Creating a Family: Talk about Adoption & Foster Care

Primary Ovarian Insufficiency

October 06, 2021 Creating a Family Season 15 Episode 41
Creating a Family: Talk about Adoption & Foster Care
Primary Ovarian Insufficiency
Show Notes Transcript

Primary Ovarian Insufficiency is a difficult and little understood diagnosis for infertility with ramifications for your general health as well as for your fertility. We talk with Dr. Alex Quaas, a Board Certified Reproductive Endocrinologist with Reproductive Partners of San Diego and an Associate Professor at UCSD.

In this episode, we cover:

  • What is Primary Ovarian Insufficiency (POI)?
  • Is there a difference between the labels/diagnoses - Primary Ovarian Insufficiency, Premature Ovarian Failure, Premature Menopause? 
  • What are the symptoms (other than an inability to get pregnant)?
  • Is there a decrease in egg quality and increase chromosomal abnormalities?
  • How is POI diagnosed?
  • How does the diagnosis differ from PCOS?
  • What causes primary ovarian insufficiency?
  • Is there any correlation between POI and taking Accutane (a treatment for acne) as a teen?
  • Is there a link between premature ovarian failure and the HPV vaccine (Gardasil or Cervarix)?
  • Can losing one ovary lead to Primary Ovarian Insufficiency?
  • Are those with autoimmune diseases more susceptible to POI?
  • Can IVF lead to Primary Ovarian Insufficiency? Is there any evidence that aggressive stimulation of the ovaries during a typical IVF cycle can contribute to POI?
  • How effective is IVF with woman with Primary Ovarian Insufficiency? 
  • What are the odds of a spontaneous pregnancy for a woman with POI?
  • What is the role of the infertility nurse in helping women with POI?
  • Is there a medical way to slow down the diminution of ovarian egg reserves?
  • Are their lifestyle choices that contribute to POI or contribute to increasing a woman’s ovarian reserves?
  • Are there supplements or vitamins that help improve fertility for women with Primary Ovarian Insufficiency?
  • Has alternative medical approaches or Eastern Medicine been effective with increasing fertility for women with POI?
  • What are the other health implications for women with Primary Ovarian Insufficiency?

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Welcome everyone to Creating a Family talk about infertility. I'm Dawn Davenport. I am the host as well as the director of creating a and that's the place you can go to get all types of unbiased medically accurate information on infertility. Today we're going to be talking about primary ovarian insufficiency with Dr. Alex Quaas. Dr. Quaas is a Board Certified are he at reproductive partners of San Diego, as well as an associate professor at UCSD. Welcome Dr. Quaas to Creating a Family and thanks for talking to us about primary ovarian insufficiency.

Thank you for having me.

I think it helps to begin just with a definition. What is primary ovarian insufficiency?

Yeah, primary ovarian insufficiency is essentially the onset of menopause before the age of 40. So usually, women go through menopause at an average age of about 5051 in the United States. And menopause is usually a retrospective diagnosis. It happens when somebody doesn't have periods for 12 months. And so in women who go through this process before the age of 40, we talk about premature ovarian insufficiency.

Okay, and so it does go by a number of different names, and I think that causes confusion. Alright, so the currently preferred term is primary ovarian insufficiency. Is that correct?

Correct. Yes. So, you know, even when I was a resident, it was still called premature ovarian failure. Right. And if you look, look at the literature, some of the review articles on the topic and some of the, you know, prior research talked about POS or premature ovarian failure. Exactly. But I think we tried to avoid the word failure in medical diagnosis these days.

And that another thing that it no longer its use is is the term that's no longer used. But quite frankly, I think it is a a very descriptive term, and that is premature menopause. And you'll see that sometime in the older literature. I guess we're not using that, though much. Is that correct?

No, but I mean, it wouldn't be completely unreasonable to sort of refer to that term to illustrate. Yeah, because essentially, I mean, it's that that is ultimately what it is. It's premature menopause. And so when talking to a patient, you know, if a variant insufficiency is difficult to describe, then, you know, I sometimes say it is as if going, you were going through menopause at an earlier age. And I do

think from a medical standpoint, that using terms that everyone understands, I mean, we could certainly use the the the correct term, which is primary ovarian insufficiency, but explaining it as premature or early menopause, I think can cut through some of the jargon at times, with, especially with patients.

