Creating a Family: Talk about Adoption & Foster Care

Understanding and Preventing Miscarriage and Recurrent Pregnancy Loss

March 02, 2022 Creating a Family Season 16 Episode 9
Creating a Family: Talk about Adoption & Foster Care
Understanding and Preventing Miscarriage and Recurrent Pregnancy Loss
Show Notes Transcript

What causes miscarriage and recurrent pregnancy loss? What is the best treatment and what are the controversies in the diagnosing and treating of miscarriage? In this episode, we talked with Dr. Lora Shahine, Reproductive Endocrinologist and Director of the Recurrent Pregnancy Program at Pacific NW Fertility and clinical faculty at the University of Washington in Seattle, and author of the book Not Broken: An Approachable Guide to Miscarriage and Recurrent Pregnancy Loss.

In this episode, we cover:

  • What is miscarriage? What other names do medical professionals use?
    • Does the name change depending upon when in the pregnancy it occurs? 
    • What is a biochemical pregnancy and is it a “miscarriage”?
    • When does miscarriage become “recurrent pregnancy loss”?
    • How common are miscarriages? How common is recurrent pregnancy loss?
    • Who should you see?
    • What is the role of the male in miscarriage and recurrent pregnancy loss?
  • Common causes and treatment 
    • What are the common causes for first trimester miscarriage?
    • What are the common causes for recurrent pregnancy loss?
    • How to diagnosis the cause of recurrent pregnancy loss?
    • How to treat/prevent recurrent pregnancy loss?
    • What should patients do to reduce their chance of a miscarriage?
  • Understanding the controversies in treatment of recurrent pregnancy loss.
    • Inherited Thrombophilia
    • Methylene Tetrahydrofolate Reductase (MTHFR)-how our body processes folate
    • Luteal Phase Defect and progesterone treatment
    • Infection
    • Thyroid
    • Immune system & immune treatment for RPL
    • Aspirin treatment
    • IVF as treatment for recurrent pregnancy loss

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Please pardon the errors, this is an automatic transcription.
0:00  
Welcome to Creating a Family talk about infertility. I'm Dawn Davenport. I am the host of this show as well as the director of the nonprofit creating a family.org. Today we're going to be talking about miscarriage, understanding and preventing this carriage and recurrent pregnancy loss. We will be talking with Dr. Laura Shahine. She is a reproductive endocrinologist and the director of the recurrent pregnancy loss program at Pacific Northwest fertility and clinical faculty member at the University of Washington in Seattle. She is also the author of a terrific book called not broken an approachable guide to miscarriage and recurrent pregnancy loss. I love talking with Dr. Shahine. She is so personable and she is so approachable and understandable. This is a re-air of a show that we did a while back. It was too good not to let you hear again. I hope you enjoy. Welcome Dr. Laura Shahine. Thank you so much for being with us today.

1:06  
Thank you so much done. That was a lovely introduction. And I'm so happy to be here.

1:12  
Well, we're going to start with talking about what is miscarriage and what is recurrent pregnancy loss and why does it happen? So how do we define a miscarriage? And what other names do medical professionals use? That might be confusing to a patient?

1:27  
Absolutely. So a miscarriage is any pregnancy that does not continue beyond 20 weeks of gestation. And there are different terms that are used clinically and in textbooks. And sometimes patients even get confused when they get medical bills and they see upsetting. Like the word abortion abortion means a pregnancy that does not continue. We associate that word with a voluntary termination of pregnancy but abortion really means that a pregnancy doesn't continue for whatever reason. So the biggest differentiation and textbooks and sort of can be confusing for patients to is a biochemical miscue versus that's a question that often comes up. So if someone has a positive home pregnancy test or a positive blood test, that confirms pregnancy hormone, if that pregnancy stops developing before it gets to the point where we could see anything on ultrasound, or maybe even have a tissue diagnosis, we call it a biochemical miscarriage or a biochemical pregnancy loss and later losses where we can do more testing or have more information. We call those clinical miscarriages.

2:46  
Okay, so and even if you've had a pregnancy test, a blood pregnancy test at your doctor's office, if you lose the pregnancy before it's confirmed by ultrasound is that when it becomes what we call a biochemical pregnancy?

3:00  
Correct? It's okay. Yeah, biochemical miscarriage or a biochemical pregnancy loss.

3:06  
Okay, so that's miscarriage. So what do we mean by recurrent pregnancy loss and I assume the emphasis is on the word recurrent on that one.

3:15  
Absolutely. And patients often get confused because textbooks and websites and even their own, doctors can say different things. The traditional textbook definition of recurrent pregnancy loss is three or more clinical miscarriages. There's a lot in that definition. So again, it's a clinical miscarriage, it gets further along than a biochemical miscarriage. Some of you can see on ultrasound or tissue diagnosis. And this has to happen three or more times to meet that textbook or traditional definition of recurrent miscarriage. Now, in 2013, or 2012, ASRM, the American Society of Reproductive Medicine put out a new definition and clarifying document in their guidelines. That says for the purposes of investigation and evaluation, and medical discussions and sort of reasons to see your doctor. recurrent pregnancy loss is defined as two or more clinical miscarriages. And so it is okay according to the American Society of Reproductive Medicine to start doing evaluation and testing if someone's had two or more of these clinical miscarriages. Now a big issue is that leaves out biochemical miscarriages, I was

4:44  
just gonna ask about that. Yeah. Okay. So if you're not ever able to get past six weeks or eight weeks before ultrasound, and your Doesn't that count for something?

