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

welcome to the huberman Lab podcast where we discuss science and science-based tools for everyday [Music] life I'm Andrew huberman and I'm a professor of neurobiology and Opthalmology at Stanford School of Medicine my guest today is Dr Natalie Crawford Dr Natalie Crawford is a medical doctor specializing in Obstetrics and Gynecology reproductive endocrinology and infertility she also holds a degree in nutrition science Dr Crawford runs a clinical practice seen patients daily as well as being actively 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 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 discussed topics such as the timing of puberty and what the timing of puberty in girls means for their fertility and we discussed 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 invitro 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 relate to female hormone Health generally indeed Dr Crawford provides us with a master class 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 about science and science related tools to the general public in keeping with that theme I'd like to thank the sponsors of today's podcast our first sponsor is Maui Nei venison Maui NE venison is the most nutrient-dense and delicious red meat available I've spoken before on this podcast in Solo episodes and with guests about the need to get approximately 1 gram of highquality protein per pound of body weight each day for optimal nutrition now there are many different ways that one can do that but a key thing is to make sure that you're not doing that by ingesting excessive calories Maui Nei venison has the highest density of quality protein per calorie and it achieves that in delicious things like like ground Meats venison steaks jerky and bone broth I particularly like the ground venison I make those into venison burgers probably five times a week or more I also like the jerky for its convenience especially when I'm traveling or I'm especially busy with work and know that I'm getting an extremely nutrient-dense highquality source of protein if you'd like to try Maui Nei 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sleep needs I sleep on the dusk DUS us mattress and when I started sleeping on a dusk mattress about 2 years ago my sleep immediately improved so if you're interested in upgrading your mattress go to helixsleep.com huberman take their 2-minute sleep quiz and they'll match you to a customized mattress for you and you'll get up to $350 off any mattress order and two free pillows again if interested go to helixsleep.com huberman for up to $350 off and two free pillows I'm pleased to announce that we will be hosting four live events in Australia Each of which is entitled The Brain body contract during which I will share science and science related tools for mental health physical health and performance there will also be a Live question and answer session we have limited tickets still available for the event in Melbourne on February 10th as well as the event in Brisbane on February 24th our event in Sydney at the Sydney Opera house sold out very quickly so as a consequence we've now scheduled a second event in Sydney at the aware super theater on February 18th to access tickets to any of these events you can go to huberman lab.com events and use the code huberman at checkout I hope to see you there and as always thank you for your interest in science and now for my discussion with Dr Natalie Crawford Dr craw welcome thank you so much for having me I'm honored to be here well 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 about hormones it actually relates to things like behaviors yes sex behaviors and other behaviors nutrition supplementation so we'll get into all of 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 menstration is uh in terms of their age Etc that provides hints or maybe even facts or directives about her future fertility or how long 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 your mom you have the most eggs you're ever going to have at about 20 weeks gestation you have about six to seven 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 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 thearchy 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 hypo L sends out G&R and then we have FSH coming out which really starts to stimulate those follicles so FSH or follicle stimulating 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 menarchy um so you said uh breast Bud development and then breast development on average about two years before years before you have sexual hair development so actually adrin Archy 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 And so genital hair underarm hair ex yeah genital hair usually first and then underarm hair um and uh we're getting right down into the weeds here which is good um you know a goal of this podcast is to normalize all aspects of Health including sexual health and and reproductive Health um is that commencer it also with um the development of body odor yes 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 um 48 um I can tell you that the the locker room smelled a lot different um be before and after Middle School right right like the in other words boys start to smell stinky um right 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 stink 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 test SE or ovaries are now starting to respond to those brain signals 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 asked that question is not to get people thinking about um stinky smells but um and by the way some people love the musty smell of of their own uh armpits or others you know we're referring to adults um by the way um but the reason I ask is that there's a wealth of data in animal models including non-human primates suggesting that um exposure to the odors of others can either um stimulate or accelerate puberty um 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 tox 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 menarchy or their period at a much younger age how much younger I I've seen the various graphs for different countries but can we say that you know 10 years ago on average um girls in the United States and Northern Europe were getting menarchy at about what 12 to 13 years of age yeah so you know start we'll use menarchy for the purpose of this so having your period you know 10 to 20 years ago you will see most data would say 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 1314 so most girls are definitely going through the puberty change earlier and the other thing to note is that most girls get their final 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 menstrating once the ovaries have really started to learn how to respond to that FSH 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 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 it's happening earlier that earlier puberty means that your growth spurt uh in terms of height is going to be uh truncated not the same and you probably most men will say oh but I had my growth spur 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 gross bir really your final height is within that year of when your period starts interesting yeah this uh 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 134 um let's just say I knew I did um but I didn't shave until I was after college my growth spurt between freshman and sophomore year I grew a foot right so I was like you know 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 um you know some people in my life would argue that puberty is still occurring for me it feels like it's very long and protracted which leads me to a a a um very specific question um if puberty arrives let's again Define as menarchy um 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 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 in um as a fetus um I think most people sort of assume that the reduction in egg count is due to obious ulation and the fact that you know one egg ovulates typically but that other eggs are deployed in that ovulatory cycle and then those those basically 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 cull From the Vault starting from early embryonic development and that ovulation is a distinct step in some sense unrelated to to 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 a lot of misconceptions that you're losing eggs from your Vault and that's not the case you're just accessing the ones outside gosh so you're not um 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 later or freeze them for later um if they want to use them eggs or or fertilized embryos that one is not reducing the total number of eggs any more than they would had they just let their their Cycles proceed naturally exactly that's such an important point I think that I think a lot of people believe the opposite they 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 into menopause earlier 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 relase or excessive release of eggs it's about stimulating the growth both of the ones that have been released so that they can be Frozen as stage either for later fertilization or fertilized in addition than Frozen as 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 uh head to the IVF Clinic I think again I really want to highlight this I 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 you're making the withdrawal no matter what great well um such an important point for for people to know and and propagate um getting back to puberty uh a little bit later on I wanted to get into endocrine disruptors and things of that sort but since you brought it up um 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 um precocious breast Bud development keep in mind folks that some transient breast Bud development is um characteristic of some normal puberties in males it sometimes 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 in it passed for for some right it occurred um normally and then passed but I've heard that things like exposure to evening primrose oil maybe even just through contact with Mom can um increase the the frequency or degree of that male breast Bud development is it also true that young girls can undergo precocious puberty or let's just say accelerated or exacerbated puberty um 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 breast Bud 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 primrose or lavender or tea tree oil o 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 breast bed 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 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 endocrine disruptors and plastic exposures and chemicals and all of this processed stuff let's just say that people have been exposed to that we're really seeing that those that ovarian susceptibility to egg quality and quantity happens in that fetal development period it's interesting uh because there are some uh parallels to male fetal development like the the fact that you have these or early organized izing effects of hormones like dihydrotestosterone which essentially stimulate the growth of the penis but also then establish a 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 so I only mention that because uh what I'd like to kind of illustrate in the background here is that um basically our reproductive Health begins really prior prior to conception really it's a dependent on M and Dad but um certainly to a great degree on on mom um but then fetal development is going to be important so sort of um us uh being able to pick our parents um I I do have a couple questions about lavender tea tree oil and evening primrose oil I was aware that evening Prim o oil oil excuse me can um somehow bind estrogen receptors it or mimic uh some of the estrad or something similar to it I wasn't aware of tea tree oil or lavender um here are we talking about oils what about Aromas and how concerned do people have to be about this stuff because I mean you know you'll go into a restaurant bathroom they'll be poer uh some people wear perfume I mean we don't want to set a paranoia but but I but I think people should know about this stuff tetri is in a lot of those um natural shampoos bur yes the one that tingle your scalps some people love them though constant exposure is very different than a onetime handwashing in the bathroom 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 physiological changes and so you know using unscented products especially with children is 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 sensor 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 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 and why uh what about cloth diapers versus non- cloth diapers i' I've heard you know that you have your like very strong cloth drier proponents right and that because they seem to um feel or believe that um non- cloth diapers somehow contain things that can get into baby's skin and and