Chronic Stress, Inflammation & Egg Quality: How Immune Signaling Affects Fertility

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In this episode of the Love & Science Fertility Framework, Dr. Erica Bove explores the relationship between chronic inflammation and oocyte quality.

Chronic inflammation affects folliculogenesis, meiotic integrity, hormonal balance, immune signaling, and embryonic developmental competence. While acute inflammation is essential to physiologic processes like ovulation and implantation, persistent immune upregulation may disrupt reproductive outcomes.

Topics discussed include:

• How cytokines and oxidative stress affect egg maturation

• Inflammation and meiotic spindle abnormalities

• Smoking and DNA methylation changes in granulosa cells

• Insulin resistance and inflammatory signaling in PCOS

• GLP-1 medications and inflammatory pathway interruption

• Autoimmune disease and fertility outcomes

• Endometriosis and inflammatory pelvic microenvironments

• Ovarian fibrosis and follicular atresia

• The role of adipose tissue as an endocrine organ

• Diet, microbiome health, and anti-inflammatory nutrition

• CoQ10, vitamin D, and antioxidant support

Dr. Bove also discusses modifiable lifestyle factors that influence inflammatory signaling, including diet, exercise, smoking cessation, stress reduction, and sleep optimization.

Chronic inflammation represents both a risk factor and an opportunity — as many contributors are within our control.

This episode is part of Season 1 of The Love & Science Fertility Framework: The Biology Beneath the Surface — a clinical series examining the physiology that drives reproductive outcomes.

Transcript

Hello, my loves, and welcome back to the Love and Science podcast. Today we're going to talk about a very important topic, which is chronic inflammation and oocyte

quality. We know that chronic inflammation can lead to changes in oocyte quality,

folliculogenesis, hormone production, and immune signaling. This is likely related to myiotic and cytoplasmic oocyte maturity, which we know can affect developmental competence, both of the egg prior to fertilization because we need mature eggs to be fertilized, and also developmental competence of the pre -implantation embryo. Now, many of us learned in medical school that there is acute inflammation and chronic inflammation. Acute inflammation is very important, right? Say we have a cut, right? And then we get all the reports.

And we also get proliferation of connective tissue and blood vessels. When this happens, we have enzymes and cytokines that rest to the area. And over time, that can do long -term damage to cells, tissues, and organs.

Now, we know that some inflammation is important to allow the fertility processes to happen, right? We need this for egg health. We need this for implantation. There's the whole field of reproductive immunology, which I think there is a lot of promise for the future. As of right now, we don't have a ton of data -driven treatments, although I think we can all acknowledge within reproductive endocrinology that the immune system and inflammation is important in the process, right? But I think that immune upregulation can also cause a lot of destruction, and we should talk about some of the factors which can lead to that.

I get a lot of questions in both my medical practice and my coaching practice about

the role of lifestyle factors as pertains to chronic inflammation and overall

fertility. Now we know we have really good data that lifestyle factors such as

smoking, exercise, diet, and sleep play a critical role in both fertility and chronic

inflammation.

In terms of diet, diet may either increase or reduce the progression of chronic

inflammation. We know that diets that are high in salt, also diets that are high in

saturated and are trans fats with a lot of processed foods such as refined starches

and sugar, they have been reported to contribute to systemic inflammation. And by

contrast, foods rich in omega -3 fatty acids, fiber -rich diets, and antioxidants,

Those turn out to be key players in anti -inflammation.

We also know that adipose tissue, if and of itself, is a highly active endocrine

organ, and we know that obesity can lead to chronic inflammation,

and that's actually been really one of the targets of a lot of research recently in

terms of the overall environment for women who are trying to get pregnant, as well

as egg quality in and of itself.

Now, physical activity in moderate amounts can be very beneficial to the process as

well. So it's really interesting. There is actually some data, so many,

much of which is in animals, but looking at, you know, what happens when you have

animals exercise over time. And, you know, when we do engage in moderate exercise,

we can see, you know, basically cytokines that increase or decrease when we do these

things. And there are some data looking at an improvement in fertility when rodents

were exposed to, you know, regular exercise as well as a reduction in CRP levels.

This data has also been shown in women with PCOS that regular exercise can reduce

CRP levels in them as well. I will also say a lot of the newer data about GLP -1s

in people with PCOS shows that pregnancy rates increase, sometimes even before the

weight falls off, which does suggest that GLP -1s are interrupting the pro

-inflammatory pathway, and perhaps that's what's most destructive. You know, obviously

we need to pay attention into obesity for many reasons in terms of maternal and

fetal risks, but perhaps a lot of the pathogenesis in PCOS, even in IVF settings,

is related to inflammation.

Now, smoking is a whole other topic altogether. You know, fortunately, I don't see

too many people these days who are smoking cigarettes. I do see a lot more that

are smoking marijuana. But if you look at what smoking is doing at the level of

the egg, you know, it actually causes DNA methylacid changes in the granulosis cells.

of more spontaneous settings and also IVF settings. Interestingly, even exposure of

mice to cotanine and the mouse oocytes to cotanine, which is one of the major

metabolites of nicotine and cigarette components, showed that that can affect the

exclusion of the first polar body, which we're getting super nerdy here, but we know

how important that is in the myotic processes of, you know, egg maturation and So

subsequently, there is fertilization, right, that happens as well.

And so I think that if we're thinking about, again, developmental competence of the

oocyte in the early embryo, we know that because cotenine increases oxidative stress,

it causes abnormal spino morphology and chromosome misalignment, that there may be

some data that lead to a pathogenesis of aneuploidia as well. We talked a little

bit about the effect of diet, right?

involved in the inflammation that we have in the pro -inflammatory signals. And the

nice thing is, this is actually a modifiable factor, right? So if we can eat the

foods that are good for us and change our microbiome, I think we might see some

beneficial effects and fertility.

