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

49:56It's called middle schmarts 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 schmarts? Okay We'll put that in the show no captions and whoever does is gonna have to get the spelling right middle schmarts amazing amazing um Amazing and foreign to me, but for obvious reasons uh, but amazing uh, I'm always astonished in the How Incredibly well orchestrated this whole process is it's just 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 what an incredible dance.

50:42That's just amazing Beautiful. I mean, I'm so nerdy because I just love how everything has to communicate just perfectly It makes you and all 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 is 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 every day people Have sex every day you will 100 % hit intercourse throughout your entire fertile window on the day that you ovulate You're depositing the same sperm there because you're not generating new sperm It's whether the load went half and half and half and half or if it went In you know one big group But if you're constantly putting more sperm out there you have a higher chance And so studies go back and always say Daily intercourse associated with the highest chance of a condibility especially during the fertile window However for couples who are not sex every day people That idea can cause a lot of stress Stress of course impacts the system in a lot of different ways It can also cause sexual burnout where they no longer feel like being Intimate or having sex on the day they're actually ovulating because they've been doing it this whole time leading up And that's where the time period of saying Have sex every other day throughout the fertile window so starting five or six days before you think you're going to ovulate And then try to target having an 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 Not ejaculate for 48 to 72 hours prior to um, let's just say depositing sperm is such a funny word But it works so Two points one if we're doing a semen analysis now We're trying to evaluate this sperm and any test has certain normal parameters and these are all based on a 48 to 72 hour Absinence 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 intrauterine insemination Also known as artificial insemination or where we take the sperm and put it in a catheter and put it in the uterus We're trying to get more players further on 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.

54:03We're trying to get them further So we want more because that's part of that treatment process and similarly with IVF I want to have as many sperm as possible to sort through and pick out the best looking the most modal the most normally shaped ones So we're trying to get just a better sample and by having these normal guidelines We're able to judge this is low for what it should be which can also be a clue to other problems I definitely want to talk about chemistry both sort of interpersonal chemistry and literally ejaculate and vaginal chemistry but before we do that 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 at quality in either direction alcohol would be the next and then i'm going to assume And i have to do this it strictly because of what i understand about you know Drugs of abuse like cocaine and emphetamine 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 episode on cannabis that shocked me which is that 15 % one five percent Not one point five 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 the fetus, but i have a hard time believing that so What gives i mean here we're to end and there i actually just threw in fetal development so is cannabis is alcohol Alcohol bad for egg quality.

56:03So there's different things that 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 got 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 when we think about egg quality right impacting Those myotic spindles inside the eggs which hold the chromosomes and their perfect position They are Associated they get wear and tear from things that cause inflammation or our toxic So cigarette smoke we know decreases egg quality egg quantity increases miscarriage and then of course has fetal impacts Could i just ask you because 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 and 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?

57:24Of course there's not as much data because it just hasn't been around as long but yes vaping definitely has chemicals that looks like it's associated with poor Success rates and IVF cycles and that's really kind of one of the most finite measures of egg quality we can see because we're really testing the egg At a level in a lab versus just are you getting pregnant naturally and it started 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've vaped every day and i've had three healthy babies and i think that my response is always okay There's gonna be a distribution of responses and then of course how much healthier could your babies have been Had you not vape during pregnancy or vaped prior to pregnancy 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 on 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 quality 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 it 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 I don't know right because you can't study something that's illegal So a lot of this data is just more new and a lot of it's going to be observational and in states like Colorado and California where You know canvass is essentially legal Yeah, I'm assuming that they're more data, but okay, so um smoking Endor vaping 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 Your child will not be as high as the quality of that baby if you didn't do that is that right?

59:42Yes, and 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 in anticipation of future pregnancy Yeah, and when you're trying to set yourself up for success because we know Infertilities 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 these 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 Three persons not zero and you're talking about natural Right Having an old fashioned way yes, right?

1:00:43But 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 zero percent of alcohol should be The acceptable level and pregnancy and then does alcohol impact fertility such a complicated question And this is probably due to the amount you consume in 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 an in moderation One or two drinks a week at the most and you should not do it at all once you find out your pregnant When we were talking about birth control I Unfortunately moved us forward and and forgot to ask about iud's 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 yeah, I don't like copper copper likes to kill sperm There's some interesting History i've been reading along the history of medicine of um people who you know for whatever reason we're forced into or chose to be in the sex trade prostitutes using inserting copper coins into their vaginal tract to try and kill sperm but two varying degrees of success Obviously, there's a whole socio economic landscape around that so 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 their iud's and then there's of course the ring We didn't talk about that so maybe we just touch on a few of those within the context of whether or not It alters egg quality and or future fertility when one takes the ring out takes the iud out This is a great question because a lot of people don't know this and i'll roll through a few of the top -barth 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 irregular That's a sign of a hormonal issue because you still ovulate with the copper iud Is it literally a copper wire woven in the tissue of the ice?

1:03:17Well the iud is a little t 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 and that toxic environment and is it toxic to the environment in ways that are detrimental to the woman or just a sperm both I mean implantation is not going to occur Likely right? I mean nothing has a hundred percent successful But it's much harder for an embryo to implant within that highly inflammatory environment to me amazing that people figure this out before The acidity Laboratories right let's just put some copper and some uteruses and see what happens You know it it really speaks to the the urgency that must have existed to preventing pregnancy and that just how costly Biologically and the pregnancy is 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 iud so iud is that more people are more familiar with are the progesterone based iud's This is going to be your marina chalina 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 and 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 iud's in fact most of them don't prevent ovulation only in about 50 percent 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 are already ovulating No problem the problem we do see in some people with progesterone iud's that maybe isn't talked about as much Is that this prolonged progesterone exposure because people are putting iud's in for five to seven years And not having a period for that length of time because the endometrium has become so atrophic or Non -existent that you're no longer bleeding despite the fact that you may be ovulating It can take a while for that lining to grow back And so it's not uncommon to have an iud in place And if you have no period you're going to say this is great.

1:05:46I 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 on the follicular phase to get it thick enough to finally bleed when you're ovulating So I do tell people if they have a progesterone iud to get it removed three to six months before they want to get pregnant You some other form of contraception But give their body time to make sure they have that regular period pattern back important distinction If you're still ovulating and having a period on an iud then this is going to be less of a concern because if you're growing Enough of aligning to then shut it We're less worried about it But if you are aimentaryic 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 You didn't ask that I want to mention is the depopravera shot The double -prevera 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 Double -prevera is proven to prevent ovulation for three months So when you take it you need to get it every three months to have a proven contraceptive benefit However, it can last in your system for 18 months and prevent ovulation for up to 18 months So I will see people who liked that option for contraception And now they haven't had a period in a long time But their last depot shot was six months ago And they're all frustrated by the fact when I tell them Well, you still may not have another period for a year plus because This high level of progesterone that you've already injected into your system Can last a substantial amount of time So that is a contraceptive option that I tell people to discontinue a year and a half to two years before they want to get pregnant Which sometimes People don't know that yet And so that's something that can be a contraceptive option from if you're very remote from wanting to have a child But in people who are in their child -bearing years contemplating family building soon That is not my favorite option So you haven't mentioned because I haven't asked any Negative consequences of birth control of any kind And I'm not encouraging you to if you don't believe in them I know that this is a very controversial topic, but You know one of the more popular studies discussed on social media is one that I've spent some time with the paper And a few of the papers that stemmed from it Not a huge study but describing that How women rate the faces of men as either more Essentially what happens is there there seems to be at least in this study a there was a statistically significant bias 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 air quotes, right?

1:09:08This is what the study found But that when women were on oral contraception Presumably estrogen progestin type oral contraception that that effect Was smeared They had a not a statistically significant tendency to Choose the quote -unquote more masculine face 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 It's gonna throw off their partner choice um now of course It is a small study Studies like it are not always so well controlled um, but is there any evidence that birth control The 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 Function or health that that's really like a rock solid result.

1:10:07It'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. It's 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 gonna 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?

