Season 7, Episode 5: Supporting Longevity in Fertility with Dr. Kalea Wattles

Evelyne: Me too. In this episode, we explore how Dr. Kalea applies a functional medicine lens to fertility, highlighting the clinical relevance of mitochondrial health, oxidative stress, inflammaging, and more when it comes to female and male fertility. We’ll talk about the narrative of the fertility cliff, how to assess diminished ovarian reserve even in patients in their 20s, how to interpret AMH values in context. You’ll get actionable insights into preconception care protocols, fertility focus, lab interpretation, and how to personalize support for patients preparing for IVF or egg freezing as well.

So Kalea, to start us off, what is lighting you up this week?

Dr. Kalea Wattles: Such a good question. And it’s actually really relevant to what I think we’ll talk about on the show today. And I don’t know if your social media algorithm looks like mine, but my social media this week is full of all of these posts about some new CDC data that we have that showed that for the first time, women over 40 are having more babies than women in their teens.

Evelyne: I saw that!

Dr. Kalea Wattles: Yeah. It’s everywhere. I think it’s really reflecting this cultural shift where we’re kind of adjusting our timeline, our reproductive timeline to fit our needs and our hopes and our dreams and how we want to experience our life. And this is my time to shine, because my great clinical love is reproductive longevity. And so when I see more and more women are starting their families into their 40s, this is the absolute perfect time to employ all these tools that I know we’ll talk about on the show today to support our cellular health, make sure that our lifestyle factors are locked in, and really do everything we can to support longevity in our fertility, so that we can also have robust, abundant health to enjoy that family that we’ve worked so hard for. So I was just so excited that this feels like a real opportunity to do what I love to do.

Evelyne: That’s amazing. Thank you for sharing. And you’ve actually focused on fertility your entire clinical career, right? So you told me that you had babies when you were in school to become an MD. So tell me more about that.

Dr. Kalea Wattles: Yeah. I mean, people always ask, oh, can we talk about your journey to motherhood while you were in school? And I always tell people, I can’t recommend it, really. It was the path that I chose. So halfway through my MD program, I had my first baby. And that entrance into motherhood was so special and so sacred.

And I realized I desperately want this feeling for anyone else who wants it. And it was such I mean, it was such a perfect time in the middle of my training when everybody’s figuring themselves out and where you want to go and where you want to focus. And it felt so aligned and so clear to me, and it gave me the opportunity to really spend the last half of my MD training focused on fertility and reproductive health. So for me, that meant I was cold calling the IVF clinics in our area. And I’m in Seattle. We’re really lucky to have some wonderful fertility clinics in the area, but I just reached out and said, listen, I know I’m not a traditional OBGYN student, but please can I come and be in the clinic with you and watch what you do and see how what I do could complement and enhance what you’re doing?

And I was so fortunate that three clinics said, yes, they let me come. And so I was able to sit in with the reproductive endocrinologist through their intake, through, you know, in the operating room. We were doing IUIs, we were doing embryo transfers, and it was so amazing. And I think one of those moments where you really can see your purpose in what you’re doing.

And I knew that I could help people get pregnant on their own. I could help them take charge of their fertility if they were moving on to IUI or IVF, I could help them get ready and improve outcomes and everybody wins in that scenario, right? So it was just a really special, a really special sign from the universe that this is the work that I was supposed to do. And I ended up having another baby in the last year of my program. So there was just a very maternal time all around.

Evelyne: I love that, and I love that you were able to do that while you were a student. What a truly unique experience. And also to even forge those connections with providers in allopathic medicine.

Dr. Kalea Wattles: Absolutely. And when you’re a student, it’s a great opportunity because you’re in the zone of learning. People expect you to ask questions. They expect you to be curious. And so it’s just a great opportunity to pick the brain of everyone who you consider a mentor and a teacher.

And then after graduation, I was able to go on and do training through the Institute for Functional Medicine. And I think this layering on of the functional medicine model, or what we might call systems medicine onto my natural therapeutics, I always tell people functional medicine is, we call it an operating system, right? It’s a way of thinking. And so it allowed me to take these really complex cases, because who’s not complex? Humans are all complex. There’s not a single case that simple and organize it into a framework where I could really see what’s happening in each body system, how these body systems are communicating, and then use my tools from naturopathic medicine to really understand what’s driving dysfunction in someone’s health. So it felt like a really beautiful combination.

Evelyne: Yeah. And let’s get into some of that. So your passion, you have many passions in this field. But around ovarian aging, I’d love to get into that more. So what are some of the things that you are assessing, like markers, clinical patterns? What’s the latest and greatest when it comes to ovarian reserve that maybe we’re not even talking about enough?

Dr. Kalea Wattles: Well, I think maybe before we dive into all the things that someone like me looks at, should we address AMH, the elephant in the room?

Evelyne: Sure. We can start with that if you’d like. Sure.

Dr. Kalea Wattles: I just I feel like whenever we, whenever we’re talking about ovarian reserve, a people are immediately going to AMH. That’s what’s out there. That’s what everyone thinks about. That’s what everyone’s having tested and searching on the internet to see how they can get this in the mail. They can do it at home. And so I think it’s really helpful if we start to set the scene about what AMH is and what it is not, because I will say this one biomarker, I think causes more anxiety to my patients than any other single biomarker.

I mean, it feels really loaded. And when you read about it, it seems like this is the make-or-break thing for your fertility, and you have to base all of your decisions off of this marker. So, I hope I can ease listeners minds about this. But so AMH, what we know what it is, it’s a hormone produced by granulosa cells in the ovary, which granulosa cells, for the record, are my favorite cell. I love to talk about them. They are the helper cells that surround our egg cells within the ovary. So they’re collecting signals from the brain. They are essentially nurturing our egg cells. So AMH is produced by granulosa cells. That’s why we use it as an indirect marker of ovarian reserve. The more eggs we have, the more granulosa cells we have, the more AMH that we’ll produce. So that’s what it is.

It’s really just one piece of information to see how many follicles are active at any point in time. It can change. I know people say it can’t change. We see a change all the time. It is one piece of information, and it’s helpful for us to think about how someone will respond to their fertility meds if they need them for IVF or egg freezing, so it is valuable. There is a lot of value. It helps us to make clinical decisions in the right setting.