maybe there's a bigger question here is baby skin more permeable than adult don't know that baby skin is more perme I don't either I just to me it seems it seems like it' be hard to imagine it is but but babies do seem to have this incredible skin right their skin is so smooth and you want to squeeze their cheeks and all this kind of stuff but um yeah the idea they would be more permeable 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 in 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 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 anytime you can decrease toxin exposure to a child is going to be very important is there any evidence for um you know breast milk versus Formula in terms of impact on future reproductive development of or reproductive status of of a child that's a complicated question because breast mil milk exposure at least for the first 6 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 okay okay so if we're um thinking about a young girlwoman 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 I'll offend and um somebody no matter what um but a girl who under goes puberty right so a young woman um who's maybe 13 or so so she's early teens um under goes puberty and therefore is continuing to lose eggs from the Vault um but now is undergoing uh presumably roughly every 28 days manarchy but let's talk about this 28 days thing because I think a lot of people think that um quote unquote normal menstruation is always 28 days and and we know that's not true so what is the the range of uh normal durations between um menstration uh Cycles or duration of the menstruation cycle and let's also Define when the menstration 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 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 of Menses this is when you're actually bleeding at this time period we like to think about all of those new eggs being out of the Vault being susceptible to that FSH 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 and 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 FSH dominant phase where you have a lot of estrogen and people feel great when they have a lot of estrogen because women feel good with estrogen because of the relationship between estrogen and other neuromodulators like dopamine serotonin and and is that happening in parallel or are they somehow related like is estrogen controlling the release of Serotonin somehow and vice versa or are they just kind of coincidently 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 anadon lack of response to things which would normally give you pleasure happens more frequently 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 pams 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 lutenizing hormone and now you ovulate and when you ovulate the follicle opens up releases closes back and then it's the Corpus ludum and we've entered the ludal phase and the Corpus ludum as the name suggests a corpus it's like a body that's basically the it's Bas it's basically the the corpse of of what yeah in sheath the egg before um and it what I find so amazing I mean biology so beautiful right it instead of just taking that tissue and saying okay like let's just discard this or um that becomes the trigger for the next phase of the it is essential for life right the Corpus ludum which makes progesterone opens and closes the implantation window it is what allows somebody to get pregnant and for our species to continue it's so it's extremely fascinating and that Corpus ludum gets stimulated to produce progesterone imp pulses throughout the entire ludal phase because it's still controlled by the brain unless you get pregnant and then in that ludal 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 suddenly saying let's just protect this potential implantation that you're going to have if that pregnancy doesn't come the Corpus ludum 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 because the ludal 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 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 short as 21 days as long as 35 days and that can all be normal but people will hop between 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 see as women start to have fewer eggs in the vault is a shortening of their cycle 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 FSH 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 ludal phase is still set but the person who comes to see me and says my period have always been 28 to 30 days but now they're every 24 I just figure it's no big deal I am 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 say your periods a Vital sign and what we really mean is the regularity at which it comes and the predictability of it is telling us if your hormones are all communicating in a normal fashion or if something could potentially be off as we all know quality nutrition influences of course our physical health but also our mental health and our cognitive functioning our memory our ability to learn new things and to focus and we know that one of the most important features of highquality nutrition is making sure that we get enough vitamins and minerals from highquality unprocessed or minimally processed sources as well as enough probiotics and prebiotics and fiber to support basically all the cellular functions in our body including the gut microbiome now I like most everybody try to get optimal nutrition from Whole Foods ideally mostly from minimally processed or nonprocessed Foods however one of the challenges that I and so many other people face is getting enough servings of highquality fruits and vegetables per day as well as fiber and probiotics that often accompany those fruits and vegetables that's why way back in 2012 long before I had a podcast I started drinking ag1 and so I'm delighted that ag1 is sponsoring the hubman Lab podcast the reason I started taking ag1 and the reason I still drink ag1 once or twice a day is that it provides all of my foundational nutritional needs that is it provides insurance that I get the proper amounts of those vitamins minerals probiotics and fiber to ensure optimal mental health physical health and performance if you'd like to try ag1 you can go to drink a1.com huberman to claim a special offer they're giving away five free travel packs plus a year supply of vitamin D3 K2 again that's drink a1.com huberman to claim that special offer let me see if I have this correct um we've got this thing that we call the menstrual cycle the ovulatory cycle the there's two phases a follicular phase and audial phase folicular precedes the ludal phase the ludal phase tends to be if I heard correctly um fairly fixed about 14 days um the follicular phase can vary in duration maybe 10 to 14 days maybe even 10 to 18 days depending on the something about their brain to ovary communication for those that um aren't familiar with this um the I always learned that estrogen primes progesterone is kind of the really basic top Contour description of the ovulatory cycle that you know estrogen is going to slowly climb toward the the point of ovulation and then there's there's rep and then a drop and then progesterone is going to dominate in the ludal phase the second half you said that estrogen um is associated with with a psychological level and a physiological level more energy um feelings of Vitality and some of that estrogen increase is actually coming from the one egg that got stimulated the most the the one that got selected right so picked for the team um potentially for the team but got picked uh potentially for fertilization and that egg sheds its Corpus ludum uh which is this piece of the of the egg that then triggers the progesterone that dominates the ludal phase do I have that right mostly mostly yeah please correct the follicle in which the egg grows right when you ovulate it ruptures the cyst bursts a follicles a cyst a cyst is a fluid fill structure follicles a fluid fill 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 reheal and becomes the Corpus ludum 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 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 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 are to be clear um this 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 so there are um hormone based birth controls aka the pill there are also hormone based birth controls that are not in pill form um there are iuds that are copper iuds there are other iuds let's just talk about hormone-based contraception in females okay uh if which many of them as I understand 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 fantastic question let's talk about what people say is the pill so let's specifically talk about combined oral contraception the pill which has ethanol estrad 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 FSH from coming from the brain so you have the group of eggs still come out of the Vault there's no FSH 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 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 the body is smart and the ovaries start to say we're not really doing anything and one of those markers of ovarian reserve we have is amh and that's antimullerian hormone and amh is made from the granulosis cells or the cells that surround every follicle so in the shortest weight 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 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 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 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 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 reserve 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 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 exposure 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 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 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 FSH 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 spermatogenesis 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 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 your 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 inand 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 care 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 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 FSH LH really impact sperm quite significantly you mentioned bad Deeds um for sperm um not by sperm I said for sperm um and you know we we know that heat is is a uh you know a pretty dramatic insult to the um to the spermatogenesis cycle um saunas and hot tubs and whatnot and I did receive the question as to whether or not um heat exposure saunas hot tubs Etc are they um detrimental to ovulation or egg production in any way I mean obviously things are more internal in females the ovat 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 ovul 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 embryo can be more sensitive to certain things and that heat exposure at that time whether it's hot tub abuse 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 but I don't want anyone to run out and um 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 is one especially when you're younger your period Cycles tend to be irregular they're not your body hasn't fully matured to have that regularity 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 5 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 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 5 days and be right there when you have the egg and 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 um can we conclude then that the most fertile time is going to be when sperm meets egg let's save timing of intercourse for yep for the time being but because there's can be a delay there uh when sperm meets egg um on obviously day of ovulation or day uh 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 5 days so we'll say the fertile window is this 5-day 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 ovulate it on and if the egg has 24 hours then that extra day could potentially be helpful but really it's 5 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 Rel reltionship between estrogen libido and ovulation in females 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 have to be careful here um uh can sense the literally the deployment of the of the egg the the ovulation they they report that they can feel yeah that this let's just say the the departure of the of the uh egg um is that an imaginary thing I mean I always liked I always like that image that people can know when that happens after all men generally know when when their um when their sperm are leaving their body let's hope they do um but um why wouldn't that there be an internal sense for for women also of what's going on I mean we have interoception there's a ton of nerve inovation of that area 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 paranal 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 Schartz the pain almost feels like a crampy pain that happens in