Ozempic babies? Unpacking fertility, metabolism, and GLP-1 medications
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Welcome to today's episode of Lexicon. I'm Christopher McFadden, contributing writer for Interesting Engineering. Today we're diving into a fascinating conversation with Dr. Ilana Ressler, a leading reproductive endocrinologist at Illume Fertility. Join us as we explore the connection between metabolic health and fertility, uncover the science behind conditions like PCOS, and discuss why medications like Adzempic are making waves in reproductive wellness.

Gift yourself knowledge. RU+, is a premium subscription that unlocks exclusive access to cutting-edge stories, expert insights, and breakthroughs in science, technology, and innovation. Stay ahead with the knowledge that shapes the future. Ilana, thanks for joining us. How are you today? Doing well, thanks. Thanks for having me. Our pleasure. And for our audience's benefit, can you tell us a little bit about yourself, please?

Sure. So I'm Dr. Alana Ressler. I'm a reproductive endocrinologist. I practice in Connecticut and New York at a practice called Allume Fertility.

Fantastic. Brilliant. Get on to our first question then. So, can you briefly explain the relationship between metabolic health and reproductive function, especially in conditions like polycystic ovary syndrome, PCOS for short? Also, could you explain to our audience what that is, what that condition is, please? Sure. So,

Metabolic health and reproductive health actually have a lot to do with each other. Metabolic health can affect many different aspects of someone's health in general.

In terms of just the basics of reproductive health and function, a woman's menstrual cycle is dependent on hormonal signaling that happens between two places in the brain down to the ovary and it feeds back. This is referred to as the hypothalamic pituitary ovarian axis. Yeah.

And if there are any disruptions in this axis, then that can alter or change a woman's normal cycle. If there are changes to that, that can affect ovulation. And the timing of ovulation is very important in terms of timing of conception because ovulation

When a woman ovulates, for example, the egg is only available for a very short window of time, only about 24 hours. And if a woman is having irregular cycles, then she may not know when she's ovulating. She may not be ovulating at all, which can lead to more challenges with fertility and conception. So one of the most common scenarios in which we see this occur is in women with PCOS, polycystic ovary syndrome.

This is actually the most common endocrine condition that affects women of reproductive age, up to about 15% to 20% of women may have it. And it involves several different systems, if you will. It's categorized as a reproductive condition, but it's really much more comprehensive and broad than that. But at the basis in terms of how it's diagnosed, a woman has to meet two of three things. One is having irregular cycles.

meaning outside of the 21 to 35 day window. The second is having elevated hormones called androgens. These are hormones like testosterone or DHEAS, which may by blood work show abnormalities or these

hormones drive symptoms such as acne or excess hair growth called hirsutism or scalp hair thinning. So those symptoms would qualify for that second criteria. And then the third part is having polycystic appearing ovaries on ultrasound, which really just means having a lot of follicles. Follicles are structures that contain eggs. So it's not actually, it doesn't have anything to do with cysts. It's kind of a misnomer. It should really, in my opinion, be called polyfollicular.

syndrome not polycystic because it's really follicles that are in there, not cysts. So if a woman has over a certain number of follicles in her ovary, that means it's like polycystic appearing. So if a woman eats any two of those three, then she has PCOS. And PCOS is associated with metabolic dysfunction, specifically commonly involving glucose and insulin. And so I think we'll get into this a little bit more, but the glucose and insulin function

you know, metabolic disturbances can also play a role and disrupt that ovulation function. So it all kind of feeds together and no one is really clear what comes first, the chicken or the egg. It's all kind of intertwined. So it's not a genetic disorder, then it's a dietary one, a lifestyle. How do I say? It's

So interestingly, there is actually thought to be a genetic component to it. The mode of inheritance isn't exactly clear, but it does tend to run in families. So there is actually likely a genetic component and it is thought to be something that someone's born with. So just like, you know, someone's born with

brown eyes they might be born with PCOS and it's always kind of there in the background now it can be well well managed and someone can be symptom free with it but it always is there you know thought to be there in the background unfortunately there's no cure or way to totally eradicate it all right so you mentioned glucose um presumably you're talking about diabetes then

So, yeah. So glucose rate is sugar. It's in like everything we eat. Right. So let's say someone eats like an apple, then their blood glucose levels start to rise. And normally the pancreas, then there was the response is to send insulin out into the bloodstream to bring that glucose up into other cells. So our blood glucose levels should, you know, maintain within a certain range all the time.