4:56  
Absolutely. And I often tell people, that it It's just as devastating when you're trying to start your family, whether you have just a period that comes there goes another month, or it's more devastating to have a positive pregnancy tests you've been waiting for for so long and then go on and have a late period. And to go to a medical provider and sort of say I'm having pregnancy losses, and have that medical provider say, Oh, that's not a real miscarriage. That's really disheartening for so many women. And the medical literature and textbooks and even different doctors say different things. The European Society of Reproductive Medicine estery, they do endorse doing testing with biochemical miscarriages, because they've had a more recent update in their professional guidelines. But that's not necessarily adopted by a lot of practitioners in the United States or kind of anywhere. So it's really up for discussion. And in my own practice, I'm happy to share with you that I do do testing for people with recurrent biochemical miscarriages, because I don't want to miss something in the patients that I could intervene with, and decrease their risk of another miscarriage, whether it's biochemical or clinical.

6:21  
And then but that might change by the doctor, by your reproductive endocrinologist.

6:25  
Yes. And it is confusing and frustrating for patients to get different interpretations and different recommendations from from different providers. And that's because we still have so much to learn.

6:38  
Yeah, exactly. Alright, so how I'm going to make a distinction here between miscarriage and recurrent pregnancy loss. And if you want, we can make a distinction between biochemical pregnancy or biochemical pregnancy loss. But the whole point is, how common How common is it? How common are miscarriages and how common is recurrent pregnancy loss? Because I suspect that that there's a distinction there on this frequency?

7:02  
Sure. So one in four pregnancies will end in miscarriage. And that is a definition that you'll see in a lot of textbooks and literature. And I would argue that if you include biochemical miscarriages, it's a lot higher than that. And I believe that most women getting together with their girlfriends for dinner, it's someone at the table is going to have had a miscarriage and maybe even more than one or two people sitting at that table.

7:35  
Yeah, so miscarriages are amazingly frequent.

7:38  
Absolutely. And that increases with age. So as women age, there's a higher risk of miscarriage, such that when someone's 40 years old, it's really 50% of positive pregnancy tests will not result in a baby.

7:56  
So now how common is repetitive miscarriages, recurrent pregnancy loss of two or three, depending on your definition,

8:04  
or so the American Society of Reproductive Medicine says that it is rare, it's less than 1% of women will have two or more clinical miscarriages. And I think I just see a lot more than that. Because of my personal practice. It seems like a lot.

8:23  
Yeah, well, you're because you're specializing. So yeah, I would assume you would. Alright, so for a woman who has just and let's say she's not in fertility treatment, and she has a miscarriage and it's her first one. Should she do anything? Or at that point, should she go? Well, she needs to see her OBGYN and let her OBGYN know that she's had one. But other than that, does she need to do anything with it just one?

8:50  
Well, most people that have a miscarriage go on to have a healthy baby, and without any intervention, because each pregnancy is a new opportunity. And most miscarriages are a result of something going on with that embryo. So the next pregnancy has a high chance of being successful. So I don't want to dismiss any miscarriage whether it's a woman's first miscarriage or her fifth. But usually, providers would say, try again, maybe would go through any chronic illnesses that the woman has or medications that might be associated with miscarriage, or ask some questions. But I would not do extensive testing with one miscarriage and without some other history leading me down a certain path and most providers would not and try to provide reassurance comfort and encourage the couples to try again.

9:53  
And if you've had two or more miscarriages, what type of doctor should you see? I mean who specializes, because I'm a big believer in saying specialists who specializes in recurrent pregnancy loss.

10:07  
Sure, the specialist for first trimester miscarriages and especially recurrent first trimester miscarriages are reproductive endocrinologists like me. And so these are physicians that have done obstetrics and gynecology training for four years outside of medical school. So they've done that OB GYN residency, but then they've gone on to study three more years and a fellowship for reproductive endocrinology and infertility. That being said, there aren't a lot of reproductive endocrinologist in the United States, and most women will probably start an evaluation with their OB GYN or primary care provider.

10:52  
Okay. And before we move past, the initial, you know, what is and what to do about it, or not what to do about what is and why does it happen? We shouldn't leave our male partners out. So what is the role? Or what do we know about the role of the male in contributing to miscarriage or recurrent pregnancy loss? Or is this solely a female problem?

