, you can take it that way you described where you have a, a bleed every month, but you don't have to. Many people take it continuously these days so you don't have a period at all.

   11. PAPeter Attia50:16

       But then doesn't that address the issue that you were talking about, or does the synthetic estrogen, uh, the synthetic progestin offset the hyperplasia and then you don't care?

   12. PAPaula Amato50:25

       Right.

   13. PAPeter Attia50:26

       Okay.

   14. PAPaula Amato50:26

       When you take the combination of estrogen and progesterone, usually the lining becomes quite thin.

   15. PAPeter Attia50:29

       Thin anyway, okay.

   16. PAPaula Amato50:30

       You don't have to worry about it. Yeah.

   17. PAPeter Attia50:31

       Okay.

   18. PAPaula Amato50:31

       So two, two mechanisms of action. When you're taking those high doses of estrogen and progesterone, it's suppressing the pituitary hormones, namely the LH and FSH. But the LH is what drives the testosterone production in the ovary, so that's one mechanism. And the other one is the one you described. So the estrogen component of the pill will increase the sex hormone binding globulin, so you have less free testosterone around.

   19. PAPeter Attia50:56

       Yep.

   20. PAPaula Amato50:56

       So again, that will help with, um, those symptoms we talked about.

   21. PAPeter Attia51:00

       Okay. So woman with PCOS doesn't want to get pregnant-

   22. PAPaula Amato51:05

       Right

   23. PAPeter Attia51:06

       ... just wants to reduce the androgen impact and protect her uterus, a constant os- oral contraceptive is a great strategy.

   24. PAPaula Amato51:15

       It's a great strategy, yeah. There are others. You know, it could be a progestin IUD. That's a hormonally active-

   25. PAPeter Attia51:21

       Yep

   26. PAPaula Amato51:21

       ... IUD. Um, so there are a n- a number of different ones, or just taking progesterone every few months. That usually will help protect the lining, but probably won't decrease the androgen levels.

   27. PAPeter Attia51:31

       And how often do you place women who have PCOS also with insulin resistance on metformin? Do you find that or any of the other diabetic agents to be particularly useful?

   28. PAPaula Amato51:41

       Occasionally, yeah, and that's an important point because women, as we said, who have PCOS are insulin resistant, which predisposes them to diabetes, so those women need to be screened periodically for diabetes, and we commonly use metformin to either treat prediabetes or to try and prevent diabetes, so.

   29. PAPeter Attia51:59

       Does insulin resistance and type 2 diabetes independently, uh, impair fertility, all things being equal, absent PCOS? That's a loaded question.

   30. PAPaula Amato52:10

       Yeah. Um, in some cases. I mean, there's some data that shows that, you know, metabolic diseases or chronic diseases can impact fertility. Mechanisms, again, are unclear, but probably related to both ovulation, uh, dysfunction and also endometrial receptivity.
10. 52:32 – 59:11

    The treatment approach for women with PCOS who are trying to conceive: GLP-1 use, ovulation induction, & timing protocols

    1. PAPeter Attia52:32

       I assume that's the easier way to treat PCOS is the woman who does not want to get pregnant.

    2. PAPaula Amato52:37

       Yeah. [laughs]

    3. PAPeter Attia52:37

       So, so now let's talk about the woman with PCOS-

    4. PAPaula Amato52:40

       Mm-hmm

    5. PAPeter Attia52:40

       ... but who is also trying to conceive.

    6. PAPaula Amato52:42

       Right.

    7. PAPeter Attia52:43

       What is your playbook?

    8. PAPaula Amato52:44

       So we always counsel these, these patients as well, I should mention, whether they're trying to get pregnant or not, especially if they're overweight or obese, weight loss helps, you know, with all the symptoms of PCOS, so healthy diet, lifestyle, et cetera.

    9. PAPeter Attia52:57

       And how much of a role are GLP-1 agonists playing in this now? How much more success are you having with treating PCOS that way?

    10. PAPaula Amato53:04

        Yeah, increasingly, and, and they're very successful, as you know, for weight loss, and there have been some studies on PCOS patients specifically, very effective.

    11. PAPeter Attia53:13

        What if, yeah, do you know any of those data? I'm not familiar with them.

    12. PAPaula Amato53:15

        Yeah. Yeah, they work really well, just like they work in people with diabetes or people who, with obesity without diabetes. Problem is you can't get pregnant while you're taking them, and the current recommendation is to stop for at least two months.

    13. PAPeter Attia53:27

        And pardon my ignorance. Why?

    14. PAPaula Amato53:29

        Because we don't have any data on-

    15. PAPeter Attia53:30

        I see

    16. PAPaula Amato53:31

        ... whether they're safe in pregnancy.

    17. PAPeter Attia53:31

        Yeah. So FDA is saying, when FDA-- I, I, I forget the FDA's classification for this. There's like A, B, C, X or something like that for every drug?

    18. PAPaula Amato53:40

        Yes, and I haven't looked for that one specifically, but I'm sure it's like X because we have no data.

    19. PAPeter Attia53:45

        Okay.

    20. PAPaula Amato53:46

        Yeah.

    21. PAPeter Attia53:46

        So impor- that's an important message for anybody listening.

    22. PAPaula Amato53:49

        Yes.

    23. PAPeter Attia53:49

        If you're trying to get pregnant, you should not be on a GLP-1 agonist because we don't understand the impact of that.

    24. PAPaula Amato53:55

        Right. You can be on it pre-pregnancy, just the recommendation is to stop for at least two months.

    25. PAPeter Attia53:59

        Okay.

    26. PAPaula Amato54:00

        Now, having said that, there have been lots of, you may have read about Ozempic babies, like people getting pregnant on GLP-1. So there is a registry, and so far, to my knowledge, there haven't been, um, reported birth defects and that type of thing, but obviously, we're talking about a small number of patients at this point.

    27. PAPeter Attia54:17

        Yeah, that's an interesting point. I, I, and now that you mention that, I, I now recall hearing about that.

    28. PAPaula Amato54:21

        Yeah.