1:10:46It's ethanol estridial with your brain and terprates as an estrogen But other parts of your body may not and then it's Various types of progestins some of which have even androgenic or male hormone -like properties and some of which do not So there's a ton of variation even the amount of ethanol estridial that each pill has With your low low in your low pills having less and even with the modern day average Having a lot less estrogen than it used to When you're on the birth control pill your ovaries aren't making Estridial and that estridial is important in growing the uterine lining But also for the genital structures and so we think about vaginal health and both our health We certainly see that especially with continuous use so if we distinguish You take the pill for 21 days and you have a seven -day break where you might bleed or you take sugar pills And then you take them again A lot of people now are taking continuously where you have exposure to these Compounds every single day So in like the The wheel the little little pouch with the wheel of different colored pills They've seen these on the on the countertop and previous relationships And then there's the ones that sometimes people just opt not to take because those are the Not the placebo there's sugar pills over like that there's no need to take estrogen during that phase And then and then they repeat is that okay, but some people are taking estrogen Continuously very common right now so people and they're not wrong.

1:12:19They 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 Vaginolable var changes right and so a trophic vaginitis people who notice increase sensitivity decrease elasticity Increase 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 pre -minceral dysphoria syndrome where they're 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 and 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 five broids 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 Androgens that excuse me androgenization of other tissues like like body hair deepening of voice Typically the level of testosterone made in PCOS isn't truly debuting 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 patterned baldings some temporal baldine of women So some hair loss Like the widow's peaking And then sitting out in these two areas And then we see an increase in body composition toward the male level So if we think about a male body Holding your fat in your abdominal reach 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 Picograms of estrogen But if you have 50 of them each month you're having some constant estrogen exposure So that lining of the uterus is being constantly stimulated to grow And you're never getting the progesterone to stabilize or the progesterone would draw 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 and 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 lodeum 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 Ten years of pill use has dropped the chance you could ovarian cancer by more than 90 percent And of course ovarian cancer is super hard to diagnose because The innovation to the paratoneal system is poor and you don't have any outward signs often till late stage disease that being said Could you potentially have an increased impressed cancer in some key 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 You might have brachimutations or something like that And then is there A situation where the pill certainly masks what's going on with your menstrual cycle and I really think This is where women's health has a huge history 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 periods of vital sign and I don't know what it is because the pill Is producing a different environment The pills 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 brachimut control pill Increase risk of blood quads because of how it's processed in the liver increasing your clotting factors I just uh, yeah, yeah, yeah, go there, you know, I'm aware That a fairly fairly high percentage of people have Mutations in factor five lighten a clotting factor Fewer people are as we say homozygous have two deficient copies Mutant copies I should say But there are many people out there that have one mutant copy of factor five lighten and my understanding is that oral contraception in females Can really exacerbate the factor five lighten mutation do you suggest that people get Get their factor five lighten Genetics analyzed I mean, it's pretty inexpensive to do right?

1:18:32I think on a standard blood test You can just ask for the factor five Analysis and it's not like a really in -depth thing you don't have to fly to say that it's a good deal Yeah, you don't have to fly just 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 clot 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 a e -cary factor five you should no longer take the birth control pill And specifically the pill Because it's an oral pill and how it's metabolized in the liver is actually What is causing The change in those clotting factors because that's where they're made as well So it doesn't mean you can't take any form of contraception But we do want to make sure that we counsel you appropriately I never think it's wrong to be an advocate for your own health or to ask questions It's important to know that screening I mean, I'll get on my soapbox because we'll talk about screening For ovarian reserve and it is a hundred percent not recommended even though I think it should be Yeah, the my next question was gonna be about testing AMH levels And and we'll return to that for those that hear that and and it sounds cryptic as well as getting an ultrasound Just seeing basically how many My eggs are are 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 pap smear guidelines and your colonoscopy and your mammograms Everything is all based on when are you going to find enough cases at some age to make it worthwhile Testing which is a crazy principle especially in the US because the government's not paying for our health case So why should these guidelines be based on when is it cost effective to do testing?

1:21:05Well, 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 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 for some not all but for some people So above the hyperchandriatic type sometimes more information leads to more anxiety which leads to more problems But that's a rare instance I always think that in general Data is always good.

1:21:56I agree having the information at hand about your body and being able to make educated choices versus being in a position where you say I had no idea that I had factor five light in and I had this terrible blood clot because Pulmonary embolism 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 made 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 pain 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 a cog the American College of OB -GYN 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.

1:23:23I mean to me it just seems nuts. Okay, oh or ovaries rather I mean the the AMH is a blood draw AMH is a blood test blood draw it one could opt to do the Ultra sound as well, which is of course more invasive But but a women who are seeing their OB -GYN are probably familiar with with Public exams. Yeah, I mean it's a vaginal ultrasound, but it's not painful not painful 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 don't want to throw out numbers because this actually can get tricky You know, they'll say oh you have whatever you know four follicles and then someone in their Early four days will have 20 follicles and then people start to sort of becomes a scorekeeping thing and and of course follicle quality there a bunch of other things And then you can tell us more about those but Let's say someone did not have insurance or or insurance permission to To get this pay for what is the proximate cost of getting ones AMH levels Analyzed 79 dollars 79 dollars to find out essentially where your ovarian reserve is at.

1:24:43So let's talk about this I already said this in my soapbox so A -cook says you shouldn't screen it because AMH does not predict your Fakund ability 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 of two people One has low ovarian reserves. 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 Sort 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.

1:25:35It 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 antrophilical counter and 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 This is going to show up as so what it looked like Little hollow spaces like so not gray stuff, but yeah, I say chocolate chips and the chocolate chip cookie If we can imagine that over here. Yeah, like looks like a chocolate chip cookie the chocolate chips Small little dark fluid fill follicles each one of those houses and eggs some bigger than others because they're more mature than others Based on when you check in the cycle So if you're looking in that early follicular phase when somebody's on their period They all should be small because nothing's been stimulated if I'm looking periobulatory I'll see that dominant follicle that's about to ovulate and then everything else will be small And is there a graph that people can look at or that we could link to that says okay the the average With a distribution of you know standard error on either side for let's say a 28 year old woman or a 37 year old woman or a 45 year old woman of The number of follicles on the right and left side and as I understand asymmetry is a common yeah Tens to be you know like as 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 whether at One because their doctor should tell them but that doesn't always happen But yes, we we add these counts together to get your antropolicle count because there is often a symmetry But what we should expect to let's say in somebody who's 30 is you should have in the 16 to 20 range of total follicles per month right and left side combined okay, okay when you're 35 that number is closer to like 14 to 16 so starting to drop.

1:27:24It's still pretty good when you're 40 it's 8 to 10 when you're 44 Two to four right so you start to have this immense drop that exponentially starts to increase really around age 37 So things start to kind of get into this severe zone Really after age 37 and we didn't really talk about Ages 18 to 25 but there are people who get pregnant in that age bracket are Is the follicle count very very high is there sort of an ace is that nonlinear drop off or yeah their follicle count will be higher And I mean I occasionally have patients who are very young but have infertility or want to freeze their eggs I also had patients and that age range who are in premature ovarian failure right because there can be things that go wrong even early And 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 Not you can't right that those eggs are spent you you now have the opportunity to turn them into potential pregnant 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 and vitro maturation people are trying to figure out How can you get eggs from the vault and get them to grow in the lab because That would open up possibilities for people who have fewer eggs to have our higher efficiency of this process because one of the limiting factors when you're doing fertility And 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 vault you're ovulating one So you're trying to get pregnant naturally That's what fecundability is probability of getting pregnant per month naturally You have the same chance if you're the same age regardless of if you have five eggs or you have 20 eggs And that's why a cog came in and said well AMH doesn't impact fecundability It doesn't predict your ability to get pregnant or who's gonna have infertility and who's not gonna 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 Through natural conception um But it completely erases the very very very real Situation where people are making choices about for instance whether not to stay with a given partner Whether not to leave a given partner whether or not to accelerate the process of building a family I have a baby now.