11:15  
It is absolutely not just the woman's fault. The male partner is contributing 50% of the genetic material. However, your specific question is, how much do we know? And my specific answer is shockingly little amazing. I mean, I did I devote a whole chapter to the male partner in my book, because I believe that it's so important to address their participation and the emotional impact. But yet most of the chapters saying that we have very little research into the role of genetics. We're starting, we're doing a lot more. A lot of this is just research bias. If there's going to be any money thrown at the problem, we as a society have focused on women for so long. Anything to do with family building, is the woman's fault. But exactly, yeah, so we're starting. I mean, there's some small studies looking at maybe slightly higher DNA fragmentation in sperm from couples with recurrent loss, maybe in association with age of sperm. We know there's an association with age of eggs and miscarriage, but now maybe also age and of sperm. But these are small studies are to replicate. And I think we're just getting started. Okay,

12:37  
let me pause for a moment and remind everyone that this show is underwritten by our corporate sponsor faring pharmaceutical. They want you to know about an app for to calm. It is an app. It's for your phone, either Apple or Android. And it was developed by reproductive psychologist Dr. Ellis Domar and Dr. Elizabeth grill. And it was designed specifically to help women address the many challenging emotional life situations that arise when you're struggling to conceive, and it uses lots of techniques cognitive behavioral, and as well as relaxation techniques. It is a great app, it is available for no charge, and you can get more information at verta. Calm app.com. All right, part two, what are the common causes and treatments for miscarriage and recurrent pregnancy loss? So what are the common causes for and when talking about miscarriage? I think in this session, we talked about causes we need to divide by trimester. So let's start with the first trimester miscarriages. What is the most common cause?

13:45  
Absolutely, it's a genetic issue within the embryo is the most common cause of miscarriage if we're able to test pregnancy tissue, so if someone gets far enough along we can get a tissue sample, we find that anywhere from 60 to 70%. Of first trimester miscarriages will show a chromosomal rearrangement and imbalance of chromosomes that is associated with miscarriage.

14:13  
Okay, now for recurrent pregnancy loss. Let's go through there's a number of as well as percentages that have been shown through research to cause recurrent pregnancy loss. And I will the teaser spoiler will be that I'll go ahead and give it is that about 50% are unexplained. But let's we'll come around to that at the end. Let's start with uterine issues, and that's about 15% of recurrent pregnancy losses are caused by uterine issues. So what do we mean by uterine issues and what do we do about it? First of all, what do we mean by

14:51  
door and I just want to clarify when I'm doing an evaluation for recurrent loss, these are the things that I look for, like uterine issues. But I always warn people before we start doing the testing, that it's most likely that we're not going to find anything with the people getting pregnant. Because the most common causes within the embryo we're going through are the typical evaluation and testing that should be initiated, I believe if someone's had two or more miscarriages, and so one of the first things that we do is a uterine cavity evaluation. And what we're looking for is any anatomical cause that could be impacting the ability of the embryo to implant. And something that a woman could be born with is a uterine septum, we can find this on a uterine cavity evaluation. It's a fibrous band of tissue that comes down in the center of the uterine cavity that really should resolve at birth. We all have one when we're developing, but it gets removed just in our our own embryonic development. But if it's there, it can be associated with a higher risk of first trimester miscarriage. Other uterine issues that may come up over time something that someone might not be born with, but could be associated with a higher chance of miscarriage could be a uterine fibroid that's located inside the uterine cavity, maybe a large uterine polyp. And sometimes people who have significant scarring inside their uterine cavity or adhesions might have a more difficult time with miscarriage. Okay, and

16:33  
what tests do you run to determine uterine causes,

16:37  
so there are three that are available, the gold standard is doing a diagnostic hysteroscopy, where a small camera is passed through the cervix in order to look on the inside of the uterine cavity. The other two tests that are considered less invasive, are a saline infusion sonogram, or water ultrasound, or a lot of people use different terms for it. But it's putting sterile saline or salt water into the uterine cavity to expand it, and look at the cavity closely under ultrasound. And then the third option is a history of South pinga gram or H S, G. And which dye or contrast material is through the cervix and watch that fluid fill up the uterine cavity, and then spills through the fallopian tubes.

17:30  
Okay, so if you find through any of these tests, that there are uterine issues that may be contributing to miscarriage, what do you do about it?

17:40  
Usually hysteroscopy is the first next step. So taking a small camera, looking inside the uterine cavity, if it's a septum, it's very, usually very easy to just snip the septum through, you know, with little small scissors through the cervix. If there are fibroids, sometimes that can be removed through the history of scope, polyps to you really hoped that it would be a simple surgery like that, rather than something that you would need, like an abdominal incision for something like that.

18:11  
Okay, so now we've talked about uterine issues. So as you're going down your diagnostic checklist, what would be the next thing that you would consider assuming I guess uterine issues are not are not the cause? Sure.

18:25  
So the professional societies recommend, the next test should be parental carrier types. And so this is a blood test that is looking for the karyotype or chromosome balance in the female and male partner that are having miscarriages together. And it's looking for something that's very rare, we only find it 3% of the time or less, but it's called a balanced translocation.

18:53  
Can you give us a a crib note the simple version for the you know, the, let's say, let's don't say high school biology, let's say middle school by ology version of what that is now, maybe better to high school?