    29. PAPeter Attia54:21

        So, so presumably these are women who have taken either, you know, semaglutide, tirzepatide, and presumably they get pregnant-

    30. PAPaula Amato54:30

        Yes
11. 59:11 – 1:06:44

    Barriers to getting informed fertility care for PCOS

    1. PAPeter Attia59:11

       So would you say that every single woman out there with PCOS who wants to get pregnant has access to a doctor that understands what you just described and can do that for her, or do you worry that too many women are being shunted to IVF too soon without an attempt at something like this?

    2. PAPaula Amato59:30

       I, I definitely think there are probably not enough people who totally understand management of PCOS, especially in the context of fertility treatment, uh, for sure, and even in the context of non-infertility treatment. Often, what I hear from patients is they had irregular periods. Somebody told them to start, go on the birth control pill. They never told them why. They didn't even know what they had PCOS, right? Happens to be the r- correct treatment, so great, but you know, they've gone years now not understanding that they have PCOS and the implications of that, which, as we talked about, there are metabolic implications, et cetera. Uh, so that's a problem. But once they want to become pregnant, very few general gynecologists are set up to be able to treat patients with either Clomid or Letrozole. Some of them do, uh, but it's not like a fertility clinic with reproductive endocrinologists, 'cause we're set up to do monitoring seven days a week and that-

    3. PAPeter Attia1:00:27

       Yeah

    4. PAPaula Amato1:00:27

       ... type of thing. But not everybody has access to a fertility specialist, kind of very dependent on where you live. A little bit better now with telehealth, but, um, still, access is a big problem.

    5. PAPeter Attia1:00:38

       Do you have to do the sonogram when you're doing this?

    6. PAPaula Amato1:00:41

       You don't have to, but You, you wanna know whether the woman's responding, meaning that she's actually ovulating.

    7. PAPeter Attia1:00:48

       Yeah.

    8. PAPaula Amato1:00:48

       There are other ways to assess that. If she gets a period at the right time, then she probably ovulated, or if she gets pregnant, of course. Um, or you can check a progesterone level in the luteal phase, the second half of the cycle.

    9. PAPeter Attia1:00:59

       Yeah.

    10. PAPaula Amato1:00:59

        And if it's elevated, she probably ovulated. Yeah. We just happen to use ultrasounds, just easier.

    11. PAPeter Attia1:01:05

        And how much of what you're describing is covered with typical health insurance?

    12. PAPaula Amato1:01:11

        Depends. Uh, kinda depends where you live in the United States. It's very state dependent.

    13. PAPeter Attia1:01:16

        I see.

    14. PAPaula Amato1:01:16

        So some states have infertility insurance mandates where your employer's insurance policy has to provide infertility diagnostic and treatment, but many states, infertility is not covered. Or they might just cover the testing portion, but then not cover the treatment portion. So that's a huge problem.

    15. PAPeter Attia1:01:35

        Okay. You're, you're in Oregon.

    16. PAPaula Amato1:01:36

        I'm in Oregon. Yeah.

    17. PAPeter Attia1:01:37

        And what is the, what is the state there?

    18. PAPaula Amato1:01:38

        We, we don't have an infertility insurance mandate yet, although we're working on it. There's actually a bill in session this, uh, this regular session now that we're trying to get passed because, you know, we-- infertility is a disease like every other disease, and we think it shouldn't matter where you live. You should have access to the appropriate treatment. So, so in our state, it kinda depends on your employer and whether they provide that particular insurance coverage.

    19. PAPeter Attia1:02:06

        And so if a person has health insurance that does not cover reproductive care-

    20. PAPaula Amato1:02:11

        Yeah

    21. PAPeter Attia1:02:12

        ... how much would be the cost of what you just described? The out-of-pocket cost.

    22. PAPaula Amato1:02:16

        Yeah. So letrozole and Clomid are just oral medications.

    23. PAPeter Attia1:02:19

        Yeah, they're cheap drugs.

    24. PAPaula Amato1:02:20

        They're pretty cheap, yeah. But then you add the ultrasound monitoring.

    25. PAPeter Attia1:02:23

        Yep.

    26. PAPaula Amato1:02:23

        That could be another three hundred dollars-

    27. PAPeter Attia1:02:25

        Yep

    28. PAPaula Amato1:02:25

        ... that you're paying out of pocket. And then if you're doing, like, intrauterine insemination, for example, which we haven't talked about yet.

    29. PAPeter Attia1:02:31

        No, but let's just say just what we talked about-

    30. PAPaula Amato1:02:33

        Uh-huh
12. 1:06:44 – 1:10:57

    Fertility treatment for women with unexplained infertility, risk of multiple pregnancies with superovulation, & more

    1. PAPaula Amato1:06:44

       otherwise, and if you have a patient who is ovulating And has maybe unexplained infertility, tubes are open Yeah, yeah, yeah

    2. PAPeter Attia1:06:51

       ... sperm looks fine. In this case, you don't have to use a hormone to make her ovulate, you just need an ultrasound, which is relatively cheap to know when she's gonna ovulate.

    3. PAPaula Amato1:06:59

       Yeah. We still use the medication, though-

    4. PAPeter Attia1:07:01

       Oh, you do

    5. PAPaula Amato1:07:01

       ... because we superovulate. So normally, you just make one egg.

    6. PAPeter Attia1:07:04

       Mm.

    7. PAPaula Amato1:07:05

       So when someone's already ovulating, the goal of the fertility medications is to get them to release more than one egg. So two eggs, three eggs, more eggs around, higher chance that one of them is gonna be normal and one is gonna fertilize.

    8. PAPeter Attia1:07:16

       What does the graph look like of number of eggs versus probability of twins, triplets, et cetera?

    9. PAPaula Amato1:07:23

       Yeah, that's one of the downsides, right? So the risk of multiples with the oral medications, like Clomid or Letrozole, uh, is about 5 to 8%. So not super high, but definitely higher than if the patient were to conceive without medication. So that's something we counsel them a- about. But it's very common as a first line treatment to do oral medication with IUI, even in the context of normal sperm, I would say, although it's more important, of course, if there's a male component. And then if that didn't work in three cycles, then move on to IVF.

    10. PAPeter Attia1:07:58

        And with the injectables-

    11. PAPaula Amato1:08:01

        Yeah

    12. PAPeter Attia1:08:01

        ... what is the risk of multiple pregnancies?