Definitely. Yeah, I mean, whatever it takes to illustrate the concept, we'll go through this later. But, you know, I was just thinking already, by the way, when this process of explaining what it is happens, that should be in person. So we'll talk about that later. But excellent, in addition to being very sort of descriptive and trying to explain it as well as possible, the setting for that moment should also be, you know, different from just a phone call, or, you know, a five minute appointment. You know, when patients get that diagnosis, not only should it be explained well, but the setting for that should also be very good.

Well and to further complicate things, the the there are two terms that are used, that currently one is primary ovarian insufficiency, and the other is premature ovarian insufficiency. From what I can see, it looks like the American Society of reproductive medicine usually uses premature ovarian insufficiency. But many other researchers including the National Institute for Health uses primary ovarian insufficiency. Both of them go by the acronym poi, and in this interview, we will be using those two interchangeably. Alright, let's define the symptoms other than Well, I shouldn't say that what are the symptoms and that would lead you to suspect that a patient has poi or primary ovarian insufficiency. Yeah, so

if we think back about what the ovaries do in the female, so basically the ovaries are the sight, off the eggs of where the female gametes are stored. And essentially, where eggs are sort of resting in a certain stage in order to become available to get fertilized at some point if they ovulate. So that is one function of the ovary, the other function of the ovary is the endocrine function. So hormone production, in particular, estrogen and progesterone. So a regular cycling woman in her reproductive years has, you know, the sequential and concomitant production of estrogen and progesterone in a regular menstrual cycle. And over the years, not only does the pool of available eggs diminish, so the quantity of eggs goes down over the course of the robotic lifespan of a woman, but also the quality of the eggs, but ultimately, also the endocrine function. So that means that the cells in the ovaries that produce estrogen, the granulosa cells, they do that less than less than less. And so towards the regular menopause, you know, let's say at the age of 5051, there is a relative estrogen deficiency or a low estrogen state, that comes from the cessation of the regular endocrine function of the of the ovaries, or at least reduction of endocrine or hormone production, endocrine function, hormone production. And so then you get symptoms of hypo estrogen emia. So symptoms of low estrogen, a low estrogen state, and estrogen does all sorts of things. So as we know, it supports your bones, but also it it's a feel good hormone in some ways, and so it makes you feel energetic it, you know, it's a it's a hormone that, you know, if, for example, somebody is deprived of estrogen, and then they get it back, they feel better. And so, the concretely, the, the symptoms are hot flashes, just like a woman who goes through the menopause at the natural age, and then maybe night sweats. And then you know, bone density ultimately, like this is a longer term bone density reductions. But also, then, you know, vaginal dryness is another symptom because the vaginal mucosa relies on estrogen to, you know, essentially keep it healthy. So you get, ultimately what we call vaginal atrophy. So those are the type of symptoms along with maybe also mood swings, and sleep problems. So basically all the symptoms of menopause. Really,

I would assume that another symptom, for lack of better word is difficulty in getting pregnant. Is that also true?

Correct, yeah, because ultimately, the depletion of the follicular pool, so the depletion of all the eggs in the ovary leads to an inability to get pregnant. So I mean, in the regular menstrual physiology, or the regular reproductive physiology and women, we have to remember, menstrual periods continue until the age of 50. But infertility, you know, like, often women equate the presence of menstrual cycles with the ability to get pregnant, but the ability to get pregnant is pretty much gone, you know, about five years before the onset of menopause. And so, you know, the egg pool diminishes. And then ultimately, when the periods stop, that means they're literally like almost no eggs left in the ovaries. And in the, in the regular physiology, we estimate that a woman at age 37, like so just sort of to take a step back, a female fetus has 6 million eggs. At birth, a woman has about 1 million eggs at puberty about 300,000. And then at age 37, there's about 25,000 eggs left and then at menopause, about 1000. So when a woman goes through menopause, there's still a few eggs left, but they're poor quality, that they're not really usable, or they can't really be fertilized. Now occasionally women with and we'll talk about that too, I'm sure, occasionally women with premature ovarian insufficiency will actually have a pregnancy. So in general, the rule is that women with premature ovarian insufficiency are unable to get pregnant, but it happens occasionally. And it's certainly something that we see especially You know, some women get diagnosed with this condition at the age of 25. So there's 15 years left or so like me and however many 11 years left to have maybe a chance of 0.01% per month or so. So occasionally it does still happen that women get pregnant. But in general, you know, we tell these women that unfortunately through the premature ovarian insufficiency, they are in fertile and if they really are desiring a pregnancy, most women in that situation have to use donor eggs.

