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Miscarriage and Recurrent Pregnancy Loss | Dr. Lora Shahine

Dr. Lora Shahine, a reproductive endocrinologist practices out of Pacific NW Fertility and authored Not Broken: An Approachable Guide to Miscarriage and Recurrent Pregnancy Loss. She speaks to Fempower Health about important tips to further empower you in your conversations with medical professionals.

Transcript


Dr Lora Shahine  01:59

Thank you so much for the opportunity. I'm really happy to connect with you.

Georgie Kovacs  02:03
I wanted to meet with you because I'd asked some of my connections who would be the expert on miscarriage and recurrent pregnancy loss. And your name came up. And then I learned about a great book that you wrote called Not Broken:  An Approachable Guide to Miscarriage and Recurrent Pregnancy Loss. And I did read the book. Tell us about yourself.

Dr Lora Shahine  02:26

Thank you so much for those kind words. I really appreciate that. It was a real joy to write that book. I really wrote it for my patients, because it's such an overwhelming emotional and complicated topic to be dealing with - miscarriage. I kept looking for a resource for my patients to provide for them to get those questions answered, and I just couldn't find it. =


I'm a reproductive endocrinologist, which means after medical school, I did residency in obstetrics and gynecology at San Francisco’s University of California and then did subspecialty training and reproductive endocrinology and infertility at Stanford. And so that's really training kind of beyond your typical primary ob gyn to really focus on reproductive health.  A big part of that training has to do with recurrent first trimester miscarriage. It's really common for people to not really know who the real specialists are to focus on recurrent first trimester miscarriage and it really is reproductive endocrinologists.  We really are the focus. 


I happened to do my fellowship at Stanford when my mentor Dr. Ruth Lathi was starting the Center for Recurrent Pregnancy Loss at Stanford. So just the right place, right time, incredible learning. She really brought together a multi disciplinary approach to recurrent loss. Even though we are the specialists, it takes learning so much more about genetics and the immune system and the blood clotting system.


Georgie Kovacs  04:28
Yes. In your book, you talked about so many light bulb moments. If I recall, the first one was women would come in and test positive for pregnancy and they would have severe anxiety and you were like, “Oh, my God, like, this is not, “Yay, I got pregnant.”  It's, “Can I keep the baby?” 

Dr Lora Shahine  05:04

Absolutely. I talk to people about the innocent joy of a positive pregnancy test is really taken away from someone after a miscarriage. What we're taught growing up is that it's easy to conceive, it can happen when we're ready, and that a positive pregnancy test means a baby. 


When the narrative shifts in any direction, like it takes longer to conceive than what you expect, or you have a miscarriage, itself, it’s such a shock.  We don't talk about what can really happen enough. 


I very distinctly remember my first fertility patients in training.  While you're still learning, you are still training, but you are a physician.  I just loved calling with positive pregnancy tests. And I'll never forget the first time I called with a pregnancy test, and the patient just sort of sighed. And I was taken aback.  She said, “Oh, Dr. Shahine, this is really just the beginning for me.  I'm just really not sure what's going to happen.” It was such a learning experience for me. 


Part of having a program for recurrent miscarriage is teaching everybody on the team that we all are joyful and happy with a positive pregnancy test, but to not be surprised if someone's emotions are guarded, and to really walk them through that process and make sure that they know that that's normal.

Georgie Kovacs  06:40
I like what you said earlier, too, because that's something I'm learning. I think when a lot of people think of a reproductive endocrinologist, they think of a fertility doctor. And you know, it's becoming clear that it's broader than that. And if someone is having issues outside of the basics, sometimes going to that specialist early on seems to be key.

Dr Lora Shahine  07:25

Yeah, that's a really important point that you bring up. I think that there's a real assumption that primary care doctors and primary Obstetricians and Gynecologists have a lot of expertise in fertility. And quite honestly, this is not true.


I can speak from my own experience that, in medical school, I did not learn a lot about women's health, in obstetrics and gynecology residency, it was really focused on delivering babies and surgical expertise, as far as women's health is concerned. And contraception was really a focus, but fertility wasn't really a focus. I hope that that's changing and training. 


When anybody goes to see a doctor about fertility issues or miscarriages that they have a really open discussion with that provider about what that provider is comfortable with. Things change so much to that if anybody is really more than five or 10 years outside of training, the recommendations have drastically changed. 