1:30:06There's so much I believe that this American college of whoever whoever is like completely Oh, but you want to say that they're crazy and that's what I say they they argue in their statement that Finding that you have sorry. I'm like No, it's like I mean I think it's right. I think of 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 and 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 right in the future But we're not gonna do that because if you can walk now you can walk now.

1:30:43It'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 Undo 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 But if it were just stress like hey, guess what and you know I know people who have family members with hunting and transmutations and some opt to not know Whether or not they themselves have have the hunting and transmutation and it's a very personal choice, right?

1:31:14But here that whereas Unfortunately, there still isn't a cure for hunting. Then hopefully someday there will be knock on wood But in the meantime There is essentially a cure for this situation which is the harvest and potential Foralization 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 gonna 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 we're just waiting Well, my change the conversation with your partner too, right?

1:31:59Because a lot of people think they can just wait Because of age right? 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 that the attitude is completely?

1:32:38I'm not going to think about it until later and then I'll deal with it if it becomes a problem Because you can make 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?

1:33:39The same question should be will 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? So glad that you're highlighting this because my understanding is at least in the state of California I don't know about other states or if it even varies by state that the opportunity to harvest eggs and freeze them um There's a hard cut off at age. I think it is 42 prior to age 42 They'll do it after 42 They'll do it if and only if you're willing to do in vitro fertilization to actually fertilize and then they'll freeze embryos But they're far more reluctant to collect eggs after age 42 Yeah, yes and no so When you think about egg freezing and IVF are really the same process, right?

1:34:33When 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, a 90 % of eggs now survive the freestyle So 90 % is not a low number by any means embryos are much stronger right and egg is a single cell it's a single cell And 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.

1:35:26So 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 we 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 normalcy and we know that the rates of aneuploidy or abnormal chromosomes Increases proportionally to your age which for people that aren't aware are going to predispose not always To miscarriages if they're implanted or potentially even the formation of it of a fetus that carries for instance trisamies So chromosomal repeats or Lack of lack of certain chromosomes these could be deadly or they could be capable of carrying to term and then but have Undetectable to mild to severe developmental Abnormalities correct correct and this is this is why it you have a lower probability of pregnancy per month as you get older So if we look at your natural fecundability It's not because you have fewer eggs because we already said your egg count per month that doesn't impact your probability of getting pregnant It's because the normalcy of those chromosomes has changed so dramatically that the odds that your bodies 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.

1:37:31It's 40 % at age 40 right? So you have a much lower chance A scene 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 cutoff and every clinic is going to be a little bit different A lot of different reasons why we actually probably have an older cutoff so we will Let somebody go through IVF or freeze their eggs up to h45 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 mean, 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 a 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 3536 for your first kid But you want to or three We've got to really look forward about is that Is that strategy make sense?

1:39:47Well, what is your AMH one? Are you going to run out of eggs before then to How what other issues could be going on is the sperm fine or the tubes open because we are seeing that when people start families later When people have more chronic illness and autoimmune disease and obesity That it's much harder to get pregnant and so the birth rates right or for the first time in a long time across the border 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 quite quite strong compared to a few years ago So that's great 90 % recovery when they fall 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 and egg quality for most and these are averages Right so everyone so the people they like to pregnant with healthy kids in their late threes and forties You know, yes, we hear you um Congratulations, we're happy um but This speaks to the kind of the logic anyway.

1:41:11We'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.

1:42:05I mean it's so going back to what you said earlier This is going to be injecting synthetic mimics of fsh and lh Um, follicle stimulating hormone and luteinizing hormone maybe some growth hormone. I hear nowadays. There's also the practice of injecting um Uh, these are essentially uh platelet rich plasma PRP uh platelet rich plasma excuse me uh PRP and perhaps even into the ovarian vault We can get back to that So there's a bunch of stuff that's being done to someone. There's low stem where people are getting Like low doses of these drugs. There's high stem where it's like a full blast Maybe you could walk us through that procedure and just sort of general contour because it you know Would require a lot of time to go through it all in detail But is this a horrible thing to go through?

1:42:46Is it mild to go through? Is it like a walk in the park um Let's walk through it all so i love this and this is my bread and butter 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 is the optimal time for the average person to intervene and freeze their eggs It's not up for debate. It's when you have both the intersection of still a good egg quality and good egg quantity on average And so that is younger than a lot of people are thinking about having families 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 freeze though About 75 % will be fertilized by sperm and about 50 % of those will even make it to an implantation stage embryo or a blast as well We're assuming healthy sperm so sperm sperm no DNA excessive DNA fragmentation You already hit the nail in the head one of the biggest issues with egg freezing is i don't know The future i don't know if this sperm is going To be great or not i don't know from a pot smoker just kidding pot smoker not kidding pot smoker 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 survived the freeze though And 14 fertilized and seven make it to the blastocyst stage If your age 30 we would anticipate Around 60 to 70 % of them are going to be genetically normal and you're young so that's already kind of a big head at that age So let's say of the seven four of them are genetically normal When i go to transfer them i have up best a 65 % chance of live birth per embryo Which is really good when you put in the lens of accountability and peak success tends to be closer to 20 % 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 to it is It lowers live birth rates if we're looking at Giving each embryo the healthiest opportunity at becoming a baby number one Embrose with IVF have a slightly higher chance of monoseigotic 20 right so 20 For tunnel 20 comes if you ovulate two eggs they both get fertilized so each Baby is completely different genetically own egg on sperm Monoseigotic 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 monoseigotic 23 % chance of monoseigotic twins with IVF and the natural chance is 0 .03 percent 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 monoseigotic twins And if I put two embryos in I've now won taken this from a potential twin pregnancy to a Tripletter even a quad if they both split so I hence presumably like the octomum cases and things like that When 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've spent a significant amount of money a huge portion of fertility as embryo Quality right the competency of the embryo of 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 uterine environment Statistically doesn't make sense.

1:46:38It 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 Simultaneously, I've definitely done that and had patients do that It's not common because Serrigacy using a gestational carrier is so expensive and there's such a 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 You employed genetically normal embryos, okay, and then if you go to the third So cumulatively after three you played embryo transfers each one being a single embryo 95 % of people have a baby in their arms Meaning the incidence of her 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 or 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, 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.

1:48:53I 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 I ask you a question?

1:49:32So this you mentioned age about 32 -33 in an ideal circumstance with The finances there etc one would harvest Unless they're already starting a family through natural means What about for sperm? I mean we we've all heard the studies that With increased age of the sperm that there's a higher although still statistically pretty small in sense of things like spectrum conditions So do you recommend to young Girl males Men in their late 20s early 30s to free sperm I mean it's never going to be wrong to save your gametes because we don't have crystal balls for the future Right so your gametes are your eggs 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 in 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.

1:50:43It's so cheap and easy to free sperm eggs I haven't even answered your primary question and the process of collecting sperm well not entirely 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 hypogonadil or something But if you're going to freeze your sperm you're right You're typically you're going to get some blood work done because most places that store sperm Per FDA guidelines have to make sure that if you carried an infectious disease It's stored in a special tank so you'll have to get blood work done Then you have to abstain for your two to three days Collect into a cup You're done which by the way guys you can do at home and bring it in sperm or so stable If you've ever done this you just bring it in.

1:51:27It's pretty Listen a little bit a little bit of I think I'm I'm not going to feign that my friend did this and told me But you know, it's it's kind of outrageously easy in the sense that you just bring it in and they'll like take it out in the lobby And be like is that your name and they'll do like the very different than the egg collection procedure So here's the here's what I'll say about sperm and what I wish more men knew slush more men dead If you're going to get a vasectomy because you're 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.