the middle of the cycle and that is your ovulatory pain oh interesting what is it called middle Schurz okay we'll put that in the show note captions and whoever does it is going to have to get the spelling right middle Schurz amazing amazing um amazing and foreign to me but for obvious reasons uh but amazing uh I'm always astonished in the um how incredibly well orchestrated this whole process is it's it's just a such an incredible feat of biology just I mean the number of things that have to be timed correctly and the use and I don't want to say reuse but the the repurposing of tissues for different things and like it's what a what an incredible dance 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 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 inter course 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 and so studies go back and always say daily intercourse associated with the highest chance of fundability 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 and 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 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 um donating or freezing sperm or doing IVF why they instruct the male to um not ejaculate for 48 to 72 hours prior to um let's just say depositing sperm it's such a funny word um but it works so two points one if we're doing a seen analysis now we're trying to evaluate the sperm and any test has certain normal parameters and these are all based on a 48 to 72h hour abstinence period so yes if you ejaculate more frequently you're going to have less sperm and that can be very normal 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 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 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 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 guid lines were 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 um sort of interpersonal chemistry and literally uh ejaculate and vaginal chemistry but before we do that um 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 um but for instance um does cannabis either by edible or by smoking cannabis impact Ed quality in either direction uh 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 provide they create so much stress for the body um but let's just say alcohol and cannabis um I read a statistic when researching the episode on cannabis that shocked me which is that 15% 15% not 1.5 15% of American women at least in this one study 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 fetus but I have a hard time believing that so what gives I mean here we're and and there I actually just threw in fetal development so is cannabis is Al alcohol bad for egg quality so they're 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 which is what we really think about we think about egg quality right impacting those myotic spindles 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 when we talk about um there's nicotine which itself is not carcinogenic and then there's the smoking process which brings in a bunch of other things the the question I know is burning in everybody's mind is vaping yeah right because vaping is I'm 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 um without doing too much of a deep dive is 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 in 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 and sorry to interject again but anytime a conversation like this comes up especially between two people in the health science space um there are these shouts because I hear them literally where people say well listen I Vaped every day and I've had three healthy babies and I think that 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 Vaped during pregnancy or Vaped prior to pregnancy or I mean I think these are the the key issues that like you can't you can't rewind the clock as far as I know right in the absence of a time machine you can't rewind the clock so um I mean basically everything you're saying is that smoking cigarettes or vaping nicotine just can't be good for egg 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 changes sperm morphology 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 miscarriage because of the sperm association with the Cannabis now edible cannabis as well as 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 um yeah I'm assuming there more data but okay so um smoking Andor Vape keeping nicotine cannabis either 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 the 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 I'm not trying to demonize anyone that did did do this during pregnancy a lot of people didn't know but this is this is really about people trying to make choices and an ation 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 3% per month and every single person is going to be like but my Aunt Barbara or I know this person who did because 3 person's not zero and you're talking about natural pregnany there by by uh inter old fashioned way yes okay right but yes 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 0% 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 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 I'd like to take a quick break and thank our sponsor insid tracker inside tracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals I've long been a believer in getting regular blood work done for the simple reason that many of the factors that impact your immediate and long-term Health can only be assessed with a quality blood test the problem with a lot of blood and DNA tests out there however is that they'll give you information about certain lipid markers or hormone markers but no information about what to do with all of that data inside tracker makes it very easy to look at your levels of hormones metabolic factors lipids Etc and then to assess what sorts of Behavioral nutritional supplementation or perhaps other interventions you might want to use in order to bring those numbers into the ranges that are optimal for your health inside tracker's ultimate plan now includes three new hormone markers that are critical to measure during a woman's reproductive and menopausal years these are estrad progesterone and thyroid stimulating hormone if you'd like to try insid tracker you can go to insid tracker.com huberman to get 20% off any of insid tracker's plans again that's sidet tracker.com huberman to get 20% off when we were talking about birth control I unfortunately moved us forward and and forgot to ask about iuds oh yeah so my understanding is that the copper IUD works by creating a sort of um not actually electric but a kind of a electric um fence that kills sperm like sperm don't like copper sperm don't like copper copper likes to kill sperm um there's some interesting uh history I've been reading a lot on the history of Medicine of um people who you know for whatever reason were forced into or chose to be in the the sex trade prostitutes using um inserting copper coins into their vaginal tract to try and uh kill sperm but to varying degrees of success obviously there's a whole um socioeconomic landscape around that so um I think it's obvious what I'm referring to but um very interesting but that's just one form of IUD right there 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 in within the context of whether or not it Alters egg quality Andor 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 and I'll roll through a few of the top birth control methods and just thinking through copper IUD as you already said no hormonal involvement it causes inflammation and a toxic environment inside the uterus isolated does cause sometimes heavier periods but they should still be regular if they are irre 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 the well the IUD is a is a little te and the arms are have copper wires wrapped around them and they and those are they grow into the uterine lining they don't grow into the uterine lining the IUD just sits in there and just the presence of that copper causes that inflammatory reaction in 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 100% 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 like Laboratories right let's just put some copper in some uteruses and see what happens right you know it I it really speaks to the the urgency that must have existed to preventing pregnancy and they just how costly biologically and pregnanc financially pregnancy is and pregnancy is not Health neutral so it is something that somebody needs to be in 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 Kina liletta they have a bunch of different names based on the amount of progesterone and how long they last for 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 already ovulating no problem the problem we do see in some people with progesterone iuds that maybe isn't talked about as much is that this prolonged progesterone exposure because people are putting iuds in for 5 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 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 in 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 3 to 6 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 a lining to then shed it we're less worried about it but if you are aaric 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 when it comes to some of the other things that you mentioned one I you didn't ask that I want to mention is the Depo pra shot the Depo pra 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 not going to get pregnant Depo PR is proven to prevent ovulation for 3 months so when you take it you need to get it every 3 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 Deo shot was 6 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 for if you're very remote from wanting to have a child but in people who are in their childbearing years contemplating family building soon that is not my favorite option so you haven't mentioned because I haven't asked um 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 that this is a very controversial um topic but um you know one of the more popular studies discussed on social media is one that I I've spent some time with the paper um and a few of the papers that stemmed from it um not a huge study but describing that how women rate the faces of men as either more essentially what happens is there there seems to be at least in this study a there was a a statistically significant um bias uh for women to select particular male faces as attractive and those male faces tended to be of the more you know square jaw AKA masculine features right in a quotes right this is what the study um found um but that when women were on oral contraception presumably estrogen progestin type oral contraception that that effect um was smeared they had a not a statistically significant tendency to uh choose the quote unquote more masculine faces 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 think that birth control is going to throw off their partner Choice um now of course it's a small study um studies like it are not always so well controlled um but is there any evidence that birth control oral oral estrogen progestin based birth control just to keep it specific can increase rates of cancers can decrease rates of cancers can lead to um any sorts of disruptions in um bodily uh function or health that's really like a rock solid result that's been seen by multiple studies clinical trials um 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 and 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 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 estradi 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 hormonik properties and some of which do not so there's a ton of variation even the amount of ethanol estradi 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 estradiol and that estradiol is important in growing the uterine lining but also for the genital structures and so we think about vaginal health and bulvar health we certainly see that especially with continuous use so if we distinguish you take the pill for 21 days and you have a 7-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 H so in in like the the um the wheel the little little pouch with a wheel of different colored pills um may have seen these on the on the countertop in previous relationships um and then there's the ones that sometimes people just opt not to take because those are the not the placebo sugar pills so like that there's no need to take Esten during that phase and then and then they repeat is that exactly okay but some people are taking estrogen continu 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 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 Ric vaginitis people who notice increased sensitivity decreased elasticity increased discomfort with intercourse increase in like yeast infections that can sometimes be see 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 dysphoric syndrome where their mental health when they change from high to low estrogen it's always the