What AMH is not, it is not our destiny. It is not proof that we cannot get pregnant. It is not a guarantee that we won’t have a baby. And most importantly, it’s not a measure of egg quality. So we cannot make, you know, judgment calls about the quality of someone’s eggs based on their AMH. So that is historically the marker we have used most commonly to assess ovarian reserve. We have to interpret it in the context of someone’s menstrual cycle, regularity, everything else they have going on their age. And we have to be really careful to create a container that is very clear about what information AMH offers us and doesn’t turn into a really scary, fearmongering conversation. So that’s a good starting place, right?

Evelyne: Yeah. Do you find as a clinician and for other practitioners listening, I don’t know how common it is that somebody actually comes to you because they did one of these at home fertility kits, got their AMH tested, and then they freaked out? Do you find that that’s the case a lot.

Dr. Kalea Wattles: Absolutely. Happens all the time. There’s several direct to consumer options for AMH. It’s usually a finger prick. They send it in, they’ll get a report back, and there’s not really a lot of information about what it means. It’s just a number, right. You get your PDF back and you open your email and you see that and immediately your heart sinks and you’re Googling. And then people come into the office and they are honestly devastated. They’ve probably been spiraling. They are convinced that they’re never going to have a baby now. And so we have to do some unwinding.

But it’s just it’s such a shame to me because I think then the nervous system is really holding on to something that’s so fearful and so negative. So I try to dissuade my patients and clients from using some of this testing that doesn’t allow them to have a conversation with someone like me who can put it into context, certainly valuable as part of a larger conversation, but we have to also look at some other hormones.

We can talk about that FSH, LH, estradiol, those are all important. And then further looking at, well, what are the things that are impacting the health of our eggs as well. So, I always want to do some unwinding when we have this single biomarker that is very scary.

Evelyne: So when it comes to some of the other things that you’re looking at, maybe ovarian reserve is not even the right word to use, but egg quality and all of those things. What are the markers you’re looking at in relation to, say, oxidative stress, inflammation and all of that?

Dr. Kalea Wattles: Yeah. So it’s kind of a tiered approach that we’re going to get here. Because I always like to start with the labs that are going to be quite easy to get from just a simple blood draw. Any of the big national labs will have these. So on cycle day three, I’m typically doing quite a bit of hormone testing on cycle day three, because when we look at studies that are mostly out of the IVF setting for ovarian reserve specifically, I know we’re going to expand from here, but, we have to look at FSH and estradiol on cycle day three. I also add luteinizing hormone or LH on there because I like to look at an LH to FSH ratio. So let me I’ll kind of dive deeper into all of these really quick.

So on cycle day three, I like to see an FSH that’s below seven, seven or below. And then I look at LH-2 and it’s interesting we have some research to show that we, we really want to see LH and FSH in a roughly 1 to 1 ratio.

When LH starts to be greater than FSH, let’s say LH is twice that of FSH. We have an LH that’s 15 and FSH that’s seven. That raises our index of suspicion for things like PCOS. So I like to look at those together. And then estradiol as well. I like to see this below 50 on cycle day three. Once estradiol is elevated we want to have some conversations about that. And then really importantly, if FSH is elevated, we’re starting to think, oh, we might be losing some ovarian function here. I really want to focus on all the things we can do to support the health of those follicles, the health of those granulosa cells.

So usually that combination is going to be LH, FSH, estradiol, AMH. And then there’s some other things that we can look at just at a standard lab that give us a lot of great information. You mentioned inflammaging. This is one of my favorite terms because inflammation really drives aging in our reproductive system. We see that when someone has chronic systemic inflammation, I always tell my patients, there’s a lot of inflammatory messengers in your bloodstream, they go everywhere, right? They have access to every tissue type. And that extends into the endometrium, where we can see lower implantation rates. Because that endometrium gets so inflamed, it’s hard even if an egg is fertilized for it to implant. And it can also extend into our ovarian tissue where it can impair the way that we produce progesterone. So in our patients that have a short luteal phase or luteal phase dysfunction, they have a low progesterone midway through their luteal phase. It’s really important for me to assess inflammatory markers. So my favorite’s hs-CRP. We all have our fave inflammation markers. But I do an hs-CRP on every single person that comes into my office. So that’s a great indication. And then I think a fasting insulin is super, super important here. We know hyperinsulinemia is one of the major drivers of oxidative stress in the reproductive system. So making sure that I’m also assessing that metabolic piece. And then homocysteine, we know that homocysteine, an elevated homocysteine can actually kind of concentrate in that follicular fluid, the soup that our egg cells are swimming in, and cause some damage to our egg cells. So lots of things we can do just with a standard blood draw.

Evelyne: Yeah. That’s super interesting. And then what are some of the things that you do beyond that.

Dr. Kalea Wattles: Yeah, the next tier is the next tier, top shelf oxidative stress markers. So these are the things that I will use in the right setting. Because of course they’re going to be a little bit more expensive. They’re going to be a specialty lab draw. But they’re becoming more and more available. And I think the one that I’m seeing maybe most often on panels now is 8-hydroxy-2’-deoxyguanosine, or I always say 8-OHdG if you’re fancy.

So, this is a really important marker of oxidative stress. And it actually reflects oxidative damage to mitochondrial and nuclear DNA. And we should probably we should probably talk about the role of mitochondria in fertility shortly because it’s so, so, so important in terms of aging. But 8-OHdG, we see this on a lot of the commercially available panels that look at hormones or oxidative stress. So that’s a really important one.

Another marker of oxidative stress that we can look at is called F2-isoporstanes (F2-IsoP). And this measures oxidative stress to lipids specifically, which indicates mitochondrial oxidative stress again and mitochondria is so important for both male and female fertility. So this is something that I’m measuring in both my male and female patients.

We can look at total antioxidant capacity. I love to understand someone’s ability to kind of quench, oxidative stress with their antioxidants. So this is going to evaluate our body’s overall ability to neutralize those free radicals. It’s pretty essential for, again, reducing that mitochondrial oxidative stress. We can also do some organic acid testing. We can look at things like citrate and sex cynic acid. This is going to help us to understand that Krebs cycle. We’re all going back to hearing our biochem professor talk about the Krebs cycle. So that’s going to be super helpful in understanding how our mitochondrial energy production pathways are working.

And then I love, I had a nutrition degree before I got my doctorate. So I love a nutrient moment. I love to understand nutrition and some of the most important nutrients we can measure. CoQ10, we know how important that is for our electron transport chain.