1:52:07Why are so many men getting vasectomies? I don't have the answer to that. I hadn't heard this. Yeah a lot of men are getting vasectomies Even I think to just take control over not having child out there when they don't want to So maybe this explains the drop in birth rates And I'm just kidding. There's multi -vectorial But so many people even if you're in your family let's say you have two kids and you all decided You're going to get the vasectomy so that you don't have any more children Things happen terrible things happen life changes there might be a circumstance Where you potentially would have another kid if something really bad happened or you just changed your mind Freezing sperm is so easy and so much easier than if you don't Not all the septomy 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 and sufficient levels for a timed intercourse and you're seeing me in the office and Freezing sperm is cheap.

1:53:06I mean it's relatively cheap. It's like $400 right so it's it's much much cheaper all in 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 and are changeably 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 in 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 three 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 Good natatropans, which is FSH and LH FSH is now synthetically made in a lab It's very easy as 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 here some that we've covered male hormone health before And there's been a discussion of HCG human chorionic genatotropin and which is essentially mimics LH In the receptor it does, yeah So is Pregnal human chorionic genatotropin is it purified from Postmenopausal women's urine or is it synthetic?

1:55:26HCG is synthetic And so what why can't what's a mountain it's called menopure Menopure 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 are 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 Folicular 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 Well the offshoot would be like the PCOS patient who has some naturally high LH Sometimes they don't actually need LH in their protocol So who are these postmanopausal women that are supplying their urine?

1:56:36They're paid right? Yeah, I sort of imagine them on some island in some place Yeah, yeah Go to the menopause Gang paid to urine it It is called menopure like it's purified menopausal urine right I did not know I did not know that They know now Now they know and so we use FSH and LH will 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 trans -vaginal 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 46 XX 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 great metaphase chromosomes meet in the middle and they're held apart by these myotic spindles And this is why eggs are so stinking 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 is to think about Like a zipper And you're pulling a part of a of a zipper that then you now have the The chromosomes just one one you now have halved the chromosomes because why because it's successful for realization the other chromosomes are going to come from Spirum this sperm and that's why this process Has more error the older you are and the longer your chromosomes have been sitting there Because those spindles are going to break down and we're going to have that increase in aneuploidy like we already said Purely because of this impact Can I ask a question about that specifically?

1:58:58I think now would be the right time to ask which is that my understanding is that a lot of the dynamics of pulling a part of this Is it for like thing these chromosomes and then um is related to mitochondrial DNA Because there are a lot of mechanics. We're literally talking about an egg splitting itself You know in half and then it's powerhouse Yeah, and the mitochondria and so mitochondrial health is a big topic these days And so we we should have touched on nutrition supplementation and prescription drugs that impact mitochondrial health But I've heard of a new procedure Called three -parent IVF where they're taking basically the DNA from The intended mom the DNA from intended dad um and then putting it into 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 mitochondrial DNA.

1:59:52So you're essentially Let's say you've got a couple in there like let's say late 30s early 40s And they're not getting successful embryos or implantations or whatever the 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 encapsulation that there are clinics that do this I know that a lot of this was actually been done in eastern europe until until recently Mexico offers either places in Mexico that do this In England it's been used to solve mitochondrial dysfunction But in the u .s. This is still not legal is that right? Yes, so the purpose of what you're talking about essentially and we think about utilizing um A donor mitochondrial or donor egg The point of that technology existed to help cure mitochondrial diseases Which are a hundred percent 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.

2:01:00So the idea of this was first to say hey, can we overcome this mitochondria disease and give up 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 and 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 To be clear It would also require that The Abortions be performed differently because suction abortions destroy embryos in ways that extraction abortions don't so that this is a very controversial topic I mean it's it's something that maybe we'll return to in an episode about stem cells in the future It's fascinating because especially if you look at IVF My whole separate issue is that there's millions of embryos that people are no longer using because they Have had success.

2:02:47They 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? 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?

2:03:38It's a fantastic question right now. They sit in storage This is well, this is a new problem. Okay IVF is only 40 -ish years old embryo freezing alone right the first IVF We haven't even gone through the whole process but the first IVF baby There's no 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 thawing embryos better process of getting more embryos to grow But now we have a lot of embryos in storage that may or may not be used I Personally tell people you should keep your embryos you should pay the storage fee Until no matter what the worst thing on planet earth happens to you You're done having children because sadly I live in a spectrum with my field where I see a lot of sadness and people who maybe you have lost a child Something else has happened and they have maybe a sibling who they feel like they really want to get 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 gonna be really upset if you find yourself in that circumstance So I always say you should save them until you know That you don't are not going to need them And then what do you do with them?

2:05:33Most people just discard them Some people will donate them to labs which is called for research But mostly it's for Embriologists training to get better at doing it Which is also important okay, but embryo donations a new thing So being able to just like we have people who donate sperm and donate eggs Embriodonation 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'm realizing now Remembering rather that when I was in college and graduate school you would see these Adds in the student paper for for egg donors and sperm donors It's a former generate 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 The egg donors were often paid Whatever whatever they were paid I'm not gonna say it was reasonable amounts or 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 people are giving up eggs that they could otherwise use But we now know that's not true so 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 her again.

2:07:21So 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 I'll be able to some of us about proper informed consent especially at An age where the financial incentive can be very persuasive without understanding 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 I mean it should but there's this whole donor conceived community where people are really talking about Putting new restrictions on will you sperm donation for example?

2:08:12There are sperm donors You have hundreds of children Hundreds right there are these sibling pods because it's been so unlimited and sperm banks are a business That work to make money and they make money by selling more sperm But that's not healthy one for a population. You need genetic diversity But also it's not healthy necessarily for one person 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 that this guy at the bar that you like Do you have to worry about that if your donor conceived? So we're starting to see sperm banks finally start to reel back and put limitations on how many families Total children's telfray 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 then we have to believe that technology is only going to improve over time.

2:09:34So What people do for money especially when they're young I think without understanding the potential ramifications and I don't want to act like sperm donation or egg donation are bad They give people the opportunity to become parents That otherwise might not be able to and that is a lovely and a beautiful gift But you need to understand what that might mean and how that might impact your own potential children later too To know that there you have genetic half siblings out there Egg donation people do get compensated much better than sperm donation There's 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 freeze some eggs for you too if you're going to do that you're at the perfect age to freeze your own eggs And there's been strategies to try to mitigate this and I don't want to get off too much on a tangent but It's a really fine line that you walk with what people understand so there is a company and I won't name them But they are promoting that young women donate their eggs and they will freeze half of them For you and half of them will go and become donor eggs Interesting business model, but I could see the potential ethical concern So I think ethically this sounds good because you get to freeze some eggs but I Think more people will donate eggs and otherwise would have for some of the reasons we previously stated And I also think you would get more money by simply donating your eggs and then turning around and paying for us around a freezing your own eggs You would get paid more and you'd have more eggs because one of the issues is do you now falsely 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 map 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 gamy and embryo donation It definitely is the Wild West and there's an uncharted territory Even in embryo donation there's places who are very unethical about it who will only Allow people to have embryos if they are heterosexual been married for three years Make a certain 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's date what quality and they're taking people's money and putting terrible embryos inside of them And really wasting their resources which could have been used in another way You know the dangers of profitization of biology right and tech I mean tech entering spaces is amazing But also Technology starts to advance before studies right tech is gonna become has more finance backing Then we see scientific studies get I feel like One of the major questions out there is whether or not IVF babies.

2:12:52We'll just call them that have a higher incidence of Things like spectrum conditions or other developmental trajectories. Let's call them And I'm not trying to be politically correct here, but you know, I think nowadays that the word disorder has to be like really carefully examined when considering any neurologic and psychiatric Situation and 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 Then 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 you have 200 something you have progesterone being made the placenta is implanting And what is the main difference with IVF babies and a lot of it has been tied back to the uterine environment especially in what we call fresh embryo transfers Which is really not a common practice anymore 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 five days later at the natural time of implantation And if we rewind the clock, that's how IVF was done, right when you couldn't freeze embryos very well And they didn't survive and you'd put lots of embryos inside because they wouldn't survive And that's the early days of IVF when you saw a lot of multiples a lot of high -order multiples And of course multiples have their own distinct issues that put them at higher risk for developmental disorders and issues with development and birth risk in general right there They're common to be fair.