Now, I think of it kind of as a spectrum from like totally normal glucose and insulin metabolism to type 2 diabetes. And there are different changes that can occur along this spectrum. And women with PCOS are at increased risk of having some of those changes occur. And so we evaluate all women with PCOS for those changes. And addressing those aren't only important for like

overall general health, diabetes prevention, things like that. But correcting that could also help with the reproductive piece and may even help cycles become more regular. Gotcha, gotcha. So as someone with type 1 diabetes, which if I recall is you're born with that, with diabetes as a disorder, are you at higher risk of also suffering from PCOS or they're not

related like that? Yeah, that is actually a different type of diabetes than what we're talking about. So type one would be, you're right, something that's usually like more juvenile and onset, like occurs at a younger age, whereas type two is usually later developing. And that's what's more closely associated with PCOS. Okay. All right, then. So it's more your habits that can lead to this syndrome. Yeah.

If you're not genetically born with diabetes, the type two is what you give yourself, right? From your diet, poor diet, et cetera. So it's damage your body with then PCOS. Is that right? Yes. Although there is, you know,

Yes, that is correct. And that lifestyle plays a huge role. So like at the core of managing PCOS is like good nutrition and exercise. That's kind of first line, you know, for everyone with PCOS to really focus on. However, there are still biochemical changes occurring that even I've seen, you know, women who have

super healthy lifestyles, eating very well, very regular exercise, and still may have some of these changes occur because, again, some of this is more at a biochemical level and can't be

totally controlled by lifestyle, although that does play a very critical role. Gotcha. I think that makes sense. Okay, Robin. Okay then, why are GLP-1 receptor agonists, such as a Zempik, becoming so popular? And how do they specifically impact metabolic health? It might be useful to explain what GLP-1 receptor agonists are.

So yeah, GLP-1 receptor agonists or glucagon-like peptide 1 receptor agonists. That's a long title, hence referred to commonly as GLP-1s. They are a class of medications that were originally designed to treat diabetes and

So agonist means like acting like. So the medication acts like glucagon. And it works through several different mechanisms. So one mechanism is to improve insulin secretion. So to help the pancreas with the efficiency of making the insulin secretion.

Another mechanism is to slow gastric emptying. So make it the, it's slower, the food to move through the stomach and the GI system. So it has more time to absorb. It lowers glucagon secretion. So glucagon is made from the pancreas and tells the liver to send glucose into the blood. So it, yeah.

Basically helps keep glucose levels lower in that way. And it also promotes a feeling of satiety, like people will feel more full after they eat. So they're likely to actually consume less when on the medication. So it works by several different mechanisms and they gained popularity.

you know, a lot of popularity recently, I think in part from celebrity use, media, you know, promotion of them. So now they're being much more commonly used. And, but the, the, again, the original intent was to help with treating things like insulin resistance and diabetes. Okay. Well, so it's being used to treat weight then, is it for weight loss? Yes.

Right. So it's been seen that weight loss is definitely promoted by these medications. And some of them do have approval for that and or like, you know, specific FDA approval for weight loss. So they're being commonly used as weight loss agents. There's another medication called metformin that has been commonly used for a long time to help with insulin resistance.

But with metformin, weight loss can definitely occur, but seems to not occur as readily as it does with the GLP-1s. So many people have begun using those. All right. It's not recommended if your metabolic system is perfect. But if you're not type 2 diabetic, you shouldn't really use this, I presume. You wouldn't be advisable.

Right. Although for some with obesity, it has been approved for use for weight loss specifically. Right. Okay. Fair enough then. So are there potential fertility implications for patients using medications like a Zempik or other GLP-1 agonists, as you've mentioned? Sure. So, yeah.