Now, let's talk a little bit about autoimmune diseases, right? We've long known that

autoimmune diseases are not good for the fertility system. It's been a little bit

hard to pin down exactly why. So we know that women who have other autoimmune

diseases tend to have worse outcomes, right, in infertility, whether it's outside of

IVF or within IVF. And, you know, some of that may be because there's also

autoimmune antibodies to the ovaries that are just really hard to measure. Like we

see this a lot in primary ovarian sufficiency where somebody may also have

Hashimoto's and they may also have, you know, type 1 diabetes and other autoimmune

issues. But I do think that, you know, when we think about even,

even if somebody's ovarian reserve is normal and they have an autoimmune condition

such as rheumatoid arthritis or, you know, SLE, which is lupus, we will often see,

you know, worse ed quality in those patients. And it can be, you know, more of an

uphill battle to get pregnant. And what we say is, you know, if those conditions

are controlled, we often see better outcomes, which is likely related to the

autoimmune and inflammatory pathways.

Now, I will say that I've thought for a long time that endometriosis may have an

autoimmune etiology. Regardless of the etiology, we know that that endometriosis and

inflammation go hand in hand, right? And so when the, when the blood, the menstrual

blood is in the pelvis, it creates inflammation. The body has a hard time getting

rid of that tissue. And then we can get all sorts of cytokines and scar tissue

formation. And we know how much damage endometriosis can do, you know, to egg

quality and also the overall environment of the reproductive system. And so I think

we're going to be seeing more and more data about that, but I think understanding

the, you know, maybe breaking the anti -inflammatory pathways of endometriosis can be

quite powerful in, you know, helping people finally get pregnant and stay pregnant.

And then also, you know, even PCOS, it's interesting. Like there's even some emerging

data that women with PCOS are more likely to have other autoimmune conditions and

positive ANAs and anti TVO antibodies, and I think that as we're looking at long

-term clinical management, I think that we may be looking at this more and more.

So why is it that inflammation is so hard on the system? You know, I think there's

some proposed mechanisms. One is that there's a disruption of hormonal balance, right?

And we know that when there's chronic inflammation, that that can interfere with

hormone secretion, It can make the hormones bind less well to the receptors. And it

can also activate the, the HPA system as well, right? So it's like kind of the,

this self -promoting cycle, is it the chicken or the egg? But when our adrenals get

involved, we have increased corticosteroids and, you know, we don't sleep as well.

And, you know, there is like this whole host of positive feedback loops that can

get involved. Also, insulin resistance. We know that when people have chronic

inflammation, they can often have issues with their metabolism hormones, such as

leptin, gurellin, insulin. And again, that's perhaps why these gLP ones are,

you know, so effective. But I think that we really need to think about the link

between inflammation, metabolism, and fertility, because it's really a window of

opportunity.

It's also really interesting when we think about chronic inflammation at the level of

the ovary, right? So we know that chronic inflammation can alter the immune cell

population in the ovary, both in terms of cell types and the ratio between the

different cells.

The thought is that the cytokines that are affecting the immune cell populations of

the ovary can do long -term damage over time, such as ovarian fibrosis, problems with

meiosis, and can lead to oocyatrician and inhibit folliculgenesis, right? And we know

that all these things are related to infertility. And so, you know, I would love to

see more on chronic inflammation and, you know, recurrent implantation failure and the

level of the endometrium as well, because, you know, I firmly believe that when we

can manage chronic inflammation, we can have improved fertility, you know, much of

which is at the level of the egg and egg quality, but I think it's also

systemically important for the overall environment of getting and staying pregnant.

So what can we then do to help with these issues, right, this chronic inflammation,

like even stress in it of itself can lead to chronic inflammation? You know, I

think that there's a lot of power in the food that we eat, right? And so if we

can eat food that is rich in antioxidants, right, fruits, veggies, food that's not

processed, that is going to go a lot farther for us than eating foods from the

middle of the grocery store, which we know can really create inflammation like, you

know, white bread, white pasta, a lot of those foods that maybe we grew up with,

but they're really not as good for the system. We can also, you know, stop harmful

behaviors such as smoking and perhaps drinking and marijuana use because we know that

those induced free radicals and really, you know, undo a lot of the good work that

we're making with other lifestyle choices. So if that's a factor for you, you know,

really make sure to get the support that you need to be able to get on a better

track with that. We can also start taking antioxidants, right? So there's coenzyme

Q10, which has been really touted recently, oh, not even just recently, but it's

been a while now, but there's good animal and human data that co -enzyme Q10 or

CO10, 200 milligrams three times a day can really make a big difference in egg

quality. And even vitamin D, right, there's been some studies looking at vitamin D

and egg quality that that can be helpful as well.

So I really think we are just starting to skim the surface in terms of research

about chronic inflammation and egg quality. But, you know, I think,

time, no matter your persuasion, right? Like there's so much wisdom in that prayer

because if we can identify what's in our control and we can identify what's out of

our control and then we can have the wisdom to know the difference, then life just

gets a lot easier and we stop resisting reality and we take back our agency, right?

So if we can really think about chronic inflammation and reducing our stress levels

and sleeping better and stopping any habits that are harmful and making sure our

diets, not 100 % at the time, right? We're not aiming for perfection, but most of

the time we're doing kind of what's good for us, good for our bodies, good for our

microbiomes, good for our egg health, then we start to see meaningful changes. And

so I hope this was beneficial to you. And we will talk more about inflammation in

the coming weeks as well. Remember how much I love you. Bye.