And is there a generally as women age we see a decrease or, let's say an increase in decrease in their quality and an increase in chromosomal chromosomal abnormalities. So would a woman with primary ovarian insufficiency have a increase risk of having a f conceiving a child, a fetus with chromosomal abnormalities or an embryo with chromosomal abnormalities?

That's an interesting question. I think one would assume so based on the based on the similarity, but ultimately, the risk of chromosomal abnormalities in women of all ages and without the premature ovarian insufficiency in some ways is related or related with how long these eggs have been dormant in the ovary with the potential to, you know, have been errors in the in the reproductive process. And so in some ways, if a woman at age 25, with premature vein insufficiency conceives, I'm not sure that there is a higher ed, the problem is we have low numbers in that area, too. Exactly. Yes. Yeah. But in some ways, it's not inevitable that there will be a chromosomal abnormality. And, and these women can deliver healthy babies sometimes. Okay,

excellent. So how is poi diagnosed? I mean, certainly symptoms would be giving you a hint as a doctor, but is there a definitive way of diagnosing it?

Yes, so usually we do lab testing, and we can also do an ultrasound. So and they use the sort of show us a consistent picture. So on ultrasound, we would not see many follicles although it is possible to see some antral follicles even in the presence of poi. But the lab tests basically show us a picture of hyper gonadotropic hypogonadism. So hypogonadism always means a state of low estrogen production. So in the context of the ovaries, so hypogonadism, meaning the the gonads, the ovaries are no longer producing much estrogen. So the estrogen level is very low, if maybe sometimes even undetectable. And then so you know, people might be aware that there is also a hypo hypo condition that we sometimes talk about in our field, i hypogonadotropic hypogonadism. So that is if the whole axis is under functioning, and there's a primary issue in the higher center of the hypothalamic pituitary ovarian axis. So you know, you have gnrh, coming from the hypothalamus, and then FSH and LH from the pituitary gland, and then ovary, the ovaries make progesterone and estrogen. And so if that whole axis is under functioning, we talk about hypothalamic hypopituitarism. And that is a condition that, you know, we sometimes see in, you know, athletes or people who are, you know, have eating disorders or other you know, like, that is a condition where the primary issue is more in the percentage of the axis when the primary issue is with ovaries. So when the ovaries are the primary source of the issue, the depletion of the follicles in the ovary is the primary problem, then the higher centers in the brain. So the hypothalamus and the pituitary gland, try to compensate for the low estrogen level by stimulating the ovaries more, but the ovaries are not able to respond. So essentially, you get in a situation where there's a lot of FSH, a lot of gnrh, so that the higher centers are trying to do what they do. And so the diagnosis can be made by checking the FSH and LH level, which would be high,

they would be high, right? Because you're high thalamus and pituitary at that point are in overdrive trying to kick your ovaries to do something that they're incapable of doing.

Exactly, exactly. I had a colleague at the University of Oklahoma who always said it's a bit like, you can imagine it that the pituitary is shouting at the ovary with a megaphone. And the ovary is not doing anything. And so, so yes, so the FSH and the estradiol levels will give you a diagnostic picture. Now in most patients, there's no question about the diagnosis. So typically, let's say somebody has hot flashes, and they come to their doctor, and they say, I haven't had a period and six months, let's say, or maybe even longer, maybe they say I haven't had a period of two years. So then we check a, you know, the estrogen and the FSH level, and oftentimes the FSH level is like 90 or 100, when usually in most women in their reproductive years, it's under 10. So most women have an FSH level of, let's say, five or seven or something of that in that ballpark. And so then you get an FSH level back, and it's like 95, or 110, or 60, for anything, you know, that basically, I think, as a sort of somewhat arbitrary cutoff, we say over 30. FSH over 30 tells us that there is a situation of poi.