    13. PAPaula Amato1:08:03

        Much higher.

    14. PAPeter Attia1:08:04

        How mu-

    15. PAPaula Amato1:08:04

        Like 25 to 35%. Yeah.

    16. PAPeter Attia1:08:06

        Okay. And how many eggs are typically ...

    17. PAPaula Amato1:08:09

        It depends on the dose of the medication. So of course, when we're doing IVF, we want a lot of eggs, so it's-

    18. PAPeter Attia1:08:16

        Yeah, yeah, yeah

    19. PAPaula Amato1:08:16

        ... 10 to 15 eggs. But yeah. But if we're doing-

    20. PAPeter Attia1:08:18

        IUI

    21. PAPaula Amato1:08:19

        ... IUI, it could be, like, three to five eggs, or it, it depends on the dose and depends on the age of the patient, et cetera. So what's fallen out of favor is injectables with IUI. That's kind of ... We don't do that very much-

    22. PAPeter Attia1:08:31

        Got it

    23. PAPaula Amato1:08:31

        ... anymore.

    24. PAPeter Attia1:08:32

        Makes sense.

    25. PAPaula Amato1:08:32

        Yeah.

    26. PAPeter Attia1:08:33

        B- back in the day when every time you were in the grocery store and you saw the cover of the National Enquirer-

    27. PAPaula Amato1:08:38

        Mm-hmm

    28. PAPeter Attia1:08:38

        ... and there was like, "This woman just had 47 babies."

    29. PAPaula Amato1:08:41

        Yeah. [laughs]

    30. PAPeter Attia1:08:41

        Like, what the hell was going on in those eras?
13. 1:10:57 – 1:22:15

    Intrauterine insemination (IUI): process, success rates, & when in vitro fertilization (IVF) becomes the better option

    1. PAPeter Attia1:10:57

       So boy, this is, this is fascinating stuff.

    2. PAPaula Amato1:11:01

       Mm-hmm.

    3. PAPeter Attia1:11:01

       So let's-- I'm just trying to take this in some sort of thoughtful order. Should we t- should we now move to IVF, or do you want to say a little bit more about IUI? We haven't really talked directly about IUI.

    4. PAPaula Amato1:11:14

       Yeah.

    5. PAPeter Attia1:11:14

       By the way, I don't know what it is about when people say turkey baster, it makes me cringe. Like, that is just such a gross-

    6. PAPaula Amato1:11:20

       [laughs]

    7. PAPeter Attia1:11:20

       ... image to me. So I-

    8. PAPaula Amato1:11:22

       I agree. [laughs]

    9. PAPeter Attia1:11:22

       I am deliberately not going to say it other than that-

    10. PAPaula Amato1:11:25

        Okay

    11. PAPeter Attia1:11:25

        ... moment ago that I just said it.

    12. PAPaula Amato1:11:26

        Okay. [laughs]

    13. PAPeter Attia1:11:26

        But, but just so that people know what we mean by intrauterine insemination-

    14. PAPaula Amato1:11:30

        Yes

    15. PAPeter Attia1:11:30

        ... um, just to be clear, you are not using a turkey baster.

    16. PAPaula Amato1:11:34

        Definitely not. [laughs]

    17. PAPeter Attia1:11:34

        Okay. Thank God. Most disgusting image. I don't know why.

    18. PAPaula Amato1:11:38

        Yes.

    19. PAPeter Attia1:11:38

        I get so grossed out by that.

    20. PAPaula Amato1:11:40

        Yes, yes.

    21. PAPeter Attia1:11:40

        So can you explain how IUI is done?

    22. PAPaula Amato1:11:44

        Sure.

    23. PAPeter Attia1:11:44

        How, um, uh, we've already said that with IUI, you're, you largely favor an oral preparation.

    24. PAPaula Amato1:11:52

        Usually, yeah.

    25. PAPeter Attia1:11:53

        Yeah. Okay.

    26. PAPaula Amato1:11:54

        Yeah.

    27. PAPeter Attia1:11:54

        So that means, so you, you're using an oral set of hormones so that the woman doesn't have a massive proliferation of follicles.

    28. PAPaula Amato1:12:03

        Right, right.

    29. PAPeter Attia1:12:03

        So the male ejaculates.

    30. PAPaula Amato1:12:05

        Right.
14. 1:22:15 – 1:25:36

    The history of in vitro fertilization (IVF), & how access & acceptance have evolved over time

    1. PAPeter Attia1:22:15

       Um, okay. So now let's talk a little bit about IVF.

    2. PAPaula Amato1:22:19

       Mm-hmm.

    3. PAPeter Attia1:22:21

       First successful IVF baby, 1978, if my memory serves correctly.

    4. PAPaula Amato1:22:26

       That's right. That's right. Yeah.

    5. PAPeter Attia1:22:27

       Referred to as a test tube baby-

    6. PAPaula Amato1:22:28

       At the time [laughs]

    7. PAPeter Attia1:22:28

       ... which is kind of weird because I would imagine it was in a Petri dish, not a test tube. But anyway.

    8. PAPaula Amato1:22:33

       Yeah. Yeah.

    9. PAPeter Attia1:22:34

       Um, we've come a long way since then.

    10. PAPaula Amato1:22:37

        We have.

    11. PAPeter Attia1:22:37

        For historical context, I don't know anything about that, that girl, but do you, do you know anything about how that was done back in 1978?

    12. PAPaula Amato1:22:45

        Yeah. Actually, there's a recent, uh, docudrama out called Joy that goes through the whole story.

    13. PAPeter Attia1:22:50

        Is that her name?

    14. PAPaula Amato1:22:50

        Uh, her middle name-

    15. PAPeter Attia1:22:51

        Oh, wow

    16. PAPaula Amato1:22:52

        ... I believe, is Joy.

    17. PAPeter Attia1:22:53

        Ah.

    18. PAPaula Amato1:22:53

        Yes.

    19. PAPeter Attia1:22:53

        Oh, that's great.

    20. PAPaula Amato1:22:54

        Louise Joy Brown is her name.

    21. PAPeter Attia1:22:56

        What's her first?

    22. PAPaula Amato1:22:56

        Louise Brown.