19:06  
Absolutely. Well, you know, I talk about this every day. And I feel like if I can't teach my patients, and I'm not being a good doctor, so hopefully, let me know if you if this makes sense to you. So the way I explained a balanced translocation, and I usually focus on the male partner if they're coming to see us for, for testing, and they're in the room, because all the other testing has to do with the female partner. So I'm kind of laser focused on him like this is the one blood test that you have to do. If someone has a balanced translocation. It does not impact their health. That's something that people get nervous about. They hear that we're doing a genetic test and like, oh my gosh, they're gonna find something wrong with me. And that's not the case. If someone has a balanced translocation, it means that when that person was being, you know, was it was an egg and sperm, you know, way back when, when the egg and sperm came together, there was an exchange of material Between chromosomes. So in every cell in our body, we suppose to have 23 pairs of chromosomes and one of the chromosomes come from the egg that we came from, and one came from the sperm that we came from. So when we are getting created, if there happens to be when those those chromosomes line up and exchange of material, such that information that should be on chromosome number 14, is over on number 18. And vice versa. That is a balanced translocation. There's no loss of genetic material, it's just rearranged a little bit. And what's really important about that is when that male partner starts to make make sperm every single day, a large portion of his sperm is going to be missing genetic material. Not all of the sperm, but let's say 50% 50% of the sperm is going to be missing big portions of DNA, and 50% of the sperm is going to be just fine. So that couple is at a higher risk of miscarriage than a couple where they don't have a balanced translocation. Because just not a lot of the sperm or eggs are going to be perfect.

21:14  
So what do you do? Okay, let's say this is a blood test a genetic test. What do you do if you find that that's the case? So what are options do couples have if that's the cause?

21:26  
Absolutely, they can keep trying. So not all of the sperm is affected. Not all of the eggs are affected. But now they know why they're having more miscarriages than their friends. And the very next time that they conceive with a new sperm and a new egg, they really could have a healthy baby. So they could keep trying naturally tentative is to test embryos before they conceive. And that requires IVF. So we have the ability to test embryos for chromosomal rearrangements and imbalances, but it has to happen in embryos outside of the body. And then we implant an embryo that tested okay.

22:12  
And the one of the downsides to that is cost. Absolutely. Right. Okay. So I mean, that's the but that is an option. Okay, so going down your diagnostic checklist we've covered to uterine abnormalities and translocation, genetic translocation, what is the balance I should add? What's the next thing you would test?

22:34  
Sure all the professional societies agree on one other test that a couple should have? And it's screening for something called anti phospho lipid syndrome, which is an immune issue associated with first trimester miscarriage and other obstetric complications even later in pregnancy?

22:55  
Okay, and what type of test is that? What is the test that you use for that?

23:00  
It's a blood test for the female partner looking for certain antibodies in her blood that really should not be there outside of pregnancy. So it is important to do the blood tests, not right when someone has a diagnosis of miscarriage. But later, you know, usually, honestly, the textbook recommendation is is about six to 12 weeks after a pregnancy is resolved is when you can really get a test.

23:27  
Okay? And if that is the problem, what are the choices? What are the options that the couple has for conception? Sure,

23:36  
the first line treatment is to take aspirin throughout pregnancy. And then sometimes patients will take blood thinners something like heparin through the pregnancy. Okay.

23:48  
Now, before we leave this part, let's talk about what patients can do from a lifestyle standpoint, to reduce their chance of miscarriage, acknowledging full well that the majority of the vast majority of miscarriages are caused by something wrong with the embryo, and there's not a darn thing you can do. But to change that, in fact, I think it's important to acknowledge that in that the loss of the pregnancy when there is something genetically wrong with the embryo is actually your body working the way it's supposed to work. So, but nonetheless, what what from a lifestyle standpoint, and I know that this is a topic you could probably talk forever on. And I've heard you talk forever on at a number of conferences. So just briefly, though, what can if you've had recurrent pregnancy losses? What should you be looking at in your lifestyle that you need to potentially address or change? Sure, and

24:45  
I think we all really know how to be healthy. And so I think about focusing on being healthy in order to have the healthiest pregnancy that you can. So things that we can do are eating well. Balanced foods, mostly plants, variety, organic, non processed, if at all possible. Think about getting sleep. And that's one of the most important things that we can do for our hormone balance and metabolism, we think about having a healthy weight. And that doesn't mean losing a lot of weight in an unhealthy way. But and it also can mean, sometimes people are too thin. So trying to have a healthy weight is important. Thinking about things that we do to our body that we know are not healthy, like smoking, drinking too much alcohol. Marijuana is there's this feeling that marijuana is natural, and it's from a plant and therefore it should be safe. And it's with the legalization of marijuana and a lot of states a lot more women are smoking through pregnancy. I don't have data to say that. Marijuana absolutely increases the risk of first trimester miscarriage, which is my area of expertise. But there are other obstetric issues that can be associated with smoking marijuana regularly,

26:09  
as long as as well. There is a growing evidence of smoking marijuana during a pregnancy can impact the baby and child both at birth and later in life. Yeah,

26:22  
thank you. I also talk a lot about decreasing the exposure to toxins, because I think that's important for everyone. But fetuses and young children are most vulnerable to endocrine disruptors. And I think it's important when you're trying to conceive and actually through your whole life to be thinking about decreasing exposure to plastics and chemicals that are in a lot of common household products,

26:48  
and just mentioned one or two that we should focus on.

