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Proov Podcast: Episode 2 - Amy & Dr. Klein


The Proov Podcast: Dr. Josh Klein

Written by: Dr. Amy Beckley, PhD, Founder and Inventor of the Proov test the first and only FDA-cleared test to confirm successful ovulation at home.


Written on 11/2/20


Amy Beckley:

Welcome to another episode of the Proov podcast. I am Amy Beckley, your host, and I am here with Dr. Josh Klein. He is the medical director of Extend Fertility Clinic in New York and he is also on our medical advisory board here at Proov. So I'm very, very excited that you could just spend a few minutes with me talking to our listeners about what you do. So welcome! Please tell us a little bit about you and Extend Fertility.


Dr. Josh Klein:

Yeah. Thank you very much, Amy, for having me and and generally for allowing me to be a part of the Proov journey, because I think it's a really cool and helpful product.


So my background is I am a reproductive endocrinologist, which is the long way of staying a fertility doctor. I am currently based in New York, but basically I grew up in New York. I did most of my training in Boston and then circled back to New York later in my professional life. I worked for one of the big academically affiliated IVF centers in New York City for a number of years. And I left that job, which was a good job, but I left that job because I was motivated by the idea that it would be, I think, a good thing in the world to help make fertility treatment more understandable in a proactive way.


I think that's the most traditional version of an IVF clinic tends to be similar to that in general, any medical clinic, which is you have a problem — in this case, you can't get pregnant and you go to a fertility doctor and they give you a prescription, says, here's what we're going to do. And that has been the mechanism. I think slowly [there has been]a generational change, both because the patients are demanding it as well as the doctors are starting to get younger. But the idea that patients should be more fully engaged and educated in their options and in the reasoning behind some of those options, I think is particularly important for fertility treatment choices in general. And for the demographic of patients, which is relatively young and usually people who are interested in knowing what they're doing and why for fertility treatment as a medical niche rather than cardiology or something.


So I basically left one of these big traditional clinics and helped co-found Extend Fertility. We actually started with the premise that egg freezing (this is back in 2015) was a relatively new idea that most people didn't know about and was also sort of opaque and overly expensive at traditional IVF clinics. So we focused on egg freezing pretty much primarily in the beginning days of Extend Fertility. We sort of crafted our center in a way that helps keep the overhead as low as possible without compromising quality. So we tried to push the price point down and we did that successfully. We tried to be proactive about how we educated people to learn about their fertility in general and how egg freezing may or may not be something that they would want to do. And we saw explosive growth actually.


So in the first two to three years of our operations, we went from being a new clinic to being what we currently are, which is the highest volume center for egg freezing in the country. So that's really cool to say. Along the way, basically enough patients have circled back who have frozen eggs and wanted us to use those frozen eggs to get pregnant or just generally people who wanted us to help them get pregnant. So we've now integrated a more full spectrum of infertility treatment, and which is to say IVF and IUI and all the kinds of things that go along with that into our clinics. So Extend is now egg freezing heavy, but not an egg freezing exclusive clinic. And I have several doctor colleagues who helped me run the place. But that's how I spend my days and it's a cool job to have.


Amy:

That's awesome. Yeah, everyone talks about egg freezing. Everyone knows what that is, right? [Who do you recommend egg freezing for?] And who do you say, “Okay, you don't need egg freezing.” How do you kind of counsel a patient to say, “This is probably something you should do.”


Dr. Klein:

Yeah. So it's a great question because it's not simple, even though it sounds simple. I mean, I think we do these public educational events just about every month called Egg Freezing 101. And it's funny because the title is Egg Freezing 101, so you'd think that we spend most of the time talking about egg freezing, but the truth is we don't — I spend most of my time talking about the background principles of the biology that supports the idea that egg freezing may or may not be worthwhile for somebody.


What I mean by that is egg freezing is a management strategy for a particular challenge, which is to say the female biological clock, right? It's pretty universally understood that as a woman gets older, she's going to have a decline in her fertility. And so if a woman is not yet ready to have her children, but knows that it may be a priority in her life down the line at some point to have children, but she also knows inherently that the longer it takes, the harder it may get, or the more likely it's going to be difficult.