    23. PAPeter Attia1:22:58

        Louise Brown.

    24. PAPaula Amato1:22:58

        I believe her middle name is Joy.

    25. PAPeter Attia1:22:59

        Okay. Got it.

    26. PAPaula Amato1:23:00

        Um, but it, it's a movie about the first IVF success.

    27. PAPeter Attia1:23:05

        Oh, that's great.

    28. PAPaula Amato1:23:06

        Now, of course, they tried for many, many years before they had the first success. The, the, these were two doctors in the UK.

    29. PAPeter Attia1:23:12

        So tell me, have you-- What, what, I mean, maybe this is all in the docudrama and I can't wait to check it out.

    30. PAPaula Amato1:23:16

        Mm-hmm.
15. 1:25:36 – 1:33:12

    The step-by-step process of IVF

    1. PAPeter Attia1:25:36

       how IVF works, and then we'll kind of dive into-

    2. PAPaula Amato1:25:37

       Sure

    3. PAPeter Attia1:25:38

       ... the ins and outs of, of some of the nuances. So, um, so a, a woman comes to you. Probably she's progressed through some layers of-

    4. PAPaula Amato1:25:44

       Mm-hmm

    5. PAPeter Attia1:25:44

       ... of treatment.

    6. PAPaula Amato1:25:45

       Yeah.

    7. PAPeter Attia1:25:45

       But, you know, you've collectively come to the decision that this is hands down the best opportunity both for success and, you know, risk. Um, so how, how does the treatment go?

    8. PAPaula Amato1:25:56

       Yeah. So typically we do a bunch of screening tests on both partners. That includes some blood tests, a semen analysis, an ultrasound to get some assessment of their egg number, the woman's egg number, and then when the cycle starts, takes about two to three months to complete a cycle of IVF.

    9. PAPeter Attia1:26:13

       And when you say egg number-

    10. PAPaula Amato1:26:15

        Mm-hmm

    11. PAPeter Attia1:26:15

        ... are you determining that through an AMH or through a-

    12. PAPaula Amato1:26:18

        Mm-hmm

    13. PAPeter Attia1:26:18

        ... physical examination of the ovaries?

    14. PAPaula Amato1:26:20

        Both. So we do an ultrasound. We can count the number of follicles.

    15. PAPeter Attia1:26:23

        How, how small are these things?

    16. PAPaula Amato1:26:26

        You know, a few millimeters.

    17. PAPeter Attia1:26:28

        And you have the resolution to see that on an ultrasound?

    18. PAPaula Amato1:26:30

        Yeah. Yeah.

    19. PAPeter Attia1:26:31

        Okay.

    20. PAPaula Amato1:26:31

        Yeah. And that gives you some sense of about how many eggs that particular patient will produce with ovarian stimulation. And we use AMH as a hormone you mentioned.

    21. PAPeter Attia1:26:41

        So explain what AMH is and how it works.

    22. PAPaula Amato1:26:42

        AMH-- Yeah. AMH is a hormone that stands for anti-Müllerian hormone. It's secreted by the cells that surround the egg, so it tends to correlate with egg number, okay? Doesn't tell you anything about fertility or, you know, pregnancy rates or anything like that. Age is still the most important factor in, in, in that sense, but it does give you an idea. Do you have a normal number of eggs for your age?

    23. PAPeter Attia1:27:03

        So just numbers. So two women that have the same number of eggs, if one woman has high quality eggs, the other woman does not, they could still have the same AMH level on a blood test.

    24. PAPaula Amato1:27:13

        Right.

    25. PAPeter Attia1:27:14

        Okay.

    26. PAPaula Amato1:27:14

        If they're different ages, their success rates can be different.

    27. PAPeter Attia1:27:17

        Yep.

    28. PAPaula Amato1:27:17

        Yeah.

    29. PAPeter Attia1:27:18

        Can you give a-- Give me a-- Remind me of the range. So, uh, a pre-ovulate-- a, a sort of prepubescent girl who has a billion e- not a billion, but, right, a million eggs, but who is not fertile, does she have a high or low AMH?

    30. PAPaula Amato1:27:33

        She has a higher AMH. We tend not to use it in that age group because it's less reliable.
16. 1:33:12 – 1:50:00

    The IVF lab process: egg retrieval, fertilization, embryo culture, & freezing

    1. PAPaula Amato1:33:12

       Right.

    2. PAPeter Attia1:33:13

       And do you harvest the follicles in the fallopian tube, or do you-

    3. PAPaula Amato1:33:17

       No, in the ovaries

    4. PAPeter Attia1:33:17

       ... you go right into the ovary?

    5. PAPaula Amato1:33:18

       In the ovaries. Yeah.

    6. PAPeter Attia1:33:19

       Okay.

    7. PAPaula Amato1:33:20

       So the egg retrieval is ha- happens two days after the HCG trigger.

    8. PAPeter Attia1:33:25

       Wow.

    9. PAPaula Amato1:33:26

       Yeah.

    10. PAPeter Attia1:33:26

        I would have thought-- So it, it would've taken two days for her to-

    11. PAPaula Amato1:33:31

        Thirty-six hours, specifically. So she usually takes it in the evening, and then the retrieval is-

    12. PAPeter Attia1:33:36

        Is the n-

    13. PAPaula Amato1:33:37

        Two mornings

    14. PAPeter Attia1:33:37

        ... the day after-

    15. PAPaula Amato1:33:38

        Yeah

    16. PAPeter Attia1:33:38

        ... in the morning. Okay, so woman comes-

    17. PAPaula Amato1:33:40

        Two mornings. Yeah

    18. PAPeter Attia1:33:40

        ... into your office.

    19. PAPaula Amato1:33:41

        Mm-hmm.

    20. PAPeter Attia1:33:41

        A day, two days later.

    21. PAPaula Amato1:33:43

        Yep.

    22. PAPeter Attia1:33:44

        And, like, t-- walk me through this. So you lay her on a table, you've got an ultrasound on her ovary, and you're literally putting a needle in there?

    23. PAPaula Amato1:33:51

        Well, first of all, she's asleep. [laughs]

    24. PAPeter Attia1:33:53

        Uh, fully asleep or just local sedation?