26:53  
Sure, I think about trying to get plastics out of the kitchen. So so many food containers to go containers, food storage, you know, heating things up in the microwave, and plastic, can absolutely make it easier for toxins like Bisphenol A, which is BPA, to leak from the plastic into the food. And it's just a really great way to introduce that into your system. Don't be lured into the marketing that is BPA free. Because any plastic i t's there's BP A through Z. And just because it doesn't have BPA doesn't mean that it's not going to harm you if you heat food up with it. So I think about the kitchen and trying to get plastic out of the kitchen. And then I think about products, think about your health products, your skin is your largest organ. And when you're using shampoos, and lotion and cosmetics that are right next to your skin, your body is absorbing it. And it is absolutely completely unregulated in the United States, and we have to be our own advocates for choosing products that are safer. And I'm a huge proponent of the clean beauty movement.

28:06  
Alright, and there is and you and I were both speaking at a conference a few months ago, and not together but separately, and you were showing me an app that you have on your phone that you allows you to read the QR code of any beauty. Well, I guess any product actually, we were doing it on lipstick. So maybe beauty product as well as, as other hygiene products. And it could tell you, it gives it a rating. So tell us about that app.

28:34  
Sure, there's two that I really liked. The one that I showed you is think dirty. That's kind of an easy thing to remember. So think dirty app. And then another great resource is e w g.org. The Environmental Working Group, sometimes people get really confused because the two different sources will say different things about different products. And that's you know, that's just a part of the part of, you know, each company has its own way of rating products. Nothing's perfect. And as long as you're learning and you're being an advocate for your care, and trying to find the safest products for you. That's the best you can do.

29:11  
Okay, excellent. And I will say that the lipstick that she showed that I think it was mine didn't come out, didn't score very well. So all right. Let me let you know that this show is brought to you not only by through our unsupportive our underwriter but also our partners. And these are organizations or clinics that believe in our mission of providing unbiased education and support to the patient's Oh hope that they along the continuum of trying to conceive and more than just believing if they put their money behind it. And that's it's their money that allows us to bring you both the show and and really all the resources on creating a family. One such organization is cryos international sperm and egg bank. They are dedicated to providing a wide selection of high Quality, extensively screened frozen donor sperm and eggs from all races, ethnicities and phenotypes for both home insemination as well as fertility treatment. Christ International is the world's largest sperm bank and the first freestanding independent egg bank in the United States. We also have Reproductive Medicine Associates of New York. They are one of the largest fertility practices in the state, and one of the largest in the country. By combining the latest innovation and reproductive sciences with compassionate and customized treatment plans, RMA of New York is able to provide the very best possible care. Alright, now for part three, we're going to be talking about understanding the controversies in the treatment of recurrent pregnancy loss. One of the things we know is that in the treatment of recurrent pregnancy loss, there are a lot of controversies. It sometimes feels like there's more controversial things that we don't know are in disagreement on and on things that we are in agreement on. But I think it's important too, from both the patient and the infertility nurse and other medical professionals standpoint, to talk about some of the controversies. So let's start with inherited thrombophilia. Is that controversial? And is it controversial in what part of its controversial the testing for it, or whether or not it causes recurrent pregnancy loss?

31:28  
Sure, it's controversial in that evidence is really shown that women who have inherited thrombophilia are not at higher risk of miscarriage. Therefore testing and treatment, which includes anticoagulation, or blood thinning for these issues, unless someone has a history of blood clots themselves, is not warranted. But this is something that has changed over the last 10 years. I remember being taught in my medical training that we should test for inherited thrombophilia. And this includes factor five Leiden prothrombin gene, protein as protein see just these genetic issues that sometimes put people at a slightly higher risk of blood clots, and all of the professional societies ASRM Estrie. So that's America, European, the hematology professional societies all around the world, all are proponents of saying that inherited thrombophilia testing for these things and treating them does not change obstetric outcome. But because lots of doctors in my generation, and those doctors are still teaching younger doctors. So patients are still getting these tests done and intervention is still happening. And it's just important to know that the evidence does not support it.

32:53  
And inherited thrombophilia means the tendency, you would have a tendency to your blood would have a tendency to clot more free. Uh huh. Okay,

33:02  
all right. So for example, factor five Liten is the most common and Caucasian population and it's, I can't remember the number exactly off the top of my head. But let's say like one in 500 patients will test positive for that mutation. But the chance that that person with a mutation actually has an increased risk of miscarriage or problems in pregnancy, unless they've had issues before it does not warrant the intervention of giving them blood thinners throughout their pregnancy.

