Maggie McKay (Host): Welcome to Fertile Edge, a podcast from the Reproductive Science Center of the San Francisco Bay Area. I'm your host, Maggie McKay. Today we'll discuss GLP-1 medication with Reproductive Endocrinologist, Dr. Ravi Agarwal. Thank you so much for being here today.

Ravi Agarwal, MD: Pleasure to be here.

Host: There is so much in the news and just things you hear from your friends about GLP-1 medications. So let's just start with what are they and how do they work?

Ravi Agarwal, MD: Yeah. I think that this is a very important and increasingly relevant topic. I think the popularity of GLP-1 agonists is, as you alluded to spreading and now with how easily accessible they are, I think it's really important to discuss the benefits, their cons, what they're all about. Almost very basically GLP-1 agonists stands for glucagon-like peptides, which are actually a natural compound produced in our body whenever we eat a meal. And it has receptors in both our gut and in our brain. And it's aimed at reducing satiety, slowing down food metabolism, and actually making our bodies more sensitive to insulin. And by taking these medications, it can basically create all those things, make all those things happen, reduce how much we eat, and therefore help us lose weight.

And what I think that's so fascinating is that it actually proves that patients who are obese, patients who have a higher BMI, there actually is some physiologic hormonal basis to that, and this medication directly targets that. So for all those patients who are just so frustrated with them, you know, I'm busting my butt in the gym every day and I'm eating well, but I'm still not losing weight, I think this medication is perfect for them because it really fits that missing piece.

Host: So I often think about fertility and medications, especially new ones, and how it might affect somebody who is wanting to get pregnant down the line. How might GLP-1s influence fertility directly or maybe indirectly, especially in people with PCOS.

Ravi Agarwal, MD: So I think this is just asking a larger question of how is weight related to fertility and what disadvantage does having a higher BMI or being overweight cause to fertility. And we know from a lot of evidence that being overweight does impact your chance of getting pregnant, mainly by causing what we call ovulatory dysfunction or makes your ovulation irregular, difficult to time, difficult to predict, and therefore makes getting pregnant difficult.

 I think it also has other effects as well. Being obese could lead to decreased egg quality, decreased embryo quality, can affect the uterus and the environment in which a pregnancy can implant as well. So logically improving your weight, improving those parameters can help you get pregnant as well.

Specifically, so GLP-1 agonists by making you lose weight can correct those things. And I think it's also just important to note as well, that losing weight can make fertility treatment easier. It can make all the, you can make your body respond to medications better. It can make certain procedures easier and less risky for you as well. And I hope this doesn't only apply to a certain number of patients, but a lot of centers will only treat patients that are below a certain BMI mainly for safety reasons. So using a GLP-1 agonist might even not only improve fertility treatment outcomes for you, but make them a possibility in the first place.

Host: Oh, that's very hopeful. That's good to know. Could taking a GLP-1 help regulate cycles or increase chances of ovulating naturally?

Ravi Agarwal, MD: Yeah, absolutely. I think you hear about these ozempic babies all the time, and I think that's the primary way that happens is that when these GLP-1 agonists help patients lose weight and when they otherwise had irregular cycles, irregular periods, now they go back to having regular cycles, and if that was the only thing stopping them from getting pregnant, then problem solved.

Host: That's great. I never thought of the connection between weight and fertility. So is it safe to try to get pregnant while taking a GLP-1, or should a patient stop before trying to conceive?

Ravi Agarwal, MD: Yeah, it's a great question. I think that jury's still out on that one. I think we're still looking at and getting more research as not only GLP-1 agonists are being used more commonly, but also pregnancies are happening more commonly. The party line right now is that we still don't recommend getting pregnant while you're on a GLP-1 agonist.

In fact, we recommend stopping them for about two months before you start trying to conceive. But with that said, we still allow patients, especially patients going through IVF to stay on their GLP-1 agonists while they're going through treatment. And really just when we're like making embryos or actually going through the egg retrieval process, and then only stopping it after patients have reached their ideal weight, they're, they feel like they're at the safest point for pregnancy and then actually attempting an embryo transfer and trying to get pregnant at that point.