We can look at a carnitine to ACL carnitine ratio, which is going to reflect fatty acid transport into our mitochondria. Really helpful to know from an energy metabolism standpoint. And then maybe I should have put this in first here. Our B vitamins, our good old B vitamins B1, B2, B3, B5, these are all cofactors in mitochondrial energy production. And we know that deficiency in these nutrients can impair the way that our mitochondria are generating energy.

So we could do a big ol’ evaluation and really understand how inflammation and nutrient status and oxidative stress are affecting the health of our eggs and our sperm cells.

Evelyne: I want to back up almost a little bit, but talk about specifically why is mitochondrial health specifically so important to ovarian health, to egg quality and also to sperm?

Dr. Kalea Wattles: I love that we’re talking about this. This is my absolute favorite thing to talk about ever. So mitochondria, I talk about these and I’m sure everyone has their little blurbs of how they talk about mitochondria, but I think about them like cellular batteries and the way that I frame this conversation with my patients is ovulation, fertilization, implantation, early embryo development. These are all very energetically expensive processes, right? Building a whole new human from scratch? That’s pretty energetically expensive and our mitochondria are going to create the energy or the currency that pays for those very energetically expensive things that we need to do to have a baby.

And it’s really fun to think about how this is all playing out in the body and a fertility fun fact I always say, like, I hope this comes up on Jeopardy! so that everyone is this question, right? But the fun fact I have to offer is that our egg cells actually have the highest concentration of mitochondrial DNA content in the human body. These teeny little egg cells have the most mitochondrial DNA. So we can kind of see how important that is in a fully grown human egg cell contains around 100,000 mitochondria. And just to put that into perspective a little bit, that’s maybe 1 to 2 orders of magnitude higher than other cells that we would think of as being very energetically, active, like our muscles or our nerves. So really, really, really important. So that’s kind of the egg health piece. It’s really generating mitochondria, generating that energy that we need for those egg cells to be successful.

When we look at a sperm cell, we have the head of the sperm and then we have the tail. And in the midpiece of the tail is where we have a concentration of mitochondria. And those mitochondria are going to essentially power the propeller of the sperm. That’s going to allow it to move forward in a roughly straight line so that it can move through the female reproductive tract, through all the cervical mucus. That’s going to create kind of a web, and then eventually meet that egg where it will be able to fertilize.

The last piece that I’ll add to this, because I think it’s so fascinating, is that taking care of our mitochondria is very important to allow our DNA repair genes to be effective. So I love to tell this little tale about, repair genes. So when we have a healthy eggshell, that means there’s plenty of cellular energy. Our mitochondria are working very well. We have plenty of antioxidants. We’ve measured our total antioxidant capacity. So now we know we have plenty of antioxidants. When those things are true, it allows the DNA repair genes in the oocyte, the egg cell, to clean up DNA fragmentation from sperm. This is a really mind-blowing process to me.

Evelyne: Wait, the egg cell cleans the DNA in the sperm?

Dr. Kalea Wattles: Yes. So get ready for this. The sperm is going to travel to the egg, right? And then the sperm head will meet the outside layer of the egg cell. And it’s going to initiate what we call the acrosome reaction that facilitates the transfer of the sperm DNA into the egg cell.

And then this is the part where it gets so juicy and so interesting, because that egg cell is going to use its mitochondrial energy production, and it’s going to go to work repairing damaged DNA from that sperm cell. This is probably the most important post-fertilization process that happens to allow complete embryonic development and avoid any developmental arrests that might happen because of things like chromosomal abnormalities.

But this only happens, I mean, really, if this process is going to be effective, we have to have great cellular energy production. We have to have all those antioxidants. So this is where functional medicine is really beautiful, because we can think about all these things that could potentially cause damage to our mitochondrial function or increase oxidative stress. And I just whenever I think about these processes, I’m like, how did any of us turn out normal? It’s so complex and there are so many steps that happen. And we need such robust and energetic mitochondria. It actually feels a little miraculous.

Evelyne: It is miraculous. It’s crazy. I want to talk about some solutions, in terms of, supplements and treatments that you use. But before that, I want to talk about the sperm a little bit more. So I know that when you’re working with men, you’re doing a semen analysis, right? We did talk about it one time on the show before. But I’d love to hear, beyond testing for sperm count and motility and morphology, what are the things that you’re looking at?

Dr. Kalea Wattles: Well, I mentioned DNA fragmentation. And this is something that we can measure on the more advanced semen analyzes. It doesn’t come standard. If you go to your local fertility clinic, which is a great option because you can sometimes get insurance coverage for a semen analysis at your fertility clinic. So I don’t want to discount that as an option. But that isn’t going to have most often a DNA fragmentation.

And like I said, the integrity of the sperm DNA is so, so, so important because our DNA repair genes can only do so much. If there’s really fragmented DNA, it’s very difficult to overcome. And so how that shows up is, in my practice, I might see a couple where the female partner, her evaluation looks really good. She’s clearly ovulating every cycle. All of the other markers look really healthy. This couple is timing their intercourse appropriately, but they are not getting pregnant cycle after cycle. Or they are getting pregnant, but they’re having early pregnancy loss every time. So maybe even what we call biochemical pregnancy, where someone gets a positive pregnancy test around the time that they were expecting, but then three days later, they start bleeding just like it was their period.

So, recurrent pregnancy loss, unexplained infertility. These are the situations I’m looking at sperm DNA fragmentation. And I’ll give you an example. In my practice, I had a couple and, they had been trying for three years to conceive. They had done 3 or 4 IUIs, those hadn’t been successful. So they were really weighing their options, kind of taking a moment to refortify and reconnect before they decided if they wanted to move on to IVF. Uploaded all of their information for me. Female partners labs looked pretty beautiful, like picture perfect. Male partner uploaded semen analysis for me. It was a standard count, it was good. Morphology was good. So morphology tells us about the shape of the sperm. Do they have a normal shaped head? I always joke if you’ve never looked at a semen sample under a microscope, you would be shocked to see how many sperm have three heads. They have three tails. They’re chasing their tails. So it’s quite stunning. But his morphology looked pretty good.

And then we have motility, which tells us is this sperm swimming roughly forward? How fast are they swimming? That looked pretty good. So by all standard measures this looked fine. I encouraged them to pursue a repeat semen analysis with DNA fragmentation. It came back 0% normal sperm. 0%.

Evelyne: Oh my gosh.