change in estrogen that interferes can cause some 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 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 dominant environment associated with lack of ovulation and having a lot of follicles inside the ovary that are not really responding and the androgens excuse me androgenization of other tissues like like body hair deepening of voice body hair 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 Bal so like the W the Widow peing yeah the Widow peeking and then thinning out in these two areas and then we see an increase in body composition towards 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 will make you know one to two peagrams 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 withdraw 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 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 ludum and then it 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 10 years of pel 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 inovation to the perianal system is poor and you don't have any out 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 by taking the pill that that's a concern especially in people who might be predisposed to this for some other reason they might have braa mutations or something like that um 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 had has a huge hist and paternalism meaning doctors would just tell people this is what you're going to do 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 happens 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 is 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 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 U up there you know I'm aware um that a a fair Fairly high percentage of people have um mutations in Factor 5 lien a clotting Factor um fewer people are as we say homo I guess have two deficient copies or mutant copies I should say um but there are many people out there that have one mutant copy of factor 5 lien and my understanding is that oral contraception in females um can really exacerbate the factor 5 lien mutation do you suggest that people get um get their Factor 5 lien um 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 5 um analysis and it's not like a a really in-depth thing you don't have to fly to BL yeah you don't have to fly you don't have to fly to another country you know like you do for many things um 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 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 work up 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 CAU in their leg or a pulmonary embolism or a PE 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 5 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 Soap Box because we'll talk about screening for ovarian reserve and it is 100% not recommended even though I think it should be yeah my next question was going to be about testing amh levels and um 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 how many eggs are are in likely to be in in the Vault on 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 papsmear 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 US because the government's not paying for our health care so why should these guidelines be based on when is it cost effective to do testing well I 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 um that there's a cost to doing these tests of any kind colonoscopy amh Etc and uh they must have figured out the you know 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 this is I mean the reality we know is that the more information you have the better choices you can make I mean the only caveat to that would be that uh for some not all but for some people sort of of the hypochondria type sometimes more information leads to more anxiety which leads to more problems but that's a rare instance that is I always think that in general data is always good agre 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 five Li in and I had this terrible blood clot because pulmonary emms can kill people we all know that right 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 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 I mean to me it just seems nuts I mean um or ovaries rather I mean the um the amh is a blood draw amh is a blood test it's a blood draw it one could opt to do the um ultrasound as well which is of course more invasive but but women who are seeing their OBGYN are probably familiar with with with um pelvic exams yeah I mean it's a faginal ultrasound but it's not painful not painful um but different than a blood draw just just for in full disclosure so um 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 I don't want to throw out numbers because this actually can get tricky um 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 it sort of becomes a scorekeeping thing and and of course follicle quality there a bunch of other things um and then you can tell us more about those but let's say someone did not have insurance or or Insurance permission to um to get this paid for what is the approximate cost of getting one's amh levels analyzed $79 $79 to find out essentially where your ovarian reserve is at so let's talk about this I already said this in my soap box so ACOG says you shouldn't screen it because amh does not predict your fundability 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 reserve they have five eggs coming out 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 because you said this earlier 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 s of like your body starts to take smaller withdrawals as you start to run out of 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 anro follicle count or an AFC it's an ultrasound based measurement of how many eggs you have outside the vault at one point in time and on the ultrasound if one looks um this is going to show up as so what it look like um little Hollow spaces like so not gray stuff but but Hollow Bodies I say chocolate chips and the chocolate chip cookie if we can imagine the overy yeah like looks like a chocolate chip cookie the chocolate chips small little dark fluid fil follow 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're they all should be small because nothing's been stimulated if I'm looking per ulatory I'll see that dominant follicle that's about to ovulate and then everything else will be small and is there a a graph that people can look at or that we could link to that says okay the the average with a distribution of you know standard error on either side for let's say a 28 year old woman or a 37y old woman or a 45y old woman of the number of follicles on the right and left side and as I understand asymmetries are common yeah um tends to be you know like if someone goes in and they you got six follicles on the left side and 12 on the other side are they how do how do people gauge what what fantas points one because their doctor should tell them but that doesn't always happen but yes we we add these counts together to get your anro folicle count because there is often a symmetry 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 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 a is a nonlinear drop off or 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've also had patients in that age range who are in premature ovarian failure right because there can be things that go wrong even early but we should probably highlight again something that you said earlier but gosh I you know this like 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're not you can't right that those eggs are spent you you you now have the opportunity to turn them into potential pregnancies 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 a 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 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 all you're ovulating one so you're trying to get pregnant naturally that's what fundability 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 AOG came in and said well amh doesn't impact fundability it doesn't predict your ability to get pregnant or who's going to have infertility and who's not going to have infertility so there's no utility and screening for it in people now for one some speechless I mean that that argument makes sense through the lens of just probabilities of pregnancy um through natural conception um 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 or not to leave a given partner whether or not to accelerate the process of building a family my egg should I have a baby now goodness like there's so many factors that this American College of whoever ever is like completely deal but they're crazy and that's what I say they they argue in their statement that finding that you have sorry I'm like reeling it in I mean think you're 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 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 like if it were just stress like hey guess what and you know I know people who have family members with Huntington mutations and some opt to not not know whether or not they themselves have have the Huntington mutation and and it's a very personal choice right but here that whereas unfortunately there still isn't a a cure for Huntington hopefully someday there will be Mal come would but in the meantime there's essentially a a cure for this situation which is the Harvest and potential fertilization there at least an opportunity and this is what I say 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 happen to you so if you're young and you find out you have low ovarian reserve 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 change the conversation with your partner too right because a lot of people think they can just wait because of age right we're in our 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 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 the attitude is completely I'm not going to to think about it until later and then I'll deal with it if it becomes a problem because you can make change choices you could freeze your eggs you could try to get pregnant sooner you could evaluate for reasons of low ovarian reserve 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 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 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 uh and freeze them um there's a hard cut off at age I think it is 42 prior to age 42 they'll do it um after 42 they'll do it if and only if you're willing to do invital fertilization to actually fertilize and then they'll freeze embryos but they're far more reluctant to collect eggs after age 42 yes 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 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 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 the freea 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 thought 99% of the time so yes there's a 9% difference that being said making embryos is a lot more 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 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 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 normaly and we know that the rates of aneuploidy or abnormal chromosomes increases proportionally to your age which um for people that aren't aware are going to predispose not always um to miscarriages if they're implanted or potentially even uh the formation of a of a fetus that carries for instance tricomes so CH chromosomal repeats or um lack of lack of certain chromosomes these could be deadly or they could be um capable of carrying to term and then but have undetectable Demi to severe developmental um abnormalities correct correct and this is this is why it you have a lower probability of pregnancy per month as you get older so if we look at your natural fundability it's not because you have fewer eggs because we already said your egg count per month doesn't impact your probab ility of getting pregnant it's because the normaly 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 but then your chance of losing that pregnancy is significantly higher as well so when we are counseling somebody about egg phrasing 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 cut off and every Clinic is going to be a little bit different a lot of different reasons why we actually probably have an older cut off 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 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 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 till age 35 36 for your first kid but you want two or three we've got to really look forward about is that is that strategy makes sense 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 are 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 for the first time in 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 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 harvesting eggs it's not the only reason but when you harvest eggs freeze them now sounds like the viability of those eggs is is quite