    25. PAPaula Amato1:33:55

        Uh, propofol. Yeah.

    26. PAPeter Attia1:33:56

        Okay.

    27. PAPaula Amato1:33:56

        Yeah. So this is done in a surgery center typically-

    28. PAPeter Attia1:33:59

        Okay

    29. PAPaula Amato1:33:59

        ... or clinic with, um, anesthesiologist present, IV sedation, propofol.

    30. PAPeter Attia1:34:04

        So it's like, it's like a colonoscopy-
17. 1:50:00 – 1:57:00

    Genetic testing & embryo selection in IVF: aneuploidy screening, polygenic traits, & ethical concerns

    1. PAPeter Attia1:50:01

       What depth of genetic testing is being done here? Are you doing whole genome sequence, or are you just looking at a handful of SNPs-

    2. PAPaula Amato1:50:11

       Yeah

    3. PAPeter Attia1:50:11

       ... that are pre-identified as the ones that matter?

    4. PAPaula Amato1:50:14

       Yeah. Good question. So it's evolved over time, and I should say it's still very controversial because there's always a risk of harming the embryos. You're only looking at a few cells, so is it really representative of the embryo? I mean, we do it a lot, and the data definitely shows that if you transfer a normal embryo, it has a very high chance of implanting. But the issue is recently has been are we discarding embryos that are maybe normal, uh, because we think they're abnormal based on the genetic testing, but the genetic testing is flawed. It's a whole different conversation.

    5. PAPeter Attia1:50:46

       So presumably, genetic testing is really easy to identify aneuploidy.

    6. PAPaula Amato1:50:53

       That's, it's-

    7. PAPeter Attia1:50:53

       Chromosomal analysis is trivial.

    8. PAPaula Amato1:50:55

       Yes. It's geared up to do that, right.

    9. PAPeter Attia1:50:56

       Okay.

    10. PAPaula Amato1:50:56

        You're right. So most of the time we're using something called next generation sequencing, which is, you know, very, uh, high level sequencing, but it's not whole genome sequencing.

    11. PAPeter Attia1:51:05

        Yep.

    12. PAPaula Amato1:51:05

        So you're getting-

    13. PAPeter Attia1:51:06

        Targeted.

    14. PAPaula Amato1:51:06

        Yeah. And you're looking mostly at chromosomal abnormalities, unless you know that the couple is a carrier for some genetic mutation that you also want to screen for.

    15. PAPeter Attia1:51:17

        Yeah. So let's say one of the parents... Well, this would be a bad example, but-

    16. PAPaula Amato1:51:24

        Cystic fibrosis, like let's say both patients are carriers.

    17. PAPeter Attia1:51:26

        Yeah. So both of them have-- are a carrier for CF.

    18. PAPaula Amato1:51:30

        Right.

    19. PAPeter Attia1:51:30

        And so there's a one in four chance-

    20. PAPaula Amato1:51:32

        Right

    21. PAPeter Attia1:51:32

        ... that you're gonna get two copies of the CF.

    22. PAPaula Amato1:51:33

        Right.

    23. PAPeter Attia1:51:34

        So then you're looking directly for the CF genes.

    24. PAPaula Amato1:51:36

        Exactly. Exactly.

    25. PAPeter Attia1:51:37

        Okay. Beta thal.

    26. PAPaula Amato1:51:38

        Exactly.

    27. PAPeter Attia1:51:38

        Uh, sickle cell.

    28. PAPaula Amato1:51:39

        Yeah.

    29. PAPeter Attia1:51:39

        The standard.

    30. PAPaula Amato1:51:40

        There's a whole bunch of them.
18. 1:57:00 – 2:01:00

    Embryo transfer in IVF

    1. PAPeter Attia1:57:00

       um, now it's time to implant. So how does that process work?

    2. PAPaula Amato1:57:05

       So that process is, uh, much less complicated, but equally important. Um, so usually does-- it's timed, right? It has to happen at a certain time in the cycle. So we either use the woman's natural cycle to time it, and time it at the time that implantation would normally occur, which is like the second half of the cycle, or we use what we call a controlled or programmed cycle, where we basically give the woman the hormones and then again, time the transfer to happen at a s- specific time. Um, the actual process, kinda like a Pap smear. It basically doesn't require any anesthesia or anything. We do do it under ultrasound guidance, so abdominal ultrasound. We thaw one of the embryos, draw it up in a little catheter with a little syringe on the end, place a speculum in the vagina, and then just pass the catheter through the cervix, and we're looking on the ultrasound for the placement. And then-

    3. PAPeter Attia1:57:57

       And where are you implanting it?

    4. PAPaula Amato1:57:58

       About one and a half centimeters to two centimeters from the top of the uterus. So a few centimeters through the cervix.

    5. PAPeter Attia1:58:07

       And how do you make sure it doesn't come out?

    6. PAPaula Amato1:58:10

       I mean, you can't, but it doesn't usually. You put it in there kind of... It's like, I describe it kind of like more like peanut butter in there. It's not like, uh, you stand up and it comes out, and it s- stays in.

    7. PAPeter Attia1:58:21

       What's the total volume you're injecting-

    8. PAPaula Amato1:58:23

       Like-

    9. PAPeter Attia1:58:24

       ... of fluid?

    10. PAPaula Amato1:58:24

        ... 50 microliters, like really small.

    11. PAPeter Attia1:58:27

        Okay.

    12. PAPaula Amato1:58:27

        Yeah.

    13. PAPeter Attia1:58:28

        And what, what does the inside of a uterus look like at that stage? 'Cause you've t- you've timed it so that this is a uterus that doesn't have a lining yet, right? Like you-

    14. PAPaula Amato1:58:38

        It does have a lining.

    15. PAPeter Attia1:58:39

        How thick is the lining?

    16. PAPaula Amato1:58:40

        It's about seven to 10 millimeters.

    17. PAPeter Attia1:58:44

        But it's gonna get a heck of a lot thicker. So it's j- it's still, it's, it's only-

    18. PAPaula Amato1:58:48

        Yeah

    19. PAPeter Attia1:58:48

        ... this is technically only about 14 days past her period.