Dr. Kalea Wattles: They could not find a normal sperm in this sample. And it was an empowering conversation because then they knew, okay, let’s really identify some sources of oxidative stress. Male partner hadn’t had his labs done as thoroughly. We found insulin resistance. We did find elevated inflammation. We ended up doing some further testing, pretty low antioxidant status. So these were action items for us, right?

But how frustrating that three years had gone by and they had no idea. And if we hadn’t done that testing it, I think they still kind of would have been spinning their wheels a bit. So I’m really, excited that we have some more advanced options because it allows us to add precision to our treatment plan and maybe turn over some stones that we would have left in the past.

Evelyne: Yeah. Do you think that it’s becoming more common in reproductive, health clinics to do the DNA fragmentation, or is that still not standard?

Dr. Kalea Wattles: You know, I think it is becoming more common, but it’s I really see it being practitioner specific. Just like a lot of things. We all have our preferences. It adds quite a lot to the expense. And so I think that is a great limiting factor that it’s just quite a bit more expensive.

But I am seeing it, I would say in the niche population of recurrent pregnancy loss, I am seeing more DNA frag measured, which is encouraging. It’s really helpful.

Evelyne: Yeah, that’s interesting. And just on a little side note, I’m curious, since you were in MD school and now I assume you still kind of collaborate with those professionals in that space, what you’ve seen has changed in that field since you were in school.

Dr. Kalea Wattles: I was thinking about this. When I was in school we had a reproductive health module and I remember, , so I was in my 20s when I was in that program and I remember even in that very holistic, very patient centered setting, we were very much taught that after someone’s 32 years old, they are at great risk for all kinds of fertility complications and probably shouldn’t get pregnant. And we should encourage everyone to freeze their eggs when they’re 30 so that they don’t have to have a pregnancy over 32, because that would just be so dangerous. That was over ten years ago now.

So much has changed. And I remember, I had a baby when I was 29, and I remember telling my husband, well, this is our last baby because I won’t be ready soon enough to have another before we’re 32. And I could just never have a baby after I was 32.

Evelyne: Oh my gosh.

Dr. Kalea Wattles: And, I’ll say that in the context of I’m 37 right now and in my third trimester of pregnancy with my third baby. So obviously I threw that out the window. And I’ve seen this evolution in practitioners like myself of realizing, oh, actually, there’s so much that we can do to protect the health of our eggs and to protect the health of our sperm.

And so I’ve really seen this evolution of the way that we approach lifestyle factors and supplementation and nutrition recommendations and even stress management, so that maybe someone’s not ready right now. But we know that all the things that we’re doing for a preconception plan, the metabolic health piece, the hormones, the inflammation, all of those things also support longevity just in our health.

They reduce the risk for chronic disease, heart disease, osteoporosis, diabetes. So we’re really doing preventive, proactive health care as we get someone ready to have a baby when they want to. And I love to see the way that we’ve kind of had this shift in medicine around that conversation.

Evelyne: Yeah. And congratulations, Kalea. I’m so excited for you.

Dr. Kalea Wattles: Me too!

Evelyne: So let’s talk about some of the practices that you implement with your patients. I am interested in supplements. Obviously on this podcast we do talk about that quite a bit. So I’m interested in, for the inflammation piece, for the oxidative stress, for the mitochondrial health. What are some of your top recommendations to supplement-wise?

Dr. Kalea Wattles: So my most favorite and most beloved supplement in the whole world, I think for everyone who’s getting who’s preparing their fertility in any way, should be taking a CoQ10. It’s my number one pick whether you’re trying to get pregnant on your own, you’re preparing for IUI or IVF. There’s great studies, in both settings. And this for me is for both partners. And so I always tell my patients, get your bottle of CoQ10 and you’re going to share it. Like how romantic. You have your little moment, you take your CoQ10 together. So I, I really appreciate the ability of CoQ10 to promote repair of those dysfunctional mitochondria in egg cell.

And we see that, in animal studies anyway, CoQ10 can delay the depletion of our ovarian reserve. So going back to our initial conversation about watching all these factors, we know CoQ10 kind of naturally declines in the body as we get older. So there is a greater need for supplementation. So any of my patients that are over 30, as we’re really we’re really getting into some higher doses of CoQ10. So I like ubiquinol.

Evelyne: When you say higher doses, are you taking like 300 mg, 400 mg, more?

Dr. Kalea Wattles: 300 to 600 mg.

Evelyne: Okay.

Dr. Kalea Wattles: So, I’ll usually have people start with 300 and then they’ll work their way up to 600. We see sometimes people can get some GI effects if they go up to the 600 really quickly. So I’ll usually start them at three, work our way up to six. And again, that’s for both partners. So eggs and sperm, that’s my therapeutic dose for fertility.

And what’s cool about it is, even in IVF cycles we see that the CoQ10 can help improve embryo quality, can improve the way that our ovaries respond to medication therapy. So it’s really quite valuable for lots of things. So that’s my number one pick exactly.

Evelyne: And how quickly do you see a change?

Dr. Kalea Wattles: Yeah. So I typically will say, the way that our egg cells mature, it takes about three months for a primordial egg cell, which is very small egg cell to mature to an egg cell that’s big enough to ovulate and be fertilized. So I’ll usually tell my patients I want to I want that whole maturation process to happen in the setting of adequate, adequate CoQ10.

So let’s give it at least three months before we decide if we’re going to continue on, if we’re going to adjust the dose. But typically three months is my minimum expectation.

Evelyne: Great. What else.

Dr. Kalea Wattles: Yeah. Okay. So CoQ10 being first on my list. The next one is melatonin. I love melatonin. There’s a really cool study I want to say it came out in 2023. But they were looking at different natural products that could improve the health of oocytes, specifically in ovarian aging. So ovarian aging, I think in the next five years is going to be a really hot topic in fertility research.

But that aside, these researchers said that melatonin should be considered first line therapy to rescue egg cells from ovarian aging. So they were recommending a combination of melatonin and CoQ10 for anyone who was over the age of 35, which I obviously loved. I think we always think about the way that melatonin, it can help us with our sleep, but it’s also a really powerful antioxidant. It’s actually probably one of the most important antioxidants along with glutathione, that concentrates in our follicular fluid, again, that soup that our egg cells are just swimming in, protecting them against oxidative stress.