And so this is a proactive way to say, “I don't know for sure even if I want children, but I think I might, and I don't know when that's going to happen and I don't know if then we're going to have trouble. But I do know one thing: that if I can take some of my present day potential and sort of hold on to it in a way that fast forward, a few years down the line, if I find myself wanting a child and not having an easy time getting one, I'll be happy that I have this sort of younger potential put away from me.” 


So it is inherently a “maybe” proposition. Like you may, even if you do it, you may or may not need it or want it or use it. But, that's one of the things that kind of goes into the thought process.


But it is arguable that someone who froze eggs earlier versus someone who did not, you're better positioned when you're ready to have kids if you have frozen eggs in your back pocket. Having said all of that, the question really is if this is a management strategy for the biological clock, what is the biological clock, right? In what way is it true that women have a decrease in their fertility? What's happening to them as they get older in a concrete way that makes it harder to get pregnant?


And in a very quick nutshell, what we spend time talking about is this paradigm of egg quality and egg quantity. Meaning there are two things that happen to a woman's biology as she gets older; she has a decrease in the number of eggs that are left — a decrease in the quantity of eggs — and then she also in parallel has a decrease in the quality of the eggs. 


And the quality of the eggs really is best in my mind, defined as the percentage of eggs that are normal versus abnormal. And there's nuances on each side of that paradigm. How do we think about egg quality as a testable? How do we think about egg quantity as a testable? Is everybody the same or are people not the same? And that's where the devil is really in the details. And that's how by understanding those fundamental principles, a woman can understand where she sort of is situated, in the biological clock today and how does that relate to a few years from now? And that's, I think, what really helps people make a truly informed choice about if egg freezing is worth investing time and money and effort into doing


Amy:

Okay. All right. So now I'm intrigued, how do you test egg quantity? 


Dr. Klein

So, you're starting me with the easy one.


Amy: 

I know, I totally did.


Dr. Klein:

So egg quantity...is inherently, individually variable. A fundamental take home point from these kinds of teaching sessions is that you cannot assume based on your age, just knowing your age, that you have a lot of eggs or not a lot of eggs. On average 25 year olds, if you take a thousand of them, will have more eggs than 45 year olds. That is for sure true. 


What's also true is that if you take one individual woman who's 25 and check her egg supply, and then wait 20 years and check her at 45, she's going to have fewer eggs left later in her life. But if you just have a person in front of you and her age, let's say it's 35. You could guess she has somewhere in the middle number of eggs left, but she could be way lucky for her age and have a very high egg supply or she could be way unlucky for her age and have a very low egg supply.


And that extreme variability is not rare. It's actually stuff that we see all the time — women in their late twenties, early thirties that have low egg supply, women in their late thirties or early forties that have high egg supply. It's not something you would feel. It's not something you would know without testing for it as we'll talk about. And it's something that again, until you know to think about this topic, it's kind of a hidden reality, behind the curtain of the biological clock.


To answer your question, how do we test: in the sort of most concise answer, there's the two best tests. The first is a blood test called AMH. It's a hormone that is produced by the egg supply. It stands for anti-Mullerian hormone. It's a product of the egg supply. So women who have a high egg supply will have a high circulating level of AMH or the opposite of low egg supply will have a low circulating level.


You can also do an ultrasound to look at a woman's ovaries and count the antral follicles, which is a little bit of a different subject. But basically the idea is by a visual inspection of the ovaries, we can get a directional sense if there's a lot of eggs in there or not.


So those are not things that you generally are going to get automatically at your, at your general doctor at a checkup, or even necessarily at an OB-GYN at a checkup, although maybe over time, we'll start doing stuff like that. But they're not hard to get, certainly any fertility doctor can do them. There's starting to be even mail-away kits to check AMH and stuff like that. So it's relatively easily accessible information, which can actually be very helpful to inform the conversation around egg freezing.


Amy:

Okay. So, that's a great last sentence: egg count helps you understand how many eggs you have left for egg freezing. Right? So most of our consumers that are using Proov are tracking ovulation to see if they're successfully ovulating because they're trying to conceive today. Perhaps they used one of those AMH kits — they got the mail away kit or they went into their fertility doctor — and they come back and they're like, “Oh my gosh, I have an AMH of 0.6 or 0.8, or something like around 1 or just under,” and are really worried that they're going to have trouble conceiving naturally because they have a low AMH level. Can you speak to those women that get those “bad” AMH levels back?