2:14:44They're commonly referred to as as disorders. I just think um around autism in particular There is a camp, a growing camp out there that Want want it referred to differently. We've covered this Anytime this comes up, I bring up both just to highlight the fact that yes We are aware and sensitive to that emerging issue right now unfortunately for sake of conversation There's no new nomenclature so we could easily get You can't down in the in the attempt to try and like you know I'm smooth over everything with everybody and as a consequence confuse everybody So I think we'll go for clarity forward with the understanding that the nomenclature is changing Can't even say alcoholism anymore because it's alcohol use disorder and I don't have a problem with that But a lot of people wonder if those are two different things and yeah, we want to simplify science or people 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 pg of estrogen suddenly now you have these Extremely high superphysiologic estrogen levels Higher progesterone levels because there's more corpus ludiums and this environment Is not the normal for how the placenta would invade into that maternal blood circulature and a lot of these Issues that are commonly associated became so because of placental issues So a lot of things like growth restriction small for gestational age preterm birth Which further puts you at risk for other developmental disorders We're associated with these fresh transfers the field has changed we do a lot of frozen embryo transfers on a lot of it for this reason We see huge improvement in neonatal outcomes when you Lead 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 Feetal outcomes.

2:16:38So 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 could diagnose 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 six months and you've not had success you meet the medical definition for infertility When that happens You now statistically regardless if you get pregnant naturally in the next month or you do IVF You have a 1 % higher chance of birth defects and you have a slightly higher chance of developmental disorders So is it more population -based versus procedure -based and there's probably something to that to underlying a lot of Potentially what goes in or what can cause infertility when it comes to You know quality of eggs or sperm or you don't an environment or things that we're still learning about When it comes to autism specifically the number one strongest association we have is advanced paternal age so when you look at the people and the male sperm comes from an ejaculation after age 50 That one does have the highest significance associated with autism And also with some other very interesting autosomal dominant disorders So we don't want to take advanced paternal age likely although it does get so much less attention than what we call advanced maternal age Or being over age 35 and a woman and that is purely because of the differences and the sperm and the egg environment and how their quality is impactful Thank you for that answer.

2:18:24I think It's really important for people to hear that Because you know the the lower out there is that IVF higher incidence of autism and IVF babies But it sounds like a good percentage of those Could be because of age -related factors as well as technology related factors that And that the technology is getting better all the time If I understood correctly We didn't complete the discussion of of IVF and I want to do that talk about XC 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 Around this because 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 Finish off IVF can we do that do it sort of a pause in the IVF so the eggs are out they're frozen Spurms out frozen or maybe they're gonna put live sperm on a non -frozen excuse me Spirms directly onto those unfrozen eggs will pause their intermission for those potential embryos um and talk about something that you've been um very Open about which is um and a lot of people are not frankly in your profession So I really appreciate this which is nutrition and supplementation to optimize the the health of Equality and And not just for people 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 Things that people should supplement and not supplement in order to um Optimize their fertility.

2:20:02I mean this is definitely an interest of mine right all my fellowship research cycles around Focundability 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 changes on both hormonal function and also when it comes to egg and sperm quality And so if you are somebody who just wants to live your healthiest life and have your Most regular Periods and have your hormones as well balanced as they can be for a lack of a better word We'll just say that that means that they're functioning normally Then pain 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 against 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 or 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 twofold situation here So None of this should be shocking news when it comes to nutrition But it is not talked about enough.

2:21:42You're right decreasing inflammation by the foods that we put in our body is consistently shown with an improvement in Focundability and 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 Neutrogen 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 to because What endpoint are you using is it getting pregnant?

2:22:30Is 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 Diet's high in fruits and vegetables are good for you right fiber Any accidents 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 Oh, it has fructose but it is no it's not that type of sugar is not bad for you If we can just agree on the fact that fruit has a lot of nutritional benefit Especially when it comes to vitamins and antioxidants that can be extremely beneficial in decreasing inflammation grain so whole grains especially that your body you know provide a lot of great fiber So of course if you have silly accurate 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 utilized in a dietary strategy to lose weight and losing weight can improve fertility likely because of Inflammation being the primary driver because we know that even in studies where I take donor eggs And I transfer that embryo into somebody who's overweight They have lower odds of success than if they were a normal BMI So we can't act like that Causation is just on egg quality from obesity, right?

2:24:03There's also some inflammation some inflammatory changes that impact the body's ability Or desire to allow an embryo to implant so Fruit 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 gonna have dairy have whole have the real thing the process dairy the skim milk That actually decreases your fertility and likely because The processing to make it still look like milk when you take out the fat is adding in things that are unnatural Potentially impacting your fertility. I don't drink milk anymore But when I was a teenager I drank half and half.

2:24:46I'm not recommending anyone to the memorize the skein teenager You were trying to book a well no, I just could afford to I wasn't trying at that age. I wasn't trying to at all, but It was just delicious but so cheeses Whole full fat milk 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 We're hopefully we're getting away from it There's been such a low fat craze or this real attention that fat is so bad, but fat comes in so many important forms Avocados and oils and nuts very meat Fat and cholesterol are the backbone for all hormones, right?

2:25:31So 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'm a big fan of sustainably you know like raised meats if if possible some people choose not to eat meat, but fish eggs Love it all okay, so let's just go through the meats and the myth and the facts So we'll do tofu so there's this big issue that like tofu has soy and that too much soy can be bad because soy can be a phyto estrogen Tofu does not negatively impact fertility even in men in fact It can improve it because it does have some any oxidant like properties lots of iron When it comes to fish fish our 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 head needs you know Yeah, that needs you know You know six day downs is 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 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 are they doing Japan?

2:27:27I 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. So what who's who's Been pregnant in Japan every child. Yeah, or conceived in Japan tell us don't tell us the story of the conception like But tell us tell us oh did you have sashimi? overall meat Is a really broad category and studies study it differently like is it all meat? Are you distinguishing now red meat and Chicken are you putting it all together? I mean obviously, I think we can all come to the agreement that process 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 in specifically those things like the bacon and the pro like the things that are really highly prostate hot dogs Sorry the fourth -digit -lion hot dog picnic But those things really do not provide nutritional advantages and only harm Especially then when we have red meat for the most part Red meat when isolated individually and most Circumstances in moderation tends to be fine.

2:28:37I usually tell my patients I want them to eat a plant forward diet 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 based things on quartile So who eats the lowest and the second most and the third most and the top most and people who ate in that top quartile of red meat Had lower progression of embryos through the culture. So less embryos that developed Less normal embryos and lower success rates and we're do we know anything about the how that meat was arriving?

2:29:17Or we don't like like hoagie sandwiches or we're talking about like grass fed steaks, you know 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 is getting injected with a lot of hormones Why are we thinking that it's not impacting the meat that you're then ingesting into your body?

2:29:58No, I think our audience will certainly Subscribe to that idea. I think most of them will I mean the notion that like the pollutants you breathe in the air somehow or not the The air that you breathe into your lungs is just like completely And the 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 bodies 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 talks to be 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 stevia sort of plant -based Low -calorie sweetener.

2:31:06Stevia itself hasn't been studied as much as the other ones things like sweeten low and all of those But what we do know is that they interfe - they cause inflammation inside the body and then they also Caused 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 see the same thing to every patient One cake one this one hot dog. I mean those things individually are not gonna 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 Inline with how you want to treat yourself You want to be in your best healthy 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 day to day Where you're giving your body lots of nutritious food that it needs to make hormones similarly Being you know very underway in calorie restricting we all know is really terrible for your reproductive system And can cause the brain to totally shut down ovulation because it senses that you can't have a pregnancy If people miscarry excuse me for um By virtue of being underweight does the body like I learned um some years ago I think this is still true that one of the signals for the onset of puberty and females is that leptin Hormone is secreted from body fat That then signals to the brain to the hypothalamus like okay, it's you know There's enough reserves to create 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's right our miscarriages and lack of body fat correlated On both ends of the spectrum yes, right?

