156. The Immune Evaluation Every Fertility Patient Deserves

Autoimmune disease is one of the fastest growing health categories being diagnosed worldwide — and it disproportionately affects women of reproductive age. Yet in most fertility evaluations, immune health is barely mentioned until something has already gone wrong. Two or three miscarriages. Unexplained infertility. And still no one has looked at what the immune system is doing.

In this episode of Cycle Wisdom, Dr. Monica Minjeur connects the dots between autoimmunity, cycle disruption, and fertility — and explains what comprehensive immune evaluation looks like when it is done from the beginning rather than after repeated loss. Through Camille's story, a 34-year-old who had lost two pregnancies in the second trimester and been told to wait for a third loss before any workup would be initiated, you will see what a complete evaluation can find — and what it can change.

You will learn:

• How Hashimoto's thyroid disease, antiphospholipid antibody syndrome, celiac disease, lupus, and rheumatoid arthritis each disrupt fertility and pregnancy in distinct and treatable ways
• Why thyroid antibodies increase miscarriage risk nearly threefold even when TSH is completely normal — and what to do about it
• What antiphospholipid antibody syndrome is, how it is diagnosed, and how treatment can reduce miscarriage risk from 50% to under 30%

If you have experienced recurrent pregnancy loss or unexplained infertility and immune factors have never been evaluated — this episode will show you what to ask for next. Learn more or schedule a free discovery call at radiantclinic.com.