Okay, now, women with polycystic ovary syndrome, PCs, will often also be skipping periods, not so much with hot flashes, but there will be skipping periods. So how is the diagnosis differ? What would you what would the lab tests look like for someone with PCs that would tell you that it's PCs and not premature ovarian insufficiency?

Yeah, that's a great question. So in so on ultrasound, we would see lots and lots of follicles as opposed to almost none. But then also, in women with PCs, what we often see is an estrogen level. And so the intermediate range, so the estrogen level is usually not low. It's but it's like, at one level, so most women that have regular cycles, would have estrogen levels that are like, you know, they have a bi phasic trajectory or so during the regular menstrual cycle, they get, they go down again, and then that whole thing, so it's like an up and down wave. And women with PCs have sort of basically a straight line where the estrogen level is always around, maybe, let's say 60 or so. And women with boi have a estrogen level that's very low, let's sometimes the lab says it's below the limit of detection of extra dial for that lab, or maybe it's around 20 or so. And it's also constantly low. And then women with PCs, when you check their gonadotropin levels, the FSH and LH they would be normal. And sometimes you see the Lh being high. So women with PCs, we have hyper androgenic hyper androgenic state, so they have a high testosterone often. And so the Lh level is often a little bit on the higher side. And so then you can do the Lh FSH ratio, and it will be a little bit elevated. So let's say a woman with PCs just for illustration purposes might have an FSH level of five and maybe an Lh level of nine or 12, or something like that. And then an estrogen level of 60 are in that range. Whereas a woman with poi will have an estrogen level, let's let's it's maybe 20. And then the FSH level is 60. And the Lh level is 70 or something like that. And then, of course, on ultrasound, you've seen almost no follicles in the patient with premature ovarian insufficiency, and lots and lots and lots of follicles in the in the woman with pcrs. And then last thing, usually on ultrasound, if you look, the endometrial lining is very thin in women with premature brain insufficiency because the endometrial lining is sort of a biomarker for the estrogen concentration. So that will be very thin, and then women with PCs it will be sort of like either sick or medium. Okay, excellent.

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That's a great question and a very complex question. Because in a lot of the cases, when we try to search for a cause, we don't find one. And that's a bit frustrating. Because, you know, when we have this happen, of course, one of the first things that patients ask is why why Yeah, exactly. Yeah. But there are some causes. And there are some situations where we actually can tell them why it happened. And oftentimes, in those situations, they might know that already. So for example, if a patient has a history of some sort of cancer, and for that cancer, she had to receive chemotherapy, let's say, at the age of 12, or at the age of 15. I mean, essentially, any kind of childhood cancer that was treated with chemotherapy that damages the ovaries, then that can be the reason. And that is one area. The other part is genetic. And so with with regards to genetic, there can be a situation where we know for sure, and maybe the patient has already received some sort of diagnosis in childhood that made it more predictable that this happened. So for example, Turner Syndrome, Turner Syndrome is a chromosomal abnormality, where, you know, women usually have 23 chromosome pairs, and one of them is a pair of sex chromosomes, so x x, and in turn syndrome, there's just 1x chromosome, so it's 45x. And so, Turner Syndrome is associated with other findings, like short stature, you know, and you can basically read up on on the, on the phenotype of of Turner Syndrome, but essentially, that might have already been discovered in childhood. And then, you know, women with Turner Syndrome, if they have the full blown genetic mutation usually do not go through periods and they have a depleted follicular pool. You know, already at the age of menarche, so at the age where you're using it goes through through puberty. So that would be a genetic known cause, sort of more clear cut costs, but then there are many sort of genetic mutations, you know, like, maybe hundreds that can cause this, and some of them have been described, and some of them, maybe we haven't discovered yet. And so we, you know, there's a panel of tests that can be done for this, and then we can elucidate it. But the answer is, a lot of times Unfortunately, we don't find a cause. The last thing I want to say is, or last two things is there is a condition called Fragile X that we can test for. So Fragile X syndrome is associated with premature ovarian insufficiency. And then lastly, autoimmune disease has been associated with premature ovarian insufficiency.

If your mother went through early menopause, and that's something that women will often No, does that mean that you may be at higher risk for primary ovarian insufficiency?