2:33:08So 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 where 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 than 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 and 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 You 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 some but I do want to thank you because I think I'm rarely if ever do we hear someone So a physician be really direct about like hey listen some red meat.

2:34:34Yes, not excessive amounts of remedy. So ideally from Sustainable sources Whole fat no products grains fruits vegetables. I mean those kind of um straight what like to you seem like straightforward directors are are actually pretty rare in the in the landscape of public health discussion because I'm more often than not people talk about nutrition and these kind of elimination diet type things like you know eliminate all the grains or eliminate all the meat or You know eliminate all the milk 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?

2:35:11Yeah, some veggies with your lunch right 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 gonna 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 endrogenic Yes, 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 for another Depending on where you are Certainly, you know a prenatal vitamin which has folic acid.

2:36:13We all know that folic acid is really important to prevent neural tube defects But it's also important in cell division and how the ovary is growing follicles and growing eggs. So should people Women but also men be taking a vitamin with folic acid even when they're not trying to conceive There's no harm in having it but Very often pregnancies occur when you're not trying to conceive and that is a store that needs to be built up three months ahead of time So we really need you to be taking that ahead of getting pregnant so not just Let's get pregnant right now. I'm going to start this prenatal vitamin So I recommend anybody 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 to brain development of a fetus So most prenatals now actually do have those omega -3 fatty acids in them But if they don't I recommend a patient take those Just a brief question slash insertion there the um There's a laboratory up at the University of California Santa Barbara That's published some really interesting data showing that you know Essentially brain weight which is just but one indirect measure of brain health But brain weight in 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 I think there's my studies about that my sir smarter when they have diets, you know with Omega -3 fatty acids when they are in utero right so the exposure on the time period is really important And omega -3 is 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 beneficial We're definitely gonna talk about your work about after baby is arrived and impact of essential fatty acids But what would you say is the dosage cut off?

2:38:41On 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 then we could have a whole discussion about my Get three omega -6 ratios But do you you think there's a upper limit is is it truly that you know Let's say up to four grams per day of EPA Is without the advantageous is it better than one gram? I tell people a gram a gram So that's an 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 gonna have a prenatal a thousand.

2:39:15I use a vitamin D A gram of omega -3s and then co -cutan so co -cutan which you know Essentially in general is trying to help the mitochondria. That's the whole idea here that it is helping provide support Across the body in a lot of different ways right like co -cutan is using a lot of different Areas of the body but when it comes to reproduction when it comes to Myosis and cell division and ovulation and egg quality and even sperm quality There's a place for co -cutan showing benefit Without harm right and so note 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 co -cutan a dose of 200 milligrams three times a day So this kind of higher dose than sometimes people are on often prenatals now have just like 200 total in it And so the expensive ingredients are usually the the The lower concentrations and you can adjust enough so they can put it on the label right.

2:40:16We include co -cutan Does the form of co -cutan matter because you'll find them in gel capsules You'll find that also find them in powdered capsules. I always say I mean there might be for the individual person I mean absorption of medication is really depending on 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 right A question about alkaline And researching a little bit for this episode and others I you know Oral alkaline has been associated with some improvements in forward motility and sperm maybe egg quality But we know that a very small percentage of the oral alkaline that one ingest is actually utilized so some people actually Purchase and use injectable alkaline which is kind of painful because it's in an alcohol based suspension So not not comfortable.

2:41:06It's got to be done in trimoscurally But my read of the data is kind of impressive. I wouldn't say super impressive Are you ever injecting patients or having them inject themselves with alkaline This would be both female female or male patients or both or using oral alkaline or do the data Just not impress you enough to to motivate that we use a gram of alkaline with a gram of vitamin C for our male patients You have any abnormal sperm parameter And so that is kind of what we consider these sperm enhancement protocol and so just that That with the multivitamin so those two with the multivitamin and co -cutan So that's kind of like the male protocol.

2:41:45Of 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 intimitriosis fall into a unique category where inflammation is so high That usually it's a different environment where we recommend Elkharnitine and acetyl -sistine vitamin C and E They kind of fall into a different category because they've been 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 co -cutan Elkharnitine 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 and what about women with PCOS I get so many questions about PCOS by Nostatol so um and there we're talking myonostatol or the what is it the de -kyro?

2:42:44Do I have that right? You do have that right myonostatol is the main driver of a nostatol 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 myonostatol to de -kyro And so myonostatol is probably the one that really is doing the work in PCOS What is it doing? It is definitely helping the body when it comes to insulin and sugar Helping the body be more sensitive to insulin or less resistant to it essentially Helping you respond to what you eat in a better way and it also looks like it does potentially decrease some of that inflammation pathway in PCOS in PCOS This insulin resistance correlates with this testosterone production from the ovary Meaning even metformin alone can decrease testosterone levels based on some of the change that it has the ovary Take note men So many guys taking metformin or burbrine thinking oh this is great.

2:43:44I'm a lower my blood sugar mimic fasting and live longer and And then these are also the same people who are writing me go how come when I take metformin? Either have headaches because I've you know essentially high -priced my seeming but also their testosterone levels 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 Yeah So also the evidence on metformin extending life We had Peter T on here to talk about this like that 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 wrap up my sin And so you know extending your life while plummeting your testosterone You know, I mean that's a actually that strategy has been tried in the longevity commute.

2:44:29There's a there was this whole castration Oh, I don't know. Oh, yeah, this was like the heavens gate cult where they castrated themselves Did they look longer? Well, they ended up committing mass suicide. So so um that you know they ended the experiment early um, rightfully, you know um Yeah, so in any event um Going back to supplements. Sorry couldn't help myself um supplements that um women can potentially take just to increase their fertility Even if they don't want to get pregnant as just kind of creating a milieu of health You talked about the nutrition you talked about coq 10 maybe alkarnatine vitamin C um The essential fatty acids getting at least one gram of EPA So that might require taking two grams of official to get that The EPA myonostatol so how much are you talking about?

2:45:16I've seen some pretty high dosages thrown out there for myonostatol 2000 milligrams Okay, taking before sleep or it 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 lives always alive. Sorry um, fresh They're always a lot fresh fresh sperm. They're not always live some portion of the ejaculate is gonna be um dead sperm, right? Some live some four motel some non -forged motel the twitchers.

2:45:54I read is the name of the right the um And so okay, they're gonna wash the the sperm. Why because yeah most of what people see as ejaculate or no Excuse me as ejaculate is um is not actually the sperm, right? Okay, so but sperm or wash there in one compartment um You got the eggs out you Or your embryologist at your clinic is then going to at some point decide to combine them It so is it kind of is it a sperm race or you um maybe could explain xe And and why would one want why would one opt for xe and is are there any risks with xe because they're you're really At some level. This is the only place where I kind of sit back and okay, if somebody you you know Sayed in the world 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 a 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 course all of those same ones are but about how long do you need to do them?

2:47:07And 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 know 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?

2:47:45It's not gonna make a difference But truly it can or I'll drink up until the week until the day I'll just I'll just I know I know I'm like I'm gonna have my two glasses of wine which actually equates to about six glasses of wine when you measure out by how much it actually is Right up until the week before getting pregnant or something. Yeah, 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 gonna 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 aggro process so next to the belly button Yeah, next to the belly button like how a diabetic gives insulin a very small needle I mean nobody loves shots, but they're not a big intramuscular shot It's not like a flu shot or something like that.

2:48:33This I've been lost in the Texan mosquitoes They're way worse way worse than one of these needles Exactly, so you're gonna use those medications for about 12 to 14 days You're going to have your follicles grow You're going to feel that so you're gonna 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 leak out a little bit And you're gonna get more bloated you're gonna have more water weight You're going to feel puffy air And that is very common just because of getting the eggs to grow You're gonna mentally be fine because the female brain loves high estrogen So you're doing fine as 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.