It’s we have these really cool studies where researchers looked at oral supplementation with melatonin and how that affected melatonin around the egg cells. And so we see, most of the dosages are usually in the 2.5 to 5 milligram nightly dose. But at this study, they were using three milligrams. And so they gave these women, an oral melatonin. They took a follicular fluid sample, they gave them oral melatonin. Not for a long time. Like day four to day ten of their cycle. They retested their follicular fluid, and the melatonin concentration had increased fourfold in that follicular fluid.

And they saw higher implantation rates, higher pregnancy rates. And just, healthier oocytes or egg cells. And so I am loving melatonin, especially again, in my patients who are over 35. And the sleep benefits don’t hurt either.

Evelyne: Yeah, that is absolutely fascinating. I love all the tidbits you’ve shared about the follicular fluid. I feel like that’s a piece that I just don’t hear about as often. So do you think it’s enough for somebody to just if they’re just taking their three milligrams at night for circadian rhythm regulation like that they’re covered?

Dr. Kalea Wattles: They’re covered. Yeah. That’s great. I would even say in my patients that are more sensitive to melatonin, I feel like even a lower dose is fine. You’re getting some of that antioxidant protection. It’s usually not the only thing that we’re doing. So even if someone feels good with just a milligram, I’m okay. I’m okay with that. Let’s get some in there. And then we’ll combine it with the CoQ10, with the glutathione that is so important.

This one’s probably the most important antioxidant in that follicular fluid. We see that glutathione protects egg cells against oxidative stress during follicular genesis. So that that time when egg cells are growing most rapidly in the weeks right before ovulation, they’re pretty susceptible to oxidative stress. It’s kind of a fragile process. And so having adequate glutathione in that follicular fluid is going to be really protective. So glutathione, melatonin, CoQ10, and then we can talk about I think maybe the hottest topic right now in fertility world right now is kind of our, our NAD precursors, right?

Evelyne: Yes. Tell me more about that.

Dr. Kalea Wattles: So really cool animal studies have come out. I’ve only seen studies in mice so far. But showing that, especially if most of the studies are using an NMNs, so nicotinamide mononucleotide and metabolic precursor to NAD. And we see that NAD repletion using NMA can restore oocyte quality and enhance ovulation rate. So again they’ll use these terms, they’ll rescue egg cells from ovarian aging which I love. That terminology really works for my brain I love it. So pretty interesting there.

And one theory is that, again, that maturation process can be a little bit fragile. And show NMN is protecting those oocytes from oxidative stress. It’s resulting in lower rates of aneuploidy, which is chromosomal abnormalities. Because that cell maturation going back to the mitochondrial piece is very energetically dependent and that NMN can improve that cellular energy production and reduces rates of what we call spindle assembly defects.

And so I love this, especially in someone who has gone through IVF already, and they, maybe they were able to retrieve several eggs, but then they didn’t fertilize or they didn’t grow out to what we call day five blastocysts. It’s something that I really like to bring on board if they’re taking a little bit more time to prep before their next cycle.

So people always ask me, do I have to do all of these things together? And not necessarily, but if you really want the full experience, I typically am using CoQ10, NMN and melatonin, maybe even some alpha-lipoic acid all together so that we can really take care of those mitochondria.

Evelyne: And you were telling me that you also did this yourself, right? Can you tell could you want to share about the ovarian, was it the ovarian age test that you took?

Dr. Kalea Wattles: Yes. Yes. Okay. So the self fascinating. We were laughing about this. I was laughing at myself about this. I kind of knew that I wanted to have a third baby, but I was in my mid 30s. I knew that I wanted to do really intentional prep. And so, when I was 35, I was working a pretty high stress job, really busy, had two kids. I did a biological age test. So it looked at some inflammatory markers, methylation. There’s, all of these calculations. And, at 35, my test came back with a biological age of 42 and a half. And I was devastated. Let me tell you, as a functional medicine doctor, I really thought I was doing well, but it actually opened my eyes to the fact that I wasn’t being as intentional with my mitochondrial support. I was really stressed. I wasn’t doing my mindfulness practices. My exercise, I don’t think was a good fit for me at the time. It was kind of sporadic, really high intensity actually, which maybe some more regular moderate intensity would have been better for me at the time.

So I started doing all of these things. I had my labs done my I have a whole preconception panel. We can talk about that at some point before we part ways. But I did my full preconception panel. I started a mindfulness practice that was really regular. So I love apps. I love Calm, Insight Timer, Balance, Beat, Fullness. I love Binaural Beats, but I carved out some time every day to have my meditation practice.

And then I started doing all of these supplements. We’ve talked about the CoQ10, the melatonin, alpha-lipoic acid, MNM. I actually also did some transdermal NAD patches, which was an interesting experience, really working on my exercise. And I did this for quite some time and then when I turned 37, I repeated my testing and it came back at 32 and a half. So I think I took ten years off of my biological age from employing all these things that seem simple.

I didn’t mention sleep. I really focused on sleep. But all of these lifestyle interventions that we talk about all the time for me, made a huge difference in going into a pregnancy at 37. It was reassuring to me. I was like, well, I’m only 32 on the inside. It’s fine.

Evelyne: That’s really incredible. And so you were doing those things for about two years approximately?

Dr. Kalea Wattles: Yeah. Which I know people are going to hear that and be like, wow, that was a long time. But I see results with these things. I always tell people that it’s interesting that when we get engaged, we will take a year to plan for our wedding. But when we want to get pregnant, we wanted to be pregnant yesterday. Right? And so I’m always trying to set this expectation of like prepare for pregnancy, like you would prepare for your wedding three, six, nine, 12 months is going to be amazing in terms of your experience getting pregnant and how easy that is for you and how your pregnancy progresses.

Evelyne: Yeah, absolutely. So you just brought up your typical preconception lab. What else is on there that we haven’t covered?

Dr. Kalea Wattles: Yeah. So I’ll be a little bit redundant and cover some of the things that we’ve covered already. But I’ll expand. This is the preconception lab checklist that I do with every single patient. I did this on myself. So as I was preparing for pregnancy, I knew I had been doing all this deep inner work already, so I did this panel. I saw some things that I needed to work on, and so then I repeated it three months later, and felt pretty good and was ready to move on. But that’ll look different for everyone.