33:31  
Okay, and I would assume that there's some Is there any disadvantage to taking? Obviously, if you're taking heparin or something like that? Is there any disadvantage to taking an aspirin if you're worried about it?

33:41  
Sure. So if somebody really truly has inherited thrombophilia, and has a history of blood clots, they should actually be fully anticoagulated through pregnancy. So that's not just taking aspirin, that's actually, you know, taking heparin doses that really will send someone's blood. And there are risks with that, you know, if someone gets into a car accident, it's going to be harder for them to clot and be safe than someone that's not. So it is a big intervention, and it should be something that is really reserved for people that need it. Okay.

34:16  
So that's a that is one of the controversies in the area of recurrent pregnancy loss. The next one is and I want you to know that I've been practicing how to say this. Let's see how I do a methylene tetrahydrofolate reductase MT nine. Fr. Did I do good? Yeah. I did. I seriously had to practice that. Because it's normally goes by MTHFR. So what is it?

34:42  
So it's an enzyme that helps with fully use and in like the blood clotting cascade, as well as DNA replication, and MTHFR mutations have been associated with many different medical issues all the way from psychiatric issues like schizophrenia to recurrent pregnancy loss. And so it's it's a mutation that is really important to understand that 40 to 50% of the population has a mutation for MTHFR.

35:14  
So we have a gene, an MTHFR gene in our body, and 50% of us have a mutation on that gene.

35:22  
Yes. And that would sound surprising to, you know, to a lay person, but that sort of tells me well, not 50% of the population has recurrent miscarriage, not 50% of the population has schizophrenia. This is such a common mutation, and it's something that we shouldn't ignore. But it's something that isn't just your quick answer to, oh, you're having recurrent miscarriage. Let's test you for this gene. If you haven't, this is why you're having it. We're gonna treat you in this way. And everything's gonna be just fine. It's not a quick fix like that.

35:56  
How about if it's a genetic mutation? How are you treated?

36:00  
So the understanding is that if you have this mutation, you might not be able to process folic acid or folate as easily as other people in the population who do not have this mutation. And so you might need to take extra B vitamins or extra folic acid or folate, especially during pregnancy, in order for your body and for the baby's body to get what it needs to go on to be healthy.

36:31  
Okay, so it's treated through medication that the defect effects our body's ability to process folate. Therefore, the treatment is to augment with folate treatment or folic acid treatment.

36:46  
Yeah, when patients ask me to test for it, I listened to them, I explained it to them, I validate their concern, but I say I'm not going to test you for it, because number one, there's a 50% chance that it's going to come back positive. Number two, it's very often not covered by insurance, and patients get really angry at me when I order tests that are not paid for. Number three is the treatment is to take folate, and so let's talk about that. And I asked patients to choose a prenatal vitamin with methylated folate. So methylated folate just means it has an extra methyl group on it is easier to process. And folate is the natural form, or the form of folic acid that's found in leafy green vegetables like spinach and kale. So folic acid is synthesized in a lab and folate is easier for us to digest. I really think people should try to get all their nutrients from their diet. But when you are trying to conceive, and when you're pregnant, you really should be taking a prenatal vitamin anyway. And so why not choose one that has a type of folate, it's easier for us to digest and process.

37:57  
So rather than test in a way you would just treat as if you would same similar treatment that you would if you found that they had the mutation. Alright, the next controversy would be a luteal phase defect or and I guess really, the controversy has to do more with progesterone treatment and the efficacy of it. So first of all, tell us what luteal phase defect is. And then let's talk about why the treatment is controversial.

38:21  
Sure, so just the definition. And though whether there is a such thing as a luteal phase defect, and in and of itself is controversial in the field. And so people argue whether it's even a real thing. And then progesterone treatment, whether it's empiric, or whether people are doing blood tests for progesterone to decide whether to give it to patients. That in and of itself is controversial as well. And so the way I explained this to patients is after ovulation, you know that the second half of the menstrual cycle is the luteal phase after ovulation, the dominant hormone when the embryo is implanting, and the dominant hormone and throughout pregnancy is progesterone. Progesterone is a very important hormone. It's an immune modulator. It shifts our immune system to a more receptive state. And it's what our bodies have been making for however long you want to believe we've been here to help support an embryo implant and continue to develop, you know, blood tests for progesterone are not helpful for several reasons. Number one, they fluctuate so much, they're really released from the ovary, and a very pulsatile fashion. So we can check it at 10am. And it could be five and we could be nervous that it's too low. And we could check it again an hour later. And it could be 25. When you say Oh, this is just fine. So making decisions based on blood tests has issues because you what the result you're getting back may not be very helpful. And studies have shown that what's good going on in the bloodstream doesn't always reflect what's going on in the uterus, which is where the pregnancy is anyway. And so putting this all together, I very often will talk to patients about supplementing with progesterone, not because I need a blood test to tell me that they need it, not because studies all support it, because some studies say it decreases the risk of miscarriages. And others say it doesn't make any difference. But when I give it to patients, I say, Listen, there's a real chance that you're taking something that you do not need. I just can't tell whether you need it or not. And so let's talk about it.