2:49:22It's about a 20 -minute procedure It is usually done under IV sedation like propyl and fentanyl And we are watching while we drain those follicles and get test tubes full of the eggs Do some people opt in not use any um say I hear the word fentanyl and I'm sure a lot of people like wait fentanyl crisis and I you know obviously fentanyl is a drug that has its uses valid uses in the um medical community Does anyone just kind of opt for you know just I mean we have an anesthesiologist who is really talking to the patients I mean propyl 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 great the retrieval's podcast came out from like the New York Times doing a deep dive into a fertility clinic Yale where a nurse was siphoning off fentanyl For herself for herself and replacing it with saline and giving patients saline These this clinic did not do anesthesia -based propyl so they were supposed to just get fentanyl 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 largely to pain not being taken seriously when they went and found this out.

2:50:37Well, what happened to a can't help but ask what happened to this Technician. Oh, I mean yeah, 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 Prografol 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?

2:51:15Kind of patient ask you to what specific drugs are you going to give me to kill pain? 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 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 propifol 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 this is when you'll feel you're worse and this is just the one thing I want to say about tolerability of it Can you get pregnant in that time?

2:52:05Yeah, yeah, yeah And there's a case report of an egg donor who is 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 to and she got pregnant with Quinn tuplets Whoa Okay, so you have to really tell people not to have in her course One from an infectious standpoint because we really are poking you know a pretty large -gauge needle Through the vaginal mucusa into the paratino cavity So we don't want to introduce infection but also For pregnancy and that time period and if you got pregnant Your risk of what we call a variant hyper 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 you'll be more emotional.

2:52:54You're still pretty bloated until this all heals If you get OHSS which is very uncommon in modern practice But when you did fresh embryo transfers or people who don't utilize some of the modern protocols This means that HCG continues to Encourage all those follicles to make estrogen and progesterone and if you are pregnant You're just going to have a constant yet exponential increase in HCG And so This is going to get worse and worse So we really don't want people to get pregnant in that time period So when during that time period they avoid sex so is it in the few days before the extraction? So typically I usually say it's from like day five of your stimulation Okay, so Usually the earliest egg retrievals are kind of around cycle day nine or ten if somebody goes fast Until your next period comes So that's usually about a three -week time period where we want you to abstain from intercourse So For the most part though the more eggs you have the more you're going to feel both this hormonal and physical shift Than the fewer eggs that you have So if you have a low egg count and you need to do IVF or freeze your eggs And you might do multiple cycles or rounds You're going to tolerate it actually pretty fine because you're not going to have these huge shifts physically you're going to feel fine And that's always a big concern When you mentioned earlier about different stimulation types People have this idea that things that are more natural are better right 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 the 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 the here -lost him is better.

2:55:24We're talking multiple low -stem cycles. They might be Even a fraction of the cost of a full -stem cycle, but then there many many more you got it Loast him cycles you got it 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 because there's only three And so that is a scenario where minimal stimulation does make sense and then there's the scenario where There's something called info cell has your research exposed you to this Invocell is a way to try to take IVF into To make it more financially accessible for certain patient populations Mainly people who don't ovulate like you're very refractory PCOS patient who doesn't respond to medication Or we have tubal factor infertility right so your fallopian tubes are blocked because of climidia or Indimetriosis and we just have a problem here that against sperm can't get together because you're not ovulating Or your tubes are blocked in invocell it's a device And that is plastic and you can fit Have to ten 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 eight to ten eggs because that's what fits in the device And then you put the sperm in the middle of it and then you put it Inside your vagina And you hold it in place with a diaphragm and the vagina is the right temperature to incubate And so you incubate your embryos In this little Invocell container inside your vagina and then five days later you come in and we take it out and we take the best embryo And we transfer it and you can do a fresh transfer Because you didn't make so many eggs so your hormones weren't so high Do people like this procedure?

2:57:35There's something that seems like like staying in proximity to this sperm and egg like you're taking Taking it home Okay, so I love this procedure and 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 and 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 is the problem then It's probably not smart to just presume that the sperm and egg will be fine in there, right?

2:58:10Like 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 info cell and there's no embryos And you don't really know where it went wrong Was it the fertilization step was it the growth step of the embryos in culture? So you do have less data notably. I like data You can't do genetic testing 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 -utern 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.

2:59:37There's a lesbian couple and one of them The eggs came out of and the other one incubated the embryos and then the other one had the embryo transfer So 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 That it's a more of a three -dimensional environment. I always imagine that the petri dish is not approach Is that so two -dimensional compared to the body and all these things having done cell culture before and you know cultured neurons and things 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 fluctuation and 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 is 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 To the kind of like oh like it seems more natural you're incubating in the more quote unquote more natural environment.

3:00:44Yeah, but at the same breath Why are you having infertility if you're an infertility patient right? So if you need donor sperm You maybe don't have infertility or if you have tubal disease you have a very defined reason Why we don't think that there's this huge Inflammatory issue in your body or something 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 door 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 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 antrophilical count is for you Is what we're trying to get and that's what these combination of medications is trying to do When the eggs come into the lab if you have egg freezing Very important to know is before we get into the x -ray 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 This cumulus cells are stripped off the eggs are frozen you have to do x -ray So if we're going to lead into this x -ray conversation If you're freezing your eggs you're having x -ray when you fertilize them So I don't want somebody to ever Not know that if that is what they are choosing and x -ray is you can tell us yes X -ray stands for its i -c -s -i or intracidoplasmic 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 zonal polucid of the egg and you're injecting That one sperm into that egg cytoplasm and you're picking that sperm on the basis of Shape motility you're picking what you think is the is the best sperm in the batch obviously Yeah, you're picking I mean there's gonna be one sperm per egg So there's multiple sperm that are chosen But your 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 and pretty much every cell the body like the cells always repairing its DNA So when visually selecting a sperm For x -ray 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 Yeah, are we soon to have a technology where you could actually Like get a die that could label DNA fragmentation and select Because I feel like so much like when we talk about embryology not to get too far down in the weeds, but Like the the methods of selecting eggs and selecting sperm I mean, these are the same methods that been used in embryology for like since the 1930s like oh this one looks good That one looks good and the skilled embryologists can can really develop a A real talent at over time of like knowing what correlated with healthy pregnancy and an offspring But I do like technology you would think that by now 2023 that someone would have some die that you could drop on the sperm and go Well like that one has a lot of DNA fragmentation and that one doesn't No, right there should be better ways to choose which sperm There's definitely People are trying things nothing is 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 Do we need to 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?

3:04:46So Things aren't really normal though or there's something underlying it Does that mean that every embryo failure on day three post fertilization is Not but it definitely means that None of the ones before that can be blamed on the sperm and once after that There's definitely still maternal and sperm contribution. We don't want to create any um, you know a couple uh disputes around this But it can be an in 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.

3:05:24So what is that? It is not a normal semen analysis But it is like that as far as it's a sperm sample that is then sent off to be evaluated how much Fragmentation or abnormal DNA is in the heads of those sperm The studies have shown that people who have abnormal DNA sperm fragmentation should do Xe Okay, that's like the point of the study now Xe's become very commonplace. So Xe choosing the sperm to put into the egg originally didn't exist, right? So what's the alternative? Conventional fertilization. This is having your p -tree dish your eggs are on it You squirt your sperm you cover it up you put it in the incubator.

3:06:04No, she didn't mean you squirt your sperm She meant she meant they'd take the embryologist Squirt the sperm on top. Do we clear just to be clear and then pulls it out and the next a C's 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 Xe 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 Xe 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 one percent rise of birth defects And so Xe 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 Xe almost every patient.

3:07:20I'm not gonna say to everyone but higher probability of success I probably do success and when you get to this point and so few people have Insurance coverage. So they're spending They're money. They're getting second mortgages. They're taking out loans If there's one decision that you say well, I don't know you could have zero eggs fertilize or I could Have the embryologists pick the best firm and put them inside the egg and we expect a 75 % chance of fertilization That makes sense for the majority of people Yeah, that makes sense to me I Because I'm obsessed with data and you know the blood work fairly regularly not not obsessively, but fairly you know twice a year or so Now I didn't always do that.