    20. PAPaula Amato1:58:52

        So it's-

    21. PAPeter Attia1:58:52

        Or are you doing it artificially more into the luteal phase?

    22. PAPaula Amato1:58:55

        So it's roughly, you know, seven days or so after ovulation, right?

    23. PAPeter Attia1:59:03

        Ah, got it. Yes, yes, yes.

    24. PAPaula Amato1:59:04

        So the lining is thickened already.

    25. PAPeter Attia1:59:06

        Yep. Okay.

    26. PAPaula Amato1:59:07

        Yeah.

    27. PAPeter Attia1:59:07

        Yep.

    28. PAPaula Amato1:59:07

        And that's one of the things we check with ultrasound before we do the transfer to make sure the lining-

    29. PAPeter Attia1:59:12

        And what does that, what does that, I mean, what does it actually look like? Is it like, is it-

    30. PAPaula Amato1:59:15

        It-
19. 2:01:00 – 2:05:25

    Egg donation in IVF

    1. PAPeter Attia2:01:00

       how often does a woman go through all of this and for whatever reason, you can't get enough eggs or the-

    2. PAPaula Amato2:01:08

       Yeah

    3. PAPeter Attia2:01:08

       ... eggs you get are not chromosomally normal-

    4. PAPaula Amato2:01:12

       Right

    5. PAPeter Attia2:01:12

       ... and her next alternative is an egg donor?

    6. PAPaula Amato2:01:15

       Yes. Unfortunately, more often than we would like. Uh, again, it depends on the age of the patient, but sometimes, you know, patients do multiple cycles. Maybe they don't have any normal embryos, or maybe even the normal embryos when we transfer don't take, or a number of different things can happen. Um, so the most common reason someone would need an egg donor is usually maternal age. So someone who's older and has tried to get pregnant with her own eggs, hasn't worked for whatever reason, and then now she's looking at egg donation as an option. That works really well. So usually egg donors are young women in their twenties, early thirties sometimes, and they produce multiple eggs, and then the age of the uterus doesn't seem to matter as much. So the success rate with donor egg is, is quite high. It's about 70, 75%. Whereas, you know, for women over 40, using their own eggs, success rate Might be 10 to 20%.

    7. PAPeter Attia2:02:15

       Per in-

    8. PAPaula Amato2:02:16

       Cycle

    9. PAPeter Attia2:02:16

       Per cycle.

    10. PAPaula Amato2:02:16

        Per cycle. Yeah.

    11. PAPeter Attia2:02:18

        Wow. 10 to 20%?

    12. PAPaula Amato2:02:20

        Yeah.

    13. PAPeter Attia2:02:20

        For a 40-year-old woman.

    14. PAPaula Amato2:02:21

        Yeah. Untested embryos, right.

    15. PAPeter Attia2:02:23

        Wow.

    16. PAPaula Amato2:02:23

        Or they may not get any embryos, right? Normal embryos.

    17. PAPeter Attia2:02:26

        Wow.

    18. PAPaula Amato2:02:26

        Yeah.

    19. PAPeter Attia2:02:27

        I did not realize, realize it was that low.

    20. PAPaula Amato2:02:29

        Yeah.

    21. PAPeter Attia2:02:30

        Um, how many times can a young woman be an egg donor before you worry about... Is there anything you worry about if you're counseling these women? 'Cause I, I assume the same women are coming to you as egg donors.

    22. PAPaula Amato2:02:42

        Yeah. Sometimes people do it multiple times. Sometimes they just do it once. Um-

    23. PAPeter Attia2:02:45

        Does it pose any risk to the egg donor?

    24. PAPaula Amato2:02:48

        You know, the, the, they're essentially undergoing the IVF process themselves, or at least the first half of it.

    25. PAPeter Attia2:02:52

        Yep.

    26. PAPaula Amato2:02:52

        So there's the risks we talk about. Ovarian hyperstimulation, which is rare, risks associated with the retrieval, anesthesia.

    27. PAPeter Attia2:03:00

        But is there anything that, like, uh, restricts her ability to get pregnant later in life?

    28. PAPaula Amato2:03:04

        No. Barring any complications, from major complications, the, it does not seem to impact future fertility.

    29. PAPeter Attia2:03:11

        What is the typical fee for a-- that's collected by an egg donor?

    30. PAPaula Amato2:03:15

        It's usually between $5,000 and $10,000, depending on where you live.
20. 2:05:25 – 2:13:34

    How to choose the right IVF clinic

    1. PAPaula Amato2:05:25

       couple.

    2. PAPeter Attia2:05:26

       If someone's listening to this and they're trying to figure out how to select a good IVF clinic-

    3. PAPaula Amato2:05:33

       Mm-hmm

    4. PAPeter Attia2:05:34

       ... what, what, what are the things they should be looking for? Because I would have to assume that it's like any other field of medicine, right? Not all doctors and not all clinics are created equal.

    5. PAPaula Amato2:05:46

       Mm-hmm.

    6. PAPeter Attia2:05:46

       And just because you see a lot of advertising doesn't tell you anything.

    7. PAPaula Amato2:05:52

       Right.

    8. PAPeter Attia2:05:52

       Right?

    9. PAPaula Amato2:05:52

       Right.

    10. PAPeter Attia2:05:52

        So, so, so in other words, you, you're gonna have to become a very, very intelligent consumer. For most people, this will be the single most expensive out-of-pocket healthcare expense they have.

    11. PAPaula Amato2:06:05

        Yeah. That's true.

    12. PAPeter Attia2:06:06

        And so it's not just that it's the most expensive healthcare decision they're ever gonna make, it might be one of the most consequential-

    13. PAPaula Amato2:06:13

        Mm-hmm

    14. PAPeter Attia2:06:13

        ... as well.

    15. PAPaula Amato2:06:14

        For sure.

    16. PAPeter Attia2:06:15

        And yet I, I mean, I know what I suggest to people.

    17. PAPaula Amato2:06:19

        Mm-hmm.

    18. PAPeter Attia2:06:20

        When someone says, "Peter, you know, my wife and I are thinking about getting IVF. What do you think?"

    19. PAPaula Amato2:06:23

        Mm-hmm.