Dr. Klein:

So, I mean, the short answer is don't panic and maybe even don't worry. The long answer is — so there was a great study that was published about a year and a half ago. And one of the premier medical journals that tackled this question head on so now we know that AMH reflects the egg supply.


So then the question is, does egg supply affect your chances of getting pregnant? If you're someone who is actively trying to conceive, as a lot of Proov users are, how does AMH play into your chances? So they did this study where they basically stratify, they divided up a group of about, I think it was 800 women, something like that, into three groups. The low AMH people were less than 1.5, the medium age people were like 1.5 to 3.5, and the high AMH people were like over 3.5.


And they were all women who are actively trying to get pregnant for the first time. And they basically did nothing other than follow along who got pregnant when and so it was a very nice sort of natural experiment to see, does your AMH level correlate with your ability to get pregnant or with the speed with which you can expect to get free?


And the answer was it made zero difference at all, like none, which was so surprising to a lot of people that it actually got published in one of these big medical journals. And I think it was JAMA and actually got picked up by the media with an unfortunate headline saying AMH is worthless for fertility. That's not true. What is true is that AMH does not relate to your chance of natural conception and the key simple way that shouldn't be surprising to people is because, remember, natural biology says women ovulate — they release one egg every month.


And that's true for every healthy woman. Doesn't matter if you have a huge egg supply waiting in the wings and your AMH is through the roof or if you're really running out of eggs and AMH is really low. If you have regular cycles, you're ovulating one egg every month. And so what you have in your stockroom and the inventory is not helping you get pregnant in the natural setting. Cause everybody just gets one.


So it actually shouldn't have been surprising to anyone that AMH was not a predictor if you understand the kind of the fundamental biology in the natural setting, what it is helpful for is for when you walk into a place like this, which is to say, if you're working with a fertility doctor to manipulate the natural system, meaning if you're doing fertility treatment where they're giving you medicine to get two eggs at a time or three eggs at a time with Clomid or Letrozole, or one of those kinds of treatments to increase the odds.


Or more importantly, even if you're doing something like egg freezing or IVF, where we're putting the pedal to the metal and using strong medications to try to retrieve as many eggs as possible because each egg that comes out of a woman's body is a potential baby, right? Any one [egg] can be the one. And so getting five is better than getting one and getting 10 is better than five and so on and so forth. So the usual approach to treatment for egg freezing or IVF tends to be the more the merrier, within safe limits.


So for someone like that, the reality is that IVF and egg freezing are very numbers driven. If you think about what is your prognosis — what are your chances of success if you are doing IVF or what is your prognosis if you're doing egg freezing, is this something that might work for you in the future? Well, the answer is: it heavily depends on how many eggs you get. And even though with every patient we try to get as many as safely possible at the end of the day, the reality is some patients struggle to get two or three or four at a time. And some patients can easily get 20 or 30 or 40 at a time. 


Is it random and you just find out one day what you got ‘cause it's a big investment to like find out, [meaning you’re] surprised at the end? Of course not. We can use these tests — and AMH is front of that line — to help people understand if you did this, what is realistic to expect? Are you someone who will get five eggs or 10 eggs or 20 eggs and so forth? And then of course connect that idea if you've got five eggs or if you got 20 eggs, what's the likelihood that those eggs may ever achieve a baby for you?


So that's how we try to give a picture for people looking into egg freezing. Is understanding there is this divide between the quality of the eggs and the quantity of eggs. We haven't really talked a lot about quality, but that's an important piece. Quantity is something that is individually variable, it's individually testable, and it is directly correlated with what you might get if you decide to kind of invest and make the commitment in tag freezing. And it's so in that sense, it's super important.


Amy:

Awesome. That makes complete sense. So we talk about low AMH, having fewer eggs than normal, that you are getting to the end of your supply. Right? What about high AMH levels? I know some of the people in our group are worried about, “My AMH came out as 6. Does that mean I have PCOS?” Is there any studies that correlate AMH to PCOS or any diagnostic capacity that measures that AMH level relates to PCOS?


Dr. Klein:

Yeah, that's a great question also. So, AMH is a product of the sort of follicles that are waiting the egg bubbles, which are called follicles that are waiting in the wings in any moment in time. And generally women with a higher egg supply have more of those waiting in the wings follicles, which is why they have a higher AMH. In PCOS, you have this sort of unhealthy situation where because women have a hormone imbalance that doesn't allow them to cycle normally in the sense that you don't have the monthly maturation of an egg, that kind of clears the slate and then if you're not pregnant, it turns over the slate. Then you have a new group that are available to grow. And then again, the monthly slate where one grows and the others die off.