quite strong compared to a few years ago uh so that's great 9 % uh recovery uh when they thaw them um is not going to diminish the number of eggs in the vault such a critical point um and post age 37 there's a sounds like a nonlinear drop off in egg quality for most and these are averages right so every be the people that got pregnant with healthy kids in their late 30s and 40s you know yes we hear you um congratulations we're happy um but this speaks to the kind of the 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 um and then perhaps based on their life goals and circumstances doing either one or several rounds of egg collection and freezing especially since it sounds like you don't need to fertilize those eggs so if one doesn't have a partner is concerned about what they're going to do who's who's going to be uh who's going to provide the sperm you know um because of course some people choose to raise kids on their own um but parenting is a whole other issue but um they could do that later so that raises the questions of what are the health risks if any um pain levels if any and um and that includes psychological pain of egg Harvest I mean so going back to what you said earlier this is going to be inject um synthetic mimics of FSH and LH um follicle stimulating hormone and Luiz hormone maybe some growth hormone I hear nowadays there's also the practice of injecting um uh these are essentially uh platelet FR plasma PRP uh platelet rich plasma excuse me uh PRP in perhaps even into the ovarian Vault we can get back to that so there's a bunch of stuff that's being done to some when 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 in 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 is it mild to go through is it like a walk in the park um let let's walk through it all so I 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 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 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 freey about 75% will be fertilized by sperm and about 50% of those will even make it to an implantation stage embryo or a blast we're assuming healthy sperm so sperm sperm no DNA excessive DNA fragmentation already hit the nail on 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 I don't it could be from a pot smoker just kidding pot smokers not kidding pot smokers we're not but we don't know right 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 we 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 blasticus stage if you're age 30 we would anticipate around 60 to 70% of them are going to be genetically normal and you're young that's that's 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% chance of live birth per embryo which is really good when you put in the lens of fundability 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 it is it lowers live birth rates if we're looking at giving each embryo the healthiest opportunity of becoming a baby number 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 maybe having that you know outer surface touched predisposes it to splitting after you put it into the body so more identical twins two to 3% chance of monozygotic twins with IVF and the natural chance is .3% so 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 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 I mean that's medical malpractice right but really most the time when we're talking about embryos we're talking about people with infertility or people who spent a significant amount of money a huge portion of fertility is 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 uter environment statistically doesn't make sense 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 and try and get two siblings um simultaneously I've definitely done that and had patients do that it's not common because surrogacy using a gational 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 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 euploid genetically normal embryos okay and then if you go to the Third so cumulatively after three euploid embryo transfers each one being a single embryo 95% of people have a baby in their arms meaning the incidence of a current 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 four kids it would 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 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 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 phrasing 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 ask you a question so this uh you mentioned age about 32 33 in an ideal circumstance with the finances there Etc one would Harvest um eggs unless they're already starting a family through natural means um what about for sperm I mean we we've all heard the studies that uh with increased age of the sperm that there's a higher although still statistically pretty small in sense of things like um Spectrum conditions um so do you recommend to younger males um uh men in their late 20s early 30s to freeze 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 in your sperm that increase and 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 freeze sperm eggs I haven't even answered your primary question and the process of collecting sperm well well not entirely um without its issues is is far it's embarrassing at best but it's much simpler yeah it's much simpler there's generally doesn't require hormone injections although you know maybe for rare instances where people are hypogonadal or something but if you're gonna freeze your sperm you're right you 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 have to get blood work done 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 it home and bring it in sper is so stable if you've ever done this you just bring it in it's pretty bit a little bit of I think I'm I'm I'm not going to feain that that my friend did this and told me but you know it's it's kind of outrageously easy in 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 so here's here's what I'll say about sperm and what I wish Mor men knew slm men de 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 why are so many men getting vasectomies I don't have the answer to that I think I had 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 so maybe this explains the drop in birth rates I'm just I'm just kidding multifactorial so many people even if you're in your family let's say you have two kids and y'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 freezing sperm is so easy and so much easier than if you don't not all vasectomy reversals work especially the longer 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 in sufficient levels for timed intercourse and you're seeing me in the office and and freezing sperm is cheap I mean it's relatively cheap it's like $400 right so it's it's much much cheaper Allin than the entire egg freezing process 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 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 FSH and you have a group of eggs come out of the Vault and we can imagine that FSH is their food and there is no food because you're taking the birth control pill for 3 weeks these eggs are going to synchronize be very small be very hungry for lack of a better word their FSH 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 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 FSH 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 FSH and LH levels are naturally so high because they're trying to get that egg to make some estrogen so um here are some the we've covered male hormone health before um and there's been a discussion of HCG human chonic gatot trop and and which is essentially mimics LH in the receptor it does yes all right so is um pregal at uh human chonic gatot tropen is it purified from postmenopausal women's urine or is ITN it's synthetic HCG is synthetic and so what why can't well I'm talking about it's called minpure Min minip pure is a combination of FSH and LH 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 going to go 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 FSH meaning LH is really providing some of the hormone substrate that we need to be able to make estrogen 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 and their protocol so who are these postmenopausal women that are supplying their urine they're paid yeah I S imagine them on some Island some yeah yeah go to the menopause getting paid to urinate and it's called menure like it's purified menopausal urine right wild most people don't know that they know now now they know and so we use FSH 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 ultrasound so when you're going through egg freezing or IVF you're taking these hormone shots of FSH 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 of meiosis so those chromosomes can separate right we think about the egg we remember that normal female genetics it's 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 metaphase chromosomes meet in the middle and they're held apart by these myotic spindles and this is why eggs are so stink and fragile because they're held like this and those myotic spindles just absorb the wear and tear of your life but when you use that trigger shot that LH surge 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 um like a zipper and you're pulling apart of a of a zipper that then you now have the the chromosomes just one one you now have have the chromosomes because why because 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 anupy 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 um is related the mitochondrial DNA um because there are a lot of mechanics we're literally talking about an egg splitting itself you know in half Mitri is its Powerhouse the the mitochondrial and so mitochondrial health is a big topic these days um and so we will be sure to touch on nutrition supplementation and prescription drugs that impact mitochondrial Health but I've heard of a new procedure um called three parent um IVF where they're taking basically the DNA from the intended mom the DNA from intended dad um and then putting it into a a surrogate like a donor egg that is where the DNA has been sucked out and then you know because it has Health healthier younger uh mitochondrial DNA so you're essentially um let's say you've got a a couple in their 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 and they'll they'll merge it with a third parent um encapsulation that there are clinics that do this I know that um a lot of this was actually being done in Eastern Europe until until recently um Mexico offers there are places in Mexico that do this uh in England it's been used to um solve uh mitochondrial dysfunction um but in the US this is still not legal is that right yes so the purpose of what you're talking about essentially when we think about utilizing um 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 diseases so the idea of this was first to say hey can we overcome this mitochondria disease and give people the opportunity which it has done that right now 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 will people charge you money for it in certain places yes but you're 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 US 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 of and it would also and you know I looked into this a little bit as a from an academic perspective um to be clear um it would also require that um that the abortions be performed differently because suction abortions destroy embryos in ways that extraction abortions don't so there's a very controversial topic I mean it's um 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 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 embryo implanted I don't want to carry this child but potentially could something good or could it help Advance the field build 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 fantastic question right now they sit in storage this well this is a new problem okay IVF is only 40ish 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 FSH LH 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 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 get 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 Tha 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 until no matter what the worst thing on planet Earth happens to you you're down 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 is 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 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 and then what do you do with them most people just discard them some people will donate them to last which is called for research but mostly it's for embryologist training to get better at doing which is also important okay um but embryo donation is a new thing 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 the technology is getting better I I'm realizing now um remembering rather that when I was in college and graduate school you would see these um ads in the student paper