But let me break this down into categories. So we talked about the cycle day three hormones. That’s going to be LH, FSH, estradiol, AMH. Because I have my patients going to the lab at that time anyway I throw on a couple other hormones, testosterone, DHEA sulfate and prolactin. Super important are androgen hormones, testosterone, DHEA. They’re really, really, really impactful in terms of the way that we mature our egg cells. So especially DHEA is really, really relevant for this conversation because as we are over the age of like 25, our DHEA really starts to nosedive, which I think is such an injustice.

Evelyne: 25 that’s young, really young.

Dr. Kalea Wattles: I have a lot of patients who are under 30 and they come and they have a low DHEA sulfate. And so that’s an area where I like to measure. I will supplement DHEA in the right candidate. Oftentimes if they also have low testosterone, we’ll see some conversion of DHEA to testosterone. Because DHEA is a sex hormone reservoir, right. It can become estradiol, can become testosterone. And so I like to measure that, to understand how the androgens are influencing that eggshell maturation. And then prolactin. Super important because high levels of prolactin can interfere with ovulation. So I will get all of those. So that’s what I’m collecting on cycle day three.

Now because they’re already getting their blood drawn. I will oftentimes do a lot of other things at the same time. Thyroid studies are really, really important. I mentioned my beloved granulosa cells, favorite cells. Those are our helpless helper cells. And what we know is that thyroid hormone activates our granulosa cells. So it allows those granulosa cells to collect information from the brain. So, our brain is going to release our FSH, which is going to tell our ovaries, let’s start maturing a cohort of eggs. It’s really our granulosa cells that are going to respond to those messages.

So when we see someone who has low thyroid hormone they have more irregular ovulation. Sometimes an ovulation, irregular cycles, oftentimes, a short luteal phase because their progesterone production is impaired. So when I’m getting my patients to the lab, they’re doing their thyroid stimulating hormone, free T4, free T3, reverse T3, and then thyroid antibodies. And we honestly could do a whole podcast just about thyroid health and fertility because it’s so important.

But the thyroid antibodies, I think it remains a little bit controversial to measure those for fertility, because what we know is that the standard treatment for hypothyroidism, which is levothyroxine, doesn’t decrease antibodies. And so there’s some school of thought that says don’t bother. You don’t even need to measure because levothyroxine doesn’t do anything. That’s fine because in the functional medicine world we have so many other tools to support the immune system. So it’s still really valuable for me.

And just because I love a little side note, fun fact, there’s some studies that showed that, when someone was going like they were doing a surrogate situation, if the surrogate had a hypothyroidism, it could affect the health of the egg cell. Even though the egg cell came from someone who did not have thyroid dysfunction. So it’s really important for all aspects of ovulation, fertilization, healthy pregnancy.

So really, really important to measure that, thyroid markers, and then metabolic markers. I do a CBC, CMP, I add a GGT to my CMP because it’s a little bit more of a marker of total body burden of toxicity. So I’ll add that on there. It’s people are always shocked to find out it’s like $4. We probably should be adding it to a lot of panels. I’ll do a hemoglobin A1-C, a fasting insulin of course. We mentioned our HSCRP for our inflammation and then a lipid panel because it tells us so much about especially, someone’s carbohydrate intake, how insulin is behaving in the body. So that’s really meaningful.

Some nutritional markers. We talked about a few of these already be vitamins, homocysteine. I’ll do iron studies. So ferritin, iron, total iron binding capacity. Vitamin D super important for those granulosa cells. Sometimes we see that vitamin D, if someone’s deficient and we repleat it, their AMH can get better. So to loop back to that ovarian reserve conversation.

And then uric acid. This is my another new favorite of mine. We have some great, we have some great information about the role of uric acid as a predictor of things like preeclampsia or just gestational hypertension or pregnancy induced hypertension. So it’s a great screening tool to make sure that that is healthy before someone conceives.

And then one week after ovulation, so I’m having my patients use ovulation predictor kits which is a urine test. It detects LH at home. They’re getting their positive luteinizing hormone surge. I’ll know that they’ll ovulate the next day. So I’m getting them into the lab about a week later to measure their serum progesterone. We want to ensure that they are ovulatory. So couple of different blood draws during the cycle. We’re getting metabolic factors hormones, nutrients, immune markers. It’s really comprehensive.

Evelyne: Yeah I love this. And I just want to thank you for sharing all this information so generously. This is incredible. So many great clinical pearls.

You brought up a couple questions for me while you were chatting. So we’re seeing a lot of diminished ovarian reserve, right? Even in younger and younger women like women in their 20s. So I’m curious, in your patients, what are some of the commonalities you’re seeing, is it really just like a bad diet? Is it our environment like what’s going on?

Dr. Kalea Wattles: It’s all of it. I mean, it’s all of it. It’s that inflammaging piece, right? So when we think about inflammation or inflammaging, it’s really a measurement. It’s a function of both the level of insult and time. So as time goes on we just accumulate more oxidative stress more opportunities for inflammation. So of course as we get older we’re more aware of those things. But also it’s the level of insults. So it’s everything you just talked about.

It’s diet that is a higher glycemic index. We know that higher glycemic index food plans can increase CRP. We see that relationship. So there’s inflammation happening there. It’s low intake of antioxidants. So I know we always say like eat the rainbow. And people take that for granted because it seems so simple. But that’s really the best way we can ensure broad spectrum antioxidant coverage and when we have very low intake of those phytonutrient rich foods, we see a total antioxidant capacity that’s just lower.

The toxic exposures you mentioned, I mean, no surprise, everyone’s talking about this. It’s everywhere. Just to engage in the world. We are constantly exposed to endocrine disrupting chemicals, and then our body doesn’t always have the tools that we need to mitigate the effects of those exposures. I try to find some balance in this conversation and say, we have to go out in the world and breathe air and drink water and eat food, and that’s fine as long as our body has the capacity to deal with that, meaning our liver is functioning really well. We are hydrated, we are getting adequate dietary protein, we are having a regular bowel movement. We’re sweating those things don’t happen for a lot of people. So we get this accumulation of environmental toxicants that can affect our hormone production can affect sperm health, egg health. And we’re seeing more and more and more of that in younger women.

I also cannot under understate the impact of stress. We’re all stressed. We’re working these jobs were working long hours. The light pollution aspect, like we’re sitting under fluorescent lighting. We’re not in touch with our circadian rhythm. And so a whole combination of things is probably leading us to have some issues with ovarian aging.