    20. PAPeter Attia2:06:23

        I just go down the rabbit hole of like-

    21. PAPaula Amato2:06:25

        [laughs]

    22. PAPeter Attia2:06:25

        ... here's 100 questions I would ask.

    23. PAPaula Amato2:06:27

        Yeah.

    24. PAPeter Attia2:06:28

        Um, and it usually begins with, "Tell me your success rate-

    25. PAPaula Amato2:06:34

        Mm-hmm

    26. PAPeter Attia2:06:34

        ... individually." I don't care about the national success rate.

    27. PAPaula Amato2:06:36

        Right.

    28. PAPeter Attia2:06:36

        It means nothing to me. So, so how would you counsel someone who's trying to come up with their checklist of questions to ask?

    29. PAPaula Amato2:06:44

        Yeah. There's a good-- It's a good question, and, you know, these days it's a little bit easier 'cause obviously there's the internet, and there's suggested questions online you could look at. Um, there-- It's true there is some variability amongst clinics, although there's a lot of consolidation happening in the field as well. So a lot of the, you know, practices are becoming common to, to most clinics. Um, but some of it is practical, right? Like which clinics are close to where you live. Because as, as we learned-

    30. PAPeter Attia2:07:11

        You have to go in and get these ultrasounds. Yeah
21. 2:13:34 – 2:20:12

    Innovations in fertility on the horizon & advice about freezing eggs

    1. PAPeter Attia2:13:34

       now and talk about a few other things. So what's on the horizon medically for extending fertility? So there's a, there's a study going on at, at, uh, Cornell or Columbia?

    2. PAPaula Amato2:13:43

       Columbia.

    3. PAPeter Attia2:13:43

       Columbia, um, that's looking at the use of rapamycin to extend fertility in women. Now, I have to be honest with you. I, I-- There was a day when I knew what the study was-

    4. PAPaula Amato2:13:54

       Mm-hmm

    5. PAPeter Attia2:13:55

       ... and what the inclusion criteria were. I, I, I, I don't at the moment. I'm, I'm assuming you are more familiar with this than I am.

    6. PAPaula Amato2:14:00

       Mm-hmm.

    7. PAPeter Attia2:14:01

       Uh, what is the question that is being asked and how is it being asked in this study?

    8. PAPaula Amato2:14:06

       Yeah. So there's a lot of interest in extending fertility, right?

    9. PAPeter Attia2:14:10

       Yep.

    10. PAPaula Amato2:14:10

        Like up until, you know, a hundred years ago, women were basically dying at fifty-

    11. PAPeter Attia2:14:15

        Yeah

    12. PAPaula Amato2:14:15

        ... is the average age of menopause. So it's, it's a kind of recent phenomenon that we're actually living a third of our lives, you know, post-menopause, but... And fertility starts to decline way before you go through menopause. So there's a lot of interest in trying to extend fertility. Now, of course, egg freezing, which we haven't talked about yet, um, is one of the ways you can extend fertility, and it works pretty well as long as you're young when you freeze your eggs. Um, but again, it's a relatively recent phenomenon, not every b- it's not, you're not usually covered by insurance, and it's expensive, et cetera, so it's not the answer.

    13. PAPeter Attia2:14:46

        Because you're paying basically half the IVF cycle to harvest, and then you're paying to freeze.

    14. PAPaula Amato2:14:52

        Yeah, exactly.

    15. PAPeter Attia2:14:53

        What's the cost of freezing?

    16. PAPaula Amato2:14:54

        About $1,000 a y- well, $10,000 for the cycle-

    17. PAPeter Attia2:14:57

        For the cycle

    18. PAPaula Amato2:14:57

        ... and then about $1,000 a year for storage.

    19. PAPeter Attia2:15:00

        And you're recommending that women-- If, if a woman came to you at twenty-

    20. PAPaula Amato2:15:05

        Yeah

    21. PAPeter Attia2:15:05

        ... and said, "Um, you know, I'm gonna-- I just wanna double down on my career right now."

    22. PAPaula Amato2:15:11

        Mm-hmm.

    23. PAPeter Attia2:15:11

        "Uh, I wanna do X, Y, and Z. I think I wanna have kids. I at least want the optionality. When should I freeze by?" Are you gonna just say, "Do it now?"

    24. PAPaula Amato2:15:19

        No.

    25. PAPeter Attia2:15:19

        Because... No.

    26. PAPaula Amato2:15:20

        Yeah, yeah. I wouldn't recommend all women in their twenties freeze their eggs because most of those eggs will never be used, so you'd be doing it for nothing because most of those women will probably not need IVF and get pregnant spontaneously, right?

    27. PAPeter Attia2:15:32

        Got it. Okay.

    28. PAPaula Amato2:15:33

        The sweet spot we think is like early to mid-thirties. That's where it makes the most sense, like-

    29. PAPeter Attia2:15:38

        'Cause you're about to kind of get to the probability cliff-

    30. PAPaula Amato2:15:42

        Cliff. Yeah. [laughs]
22. 2:20:12 – 2:29:25

    Optimizing fertility through lifestyle changes

    1. PAPeter Attia2:20:12

       Are there any other things that a woman can do to maximize her fertility beyond... Let's, we've already addressed sort of PCOS. We've already addressed kind of the metabolic stuff. But, um, you know, we hear things all the time, like-

    2. PAPaula Amato2:20:26

       Yeah

    3. PAPeter Attia2:20:27

       ... stress-

    4. PAPaula Amato2:20:27

       Yeah

    5. PAPeter Attia2:20:27

       ... sleep. I mean, these things si- seem self-evident.

    6. PAPaula Amato2:20:30

       Mm-hmm.

    7. PAPeter Attia2:20:31

       Um, but what, what would be kind of the most common things you would be saying to a woman who is otherwise experiencing iatrogenic, for lack of a better word, uh, infertility?