There is a genetic component to ovarian aging. So to a certain extent, there is some of that involved. And that's certainly an indicator that maybe that might happen again. But it depends on the specific situation. I mean, I think that there is still some variation in your own, you know, age of menopause. And so it's not, it's not exact, but it can be used as a little bit of an indicator what to expect. Now with Fragile X, which I just mentioned, sometimes there is actually a progressive effect, where if this is passed on, and it starts as a mild mutation, then the severity can actually increase and then the age of menopause can progressively decrease. So become younger and younger at the age of menopause. But while it's not one to one, it's at least an indication so there is a genetic component.

Another thing that we sometimes hear from patients is that they worry that there is a connection between poi and having taken Accutane as a treatment for acne as a teen or that there is a connection with poi and the HPV vaccines. Is there any evidence that would suggest that either of those return?

Yes. So the second of the two, I think it's a easy and relatively conclusive answer. The HPV vaccine has not as far as we know been associated with Primary or premature ovarian insufficiency so that, you know actually and if people want to look at this in more detail, there was actually a very nice review in the American Journal of Obstetrics and Gynecology last year by Monday Christiansen at all. So that was in the gray journal, as we call it, a review from people from Johns Hopkins University. And essentially, they stayed current evidence is insufficient to suggest or to support a causal relationship between HPV vaccination and primary ovarian insufficiency. I think what happens sometimes in our field and in medicine, in general, is when you know, all sorts of things happen in a temporal Association, but the causal association is not there. So what I often say to illustrate this concept is the very first patient that I admitted as a medical student was a patient who had a heart attack. So he came into the hospital with an acute EMI, and he had gotten prescription glasses the day before. And so of course, he was convinced that those prescription glasses cost his heart attack. And he asked me well, is this true like did these prescription glasses cause my heart attack? And I said, well, wireless temporarily related, it's unlikely that there is a causal relationship. So if you have 1000s, or even millions of teenagers receiving the HPV vaccination, even though poi is rare, some of them will have poi, but that number does not appear to be different from women who didn't get vaccinated so that I think that can be dispelled. Now with regards to z Accutane question. I do think that there's a bit more of a biologic plausibility for that, because of the mechanism of action of Accutane, which is a derivative of vitamin A, and, you know, the fact that it could have theoretically some effect on the hypothalamic pituitary ovarian axis. So with that one, I would say, we still need more research, you know, and I would say, you know, women who are in their prime childbearing years should maybe, you know, receive a lot of counseling before using that. But I think that is still to be determined. I do not think that it's, if anything, there's maybe a contributory effect. I do. I mean, we do not have evidence that it causes premature ovarian insufficiency in all patients who take it or anything. It's not a dramatic effect, but it remains to be seen whether there's a small effect.

If you have only one ovary for whatever reason. Are you at higher risk for poi?

Yes, I mean, by definition, if you take away half of all the follicles that you have, then that will deplete your follicular pool by 50%. Now, yeah, we see patients who had an ovary removed because of a dermoid cyst, like a benign ovarian cyst, or something like that. So, you know, in some ways, you can see premature ovarian insufficiency, as a continuation of decreased ovarian reserve, which is the term we use for women who goes through infertility treatments, for example, because their ovarian reserve is lower than what would be expected by age. And so removing an ovary definitely decreases the very reserved and ultimately you may go through menopause sooner, but many women who have one ovary removed still have the regular age of menopause. So you know, it's just when you take away half of all the variant tissue and half of all the follicles that can accelerate the process.

Well, then let's that leads to the question about IVF because during IVF, we hyper stimulate the ovaries to produce more eggs. And so we are more rapidly depleting the ovarian reserve. So that would lead to the question is, does can IVF lead to primary ovarian insufficiency?