The GLP-1 receptor agonists have not been approved for use in pregnancy. So while they can promote overall general health weight loss, which can then in turn, if we're correcting insulin resistance, if we're promoting weight loss, these can lead to help with cycle regulation, which can then increase

help with conception and fertility. However, they're recommended to stop eight weeks prior to conception. So for our patients who are undergoing fertility treatments, we don't have them at the same time using GLP-1. So usually we'll say, okay, if someone's interested in using them and, you know,

improving their overall health prior to conception, which is always a good idea, right? We want a woman to be really at her healthiest when entering into a pregnancy to reduce risk of things like gestational diabetes, gestational hypertension, and other complications. So we might say, okay, let's take the next six months, maybe focus on lifestyle, perhaps go on a GLP-1, see how much progress we can make over the next six months, but then we're

When we're ready, we're going to stop that medication and then start the fertility treatments. So we don't, we aren't actively trying to conceive, you know, when on one of those medications. Okay. I was going to say, how can you plan eight weeks? Right. I know. Well, that's that, you know, can be, timing is, is tricky. However, you know, for women undergoing fertility treatments, such as like ovulation induction or with intrauterine insemination or IVF,

You know, if we're coming up on an embryo transfer, for example, where we're going to be putting an embryo in the uterus, we know that prior to that time, that medication needs to be stopped. And so it is recommended to use contraception while on the medications. There is this phenomenon of like ozempic babies or what, you know, does it help women to get pregnant? And really, I think

What's happening is women who may not have been ovulating before with the, you know, with the improvements that the medication is bringing on, that might be helping them to ovulate more regularly and they might be more likely to conceive while on the medication than not. So it is recommended to avoid pregnancy while taking the medication. Okay. I suppose, you know, but it's not, is there any risk to a fetus from if they were taking a Zempik?

whilst pregnant? Do we know? So no known risks that I'm aware of. However, it is difficult to study medications basically for safety in pregnancy because essentially the best type of study, a randomized control trial can't be done with medications in pregnancy. You can't say, okay, we don't know what the effects are. Half of you take it, half of you don't, and we'll see what happens, right? That's unethical. So most data in regard to medication and like,

Pregnancy safety has to do with animal studies and with retrospective data. So I'm not aware of any known harm, but it is not proven safe in pregnancy. That's fair. You don't want to take any risks, really. That's fair enough. Okay, so what makes PCOS such a complex condition to treat? And how has recent technology or research influenced new treatment strategies? Okay.

So it is a complex condition because it's, you know, I think of it really as a condition. It's not like the same disease that affects everyone. So

So meaning a woman with PCOS, if we looked at like 10 women all with PCOS, they all might have a different experience with it in terms of how they look, what their symptoms are. And even if we take one woman from that line and look at her over the course of her lifetime, her symptoms may change over time. For example, like cycles might be regular and then at a certain point become less regular. It doesn't mean they will always remain that way. They could change.

you know, go back to being more regular. Symptoms like acne, hair growth, these can kind of, you know, improve and worsen. So that's what makes it, there's not a single like magic bullet or treatment that can kind of resolve all of the associated issues. So the way I approach treating PCOS is to treat the symptoms. So I always talk to a patient about what is

bothersome to you. Like, what really are our goals? Is someone trying to conceive or not? Are their cycles regular or not? What sort of skin or hair issues are they having? And then we look at the metabolic health as well, right? So we do something called a two-hour glucose tolerance test to assess our

really the dynamics of someone's insulin and glucose metabolism and then take those results to come up with an individualized plan for everyone because there really is not a one-size-fits-all with this condition and we really have to look at each individual.

So in terms of, you know, advances, I think the condition, while obviously it's been around for a very long time, it is gaining more like recognition and awareness. There's September is actually PCOS Awareness Month now. And so I think with increasing, you know, focus on it and research, hopefully more, you

you know, specific treatments will be available. But at this time, it's really, again, kind of looking at the individual symptoms and targeting those in terms of treatment approach. Gotcha. And is this condition sort of reversible through exercise? And if you saw your diet out, regular exercise, because I think you can bevers

I think I'm right. You can reverse type 2 diabetes, can't you? By actually regularly exercising. Is that right? Yes, yes. Lifestyle is a big role in this. I wouldn't say that you can totally eliminate it by lifestyle, but you can...

manage it such that someone is not having symptoms, right? So yes, it's very important to focus on nutrition and exercise in terms of those specifically, there isn't like a specific diet or a specific exercise regimen, right?