Transcript

Speaker 0:01

Autoimmune disease is one of the fastest growing health categories that is being diagnosed in the world, and it disproportionately affects women of reproductive age. Yet in most fertility evaluations, immune health is barely mentioned until something has already gone wrong. Today, we're connecting the dots between autoimmunity, cycle disruption, and fertility, and also talking about what comprehensive care actually looks like when your immune system is part of the picture. I'm Dr. Monica Minjeur, the host of Cycle Wisdom, where we help women and couples restore hormonal balance and reclaim their wellbeing through personalized healthcare grounded in clinical excellence. So let's start off as always with a patient story who we'll call Camille. Now, Camille came to us at 34 years of age. She was otherwise healthy, had no known medical history, took no medications other than her prenatal vitamin, but she had experienced two pregnancy losses within the past two years. Her first pregnancy ended at 14 weeks and her second at 17 weeks. Her OB doctor had told her that there was likely chromosomal abnormalities, but at the time, Camille had declined genetic testing. She had significant amount of fear with conceiving again, but knew that she wanted to grow her family. She wasn't sure that she and her husband's marriage was going to be able to survive another loss emotionally, as it had been incredibly troublesome for them in the first place. But they also couldn't accept the fact that there was no explanation for why they had these second trimester losses. She described feeling like her OB was just treating her as a statistic. After her second loss, the OB told her that they needed to have three pregnancy losses before they would initiate a full workup. She left that appointment and didn't go back to the OB. Instead, a friend sent her to see us with one clear question in mind: Why is this happening? We started as always with a complete evaluation of her cycle, lab work, and included additional immune function. What we found was not one reason for her miscarriages, but three specific reasons that came up in the lab work and additional findings that showed up in the evaluation for endometritis. Most importantly, we identified antiphospholipid antibody syndrome. This is a common diagnosis that we find with miscarriages, and oftentimes it's not picked up until a couple has three or more pregnancy losses. We also identified insufficient progesterone in her luteal phase. This was first revealed through her short luteal phases on charting and then confirmed with the low progesterone levels checked seven days after ovulation. We also found that she was severely deficient in vitamin D and in iron stores. And finally, we did a chronic endometritis evaluation looking for inflammation or infection in the uterine wall lining and found that she did not have an adequate growth of lactobacillus, the good kind of protective bacteria that were present, and instead had developed some infections that needed to be treated. Rather than coming in without any answers, Camille left with a clear treatment plan. We started on some low-dose aspirin as well as heparin with any subsequent pregnancy because of the antiphospholipid antibody syndrome. We repleted her progesterone levels as well as treated endometritis and restored vitamin D levels all before she got pregnant again. I'm happy to report that Camille carried her next pregnancy to full term. She delivered a beautiful baby girl at about thirty-nine weeks. And what had previously looked like bad luck or genetic abnormalities actually turned out to be multiple, identifiable, and most importantly, treatable causes that no one had looked for previously. Now, before you get upset that nobody has done a complete evaluation for you, let's back it up a minute and talk about what we're looking at here. Now, the big picture here is that approximately one in six couples will experience pregnancy loss or miscarriage. It's most common to happen prior to eight weeks gestation, but in some situations can happen into second and even into the third trimester. Each different miscarriage or pregnancy loss has a different story and different potential reasons, or in many cases like Camille, sometimes multiple reasons. Now, we're gonna talk specifically about autoimmune diseases today and their impact on fertility as well as recurrent pregnancy loss. However, if you're looking for a more in-depth discussion about other reasons for recurrent pregnancy loss, go back to episode 115, where we talk briefly about autoimmune diseases, but also dig into lots of the other common reasons that we find for recurrent miscarriages. So if we look just at autoimmune diseases, let's talk about the numbers. Autoimmune disease impacts approximately 50 million Americans, and women account for nearly 80% of those that are diagnosed. Most autoimmune conditions also will peak during the reproductive years, sometime between 20 to 50 years of age. So it's no wonder that we oftentimes are also seeing overlapping fertility concerns or cycle related concerns. The autoimmune diseases we're gonna focus on a bit more today because they have the greatest impact on fertility and pregnancy include Hashimoto's thyroid disease- Antiphospholipid antibody syndrome, lupus, rheumatoid arthritis, celiac disease, and type 1 diabetes. Now, when it comes to autoimmune conditions and how they impact fertility, there are multiple mechanisms that go through all of these different conditions. Most commonly, what we find is disrupted ovarian function, which can impair ovulation. This can cause cycle irregularity, impaired implantation, recurrent miscarriage, pregnancy complications, and localized as well as generalized inflammation throughout the body. In most standard fertility evaluations, we find that when women come to us, immune factors have rarely been assessed unless there was already an underlying known diagnosis, meaning many women with undiagnosed or poorly controlled autoimmune diseases are labeled with unexplained infertility because nobody has done the work to look deeper. Now, in fairness, autoimmune disease can be incredibly challenging to diagnose and can take many years before you manifest enough symptoms or manifest lab findings that are going to be a part of that diagnostic process. But again, this is why it's important to have an index of suspicion to know what you're looking for and to understand which pieces need attention based on your symptoms. So if you've ever been told that recurrent miscarriage is just bad luck, or if you don't have an underlying reason or reasons for infertility in the first place, it is worth the evaluation and working with somebody who