No, it cannot. I think that's something that we can categorically deny. So the the the principle of IVF is to take the available eggs from one cohort that would otherwise disappear anyway. So you know, this is the same same question that egg donors to ask, you know, when we before we do a stimulation on egg donors, like, you know, will I go For menopause earlier, or I do it well, I have less eggs. And so again, you know, when when when I talk about that I go back to the fact that women start off with 1 million eggs. And at the age of, you know, puberty, they have 300,000. And at the age of 37 25,000, let's say, so, you know, and we're taking 20 eggs. And so you know that that that pool of follicles is basically so every month, there is a pool of antral follicles that appears in the ovaries. And one of the those follicles releases an egg and has a mature egg that that becomes available for fertilization. The other the ones that sort of lost out on the chance to ovulate, they're not going back into the available pool that becoming a treaded, they're going away. So every month follicles disappear. And that happens, whether we do the IVF or not, or whether somebody is on birth control pills or not. And so we are only taking eggs that would have otherwise disappeared. So I do not think people need to worry about poi or accelerated ovarian aging because they go through IVF treatment.

So how effective is IVF for women with primary ovarian insufficiency?

Unfortunately, it does not work. So if somebody really haven't has an FSH level of over 30 and low estrogen levels, and a diagnosis of primary ovarian insufficiency or premature ovarian insufficiency, we cannot like IVF would be a waste of time, because it does not work. And you know, patients should not go through it. Now, you know, because, as I said earlier, like sometimes a pregnancy can happen. In a woman with premature ovarian insufficiency. In fact, it's estimated that up to 10% of all women with this diagnosis will have a pregnancy at some point. But that's more because if you take the cumulative probability of every month having a tiny probability, you know, if you add that, you know it over let's say, you know, 100 months or 50 months, then, you know, because you have that tiny probability every month, it may happen. But with IVF with one cycle of IVF, literally the chance, in a way, if it's a true diagnosis of poi, the chances essentially zero.

And so for that, for a woman who has a diagnosis of poi, she needs to then consider some form of third party reproduction donor egg donor embryo or they move to considering adoption. Now those are those are options,

correct? That's exactly right. Okay.

Do us a favor. And please follow the creating a podcast wherever you prefer to catch your podcasts so that you're going to never miss a week of important information, like this conversation about premature ovarian insufficiency. You can listen on your phone or in your car, you can also scroll through our archive of other shows that we've done with Dr costs, and other topics related to poi or uterine health, then you can listen to whatever interests you whenever it's most convenient to. Let's start, let's talk now about the role of the infertility nurse in helping women with poi I was so thankful that it's the beginning, you mentioned something that is so important, and that is this or you were alluding to the fact this is a devastating diagnosis. For the reasons you just mentioned. I mean, it means that your options of having a genetic connection to your child have certainly been diminished. And there is still the possibility of spontaneous pregnancy but generally given the age of the woman that is not something at that point that she's probably banking on. So let's talk about the role of what can infertility nurses as well as infertility doctors do in helping women with this diagnosis?

Yeah, so at the first diagnosis, really take the time to sit down, create a situation, I mean, this is essentially what we strongly recommend to the whoever has to provide this diagnosis. Make time in your schedule. So it cannot be a situation where you're already behind in a busy clinic, and you're already catching up and then you like you have a 10 minute appointment that becomes a two minute appointment that that that is not the situation that you want to give this provide this diagnosis. What you want to do is create a situation where you are you have a calm and peaceful environment not rushed not out There are people around, and you want to sit down, and really be a very sensitive to the fact that this is a major, major, major life event to receive this diagnosis. Now, of course, you can look at the background. So like, oftentimes, we are specialists, when we get the referral, sometimes they have already talked to their ob gyn about it, or maybe because of the, you know, symptoms that they have, maybe they have a suspicion. So those are things that you can maybe use. But you know, to, for example, ask, so what is your understanding of what is going on, you know, to gauge the level of understanding, because, you know, I've had many, many conversations like this. And sometimes it was in patients who were completely aware, and maybe expecting it deep inside. And sometimes it was in situations where it was a complete surprise. And of course, the more of a surprise, and the more of a shock, that is, the more time you need to take to really be very mindful about it. And so then it's just I think, education, you know, education is empowering. And, you know, like, really, you know, basically talking about the things that we've been talking about over the last few minutes, like, What is it? What can cause it? How does it affect your life? How does it affect your fertility? How does it affect your health, and all those things, and maybe take away fears as well, because, you know, other than the fertility aspect, most of the other symptoms and effects, such as on bone health can be mitigated by hormone replacement therapy. So really, the effect on fertility, in my mind is the most devastating part, and then talking about things that may be associated with it that we should rule out. But the important thing is really, to be very sensitive to the situation, and to be very empathetic.