40:34  
And the treatment is not an onerous treatment. It's how is it usually? And what manner and what method do you usually provide the progesterone?

40:44  
Well, the studies support that the best way to get progesterone to the uterus where it needs to go is either a vaginal suppository or an intramuscular shot. So sometimes people like progesterone creams, or they like progesterone pills, but the evidence really doesn't support that it gets where it needs to go. And so we cants would prefer a vaginal suppository to intramuscular shots.

41:11  
Okay, and so the we've talked about different controversies, the thrombophilia, and the treatment, automatic treatment of that MTHFR treatment and testing and then treatment for that. And the luteal phase defect and progesterone treatment. Another controversy you have listed in your book, not broken and approachable guide to miscarriage and recurrent pregnancy loss is infection. Now, why would infection be controversial? Since it makes common sense that if you've got an ongoing infection, it could impact the ability to carry a pregnancy?

41:45  
Absolutely. So the controversy is not that an active infection could be associated with miscarriage that can happen. For example, if someone has chickenpox or measles in their first trimester that can result in miscarriage. The controversy surrounds testing for people outside of pregnancy for chronic or underlying infection that might be causing recurrent miscarriage. So yes, an active infection and pregnancy might be associated with miscarriage. But outside of pregnancy months and months and months later, when the microbiome is changing, and infections, you know, me sort of come and go, do these tests? Do they really help? And if you find something, what are the antibiotics doing to the microbiome and to the balance in the genital tract? And the GI tract when you're trying to help? But are you throwing something else out of whack?

42:45  
So the it's the antibiotic treatment for an infection? That yeah, we actually have a course in our nurse ed on the microbiome and the reproductive track and how it impacts fertility in general is absolutely fascinating. And it doesn't take a lot to knock a microbiome that is very useful, and we all have out of whack. Okay, another controversy is thyroid, and I would assume that would be the testing and then the treatment for thyroid disorders. Again, why would that be controversial?

43:21  
Sure, thyroid that is significantly hyper thyroid or significantly, hypo thyroid and not treated can be associated with miscarriage and obstetric issues. The controversy surrounds some people arguing that we might be over treating for something called subclinical hypothyroidism. So what's controversial is, what is the cutoff? And when do you treat and when do you not treat? Hypothyroidism is especially associated with miscarriage because the pregnancy that fetus doesn't make its own thyroid hormone until the end of the first trimester around 10 weeks. And so the maternal thyroid does have to work 30% harder for those first 10 weeks of pregnancy. So if someone is already hypo thyroid and they're going into pregnancy, that could put them at higher risk of miscarriage. It's just these sort of soft calls or patient isn't symptomatic, or their levels are just maybe slightly above normal. Should we be treating them or not? And there's people go back and forth in the field.

44:32  
Okay. And so if you are it's for the people on the cusp, just slightly below normal, I would assume that that the controversy exists. Exactly. Okay. The next controversy, and this one is quite controversial, and that is the whole immunological connections and how that impacts our immune system in the treatment, immune treatment for recurrent pregnancy loss. So let's talk some about that. What is The current research showing,

45:02  
well, this is a really controversial topic. And the feeling is that the immune system must be attacking the embryo. And that is why somebody is having recurrent miscarriages. And so the treatment is to shut down the immune system in pregnancy to allow the embryo to implant. And controversy surrounding this is the testing the treatment, the evidence, and ultimate outcomes for patients. So there are, there's a whole area of medicine that really focuses on this, and they're practicing outside of the professional society's guidelines outside what you could consider the standard of care. And you have to believe that people are in their heart helping as best they can. But I do worry that people are getting testing and treatment that they don't need. A lot of people will take steroids in pregnancy as a way to treat the immune system and make and decrease the risk of miscarriage. I feel like giving someone high dose steroids is like taking a nuclear bomb to their immune system. And it's impacting, it's just throwing everything out of balance. Whereas progesterone, it is an immune modulator like Its job is to not shut down your entire immune system. But to shift it to a more receptive state and th two dominant immune cells, and that is sort of the natural process, but doing things that are not really supported with, with multiple high quality studies, like high dose steroids, or intravenous immunoglobulins or intravenous inter lipids, you just have to be very, very cautious with what you're doing with patients.

46:58  
Yeah, people who have gone through recurrent pregnancy loss are, are really at a pretty desperate place, and are very vulnerable. And some of the names that are utilized, you know, natural killer cells, well, that, you know, just the the image that it draws up in your mind that conjures up in your mind, is quite frightening. And so you think, well, anything that would control something that's killing my pregnancy is a good thing.