is going to dig a bit deeper. So let's break each of these down a little bit by disease process, and we'll talk through each of them. What are the symptoms? What does the diagnosis look like? And what can treatment do as far as changing your outcomes? So let's start with thyroid autoimmunity. Again, this is one of the most common things we find, and I talked a lot more about it back in episode 133, where I talked specifically about the interplay with thyroid antibodies and fertility. Now, one of the most common misconceptions with thyroid antibody disease is that if my thyroid antibodies are well controlled, there's no problem here. Or if my TSH or thyroid-stimulating hormone is normal, there's no problem here. And this is one of the most critically overlooked findings in reproductive medicine. Elevated thyroid peroxidase antibodies, even with a normal TSH, are an independent association risk factor with miscarriage and preterm birth. Oftentimes, we find that women will come in and they'll say, "I've got autoimmune thyroid disease, but my TSH is normal, so there's nothing else I need to do." A meta-analysis done of over 30 studies back in 2011 showed that thyroid autoantibodies increase your risk of miscarriage by nearly threefold and also significantly increases the risk of preterm birth, even in women who have their thyroid levels well controlled. This is why it's so important not only to optimize those thyroid function tests, like having a TSH less than 2.5, but it's also why it's important that we selectively are trying to treat those thyroid antibodies. Things like selenium supplementation and in some cases using other anti-inflammatory strategies like low-dose naltrexone or an anti-inflammatory diet can all help to decrease inflammation and improve outcomes. So again, not just enough to have a normal TSH lab test. Also important to make sure that the thyroid antibodies are well controlled, well managed, and that effective and impactful treatment is taking place The second thing we're going to talk about today is antiphospholipid syndrome, or sometimes antiphospholipid antibodies. Now, this was part of the process that was going on with Camille, and really where this plays a role is this is an autoimmune condition in which antibodies actually attack part of your bloodstream, which can cause blood clotting abnormalities. Now, these don't oftentimes show up as big blood clots like in your legs or in your lungs, but they can be microscopic clots that can impact the placenta blood flow. So if the placenta can't set up its placental blood flow well because of these microscopic clots, it can lead to implantation failure or impaired development of the placenta. Antiphospholipid syndrome is among one of the most common identifiable causes of recurrent pregnancy loss, and it's found in about 15 to 20% of women that have recurrent pregnancy losses. It can cause pregnancy loss in any trimester, as well as implantation failure, preeclampsia, preterm birth, and fetal growth restriction. The critical testing for this includes evaluation for antiphospholipid syndrome. Now, some labs will lump this all into one panel, and in some cases it needs to be checked specifically for each of these components, but it's important to make sure that this evaluation includes testing for lupus anticoagulant, anticardiolipin antibodies, and beta-2 glycoprotein antibodies. In order to confirm this diagnosis, you need to have two positive tests at least 12 weeks apart in order to determine if treatment is appropriate. And that's the critical piece here is that antiphospholipid syndrome is treatable. Most often it's going to involve low-dose aspirin and in some cases heparin injections during pregnancy, and this can significantly improve live birth rates. Without treatment, it's estimated that pregnancy loss ranges about 50%, but with treatment, that risk of miscarriage drops to less than 30% and especially when we're identifying other causes. Another important factor to consider when we're talking about autoimmunity is celiac disease. Now, this is oftentimes overlooked because it isn't considered to be specifically a reproductive disruptor. But if we think about the fact that celiac disease is an autoimmune condition, again triggered by gluten exposure, this damages the small intestinal lining and impairs the absorption of vital nutrients like iron, vitamin D, and folate, which are responsible then downstream for things like irregular cycles or the delayed onset of puberty, early menopause, and recurrent miscarriage. In fact, a study from 2014 showed that women with undiagnosed celiac disease had significantly higher rates of both infertility and miscarriage, but those rates normalized when those same women followed a gluten-free diet. Now, celiac disease affects approximately only 1% of the population, but it's estimated to be undiagnosed in at least 80% of people affected. Oftentimes, people will present with reproductive symptoms or symptoms of low vitamin deficiency rather than classic GI complaints. In our practice, one of the things we look for is do you have low vitamins in multiple areas, so vitamin D, iron, vitamin B12? And if we start to give you some oral supplementation, if we give you pills, your levels are not coming up, we wanna always consider or think about is there an absorption problem that may be going on. Now, there are certainly other things beyond celiac disease that can cause GI absorption, but celiac disease is one of the first things we always want to consider in our standard evaluation when you're not absorbing vitamins well. And then the final category as far as actual disease processes when it comes to autoimmunity that can have an impact on fertility, ovulation, and overall cycle health is going to be things like lupus or rheumatoid arthritis or Type 1 diabetes, things that have very specific lab criteria finding, but also things that typically are going to present with other significant symptoms. Now, most often when women come to us, they already know that they have a diagnosis of lupus or rheumatoid arthritis or Type 1 diabetes, but when these symptoms are not well controlled or when these disease processes do not have medications that align well with pregnancy, it's important that we would work together with your rheumatologist to make sure that not only do we have your symptoms well managed, but that the medications you're taking for these diseases are safe for fertility and pregnancy. Another common thread that plays through with lupus and rheumatoid arthritis in particular is that vitamin D is profoundly important for regulation of your immune system across all autoimmune conditions. This is why vitamin D is always a part of our standard initial screening