So you basically get like almost a backup. You have an over-abundance of eggs that are all waiting in the wings without a regular cycle of them actually growing and ovulating and being released. So because of that, PCOS patients also have a high AMH level typically because they have a lot of follicles waiting in the wings. So there's a pretty major overlap between regular high egg supply and PCOS, to put it in more concrete terms.


So the truth is that I would say there's pretty good data to show that a woman who has an AMH that's above like 8 or 10 — and I'm picking something random number there because it depends on the study — but if it's really super high, like 8 or 10 or higher, they probably do a PCOS or some PCOS-like condition.


It's actually not far from reality to say, just based on that number is a very strong suspicion. If a woman has an AMH of below 5, it probably doesn't mean a whole lot. They probably just have either normal or nice egg supply between 5-8 or 5-10 is that range where you might just be really lucky to have a really good egg supply, or you might have PCOS. But the last point I want to make on this topic is that remember PCOS is a clinical diagnosis, which is to say, if you have an AMH of six or seven and say, “Oh my gosh, someone told me I have PCOS,” okay. Maybe, you can call it PCOS cause it's really just a label. But you have nice regular menstrual cycles and you're documenting ovulation with Proov and everything.


So the reality is the main way PCOS affects fertility is because it messes up regular ovulation. So even if we give you the name, if someone wants to give you the name PCOS because you have a high AMH, but if you're having regular cycles that shouldn't stop you from getting pregnant. At least not that alone. So the title PCOS ultimately may not even be so important. It's a name we give, but it's more the clinical picture of normal ovulation or not normal ovulation. That tends to be the more important factor as far as fertility concerns go.


Amy:

Yeah, absolutely. I love that you said that. It's not about, “Oh, I have PCOS, I'm never going to get pregnant.” It's are you ovulating? Or are you producing eggs? And that's what we try to advocate all the time. It's not the PCOS that's causing you to be infertile. It's the lack of ovulation. And if you can show that you're not ovulating, you know, your Proov tests are always negative. That's powerful information. You can go take that to the doctor and get whatever treatments. Or if you have PCOS and your Proov tests are positive and you are ovulating, great, awesome. That's not going to be a barrier for you.


Dr. Klein:

Totally. Yeah. I'll piggyback on that one more level because when you go to a guy like me you hopefully have insurance, but if you don't you're paying a lot of money. And you say, “Okay, I have PCOS and Proov told me I'm not ovulating. So you got to help me.” What am I going to do? I'm going to give you medication to make you ovulate.


So it's not that I'm going to cure your PCOS. There's no such thing. Right? So again, the idea of having PCOS or not is not the thing you ultimately kind of need to worry about. It's more, are you ovulating or not? Because even the doctors won't cure it. We'll just do things to make you ovulate if we think you're not.


Amy Beckley:

Right. Okay, we got the easy one down. We're going to go for the hard one: egg quality. Is there a test for egg quality?


Dr. Klein:

I think egg quality is a topic that's less clear — although I actually think it's not that unclear and there's more, almost emotional investment in the topic — but my best answer. And I think I'm as knowledgeable on the subject as anybody, but I'm sure there's people who are going to disagree with me. My best answer is that there is no testing of egg quality. Other than if you call checking your birth certificate, meaning the only factor that we know of that correlates consistently systematically and well with egg quality is the age of the woman.


And I'm a bit of a reductionist when it comes to egg quality, because I think the most useful, because ultimately most accurate way of thinking about it is, I think I said this before, but egg quality is really the percentage of your eggs that are going to be healthy ones versus the percentage of your eggs that are going to be, or that are, that are not healthy ones, which is to say egg quality is not a mystical how great your eggs are how strong they are, how healthy they are, or how capable they are.


And the deterioration in egg quality is because eggs are not produced, right? It's not like you get them from the market and they're fresh and you put them on the counter. Hopefully you plan to hopefully eat them, I guess. And then every day in slow motion, they're spoiling, right? Like every day, they're a little softer and a little wrinkles, and they get a brown spot.