47:23  
Absolutely, that is I strongly believe that this population is very vulnerable on why it's really important to speak out for them. And to think through things. natural killer cells are required for implantation, they're actually necessary for uterine implantation. They have this horrible, horrible name, but they're really important part of our immune system. And studies have shown that the way it's sort of proposed to patients is you do blood tests to test your levels of natural killer cells. And if they're too high, then we should treat that with really high dose steroids and things to bring it down. But the level and your bunching doesn't really match what's going on in the in the uterus. And that's been shown, studies that have looked at these treatments, you know, patients with and without, these treatments have not shown benefit. And some of these treatments can really have harm. And I just feel that with how much we've learned with genetics of embryos, and believe me, we still have so much to learn that I just want people to be aware that there are other theories and to just be very careful with with treatments that might actually cause harm.

48:39  
And the last controversy that you talk about is, and I'm glad we're addressing this one, and it's using IVF as treatment for recurrent pregnancy loss. Many of the people I would assume who come to you are not currently did not start as fertility patients. They are conceiving naturally and many of them can get pregnant, they just can't stay pregnant. So when is IVF, a plausible and a suggested treatment for recurrent pregnancy loss?

49:11  
Sure, I think of IVF as an option, but it's not required. I think that there are certain patients that it makes a lot of sense, but for others, it doesn't. In IVF, we have the ability to screen embryos outside of the body for chromosome balance. And if we put an embryo back into the body that has a balanced number of chromosomes, we have a lower risk of miscarriage, and so IVF for patients that are getting pregnant, but having recurrent miscarriage is using a technology as an embryo selection tool as a way to decrease the risk of miscarriage but it does not eliminate it.

49:57  
And the downside is a couple of things. One certainly cost I mean, that's we've in particularly because generally we'll be adding genetic testing. So cost is certainly one. But also it's, you know, you're putting your body through a fair amount of stress and drugs and medications and things like that. Are there other than the cost? And the fact that that what you're doing to your body is or is are there other downsides to utilizing IVF? If you've gone through a couple of miscarriages?

50:28  
Oh, sure, I think some of my patients have real ethical challenges with using IVF. And I want to listen to them and address those. I think one of the hardest things about IVF, too, is it does take time, like it honestly can take about three months from the very start of birth control pills to a positive pregnancy test. Because with the genetic testing, we're usually freezing embryos, and it's taking time. And that's three cycles that the couple could have been trying naturally. And upside. If you have a miscarriage. There it goes six months of trying, right because it takes time to conceive time to figure out if the pregnancy is going to continue and then time to recover from a miscarriage. I think that one of the hardest situations for me is having a patient who's had multiple miscarriages, transfer, chromosomally balanced embryo and then still have a miscarriage. It doesn't happen all the time. But that is why before somebody commits to it, or before somebody thinks it's a quick fix, that they have a very thorough understanding and informed consent about what IVF can do and what it can do. I still think that when someone has a miscarriage with a chromosomally tested embryo, I still believe it's something in that embryo. I mean, all we're doing is testing for numbers of chromosomes. But there are 1000s of genes on each chromosome. And there's just got to be a gene for different stages of embryo development. And if an embryo doesn't have the gene that it takes to get from Week Six to week seven, it's not going to continue.

52:09  
I think the bottom line is making certain that patients are well informed so that they can make I mean, they're going to be in the best position to make the decision for if they're willing to take that risk. And you know, do they have them? Is insurance going to cover it? Do they have the money? Are they are they what their ages? I mean, there's so many factors, but that the idea that IVF is an automatic fix for recurrent pregnancy loss is a misconception. And it is one that I think is does exist. So making certain that the patient is truly informed before making that decision, is the challenge.

52:48  
And I think we know more about miscarriage now than we have ever before. But I think we still have so much to learn. And I think one thing from caring for these patients for now, over 10 years, is I have learned just how humble I am. I share my knowledge, we talk about the testing, we talk about how most people aren't going to find an answer in the testing. We talk about options moving forward. And I just emphasize time and time again, it is more likely that you are going to have a baby on your own without any intervention for me whatsoever. I know that you can do it. If you are conceiving, there are so many hurdles that you're getting past egg and sperm like each other. embryo is implanting. And each pregnancy is a new opportunity. I can hold your hand along the way we can talk about supportive things, we can review IVF as a way of family building, but you you know there, there is no quick fix. And and I'm going to remain open with some of this immune testing and treatment because the evidence does not support it right now. And some of these interventions have a lot of harm. But man, I still have a lot to learn. So I also don't want my patients to feel like they have to hide anything from me or like tell me hey, I went to go see this reproductive immunologist, and I'm planning to do this. Like, let's talk about it and let's have an open conversation.

54:13  
Thank you so much, Dr. Laura Shaheen, for talking with us today about recurrent pregnancy loss. Dr. Shaheen is a reproductive endocrinologist and the director of the recurrent pregnancy program at Pacific Northwest fertility, and she is the author of not broken and approachable guide to miscarriage and recurrent pregnancy loss. Let me remind everyone that the views expressed in this show are those of the guests and do not necessarily reflect the position of creating a family, our partners or our underwriters. Also, keep in mind that the information given in this interview is general advice. To understand how it applies to your specific situation. You need to work with your infertility professional. Thanks for joining us today and I will see you next week.

Transcribed by https://otter.ai