3:08:00I actually did one of these DNA fragmentation tests that they're pretty expensive You know, they're in the far more than a cement analysis. Yeah, they're there in the you know low Yeah, there's 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 And I mean I will say that there is some current thought by my urology colleagues, right?

3:08:35So I'm not a urologist But definitely when I have a male who you know needs a sperm extraction Maybe he's had a prior bisectomy maybe he's got very low sperm counts and we're going and we're doing a sperm extraction procedure That potentially if you have a patient who has an abnormal DNA sperm fragmentation and even with XC 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 ejectiatory process could cause some of that fragmentation and certain men and by going and and doing a sperm extraction and not subjecting those sperm To the rigors of ejaculation for lack of a better word could potentially Lesson 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 is to try to distinguish if potentially XC could be a helpful technology But a lot of doctors are offering or doing XC 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.

3:09:55So you're gonna have Lost throughout that culture process no matter what and you said 50 % progression so half of the fertilized embryos that make it past Let's say day seven then they're screened for chromosome 11 normalities So then okay, then you've got let's say two or three of those maybe four depending on how many eggs were harvested and your age and then and age Yes, thank you and then and then you said of those that are implanted into let's say a woman You 45 or younger you're looking at about anywhere from 30 to 65 % Successful implantation and pregnancy would like baby healthy baby It's usually a 65 % chance of life birth if it's a genetically tested embryo That that that Astra is the F and that's why you're going to see such varying IVF success rates because if you don't do genetic testing of embryos Let's use the 40 year old who makes four embryos and I send them off for genetic testing I anticipate she is one normal embryo if I do genetic testing which takes it's called PGT pre -emploitation genetic testing I am testing for aneuploidy as the traditional testing meaning does it have the right number of chromosomes You can also importantly test for single gene disorders like cystic fibrosis or honeytons But if we're just doing PGT for aneuploidy I expect an age related proportion of your eggs to be normal or abnormal So at age 40 I expect 20 to 25 % normal So I can choose that one and put it in you and have a 65 % chance that you have a baby I could not do it.

3:11:22I 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 And batch cycles so you could go into 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 embryo 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 than if I am four transfers down the road And maybe there was one miscarriage in there too We're suddenly now eight months down the road before I can go do another cycle and get more eggs Versus a five found out that none of those were genetically normal The average 40 year old might have zero to one if they have average ovarian reserve per cycle So they're going to need multiple cycles It's not that it's impossible But it's just studying 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 And a much more efficient way by utilizing genetic testing of these embryos This is where we can put an ellipse in and sort of like dot dot dot healthy baby Yeah And maybe in the future If we're lucky, you'll come back and talk to us about Healthy pregnancy Um left to go And Healthy baby onward That would be a fun and important set of discussions I would like to touch on the I want to call it the issue but the topic of menopause which I assume is defined as the cessation of mencies But there I'm guessing and I'm guessing it's a constellation of things that happen um And I have a very straightforward question which is is there an acceleration of the onset of menopause?

3:14:03Are 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 hormone replacement therapy or other other approaches? These are a 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 hyposrogenic 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 Estardial or progesterone anymore In this time period what we know is one Are we seeing a population based Increase an earlier menopause.

3:15:07There's not been a study to say that Observationally and clinically I would say yes because I see so many Younger women having low ovarian reserve or having premature ovarian failure or premature ovarian and sufficiency Which is the more politically correct way of saying it But when we think about what this is is there are notifiable 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.

3:16:04So 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 the 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 deeply 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.

3:16:54It'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 and sensitivity to have profound vulvar and vaginal atrophy to the point that you no longer want to have intercourse And the changes that it can even have on your gut and your immune system so We as a community you know of doctors especially OBGYNs really recommend hormone replacement therapy in women who are going through menopause and the key here is to initiate it Right at the beginning 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 hormones and in that circumstance They'd already been put into this higher risk category and their body had adjusted to not having the hormones And when re -exposed they had more adverse events But if you are starting On estrogen replacement and it can be various But honestly the estrogen that we try to replace in this time period much more mimics Estardial we have estardial pills if you can have vaginal inserts You know 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 Estardial more mimics that natural structure And you can't have unopposed estrogen without reaching the risk of intimeatrial cancer And so that's why we need to have some progestin So some people will choose a daily progestin Some will choose a cyclic progestin and still have periods Some will put in an IUD at this time period and then take their daily estrogen There's a lot of different options We're trying to find the lowest dose of hormones that relieves your symptoms to provide you relief from some of these lifestyle issues But also helps you not just live longer right we're not just trying to live longer We want to be healthy longer.

3:19:48We want to have a better quality of life And certainly Women's health has for long stopped at this mental -posal 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 mental pause 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.

3:20:29It's what happens naturally But by giving their bodies more estrogen and not crazy hydrosis But just these physiologic levels can really improve both the quality and the longevity of their life Is it just the presence of the symptoms that signals the onset of of Menopause or is there are there additional cues like for instance if their cycle is getting shorter or longer? Yeah, you certainly will have cycle changes and we consider that the perimenopausal period Where you're starting to really start seeing a spacing out of your period so they're no longer coming at that perfect ovulatory pattern When you get into the low ovarian reserve But you're still ovulating regularly they first shortened 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 perimenopause period You're going to start to have more prolonged periods of low estrogen and you'll feel Mentally cloudy fatigued more headaches more hot flashes lack of libido Those vulvar vaginal symptoms overall more likelihood to have depressed mood and that's a lot There's a lot Well Natalie doctor Crawford I want to extend a huge thank you on behalf of myself.

3:21:50I'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 and fertility for men along the way since truly been a Masterclass 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 considerations that really extend back to ones 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 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 does to one's fertility So first of all, thank you for joining us today.

3:22:36I know you're extremely busy. You run a clinic. You have a you manage a family as well co -manage a family. I believe but 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 I've learned so much from you over the years really um in following your content and today you've just Like far exceeded all already high expectations. So Thank you ever so much. Thank you for having me and just thank you for giving a space to talk about women's health and fertility and reproductive medicine It means a lot to me and it means a lot to the people who really are trying to do their best every day So we appreciate it We appreciate you and with some luck we'll commit to you to come back and talk to us about pregnant Bit more on some of the topics that we move through quickly Thank you.

3:23:32Thank 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 zero 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 five star review Please also check out the sponsors mentioned at the beginning and throughout today's episode That's the best way to support this podcast If you have questions for me or comments about the podcast or guests that you'd like me to consider hosting on the Huberman lab podcast Please put those in the comment section on youtube.

3:24:17I do read all the comments Not during today's episode but not many previous episodes of the Huberman lab podcast We discuss supplements while supplements aren't necessary for everybody Many people derived tremendous benefit from them for things like enhancing sleep hormone support and improving focus If you'd like to learn more about the supplements discussed on the Huberman lab podcast You can go to live momentus spelled OUS. So live momentus .com slash Huberman If you're now already following me on social media, it's Huberman lab on all social media platforms So that's Instagram Twitter now called x threads Facebook LinkedIn and on all those places I discuss science and science related tools some of which overlaps with the content of the Huberman lab podcast But much of which is distinct from the content on the Huberman lab podcast So again, it's Huberman lab on all social media platforms If you haven't already subscribed to our monthly neural network newsletter The neural network newsletter is a completely zero cost newsletter That gives you podcast summaries as well as toolkits in the form of brief PDFs We've had toolkits related to optimizing sleep to regulating dopamine deliberate cold exposure Fitness mental health learning and neuroplasticity and much more again It's completely zero cost to sign up you simply go to Huberman lab .com go over to the menu tabs Scroll down to newsletter and supply your email I should emphasize that we do not share your email with anybody Thank you once again for joining me for today's discussion with dr.

3:25:38Natalie Crawford and last but certainly not least Thank you for your interest in science