You know, and I would add one other thing, I think sometimes in the medical profession, when you have a difficult diagnosis, it's tempting to immediately rush in to the the solution. Well, you know, just you need to think about donor egg you need to think about donor embryo or you need to think about adoption, although quite often their donor egg is the thing that's that immediately jumped into. And I often liken it to call it the infertility escalator, where you're on it and the next step is coming. And and so it's quick, it's, it's tempting to immediately suggest the next step, because the next step up on that escalator, have it come immediately, when in fact, non genetic parenting is really stepping on to a different escalator. And there needs to be a pause there, not that you don't mention that that is is the is a solution for childlessness. But I do think that immediately, just making the assumption that there is no morning necessary and that the next step is automatically donor egg, there needs to be a pause and there needs to be an honoring of, of, of a grief state and also then educating on what it means to be it not moving on to the separate escalator, which is non genetic parenting

100% and also like not automatically assuming that everybody wants children. I mean, I think we always assume that everybody you know, that it's a it's an innate desire that everybody has. But you know, I mean, I think it's a bit similar to PCs, we've, I think we've talked about PCs in a different segment of this series. And likewise, PCs is a syndrome and many women have different needs, and different a different agenda, depending on their own symptom profile, and their own needs. Like for some women, the cosmetic aspect might be more important. So for some women, that fertility aspect, and likewise with this, some women may be more worried about their ability to have children and some women may be more worried about other health aspects. And again, like as you say, like let the patient digest the diagnosis, and then pause rather than trying to fix it quote, unquote, and just sort of let it sink in and then you know, if, you know maybe go more by what what do you think what what are your questions about this? And then of course, if the patient So what does this mean for my ability to have children, then maybe you can say, Well, there are options, and you can carry a child, yourself, you know, and, and these options, you know, they're kind of complicated. It's something that you have to like, process and think about over time. And I agree with you, you go a bit slower, but what I do say is the limiting factor of female fertility of the ovaries but a uterus In the most, you know, most of these circumstances a uterus is capable of carrying a pregnancy at almost any age and under almost any circumstances. So, you know, I think it is nice to know that a woman with poi is able to give birth to a child to breastfeed a child, and then, you know, raise that child herself. And so you know, but I agree that it shouldn't just be put out there as an immediate next step, more like an option.

Is there a medical way to slow down the definition of ovarian reserve, assuming that someone has a diagnosis relatively early still has some egg reserved, but just a lower, lower reserve than would be expected? Is there some way to slow down the diminution so that their childbearing years are extended?

I would like to find it and then, you know, I get the Nobel Prize and retire in the Bahamas. Yeah, unfortunately, that is, I think the holy grail, like we would love to find that. We don't have a definitive therapy like that. I mean, I think people are working on that frantically. And there are sometimes people who offer non evidence out non evidence based treatments. In that regard, I think it's a field that's being heavily worked on. But we do not have a current treatments for it. One thing we can do is if we can anticipate damage to the ovaries, like, again, the setting of a new diagnosis of cancer, with chemotherapy, that is imminent, we can freeze eggs or ovarian tissue, and that's very effective. So we can if somebody if we know that somebody is about to incur ovarian damage from like, I oestrogenic causes from doctors providing medicine like chemotherapy, then that but other than that, everything else is experimental.

And so that that begs the question of, are there supplements or vitamins? Is this snake oil that were being peddled? Or is, in fact, there's there is are there any supplements or vitamins that have been shown to improve the, let's say, the fertility because I realized that's not the only symptom, but all fertility

diagnosis is actually made. There's nothing I mean that no supplements will reverse the reversal very aging. In women with decreased ovarian reserve, we recommend certain supplements like coenzyme Q 10. But that's more if the patient is still in that sort of gray intermediate area between very healthy ovaries and menopause and there's just a decrease in ovarian reserve. But if somebody already has a complete depletion of their follicular pool, then supplements cannot reverse it either.

So but but for someone who is at the initial stages of it has a decreased ovarian reserve, at best is not full blown into premature ovarian insufficiency. There are supplements and and and vitamins. So what what, what should they consider at that point?