Host: Dr. Agarwal, what are the downsides to this medication? Are there any alternatives?

Ravi Agarwal, MD: Yeah, so I think while you're on the medication, the short term actually patients tolerate them very well, which is just adding to, why I them so much. But some patients do have some side effects, mostly GI, some nausea, maybe some constipation. I think the biggest downsides, again, are just this uncertainty regarding pregnancy and having really time when you take the medications relative to when you get pregnant.

And I think another big downside as well is that a lot of the patients, when they stop the medication, the weight comes right back. So I think it's really important to not just while you're on them, to be really scrupulous with the medication, but also really try to create long term habits, good diet, exercise that you can continue even when you're off the medication to keep the weight off and keep enjoying the benefits.

 I also just want to point out that there's nothing magic about the GLP-1 agonists. I think if you can lose weight in any way, then you're going to get the same benefit. You don't have to just be on the GLP agonist to enjoy all the benefits we're talking about undoing the effect of BMI and being overweight on fertility.

Host: And just for people who don't know, we're talking about brands like Ozempic, Wegovy, right? Things like that. Okay.

Ravi Agarwal, MD: Yep. Mounjaro is another common one. And I think another thing to just point out is that not only there's a number, increasing number of medications, but even the ways you can take these medications are expanding as well. Previously it was just an injection, but now patches, pills, all different ways of getting the medication are being implemented as well.

Host: Oh I didn't know that. I thought they were all shots. So I think you did answer this, but I think it's worth repeating again. How long does someone need to be off a GLP-1 before trying to get pregnant? And why? I think you said two months?

Ravi Agarwal, MD: So I think at least semaglutide, which is one of the GLP-1 agonists on the as one of their FDA labels says to be off of it for two months prior to conceiving, but other brands, other medications are a little bit more vague or don't list when you should be off of them by, but I think most doctors would recommend at least two months.

Host: At least. Okay. And why is that?

Ravi Agarwal, MD: Mostly because we just don't know. We don't know the effect of the medications on the metabolism and the gut essentially of a developing baby. So I think until we have more data, more research showing that it's safe, I think it's better to just be off of it before trying to get pregnant.

Host: Is there anything else in closing that you'd like to add?

Ravi Agarwal, MD: You know, I think that I, here we're talking about the benefits of the GLP-1 agonists and the benefits of losing weight in general. But I also want to emphasize that there are many factors to getting pregnant, not just weight and the effects of weight, but age, your egg quantity, your egg quality are probably as important, if not more important than weight. And I think the decision about whether to go on a medication like this and spend time losing weight and enjoying the benefits versus just going straight into some sort of treatment and trying to take other factors into consideration really is a very personalized decision.

And one that you know you should make with your OBGYN, with your infertility doctor. And really there's no one size fits all approach. There are actually some studies that have compared patients who, in the short term compared whether it was beneficial to lose weight for a few months and then start some sort of infertility treatment versus just diving into infertility treatment.

And actually it showed that some patients were at a disadvantage from losing weight in a short time shortly before going to treatment. It did not improve their rates of success with treatment, and it may have even increased the risk of a miscarriage. So I think these medications do need to be used, but even though they have tremendous benefits and do work for some patients, it's not a one size fits all approach.

It's not going to work for everyone. And the decision to start them really should be made with your doctor and really in consideration of your personalized story, your personalized history, your own individual journey thus far. And yeah, it's just one piece of the puzzle.

Host: Yeah. Well, that's so interesting. I learned so much today. Thank you so much for sharing your expertise.

Ravi Agarwal, MD: Of course. Thank you for having me.

Host: Of course. I look forward to doing it again on maybe a deeper dive. That's Dr. Ravi Agarwal. To learn more about healthy weight management and your fertility, visit RSCbayarea.com. That's RSCbayarea.com. If you found this podcast helpful, please share it on your social channels and check out our entire podcast library for topics of interest to you, I'm Maggie McKay. Thanks for listening to Fertile Edge from the Reproductive Science Center of the San Francisco Bay Area.