fre for egg donors and sperm donors um sperm regenerate throughout the lifespan so that's a kind of less controversial issue but this is now not allowed most places to advertise for for egg donors on college campuses that's my understanding um the egg donors were often paid whatever whatever they were paid I'm not going to say it was reasonable amounts or not because I don't I don't recall what they were paid everyone's circumstances are different but the argument that most people use against this is oh these these people are giving up eggs that they could otherwise use but we now know that's not true so um do you have any knowledge as to like what was the um the rationale for for kind of limiting the recruitment of egg donors um anyway I'm not arguing for or against I just I it's no longer supported based on what You' said by the um by the argument that they're losing eggs they would otherwise be able to some of it's about proper informed consent uh especially at an age where the financial incentive can be very persuasive without understanding that Mak sense not that it harms your 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 like I mean it should there's this whole donor Community where people are really talking about putting new restrictions on will use sperm donation for example there are sperm donors who have hundreds of children hundreds right they 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 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 you're 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 and ancestry people are being connected with their sperm donors with their egg donors with their sibling pods and we have to believe that technolog 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 they have genetic half siblin out there egg donation people do get compensated much better than sperm donation there are certain characteristics that are hard to find that get compensated even more so and certain you know ethnicities Doctorate Degrees and things like that where somebody can really pay for their education by donating their eggs it's a it's a dilemma because what you'd love to say is like free 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 and half of them will go and become donor eggs interesting business model but I could see the potential ethical concerns 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 a round of freezing your own eggs you would get paid more and you'd have more eggs because one of the issues is do 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 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 gam and embryo donation it definitely is the wild west and there's a 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 3 years make a 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 people's money and putting terrible embryos inside of them and really wasting their resources which could have been used in another way yeah the dangers of propertization of biology right and Tech I mean Tech entering spaces is amazing but also technology start 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 let's just call them that have a higher incidence of things like um Spectrum conditions uh 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 the the word um disorder has to be like really carefully examined when considering any uh neurologic um and psychiatric um situation um you know we've had discussions about this on this podcast before but 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 um than non-ivf 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 of 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 so in a fresh Embryo transfer I'm going to take the eggs 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 5 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 would 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 RIS in general right they're they're common to be fair they're commonly referred to as as disorders I just think um around autism in particular there is there's a camp a growing camp out there that um want want it referred to differently we we've covered this uh 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 so we could easily get um caught down in in the in the attempt to try and like you know um smooth over everything with everybody and and it 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 alcohal use disorder and I don't have a problem with that but a lot of people wonder if those are two different things and it's just confusing and we want to simplify science for people exactly so feel free 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 pams of estrogen suddenly now you have these extremely high super physiologic estrogen levels higher progesterone levels because there's more Corpus ludum and this environment is not the normal for how the placenta would invade into that maternal blood circulat 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 pre-term 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 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 had success or you're 35 and older and you've tried for 6 months 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 chance of birth effects and you have a slightly higher chance of Developmental disorders so is it more populationbased versus procedure based and there's probably something to that to underline 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 autismal dominant disorders so we don't want to take Advanced paternal age likely although it does get so much less attention than what we call Advanced maternal age or being over age 35 in 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 um it's really important for people to hear that uh because you know the the lore out there is that IVF higher incidents of of autism in IVF babies but it sounds like a a good percentage of those um could be because of age related factors um as well as technology related factors that um and that the technology is getting better all the time um if I understood correctly uh we didn't complete the discussion of of IVF and I want to do that talk about ixie and a few other things I know that's that's definitely your wheelhouse before we do that can we inject a little sub conversation um around this because uh I neglected to bring this up earlier and I know there's a lot of curiosity about this and then we'll and then we'll uh finish off IVF can we do that sort of a pause in the IVF so the eggs are out they're frozen sperm's out it's frozen or maybe they're going to put um live sperm on non-frozen excuse me uh sperm directly onto those unfrozen eggs we'll pause there intermission for those um potential embryos um and talk about something that you've been um very uh open about which is um and a lot of people are not not frankly in your profession so I really appreciate this which is nutrition and supplementation to optimize the the health of uh egg quality and and not just for people who want to get pregnant but for but for people who believe that fertility is a proxy for overall health so I mean are there things that people should eat and not eat um things that people should supplement and not supplement in order to um optimize their fertility I mean this is definitely an interest of mine right all my fellowship research go around fundability 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 but it's 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 change es 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 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 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 a twofold 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 fundability an improvement in ovulation and an improvement in success with IVF and a decrease in miscarriage right huge Studies have looked at these now the Vic 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 inpoint 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 things diets 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 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 that can be extremely beneficial in decreasing inflammation grains so whole grains especially that your body you know provide a lot of great fiber so of course if you have Celiac or you're 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 UTI itiz 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 embrio 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 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 whole have the real thing the processed Dairy the skim milk that actually decreases your fertility and likely because the pro 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 I don't drink milk anymore but when I was a teenager I drank half and half I'm not recommending anyone do that remember I was a skin teenager I was you were trying to bul up well no I just could afford to I wasn't trying at that age I wasn't trying to at all but um it was just delicious um but so cheeses um whole uh full fat milk yogurt half and half yogurt okay yeah but don't don't choose the skim 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 lowfat craze or this real attention that fat is so bad but fat comes in so many important forms 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 so healthy fats whole grains fruits veggies and what about proteins and meats because I think within those categories you know I a big fan of sustainably you know like raised Meats if if if possible some people choose not to eat meat but fish eggs um love it all okay so let's just go through the meats and the myth and the fact so we'll do Toof food so there's this big you that like 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 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 that doesn't let me guess a serving is like four to six ounces as opposed to like a real human that eats you know a real human yeah that eats yeah that eats you know you know 6 to eight ounces of fish right 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 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 do they do in Japan I don't know 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 who's um uh been pregnant in Japan yeah reach out tell us yeah or conceived in Japan tell us don't tell us the story of the conception like but tell us tell us 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 in addition to being carcinogenic those toxins do negatively impact fertility now so deli meat no bueno so yeah but and specifically those things like the bacon and the pro like the things that are really highly prosty 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 in most circumstances is in moderation tends to be fine I usually tell my patients I want them to eat a plant forward diet but that 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 base things on cortile so who eats the lowest and the second most and the third most the topmost and people who ate in that top cortile 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 the how that meat was arriving are we talking about like like hogy sandwiches are we talking about like grass-fed Stakes right the studies are not wonderful but that doesn't mean that they don't hold Merit in helping 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 sourced 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 and how those impact your reproduction probably right if this cow's 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 no I think our audience will certainly um subscribe to that uh idea I think most of them will I mean the notion that like the pollutants you breathe in the air somehow are not the the air that you breathe into your lungs is is just like completely and the idea 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 for so long did not address these factors right your doctor never talked to 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 so including stevio or plant-based art low calorie sweeteners Stevia itself hasn't been studied as much as the other ones things like sweeten low all of those mhm but what we do know is that they interfere they cause inflammation inside the body and then they also cause can cause a stress reaction and they can cause higher rates of miscarriage 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 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 dayto 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 do people Mis carry excuse me for um by virtue of being underweight does the body like like I learned um some years ago I think this is still true that one of the signals for the onset of puberty in females is that leptin um a hormone is secreted from body fat yeah um that then signals to the brain to the hypothalamus like okay it's you know there's enough reserves to create uh environment it's a signal about environmental um yeah there's enough extra fat to have a baby yeah and there's presumably enough food around uh to sustain that baby right our 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 hypothalamic