    8. PAPaula Amato2:20:44

       Yeah, I think all those things are important, like lifestyle factors. They're rarely the sole cause of infertility, but can, they can certainly exacerbate infertility as well as any other disease. So I think the, the lifestyle factors that, um, promote health are generally the same lifestyle factors that promote fertility. So healthy diet, um, you know, avoiding-

    9. PAPeter Attia2:21:11

       Is there anything we can say more on that? I mean, it, it-

    10. PAPaula Amato2:21:13

        [laughs]

    11. PAPeter Attia2:21:13

        ... it's, it's like what-

    12. PAPaula Amato2:21:15

        Yeah. [laughs]

    13. PAPeter Attia2:21:16

        You know, what, what is a healthy diet-

    14. PAPaula Amato2:21:17

        I know

    15. PAPeter Attia2:21:17

        ... as it pertains to fertility? Is it different, right? Does a-

    16. PAPaula Amato2:21:20

        Right

    17. PAPeter Attia2:21:20

        ... does a woman who's getting ready to, to conceive, does she need more fat in her diet, for example?

    18. PAPaula Amato2:21:26

        Yeah.

    19. PAPeter Attia2:21:26

        Like-

    20. PAPaula Amato2:21:26

        Yeah. Yeah. Yeah. As you probably know, the data on, on diet is not great, right?

    21. PAPeter Attia2:21:32

        Yeah.

    22. PAPaula Amato2:21:32

        For anything, especially not fertility. So the, I would say there's very little evidence that there's a particular diet that's good for fertility that's different than what's good in general. So for most of my patients, I recommend the Mediterranean diet. That diet is palatable to most people, and, uh, has fair amount of evidence that, you know, it's reasonably healthy, and that's, like, a lot of fruit and vegetables, whole grains, protein, mostly from, you know, fish and olive oil and those types of things. So it's not that different from what I would recommend for, for anybody.

    23. PAPeter Attia2:22:10

        Yeah. By the way, I think I said iatrogenic. I meant idiopathic, but you know what I meant.

    24. PAPaula Amato2:22:14

        Yes. Yes, yes.

    25. PAPeter Attia2:22:14

        I think when I, when I said that, right? Yeah.

    26. PAPaula Amato2:22:15

        Yeah.

    27. PAPeter Attia2:22:15

        So, um, what about supplements? I'm sure you get asked this question all the time.

    28. PAPaula Amato2:22:20

        Mm-hmm. Yep, yep. It's very common.

    29. PAPeter Attia2:22:21

        There's no shortage of over-the-counter-

    30. PAPaula Amato2:22:22

        Right, right
23. 2:29:25 – 2:37:00

    Promising areas of fertility research

    1. PAPeter Attia2:29:25

       back at the last decade-

    2. PAPaula Amato2:29:26

       Yeah

    3. PAPeter Attia2:29:27

       ... uh, what do you imagine you will be most excited about from an innovation perspective?

    4. PAPaula Amato2:29:32

       Yeah. It's a very exciting field of medicine. There's always sort of innovations happening. I think, let's see. Genetic testing will continue t- to evolve as we learn more about genetics. I think that'll play a, a bigger role. Um, automation in the lab. You know, a lot of the steps we talked about earlier are, like, literally embryologists sitting at the microscope doing these things, but now there's some companies developing these, like, lab-on-a-chip concepts where-

    5. PAPeter Attia2:30:00

       Huh

    6. PAPaula Amato2:30:00

       ... like you put in the egg, put in the sperm, an embryo comes out at the other end.

    7. PAPeter Attia2:30:03

       So microfluidics or...?

    8. PAPaula Amato2:30:05

       Yeah, microfluidics. It, the whole process being automated-

    9. PAPeter Attia2:30:09

       Mm

    10. PAPaula Amato2:30:09

        ... which I think is f- it's very interesting, right? And it could potentially improve access if you could put these labs-

    11. PAPeter Attia2:30:17

        So do you see this as more of a cost reduction or more of a success improvement?

    12. PAPaula Amato2:30:22

        Uh, maybe both because, you know, reduced error potentially. Um, usually the cost of things tends to go up before [laughs] anytime, anytime there's an innovation before it comes down. Maybe ultimately-

    13. PAPeter Attia2:30:34

        Mm-hmm

    14. PAPaula Amato2:30:34

        ... it'll come down, but I, I imagine costs will increase. Um, so that's kind of an exciting area. In vitro maturation, that's where the eggs are, like, maturing in the Petri dish instead of a, in a woman's body, so potentially in the future a woman wouldn't have to take all these injections, and you just take the immature eggs, put 'em in the Petri dish, and then give the Petri dish the, the medications, if you will. Um, that's in very sort of early stages, not quite as successful as conventional IVF yet, so we're not quite there.

    15. PAPeter Attia2:31:10

        I assume because it's difficult to harvest unmature follicles.

    16. PAPaula Amato2:31:14

        Partly.

    17. PAPeter Attia2:31:14

        Yeah.

    18. PAPaula Amato2:31:14

        And even that maturation process, we haven't quite gotten it down like it happens in the body. Um, other things. A, a real game changer would be something like in vitro gametogenesis, which is making eggs and sperm potentially from skin cells. So even if you run out of eggs, if we could take like a skin biopsy and, you know, reprogram that cell to make an egg, then potentially, you know, anybody-

    19. PAPeter Attia2:31:45

        Where are we in that?

    20. PAPaula Amato2:31:46

        Very early. I think we'll see it eventually. It's been done in mice. Um-

    21. PAPeter Attia2:31:50

        Yeah

    22. PAPaula Amato2:31:51

        ... so we're probably 10 to 20 years away.

    23. PAPeter Attia2:31:54

        What's the, what's the, uh, what's the obstacle?

    24. PAPaula Amato2:31:58

        Basically, reprogramming skin cells. It just, the whole process is very complicated, um, and, and not easy. People are trying. There are a couple of companies that are trying to do-

    25. PAPeter Attia2:32:11

        Meaning is the challenge taking the skin cell back to a stem cell and then the stem cell into-

    26. PAPaula Amato2:32:16

        Differentiating.

    27. PAPeter Attia2:32:17

        Yeah.

    28. PAPaula Amato2:32:17

        Yeah.

    29. PAPeter Attia2:32:17

        And, and which of those two steps do we think is harder? Skin cell back to stem cell or stem cell into egg?

    30. PAPaula Amato2:32:23

        I think they're both hard. Um- I don't know. There's a couple different approaches, including, you know, we work, do research in this area as well, where we're taking essentially the nucleus from a skin cell and putting it into a-

Episode duration: 2:37:00