And it’s hard because it’s not one thing. It’s all kinds of things. But once we do an audit of our lifestyle, it tends to be pretty clear the things that we can change right away. So I always kind of return to those modifiable lifestyle factors sleep, stress, nutrition, exercise, our relationships because that’s going to have an impact right away. And then we start to layer on some of these other things and I have seen a lot of great success because how frustrating when you’re 27 and have been diagnosed with premature ovarian insufficiency. Right?

Evelyne: Right. And then it also leads to the conversation around what people call unexplained fertility. But it’s not always unexplained, right?

Dr. Kalea Wattles: Yes, yes. Okay. So thank you for bringing up this topic because I might need another hour to talk about that. I mean, infertility, it’s this umbrella diagnosis. And what it really means is, in the female partner, she’s ovulating. So they have confirmed ovulation. And at least one fallopian tube is open because you technically only need one to be open.

And that a semen analysis, meaning a standard semen analysis, not one with DNA fragmentation is normal. So if someone meets all of that criteria, and they are not conceiving, they are going to receive the diagnosis of unexplained infertility.

But what if that’s all true? This person is ovulating. She has a tube open. Standard semen analysis is normal, but she has iron deficiency anemia that is preventing her from thickening her endometrium. And, we see a ferritin below 40 and the research is associated with less robust ovulation. So what if she has iron deficiency anemia? What if she has Hashimoto’s or autoimmune thyroid disease and has raging thyroid antibodies and suboptimal thyroid function that’s preventing the activation of those granulosa cells?

Or what if she has insulin resistance that is causing lots of oxidative stress and is affecting the way that her androgens impact her ovaries? There are a million things that could be going on that kind of offer an explanation for why someone might not be conceiving.

So I always encourage my patients to say, okay, you have received this diagnosis. This is what this means. Now let’s take a dive into what I would call the functional medicine matrix, where we’re looking at all of these body systems – our gut health, our immune system and inflammation, cellular energy production, bio transformation and elimination. We’re looking at our hormones, our metabolic health, our neurotransmitters, the structural integrity of our body because there’s probably something else going on here.

Evelyne: For sure. Yeah. Thank you for sharing that. I want to go back really quickly to something that you brought up twice, which is that androgens and the impact on eggs. Can you talk more about that?

Dr. Kalea Wattles: Absolutely. So DHEA in particular is really important for cellular energy production inside the oocyte or the egg cell. And so when we see a lower DHEA we see a poorer ovarian maturation. So this is pretty standard. Someone who is doing IUI or IVF, they will very commonly be prescribed a DHEA supplement so that they can get that DHEA, which really helps those eggs to mature and get large enough so that they can fertilize. So it’s a little bit of a double-edged sword if you will, because you need androgens to develop your egg cells. But when androgens get too high, they impact the way that our cells, that our egg cells develop, which is why, for example, in PCOS we see elevated insulin, right. That’s one of the hallmarks of PCOS is hyperinsulinemia that insulin causes the theca cells, which are different than the granulosa cells, but they’re besties and it causes the theca cells to get bigger. And then they are producing more and more testosterone. And then that testosterone interferes with the way that the egg cells mature.

So there’s a sweet spot. We need androgens to mature eggs, but androgens that are too high can also impact the way that our egg cells mature. So this is why it’s very, very important to me that I measure that DHEA sulfate and testosterone in the blood. So I understand how I can tailor those recommendations. And it’s also really important to me that I pair that with a fasting insulin, especially in someone that has a history of any metabolic dysfunction or PCOS, because really the treatment might be, okay we actually need to get your insulin, your fasting insulin down to bring that testosterone down. And then we’ll see a more regular ovulation.

Evelyne: And with DHEA and testosterone then approximately where do you like to see those optimally.

Dr. Kalea Wattles: So I like to see my DHEA sulfate. So I always measure DHEA sulfate in the blood. It’s a little bit less variable than DHEA. It’s a little more stable I should say. So I measure DHEA sulfate in the blood. I like to see it, in the upper quartile of the reference range. So for me, I always have to look at units, but it’s 200 for lab core or class, kind of the standard lab. So that’s where I like to see DHEA. And then for, total testosterone for a reproductive age female, I usually like to see between 20 and 40. Sometimes when someone has really high, insulin, I’ll see a total testosterone that’s like 60 to 80, really high. They won’t be ovulating. And as we get that fasting insulin down, we’ll see really significant drops in that total testosterone. So it’s really helpful to look at them all together.

Evelyne: And do you find that, I mean obviously with DHEA being low, for example, it’s like, yes, we can give DHEA, but we always want to go back and ask like, why is it low? Do you find that just by improving like the lifestyle markers and working on other things that you do see the DHEA go up?

Dr. Kalea Wattles: Yeah, it is a tricky one because like I said, it just decreases as we age. That’s just the way that it is. And so sometimes it’s really hard. We know that things like, a meditative practice can increase, cause modest increases in DHEA. That’s a little bit tough for some people to commit to that. Oftentimes for me, that means a supplement. I start pretty low, so I’ll usually start in the 5 to 10 milligram range, which to put it in perspective, a lot of times when people are going through IVF, they’ll do 25 mg, three times per day. So the total is 75 mg. So pretty high. For most people I’m in the 5 to 10 milligram range to start.

And then I’m measuring six weeks after I start that. And I’m tracking the DHEA sulfate, testosterone and estradiol because I want to understand how that DHEA is being metabolized. Like I said, it’s a sex hormone reservoir. If someone has had any issues with acne, with hair loss, I’m also measuring dihydrotestosterone just to kind of watch that whole androgen pathway and see how those hormones are behaving. But I’m usually able to get DHEA pretty quickly, and then we’re able to tailor our dose for either sticking to our regular dose. If we got it a little higher than we wanted, maybe we’re backing it down two and a half or five milligrams.

Sometimes I’m even doing DHEA every other day to maintain levels. So it just we monitor. I think that’s the most important part is you give a dose and then you see how someone responds. Right?

Evelyne: Yeah. Thank you for sharing all that. Okay, I have one more question quickly before our rapid fire questions, we haven’t talked yet about the vaginal microbiome. an you share just a little bit about your assessment of that? Like how important is it to the fertility conversation and also what are you using to test that.

Dr. Kalea Wattles: Oh, I love this. The vaginal microbiome again I think this is going to be super hot topic in the next few years for fertility. So I’m using the Tiny Health test. But there are other ones on the market. Evvy is another one that a lot of my colleagues are using. That’s a good choice.