Eventually they're just not worth eating because they just spoiled over the course of a few days or weeks or whatever individual eggs, or I should say the eggs in general are not all getting a little worse every day as women gets older, what's happening is that as a woman gets older, individual eggs are going to become aneuploid eggs, which means exit have the wrong amount of DNA.


And so one by one, the percentage of your eggs that are bad ones (aneuploid) versus the percentage that are genetically intact (euploid) and have an intact amount of DNA, that is what's changing slowly. It's a slowly changing math problem. It's not that the eggs are wrinkling and getting weaker and spoiling and slow motion. So in other words, if we say that a 40-year-old doesn't have good egg quality, which is somewhat true, what I would say that means is that a 40-year-old is expected to have a high percentage or relatively high percentage of abnormal eggs. And at 40 it's probably about 75:25. The 25% of our eggs that are normal, that are genetically intact, are almost certainly just as capable of making healthy babies as the 25-year-old's healthy eggs are.


It's just that at age 25, it's something like 90% of the eggs are good and only 10% are bad. At the age 40 it's 75% are bad and only 25% percent are good. So it's just a matter of how available they are, how well-represented they are and the population of eggs that are inside the woman's ovaries. But the good ones are good and the bad ones are bad. And then it's actually sort of in some way, independent of age and why I'm such a strong believer in emphasizing this is because if you think the other models, right, that eggs spoil in slow motion and the wrinkling slowly, then the math doesn't start, or the whole story doesn't make sense, right? How does anyone in their forties ever get pregnant? If their eggs are mostly spoiled by that? Right? Cause you'd say at 40 or older, your eggs are mostly gone.


And so it would be weird that you can take a wrinkled, weak egg and turn into a healthy baby. It shouldn't make sense. The other model that I think is the right one (which I'm talking about) is that it's harder to get pregnant because you need to find a healthy egg and most of what you're going to get are bad ones. But once you find a good one, you're in good shape. And that's what we see when we do fertility treatments is that women in their 40s, it's harder to get them pregnant because more of the eggs that we work with are bad ones. But if we can work with more of them, we will find, usually, a good one. And then we can have success. Or going back to the other conversation, how it connects is that a 40-year-old who does IVF and gets five eggs has a low chance of success with IVF, a 40-year-old who was unusually lucky and has a high AMH and gets 20 eggs has a much better, not a guarantee, but a much higher success rate with one IVF attempt.


So again, it's not that the 40-year-olds nature makes her eggs worse because if that were the case, it shouldn't matter how many yet, but rather it's a math problem. We just have to find healthy ones. And if we get to work with a larger denominator where we're more likely to find some good ones in the numerator, so it just takes one good egg and it's easier or harder to find that good egg depending on age.


Amy:

Right. Okay. So the next question is: is there any way...to reverse that clock and to create a higher percentage of good eggs left? You know, everyone's talking about what supplement do I take and how do I increase egg quality? Is it purely the older you get the worse it gets and that's that's biology? Is there anything women can do?


Dr. Klein:

So that's a good question. That one I don't have a great answer for. I guess my best answer is I think that in my personal and humble opinion, I think the majority of that story is something that is not controllable. Meaning I think probably at least 80-90% of what is going to be driving the availability of healthy eggs is just age. And there's not a whole lot that anyone can do to change that.


I think around the periphery, maybe in the 10 or 20% aspect of that story, most things that drive towards overall wellness are also loosely slash indirectly going to be connected to fertility wellness, which is to say, if you eat right, sleep right, get a decent amount of exercise, keep your stress levels low — that's all good stuff. And it's undeniable that if you held everything else equal and you took a hundred women who are doing all that good stuff and are in a healthy place generally versus a hundred women who have the same age who are not healthy people, you do have higher pregnancy rates in the healthy population because again, in a secondary, but also real way, overall health supports fertility health and that's undeniable.


So I think it is important for me to emphasize that even though I have this reductionist view of egg quality and it's a math problem, I also still in the same breath would say that doesn't mean that health is unimportant for fertility. I think general health is very important. That's very important. I think it's important for fertility.


Where it gets a little bit fuzzier and is taking supplements, right? Like does doing targeted things like acupuncture or meditation or you know, those things help? I think I try to rely on the science that's available and the science starts to get a little bit less clear, that you can literally pop a pill of some sort every day, and that's gonna move the needle in a measurable way on your egg quality. 