I think no enzyme kuttan has the best evidence for it. And then just a healthy lifestyle. You know, with regards to lifestyle, I always say to women who have decreased ovarian reserve, you can actively damage your ovaries with a terrible lifestyle. Let's say if you throw up the if you smoke three packs of cigarettes per day, ultimately, that may have a negative impact on everything on your whole body, including your ovaries, or if you have a BMI of 60. You know, I mean, you can, you know, with toxic lifestyles, you can damage your ovaries. But the reverse isn't unfortunately true. Like when I was working as a fellow in Los Angeles, I had lots of women over 40 who came to me, and they were age 43. And they said, Well, how can my ovaries, you know, be insufficient? or How can my ovaries cut? How can I have decreased ovarian reserve? I eat kale three times a day, and I meditate and I do yoga, and you know, I sleep eight hours a night, how can my ob So unfortunately, the ovaries age, even if you have a good lifestyle?

Yeah, it is it we hear that a lot, too. You know, I'm really I'm in the best shape of my life. And I'm very healthy, that type of thing. And unfortunately, our bodies age regardless. dadgummit Yeah,

I mean, in those situations, I usually say Well, it's true that you do look like you're 25 years old. Unfortunately, the ovaries, you know you they cannot be sort of frozen in time with a particularly good lifestyle.

Another one of our great partners is Cryos International sperm and egg bank. They are dedicated to providing a wide selection of high quality, extensively screened frozen donor sperm and eggs from all races, ethnicities and phenotypes for both home insemination as well as fertility treatments. Cryos International is the world's largest sperm bank, and First freestanding independent egg bank in the United States, helping to provide the gift of a family. Have there been any alternative medical approaches or Eastern medicine that has been effective with either with increasing the fertility of women with poi or in helping to preserve the limited reserves that are left pre diagnosis, but women who anticipate that they will have this diagnosis?

I will say, I'm not an expert in alternative medicine or Eastern medicine or, you know, alternative approaches, but I'm very open to it. And I'm very like, you know, essentially, I don't, I don't feel like close minded about it. And so I don't think that the possibility of that has been ruled out. But again, it's there's no one breakthrough treatment, because otherwise, we would certainly recommend it. If, for example, acupuncture, or other treatments, were able to reverse this process, then I would absolutely refer all my patients to it. At this point. I don't think it hurts. But I don't think I've seen anything convincing to suggest that there is something that in a clear cut fashion can reverse a very an aging.

Okay, and we've the last question is one that you've alluded to, but I think it is important to note that as you have that the decrease in fertility is only one aspect of the health implications for women with primary ovarian insufficiency. What are some of the other health implications for women with this diagnosis?

Yeah, so you know, in the natural ovarian aging, you know, usually women have estrogen and progesterone production, and also testosterone production, by the way, until menopause. And so if that happens really early, let's say at age 25, then the main, you know, then number one, it will lead to a decreased quality of life. But it also can have health effects. Now, the most important health effect is the effect on the bones. So estrogen is important for the bones and for bone health. And so the main purpose of replacing hormones other than increasing the quality of life, is to maintain good bone health as to prevent osteoporosis. So if a woman goes through menopause very early and it's left untreated, then they're at risk of osteoporotic fractures. And so for that reason, you know, we would like to replace the deficient hormones in order to prevent osteoporosis and maintain good bone health. And so, you know, one of the easiest, there's many different ways of doing it, and this is another conversation with a patient, about one of the easiest ways is to simply use birth control pills because birth control pills have, you know, a decent amount or a small amount of estrogen and progesterone are a progestin which, progestin is a synthetic form of progesterone. You know, the birth control pills have enough hormones in them to supply the replacement of the deficient hormones and prevent bone density problems and decreased bone health and osteoporotic fractures, that kind of stuff. So it's mostly the bones.

So and which of course, then you need to make decisions on on on your bone density and how much damage may have already been done and, and all of all of that which which you need to talk with your reproductive endocrinologist about as well. All right. Thank you so much, Dr. Alex closs, for being with us today to talk about premature or primary ovarian insufficiency. We truly appreciate your time.

You're welcome. It was a pleasure talking to you. Thanks for

joining me today and I will see you next week.

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