And it’s measuring a couple different things. So the first thing it’s measuring is what’s going on with lactobacilli in the vaginal canal. We want the vaginal canal to be lactobacilli dominant. It’s going to maintain the pH. It’s going to keep the overgrowth of pathogenic bacteria at bay. So we really want to see a robust and healthy concentration of lactobacilli. When we don’t, that means we probably should encourage an oral probiotic, a vaginal probiotic, which there are some good vaginal probiotics out there these days that have clinical studies showing that it actually improves lactobacilli concentrations in that vaginal canal, eating lots of lactofermented foods, avoiding harsh products, you know, washes, vaginal products.

And also we are seeing a relationship with the gut. Oftentimes when I have someone that has low lactobacilli in the vaginal microbiome, they also have low lactobacilli in the gut because there’s such crosstalk between those communities, even though they are, physically distinct. So that’s one thing it’s measuring.

It’s also measuring some different potential pathogens that can impact our fertility. So I think the one that a lot of people are talking about right now is urea plasma. This is an organism that it could be commensal. It could be commensal in, we may be walking around with low levels that aren’t causing any harm, but let’s say we also have low lactobacilli. It gives that urea plasma an opportunity to overgrow. And then we see lots of inflammation in the female reproductive tract.

So that might show up as implantation failure or recurrent pregnancy loss or even pelvic pain. Pain with intercourse. And so this is something that I’m measuring. If it comes back positive, we have to measure a male partner too, because this can go back and forth. And then the treatment is antibiotics. It’s typically doxycycline. Both partners need to be treated. And we have I mean in my practice I’ve seen a couple different cases where that was the thing we treated that and really significantly lowered inflammation improved that vaginal lactobacilli and patients were able to get pregnant. So I think this is an area where, if we’re really doing a deep dive and turning over all those stones, it’s worthwhile to take a look.

Evelyne: Super interesting. Thank you for sharing. Okay. Very quickly, what are your three favorite supplements right now?

Dr. Kalea Wattles: Okay. For myself. All right. My favorites are CoQ10, of course. I’m going to go magnesium. I maybe that needs to be my number one for myself personally, right now. I love magnesium. And then I would say for others it might be N-acetyl cysteine, but I’m kind of cheating because I’m going to say for others it’s NAC. But for me, right now, it’s L-arginine. I’m really supporting my healthy blood flow and maintaining healthy blood pressure through pregnancy. So for me, CoQ10, magnesium, L-arginine.

Evelyne: Love it. And what are your favorite health practices, like right now as you’re pregnant, but you’re also still running your business and you’re running a farm right?

Dr. Kalea Wattles: Yeah, I am running farm. We do have a baby calf in our living room as we speak, so there’s all kinds of stuff going on. My favorite health practice. So I am such a fan, I mentioned this briefly, but binaural beats final beats are my absolute favorite. I always tell my patients, when you’re trying to find your kind of mindfulness practice that works for you. We have so many choices, right? We have guided visualization, we have breathing, we have compassion meditation. There’s so many things that we can do. And for me, when I listen to a, this is going to reveal a lot about my personality, when I listen to something like a guided meditation and someone’s like telling you, and now do this and now do this, there’s this pressure to do it right.

And I think that can be counterproductive sometimes. So I love to listen to binaural beats. You listen to headphones, it plays different frequencies in each ear and shows the, middle, the kind of average of those is a third hidden beat. That’s the binaural beats. And it really kind of encourages your brain to enter into different brainwave states. And so it takes the work out of the relaxation. I just sit back, I listen to my tones, and I enter into this very relaxed, mindful place. And so for me, that has been a game changer. I do it multiple times a day. I always encourage my patients to listen to binaural beats and it’s really magical.

Evelyne: I love that. Thank you for sharing. My dad used to listen to them like when we were kids, and sometimes we’d also listen. I wonder if I would be a less stressed person in general if I had continued.

Dr. Kalea Wattles: My favorite app that I use is called Beatfullness and there’s ones for sleep, productivity, exercise. There’s a million different things in the library, so I’m usually choosing the relaxation or the like, I can’t remember what it’s called, but it’s essentially like a detox from being on screen or screens all day, just like rest your eyes. And who doesn’t need that?

Evelyne: Absolutely. Okay, last question for you. What is something that you’ve changed your mind about through your years in this field?

Dr. Kalea Wattles: Oh, okay. I think I already revealed this one and it’s that you can have a baby when you’re 37 or 40.

Evelyne: Or older. I read stories all the time.

Dr. Kalea Wattles: Or older! I mean, we just saw we saw this data coming out. More women in their 40s are having babies. And so my call to action, I guess is start now if you’re not ready now, that’s fine. But start now. Start today. There’s so many lifestyle practices. Get in bed before 11 p.m. so that you’re in total darkness and your endogenous natural melatonin can take over and protect your egg cells from oxidative stress. Get moderate intensity exercise most days of the week. Get on your CoQ10 and your melatonin. Make sure that you’re getting adequate blood flow to the ovaries through exercise, massage, acupuncture, which is my number one way to support that blood flow. Wherever you are in that journey, there are so many things you can do right now so that when you’re ready, your body is ready.

Evelyne: I love this, and I think it’s such a good reminder for practitioners listening who maybe don’t work in fertility per se, but who are seeing patients in their 20s and 30s to at least like, ask the question and see if they are doing anything about that. So thank you for sharing that.

Dr. Kalea Wattles: Yes. Thank you for bringing that part up, because when I was in primary care before and when I would do my wellness checks on women who are 22 or 25, I would say, what are your goals? What are your hopes and dreams about this, just so that we could open that door of communication.

Evelyne: Yeah, absolutely. Well, Kalea, thank you so much. This has been such a fascinating, insightful conversation and very actionable for practitioners listening. So I’m so grateful to you. Thank you.

Dr. Kalea Wattles: Thank you for allowing me to talk about all the things I love.

Evelyne: Yes. We might have to do it again because I feel like there’s so much more we could cover. So thank you again.

Thank you for tuning in to Conversations for Health. Check out the show notes for resources from today’s episode. Please share this podcast with your colleagues. Follow, rate or leave a review wherever you listen. And thank you for designing a well world with us.

Voiceover: This is Conversations For Health with Evelyne Lambrecht, dedicated to engaging discussions with industry experts, exploring evidence based, cutting edge research and practical tips.