I wouldn't say that's not true, but I'm not sure that is true. I don't think there's one pill that does that. So I don't routinely recommend supplements to my patients, but some of the common ones like antioxidants, coenzyme, and Q10. When patients ask me, which is basically every day, I say there's not enough science for me to routinely tell you to go out and spend money and take those things. But if you've read about them and you feel like it's worth a shot, I wouldn't tell you not to take them. I'm sort of a little bit neutral on that.


Amy:

I 100% percent agree. I think you can't really control the rate at which your eggs’ DNA goes bad. But we always like to say that: you have a decreasing chance that every egg that's going to come out is to be a good one, so you should prepare your body for when that good one does come. And that's increasing ovulation quality, which is supporting the hormones and the uterus. Like, do you have enough estrogen? Do you have enough progesterone? Are you not stressed out or are your cortisol levels too high?


If you think about the chicken egg, in a chicken egg you have all of this yoke  and structures that support the thing that becomes the embryo. And so you can't really change the embryo — that genetic component in there — but you can change the support structure.


Dr. Klein:

I think that's great. I mean it’s simple, but that's exactly the point. You can create the right framework for when the opportunities come and they will come more frequently or less frequently (again, it has an age factor), but they do come in. So you want to sort of be ready with preparing the right context to give yourself the best chance. Absolutely.


Amy:

Yeah. I mean, fertility is so complicated.


Dr. Klein:

Yep. You know patients are endlessly impressive with their dedication. We torture people with a lot of stuff on the medical side for sure. And people do a lot of their homework and are always asking good questions. We try to do our best and we lean on the patients a lot to be able to tolerate what we're asking them to do because there are so many components.


Amy:

So, this is a really good question. Do you like it when patients come in and they're like, “Okay, I've been charting my temperature and I'm taking ovulation tests and Proov tests, and I know this and that.” Do you think that helps you treat that woman better?


Dr. Klein:

Yeah, I think that's sort of an easy one. The answer's yes. I mean, that's a little bit personal style and my personal style is that I like being engaged with the patient. I like having a partner in the process. So, I think knowing more now, literally bringing more information to the table from the patient's side and giving the doctor more detail and concrete material to work with, for me, I think is both more fun, but also I do think it's helpful. I would say is for anyone who's having a doctor involved with their efforts at getting pregnant, I would encourage you to be proactive about your own body, about your own care, and about your choices.


I do think that at the same time, you want to ultimately say that the doctor that I'm talking to knows what they're talking about and I trust them. So I think it's psychologically hard because I have patients that — thank God too many — but who ultimately will still question things that I say. Here's what I think I'm never sure, right? We can't be! You can't be sure about what's going to work unless you're a prophet, but taking everything into account is the best path. I think psychologically it's hard. You have to get a captain of your ship, meaning if you're doing the medical way, you need to have a doctor who you feel comfortable enough to be that captain of that ship because someone has to lead the way. I think it's a balance of being engaged in and an active participant in the conversation. But at the same time being okay with there being someone who's the captain of your ship, helping when push comes to shove, giving you advice. I think we should do X or Y or Z. So that's my way of thinking about that balance of engagement.


Amy Beckley:

Yeah, absolutely. We always say you're the expert in yourself and the doctor's the expert in medical practice, and you need both components to work together to get the best treatment possible. So it's like if they're butting heads between the patient and the doctor, that's not a good match, go find, you know —


Dr. Klein:

The simple answer is maybe that's not the right fit, but you guys have a lot of good sayings.


Amy Beckley:

We really try to help educate them. We want them to be the informed patient that — 


Dr. Klein:

You're the expert in you. I’m actually going to borrow that, I think--


Amy Beckley:

You’re the expert in you and I’m the expert in medicine. We’ve got to work together now. 


Dr. Klein:

Yeah, I’ve got to use that.


Amy Beckley:

Yeah. Now okay. So I have a couple more minutes and I just saw this study that kind of blew my mind. Since you're like the egg freezing expert, there was this study that said people that freeze their eggs always have to do frozen embryo transfers (FET). Right? That's because they frozen her eggs and then they're coming back five years later, right?


Dr. Klein: 

Sort of, yeah. 


Amy Beckley: 

In the field do you do a natural FET or a hormone induced—


Dr. Klein:

Synthetic, yeah. 


Amy Beckley: 

I don't know what the proper term is. Right.