I always caution there's a lot of good and bad information online in regard to that. So just be cautious with what the sources are. But in terms of diet, like the general recommendation is good balance, right? It's not necessary to like eliminate all sugar, all carbs, all

all dairy, soy gluten, et cetera. I think there are some misconceptions about that, but really good balance, like a Mediterranean type of diet. But we don't want to over-restrict and eliminate all of a certain food group. And then in terms of exercise, generally we recommend like American Heart Association goal of 30 to 60 minutes, five days a week of some sort of movement. It can be high intensity, low intensity,

I recommend diversifying it and not doing the same thing every day and also finding things that someone enjoys to do because if you don't like doing it, you'll never do it. Yep. Kind of. Okay, that's fair enough. Okay, and could GLP-1 receptor agonists become a standard part of treatment protocols for metabolic diseases linked to fertility issues? Why or why not?

Yeah. So I think, again, they can be thought of as an approach, as a useful tool for improvement of metabolic health prior to conception. At this point, they can't be used during fertility treatments or during pregnancy. But there are many specialized centers now. There are metabolic weight loss centers with progesterone.

primarily medical endocrinologists who have certifications in obesity medicine. And they...

as I like to say, have a lot of tools in their tool belt, right, to help with someone's metabolic health. So often we work hand in hand. I'm a reproductive endocrinologist, so we focus more on the fertility and the reproductive piece. So we may, you know, refer a patient to one of those metabolic weight loss centers to really work, you know, in tandem with us for improving overall metabolic health outcomes.

you know, prior to and even in between having children, right? A lot of women, you know, gain weight during pregnancy. That's a normal part of pregnancy. There is normal weight loss following. Some women have more of a challenge losing the weight afterwards and may consider going on one of the GLP-1s, you know, in between pregnancies to help bring them back down to their baseline weight before embarking on their next pregnancy. Okay. You wouldn't recommend...

sort of liposuction stuff like that presumably after pregnancy right yeah let the body do its thing yeah fair enough um by giving you expertise uh what are some common misconceptions about weight management medications uh and their use in reproductive health if there are any um

So specifically pertaining to reproductive health, I think, again, just to be clear that the intended use is prior to conception, not during. And

And also just the awareness, again, as mentioned before, of the increased likelihood potentially of conception while on the medication. So just being cognizant of that and avoiding pregnancy while on the medication. I think also it's important to recognize that

While weight loss occurs on the medication, there is a typical rebound weight gain when coming off of it. And we are going to be discontinuing the medications when trying, you know,

to conceive while undergoing the fertility treatment. So it would be typical that some of the weight loss then comes, you know, is gained back eventually. Okay. And this PCL, I forgot to ask, as long as a woman is fertile, she could potentially be at risk of this condition. Is that right? Or is it more younger women than older women near their menopause?

Like what age group is at risk of PCOS? That's a pretty better way of asking it, yes. Sorry. So it is thought to be something that a woman is born with and will have throughout her lifetime. It can be a little bit more challenging to diagnose at a young age, in adolescence, because

A period may be irregular for the first year, like after a young woman gets a period, it may be regular for a year. But after a year, it really should regulate. So it is a red flag if a girl, for example, gets her period at age 12. Now she's 15. She's still having irregular cycles. That is not normal.

But the other criteria used to diagnose PCOS, for example, the symptoms like acne, right? Many teens have acne, so it might not be so unusual for a 15-year-old to also have acne. And then the third part, looking at the ovaries and counting the follicles,

A young woman should have also a lot of follicles. So my point is it can be a little bit more challenging at a very young age to diagnose. It's still good to seek evaluation if there's concern for it because this, you know, I always say I don't get caught up in the label. Like I'm not so worried about labeling someone as PCOS or not because at the end of the day, we're managing the symptoms.