dysfunction so maybe your brain's not totally shut off or it's sending out no hormones and you're not ovulating because you're not getting pregnant in that 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 then prolongs and then you have nothing there's the 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 has 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 yeah okay so that's eating healthy none of that's really new news for most people a lot of those things I just said well I think so but I do want to thank you because I think um rarely if ever do we hear somebody so a physician be really direct about like Hey listen some red meat yes not excessive amounts of rat ideally from uh sustainable sources whole fat milk products grains fruits vegetables I mean those kind of um straight what like to you seem like straightforward directives are are actually pretty rare in in the landscape of of Public Health discussion because um 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 um you know eliminate all the milk milk fats 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 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 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 androgenic 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 these extra added things that they're unaware of because sometimes they can have negative impact 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 3 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 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 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 um question insertion there the um there's a laboratory up at the University of California Santa Barbara that's published some really interesting data showing that you a essentially brain weight which is just but one indirect measure of brain health but brain weight in uh at Birth seems to be correlated at least in some positive way with the amount of essential fatty acids that mom consume during pregnancy does that sound does that yeah I mean that does hold and there's like there's my studies about that mice are smarter when they have diets you know with omega-3 fatty acids when they are in utero right so the exposure in the time period is really important and Omega-3s have a lot of health benefits when it comes to their antioxidant properties especially in like an endometriosis diseases that are very highly inflammatory they can be very benef icial 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 um on this podcast before I've sort of thrown out numbers like one one to two grams per day of the EPA form of essential fatty acid and we could have a whole discussion about omega3 omega-6 ratios but do you do you think there's a upper limit is is it truly that you know let's say up to four gram per day of EPA um is would that be advantageous is it better than 1 G 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 hand out to my patients and they're trying to get pregnant it's going to have a prenatal a thousand IUS of vitamin D a gram of Omega-3s and then CoQ10 so CQ town 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 kuten 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 CoQ10 showing benefit without harm right and so no we said earlier nothing's without any harm or any risk of harm but very very little so I usually recommend if you're trying to get pregnant and you take cq1 a dose of 200 milligrams three times a day so there kind of a higher dose than sometimes people are on um often and prenal now have just like 200 total in it and so the the expensive ingredients are usually the the uh the lower concentrations just enough so they can put it on the label right includes Co CoQ10 um does the form of CoQ10 matter because you'll find them in gel capsules you'll find also find them in um powdered capsules I always say I mean there might be for the individual person I mean absorption of medication is really depending 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 um a question about El carnitine um and researching a little bit for this episode and others I you know oral lcarnitine has been associated with some improvements in forward motility and sperm maybe egg quality um but we know that a very small percentage of the oral ALC carnitine that one ingests is actually um utilized so some people actually purchase and use injectable lartin which is kind of painful because it's in an call-based suspension so not not not comfortable 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 um patients or having them inject themselves with El cartine um this would be both male uh female or male patients or both um or using oral carnitine or do the data just not impress you enough to to motivate that we use a gram of ELC carnitine with a gram of vitamin C for our male patients who have any abnormal sperm parameter and so that is kind of what we consider the sperm enhancement protocol and so and just that that with the multivitamin so those two with the multivitamin and CoQ10 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 is so high that usually it's a different environment where we recommend lcarnitine and cinee 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 CoQ10 El carnitine vitamin C can be helpful especially for the male for the female partner we're going to be looking at that extra vitamin D in addition to the prenatal with folic acid what about a women with PCOS I get so many questions about PCOS osol so um and there are we talking myosl or the what is it the dyro do I have that right you do have that right myosl is the main driver of a nosl and how it can be helpful if you most Blends are going to have a combination of both of them but a much higher ratio of myo andosol to deyro and so myo andosol 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 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 met for alone can decrease testosterone levels based on some of the change that it has in the ovary 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 and then these are also the same people who are riding to me go how come when I take metformin I either have headaches because I'm you know essentially hypo hypoglycemic but also their testosterone levels are are are getting crushed not in every case but it happens 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 so also the evidence on metform an extending life we had Peter t on you talk about this like the evidence for that is is like oh so poor it's just not really that convincing it may change but then now all the excitement is about rap ay and so you know uh 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 there was this whole castration idea I don't this oh yeah this was like the heaven Gate cult where they castrated themselves did they longer well they ended up committing mass suicide so so um that you know they ended the experiment early um you know um yeah so in any event um going back to supplements sorry I couldn't help myself um supplements that um women can potentially take just to in increase their fertility even if they don't want to get pregnant as just kind of creating a milu of Health you talked about the nutrition you talked about CoQ10 maybe Al carnitine vitamin C um the essential fatty acids getting at least one gram of EPA so that might require taking two grams of of fish oil to get that the EPA uh myosl so how much are you talking about I've seen some pretty high dosages thrown out there for myos 200000 milligrams okay taken before sleep or does it matter that one doesn't matter that one doesn't matter thank you for covering the topic of supplements and supplementation um this is probably a good point to return back to those harvested eggs yeah so eggs are out um and there's a collection of them Frozen um maybe just maybe uh live they're always alive sorry um fresh sperm they call fresh fresh sperm they're not always alive some portion of the ejaculate is going to be um dead sperm right some live some for motile some non um for motile the twitchers I read is the name that hate those twitchers right um and so okay they're going to wash the the sperm why because yeah most of what people people see as ejaculate or no excuse me as ejaculate is um is not actually the sperm right okay so but sperm are washed they're in one compartment um you got the eggs out you you or your embryologist at your clinic is then going to at some point decide to combine them so is it kind of is it a sperm race or are you um maybe you could explain ixie and and why would one want why would one opt for ixie and is 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 somebody who you know St neural development like some level you're saying hey that sperm looks good whereas when you run a sperm race nature is saying hey 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 you now you're doing IVF or you're freezing your eggs and what if what behaviors are good or bad of of course all of those same ones are but about how long do you need to do them 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 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 I'll just I'll just get it in I know number people like I'm going to have my two glasses of wine which actually equates to about six glasses of wine when you measure out by much by the volume right right up until the week before getting pregnant or something like that but no so so people always ask what should I be doing it's these healthy behaviors and you should be doing them you know this whole time when we do IVF and I'm going to get all the things you just asked but earlier you said well how tolerable is it the truth is you're taking shots these are subcutaneous shots during the egg growth process so 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 worse they hurt way worse than one of these needles exactly so you're going to use those medication 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 eek 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 feel puffier and that is very common just because of getting the eggs to grow you're going to mentally be fine cuz 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 propal and Fentanyl and we are watching while we drain those follicles and get test tubes full of the eggs some people opt to not use any um say I hear the word Fentanyl and I'm sure a lot of people are like wait fentanyl crisis and I you know obviously fentanyl is a drug that has its uses um valid uses in the um medical community um 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 propal 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 fenel for herself for herself and replacing it with saline and giving patients saline these this Clinic did not do anesthesia based propofol so they were supposed to just get fentel and have kind of a less pain environment not a no pain environment and not not just a few hundreds of women reported extreme pain extreme pain through the procedure really speaks large to pain not being taken seriously when they went and found this out what happened to I can't help but ask what happened to this uh technician well I mean yeah they're they're they're trying to find fentanyl 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 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 propol 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 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 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 say most clinics use propol 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 and you'll get a period 10ish days later but you this is when you'll feel your worse 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 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 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 perinal 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 hypers stimulation 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 so when you'll be more emotional 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're 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 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 9 or 10 if somebody goes fast until your next period comes so that's usually about a 3 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 Freez 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 just like this human thought 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 them money and medication cost in order to purposely get fewer eggs because they're 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 your colleagues in your profession 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 um they hear low stem is better we're talking multiple low stem Cycles they might be um even a fraction of the cost of a full stim cycle but then there many many more got low Cycles you got it you can make a lot more money by doing things that are not in the best interest of the patient 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 CU 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 research exposed you to this