Dr. Klein:

We call it synthetic or programmed.


Amy Beckley:

Yeah. So there's this trend that these women are wanting these natural FETs. Do you see that in your practice?


Dr. Klein:

A little bit, I mean, there's so much pull in society towards natural, which again is not necessarily a bad thing.


Amy Beckley:

We advocate for natural solutions to increase balanced hormones and stuff like that. So this guy presented this data and there was like five different papers. And I can send these to you later if you want them, if you’re interested, but he did all this research on luteal phase defects and not enough progesterone in a natural FET cycle. It was so fascinating.


Some of these studies had up to 75% of the women did not have enough progesterone to support that embryo that they were implanting. And so it was like the case of supplementing with progesterone in a natural FET. And the reason that it kind of blew my mind is it was like these aren't women that are coming to you just doing IVF it's like low progesterone, progesterone issues, like poor ovulation quality that’s prevalent, right?


Dr. Klein:

You're close to being an infertile woman who just had frozen eggs and now you’re using them and getting a picture of their natural biology basically without manipulating it from a luteal phase standpoint. That is interesting. And I definitely, I would want to see details cause that, that is interesting.


I will say that when you do have people who want to do natural FETs and it's actually the data that's out there would say it's pretty equivalent in success. So I don't have a problem with that. But, maybe I cheat because I actually do something that progesterone more gently, but in other words, in a true, synthetic or programmed FET, we usually use progesterone injections plus or minus some vaginal suppositories.


So in a natural I don't use injections, but I still advise using suppository, actually twice a day, progesterone suppositories. So we're always kind of just covering or hedging on the progesterone. Maybe proactively — smartly — in light of what you're talking about, because there's going to be a lot of women out there who even in a natural cycle have a luteal phase deficiency. So—


Amy Beckley:

The luteal phase deficiency, the low progesterone, is so, so common, especially when you're getting a little bit older and closer to menopause—


Dr. Klein:

I was going to ask you that because Proov would be — is there, I don't know off the top of my head if there's good data to correlate luteal phase deficiency and progesterone deficiency. And I mean, I'm sure at really advanced ages there is but women who are 30 versus 35 versus 40, who are still fully reproductively functional. But is it something that happens to perimenopausal women, is it going to plummet or is it a slow decline or the incidents a slow rise or is it something that's sort of similar for 30 year olds and 35 year olds and then kind of just takes us to change in the forties? I'm not sure.


Amy Beckley:

I wouldn't say a steep change. There is a trend towards the older you are the less progesterone you have. And so our testing protocol is 7 to 10 days [after peak fertility]. And if we see those levels drop before 10 days after their peak fertility date, we say you could have a problem with ovulation that makes it a little bit more difficult to conceive and that's how we message it.


But we do see that the older the women are the more they tend to drop down at day 9 and 10 and have this deficiency. But diet and lifestyle 100% percent makes a difference. Those supplements that people are buying on Amazon might not help with egg quality, but they certainly help with hormone balancing and those kind of things.


Dr. Klein:

That's great.


Amy Beckley:

Cool, cool. Well, awesome. I thought about that. I saw this study probably—


Dr. Klein:

Presentations or no.


Amy Beckley:

It was like some European guy and he was basically working for a company that was testing a sub-Q version of progesterone. So not an oil, but a sub-Q and he was showing that you get the same amount of efficacy as the oil but it's not as hard as—


Dr. Klein:

That would be a good product, by the way, if there would be a sub-Q version.


Amy Beckley:

It exists, I'll find the papers and I'll send them to you. But it was very, very cool. It was like, wow, you know, all these progesterone studies are done under the context of IVF and FET and those kinds of things, but it was a natural cycle. So this is a woman that like—


Dr. Klein:

Just to have a regular, a good cycle. Yeah, yeah—


Amy Beckley:

Yeah. Cool. All right. Well, thank you, I appreciate it.


Dr. Klein:

Yeah, I guess you said it's going to be edited or whatever, if you want me to look at it, I mean, I'm not too worried about anything that went on, so I don't think I'll have anything too much to say, but it's just fun. And I think it's a cool thing. So thank you for inviting me and I guess let me know.


Amy Beckley:

All right. Awesome. Thanks so much.


Dr. Klein:

Nice to talk and nice to put the face and the voice together. One day, it'll all come into light.