So for that young woman, whether or not she's labeled as PCOS, we want to help her regulate her cycles, help her clear her acne and so on. And often as a woman gets older, it might become a little bit more obvious whether actually she has PCOS or not. But if a woman has it, even at like perimenopause, something like that, she'll still have it. But it might not be as relevant or causing as many symptoms when going into older age. That makes sense. Fair enough. Yeah.

Okay, what future technologies or scientific breakthroughs in reproductive endocrinology are you most excited about? So this is, you know, reproductive endocrinology and infertility is really a pretty young field of medicine. Like if you think about the history of IVF, right, the first baby born from that technology was born in 1978.

So we are not talking about like centuries of, you know, reproductive medicine, at least in that form of in the form of IBF. It's it's come a very long way in the past, you know, 40 plus years in terms of the technology. IBF has become a lot more successful and efficient. But I do still think there's there's still a ways to go in terms of improvements with outcome. Really, the

one of the core challenges that all of us face as reproductive endocrinologists and for patients, of course, is

What happens with the ovaries as we age, right? We're born with a set supply so that egg quantity and quality is going down as we get older. And other than the ability to take eggs out and freeze them, which maintains their current quality at the time they were taken out, we really don't know how to slow that aging process in terms of the eggs and the ovaries. So I think if, you know, that is a huge area for potential advancement and if we're

if discovered, could help so many women with their fertility issues. A bit of a love topic. Do we understand why women have so many, have a limited number of gametes, whereas men can just produce them after death? Do we know why that is or how that happened?

No, I mean, I guess I don't know like evolutionarily why or, you know, it's just it's how we were born essentially. But it is true that men are continuously making, you know, new sperm throughout their lives, whereas females are born with a finite number. That number was actually its highest like

when a girl was in her mother's uterus, right? Like in development, she had about six or 7 million eggs by the time someone's born, it's like one or 2 million puberty, half a million. And they're just rapidly lost throughout our life until menopause. That's when they're gone. And that average age in the U S is 51, but starting really in our mid thirties and sometimes earlier for some women, the changes in terms of quantity and quality really start to be noticeable. So yeah,

Yeah, it's a struggle for many in terms of overcoming that aging process of the eggs. Yeah, just one of those mysteries of life, that's fairness. Okay, with the increasing popularity of Zempik, as we mentioned, how do you see patient care changing, particularly with regards to endocrinology and fertility clinics?

Um, so I think as it becomes more accessible, there's still some challenges for patients in terms of access to it. The metabolic weight loss centers, for example, can have very long wait lists to get into even up to a year or something to be seen by one of those specialists. Insurances have pretty stringent criteria for many in terms of coverage for the medication. So

A lot of people aren't able to access it due to some of those limitations. So I think as more...

you know, of those specialists are around or even more primary care physicians who are starting to prescribe it as well as, um, perhaps a lower cost, you know, option may make it more accessible, um, to more patients because if it's not covered by insurance, it could be cost prohibitive out of pocket for some. Yeah. Yeah. That makes sense. Yeah. Um,

Last question. What's one key message or piece of advice you wish more people understood about metabolic health and reproductive wellness? So I think it's important as we started the conversation with knowing that they are interrelated and there is an importance of

for fertility success and pregnancy success and having a healthy baby with paying attention to metabolic health and really ideally optimizing it prior to conception. So I think for women who are thinking about their timeline in which they want to try to conceive,

focusing on good nutrition, on routine exercise, you know, again, being as healthy as possible, leading into that will only help them with their success. Absolutely. Definitely. So my wife, she was very good at training diets and our charts. Perfect. That's all my questions. Is there anything else you'd like to add that we haven't talked about that feels important?

I think that the only other message maybe is if someone is having difficulty conceiving or is worried that they may have difficulty conceiving, it is important to go sooner rather than later to see a reproductive endocrinologist because...

As we talked about earlier, like time is not on the side of fertility. So it's better to be proactive in terms of seeking assistance rather than waiting as the years go by and then getting help because things can change very quickly over a short amount of time in terms of, you know, female reproductive health. Excellent advice. With that then, thank you for your time, Ilana. That was fascinating. Okay. Thank you so much.

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