w- across the board to make sure that we aren't dealing with any significant immune dysfunction and to make sure that when you do become pregnant, we have enough vitamin D on board already for baby. So what does it mean to have these autoimmune conditions, and what specifically is that doing in the body? Most commonly, we have to rely upon a well-collaborated system of your immune environment to ensure that successful implantation occurs. We need to make sure that your body is recognizing the embryo is not something foreign to fight off. So we're looking for things like what is the immune environment of the uterine wall lining. Things like chronic endometritis, that low-grade uterine inflammation, is often associated with autoimmune activation, and we are increasingly beginning to recognize this as a cause of implantation failure and recurrent pregnancy loss, especially in women with autoimmune disease. For more information on chronic endometritis, go back to episode number 135 where I talk all about the female microbiome and why it plays such a role with recurrent pregnancy loss. Something else that we look at or consider is something called natural killer cell activity. Now, we know that we can look for natural killer cells in the bloodstream, but a newer thing that's being studied is uterine natural killer cells. This is being studied as a potential cause of implantation failure, and basically what happens is these natural killer cells are designed in our body to fight off anything that is foreign, especially like an infection. But if we have too much of these natural killer cells, especially in the uterus, it can actually fight off anything else that is new, like a developing embryo. This is a very complex area of reproductive immunology, and again, we're just starting to scratch the surface with our understandings of how do we evaluate it, how do we treat it, and what is the best plan of action going forward? Again, most importantly with all of these is that treatment is going to be dependent upon the cause. We wanna focus on treating the specific disease state. Is inflammation a part of the picture? Is microscopic clotting a part of the picture? Do we have uncontrolled thyroid or blood sugars or other joint symptoms? Making sure that we're managing not only the symptoms, but specifically treating everything else that goes into that inflammation. We always will talk with our patients that have autoimmune disease about an anti-inflammatory diet. So we will oftentimes try reducing or eliminating gluten, dairy, sugar, eggs, and not necessarily all of those things, and not all at the same time, but oftentimes we find that at least one of those categories, if not multiple, tend to increase the inflammation. So again, anything we can do to decrease inflammation is going to be really impactful. And then finally, one of the very important treatments that we oftentimes are also utilizing in autoimmune disease, not just for women, but for men as well, is going to be low dose naltrexone. Low dose naltrexone is a very, very old medication, and it is commonly used to treat immune function, and we utilize it frequently in the world of restorative reproductive medicine. I talk all about low dose naltrexone in episode number 88, and there is a lot of information out there online right now about low dose naltrexone, how it helps immune function, treatment of autoimmune disease, and other chronic symptoms. So let's wrap up today with a couple of common questions that we get asked. Again, can autoimmune disease be managed naturally, or does it always require medication? Again, this is going to depend upon the condition and its severity. So for example, if you have Hashimoto's disease, sometimes dietary interventions, selenium, vitamin D, can meaningfully reduce the antibody load and inflammation in many women. In others, we find that we need to do thyroid medications to help balance the thyroid hormones. For things like antiphospholipid antibody syndrome, anticoagulation with aspirin and sometimes heparin is essential. This is not a condition where natural management is sufficient, and the overall answer is an accurate diagnosis first will always lead to the appropriate intervention necessary Now, what if I've had a few miscarriages? Should I automatically be tested for antiphospholipid syndrome or other autoimmune diseases? And in my world, I would say yes. Conventional OBs won't generally test for you until you've had three or more losses. But again, we find oftentimes that there are identifiable and treatable causes, and so the cost of waiting could be another pregnancy loss. In my world, one loss is too many. So we oftentimes will test after you've had one or two losses, especially if you have other risk factors. So if your charting looks unusual, if you have other hormone deficiencies or other identifiable causes, it is absolutely reasonable to take a look and make sure we're not missing anything else. Imagine if autoimmune disease was a part of the fertility conversation from the beginning, not after a third miscarriage, not after years of unexplained infertility, but from the very first appointment. Women with autoimmune thyroid disease, celiac disease, or a history of recurrent pregnancy loss should be offered a complete immune evaluation as a matter of standard care because the tools exist for diagnosis and the treatments work. Imagine if the immune system was understood not as an obstacle for fertility, but as a system that created the conditions for a healthy pregnancy to begin and to continue when it's properly supported. That is what comprehensive reproductive care looks like, and this is the healthcare we provide every day to improve your overall health and promote fertility.

Speaker 2 20:31

If you're ready to work with our elite team of healthcare professionals, go to our website radiantclinic.com to schedule a free discovery call and learn more about our package-based pricing for comprehensive care. We are currently able to see people for in-person appointments in our Cedar Rapids, Iowa clinic or can arrange for a telehealth visit if you live in many different states across the US. Check out our website for current states that we can serve medical clients, and let us know if your state is not listed to see if we can still cover you there as we are constantly expanding our reach. Please note that our fertility educators are able to take care of clients no matter where they live. Thank you so much for listening to this episode. Please share this podcast with someone in your life who would benefit from our services. Remember to subscribe to this podcast for more empowering content that I look forward to sharing with you on our next episode of Cycle Wisdom