no invocell 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 infertility right so your fallopian tubes are blocked because of chlamidia 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 an invos cell 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 and so you go through this IVF process with the goal to only get 8 to 10 cuz 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 invos cell container inside your vagina and then 5 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 there's something that seems like yeah like staying in proximity to the sperm and egg like you're Tak you're taking it home so I love this procedure in some some circumstances and I see it applied often in the wrong case and that 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 so let's just say if you've had no like if sperm 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 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 invos 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 and culture so you do have less data notably I like data you can't do genetic testing 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 egg 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 uteran 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 this often can improve that efficacy through the process pending their age and other factors there was this 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 transfers 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 seems also um that it's a more of a three-dimensional environment like was imagine that the petri dish is approach um is so two-dimensional compared to the body and all these things having done cell culture before and you know cultured neurons and things of that sort like there's all these concerns about like the concentration of CO2 and the thing or you know you know God forbid if there's a a fluctuation in you you have backup generators and things but in the electrical flow to the incubators that's disruptive whereas the 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 there seem so here's where I sort of default in my mind anyway uh to the kind of like oh like it seems more natural you're incubating in the more quote unquote more natural environment 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 in inflammatory issue in your body or something unknown so again I'll see it applied 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 it can really open up the doors so that's the most minimal of the minimal stimulation right then we have minimal 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 anof follicle 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 before we get into the iie discussion the eggs are stripped of their outer cells which is called the cumulus that's what the sperm has to attach to in order to fertilize in order to freeze the eggs the cumula 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 xie when you fertilize them so I don't want somebody to ever not know that if that is what they are choosing and ixie is you can tell us yes ixie stands for it's icsi or intracytoplasmic sperm injection it is taking a sperm that under the microscope looks normal in shape and 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 zone of palu 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 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 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 uh for E for ixie it's 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 are we soon to have a technology where you could actually um like get a die that could label DNA fragmentation and and select um because I feel like so much like when we talk about embryology not to get too far down in the weeds but um like the the methods of selecting eggs and selecting sperm I mean these are the same methods 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 can really develop a a real talent at over time of like knowing what correlated with healthy pregnancy and and an offspring but I do like technology you would think that by now 2023 that someone would have some Dy that you could drop on the sperm and go well like like that one has a lot of DNA fragmentation and that one doesn't know right there should be better ways to choose which sperm there's definitely people are trying 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 and does that mean that every embryo failure on day three post fertilization is of course not but it definitely means that none of the ones before that can be blamed on the sperm and ones after that there's definitely still internal and sperm contributions we don't want to create any um you know couple uh disputes around this um but it can be an 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 I mean the debatable thing about a DNA sperm fragmentation so what is that it is not a normal seam in 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 ixes become very common place 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 she meant the tech the embryologist embryologist squirts the sperm on top clear 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 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 ixie 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 you know 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 and I was I mean I do I in almost every patient I'm not going to say in everyone higher probability of success higher 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 fertiliz or I could have the embryologists pick the best sperm and put them inside the egg and we expect a 75% chance of fertilization that makes sense for the majority of people yeah that that makes sense to me I um because I'm obsessed with data and you know do blood work fairly regularly not not obsessively but fair you know twice a year or so um now I didn't always do that and I actually did one of these um DNA fragment M ation test they're pretty expensive you know they're in the they are more than a cement analysis yeah they're they're in the you know low you know they're sort of $1,200 $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 it is and I mean I will say that there is some current thought by my Urology colleagues right so I am not a urologist but definitely when I have a male who you know needs a sperm extraction maybe he's had a prior vasectomy 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 patient who has an abnormal DNA sperm fragmentation and even with ixie has this drop off an embryo growth after day three because the sperm are still being made the same way right are they still fragmented 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 could be a helpful technology but a lot of doctors are offering or doing ixie because we want you to fertilize your eggs when they grow out in culture as we talked 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 they're screen for chromosomal abnormalities so then okay then you've got um let's say two or three of those maybe four depending on how many eggs were harvested and your age and then and and age yes thank you and then and then you said of those that are implanted into let's say a woman you're 45 or younger you're looking at about anywhere from 30 to 65% um successful implantation and pregnancy like B healthy baby it's usually a 65% chance of Life birth if it's a genetically tested embryo that that that Aster is the if and that's why you're going to see such varying ibf 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 embrio if I do genetic testing which takes it's called PGT pre-implantation genetic testing I am testing for anupy as the traditional testing meaning does it have the right number of chromosomes you can also importantly test for single Gene disorder ERS like cystic fibrosis or Huntington but if we're just doing PGT for anupy 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 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 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 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 then 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 the average 40-year-old might have 0 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 lips in and sort of like dot dot dot healthy baby right and um maybe in the future uh if we're lucky he'll come back and talk to us about um healthy pregnancy um and uh healthy baby onward um that would be a a fun and 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 menes um but there I'm guessing and I'm guessing it's a constellation of things that happen um and I have a very straightforward question which is is there an acceleration of the onset of menopause are we seeing that nowadays um are there good data on that um should people try to delay menopause what are some of the things that um you talk to patients about in terms of their considerations of ways to ease that transition or maybe even offset that transition with um hormone replacement therapy or other 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 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 FSH so your brain is sending out all the FSH and LH that it can your ovary is done and not making any estradi or progesterone anymore in this time period what we know is one are we seeing a populationbased increase in earlier menopause there's not been a study to say that observationally in 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 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 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 ways to go and decrease the inflammation it's that inflammation associated with endometriosis that's really causing these women to 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 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 whether that happens at the average age of menopause at 51 52 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 insensitivity 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 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 hypoestrogenic for 10 plus years in one group and then started back on the hor 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 reexposed they had more Adverse Events but if you are starting on estrogen replacement and it it can be various but honestly the estrogen that we try to replace in this time period much more mimics estradiol we have estradiol pills you can have vaginal inserts you can have patches so it depends on what's going to work for your life but it is not the birth control pill most oftenly and some people it might be that's what they choose but we really are trying to pick an estrogen that is estradi more 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 EST 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 right 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 stopped 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 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 of um of menopause or is is there are there additional cues like for instance if their cycle is getting shorter or longer you certainly will have cycle changes and we consider that the per menopausal period where you're starting to really start seeing a spacing out of your period per 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 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 per menopause 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 that'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 uh about fertility about Hormone Health for women and you've also touched on a number of important issues about Hormone Health INF fertility for men along the way this has truly been a a mass master class in fertility and hormones and 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 uh considerations that really extend back to one's teens and if one is beyond their teens like whatever age people are 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 that are prominent out there about for instance egg Harvest and what that 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 a co-manage a family I I believe but um you know this is the sort of 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 sort we will refer everyone to to those links um I've learned so much from you over the years really um in following your content and today you've just uh like far exceeded all already high expectations so um 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 convit you to come back and talk to us about pregnancy and uh bit more on some of the topics that 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 as well as to her social media Handles in the show note captions please also check out the link to her excellent podcast entitled as a woman if you're learning from and or enjoying this podcast please subscribe to our YouTube channel that's a terrific zeroc cost way to support us in addition please subscribe to the podcast on both Spotify and apple and on both Spotify and apple you can leave us up to a festar review please 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