I published my book Not Broken in March 2017. And already recommendations have changed. And I'm working on a second edition because things change so quickly in this field. So unless providers are regularly seeing patients for fertility and miscarriage, they might not feel very comfortable. Having a strategy saying like, “I really want to work with you, but how comfortable are you really caring for me,” is an important topic.

Georgie Kovacs  09:12
I appreciate you saying that because if we women are voicing some of these concerns, it may come across as being disgruntled. But having a doctor in training, say this is what you're trained on and this is what we're not is really important because I hear so many stories about women being dismissed.

You talk about it in your book, too, when it comes to miscarriage and recurrent pregnancy loss. This just echoes why it's so important to not be fearful of the questions. If you're getting dismissed, it could be defensiveness from the doctor of not having the right training. There could be a lot of things behind it. 

I hate to start with something so frustrating, but you started the book with it  - that there's no definitive way to approach recurrent miscarriage. Women need to understand that the starting point is not consistent. And you even said the guidelines are changing. 

When I read your book, I think it was two or more miscarriages that were clinically diagnosed Is that still the guideline because I thought it was three or more?

Dr Lora Shahine  10:28

It’s actually changed. Before 2013, the recommendation was three miscarriages. And we should clarify a clinical miscarriage, meaning far enough along that you can see anything on ultrasound, or have a tissue diagnosis. So this whole area where women are having a positive pregnancy test, and then a late period, or what we would call biochemical miscarriages, that was excluded for years and years and years. 


Before 2013, for an evaluation of recurrent miscarriage, it was really recommended that someone had three or more consecutive miscarriages.  And so if someone had a miscarriage and then a baby, and then two more miscarriages, the doctor could say,” Oh, I just think you should keep trying.” Sometimes people would initiate testing, and treatment before that. But I'm just saying this is what the professional medical guidelines said.


In 2013, the American Society of Reproductive Medicine, which is the professional medical society for reproductive endocrinologists in the United States, like me, stated, “For the purposes of a clinical evaluation, it's okay to start testing after two clinical miscarriages.” And they were very specific about the clinical pregnancy loss is not biochemical miscarriage, but you've seen something on ultrasound, and the pregnancy stops developing or you have tissue to test or see under a microscope. 


I think women and some doctors are still not even aware of that definition, and it's been out for seven years. And it really allowed for more testing. And the reason that the ASRM changed that is because they said, “You know what, the chances that somebody has a miscarriage after two losses is about the same as after three losses. Why not start an evaluation, even though it's unlikely that we're going to find anything?”  If you do find something like a uterine issue you can fix or a hormonal issue that you can treat, you could really prevent that third miscarriage. So that was a really big deal. 


In November 2017, ESHRE, which is the European equivalent of ASRM, came out with extensive updated guidelines and definitions for recurrent loss. They say two or more and they don't necessarily define whether it's biochemical or not.


In March 2020, ASRM came out with a brand new practice committee guideline, defining infertility and defining recurrent miscarriage. It removed the definition of “clinical” from the clarification, and it removed the word “consecutive.” So the definition of recurrent miscarriage according to ASRM, as of March 2020, is basically to pregnancy losses. And they don't have that specificity of having to clarify the tissue diagnosis or an ultrasound diagnosis. This includes biochemical miscarriages.  The fact that they deliberately removed that clarification opens the door. 


It basically says each miscarriage really should be evaluated. It validates the importance of each loss and that it's okay to do evaluations. 

Georgie Kovacs  15:34
That is incredible, because one of the questions that I've been wanting to ask a specialist like yourself is why these guidelines.  I'll give you an example. In New York City, you can't go to a fertility clinic without getting Fragile X tested for and then I interviewed a woman in North Carolina and Fragile X was part of the miscarriage panel. So she had three miscarriages and then found out she had Fragile X!  

How common is miscarriage and recurrent pregnancy loss?

Dr Lora Shahine  16:36

It happens so much more than people really talk about it. When it happens to you, if you haven't talked to your friends about it, you can feel like you're the only person that's ever had a miscarriage, but it's really so much more common - one in four pregnancies.  


There's certain things that put people at higher risk of miscarriage, like advanced maternal age, especially some chronic illnesses, like diabetes, or untreated thyroid disorders will put people at higher risk.  When women are in their 20s, I'd say with a positive pregnancy test, there's about a 15% chance that the pregnancy doesn't continue. When we're in our mid 30s, that's closer to 25 or 30%. By the time that we're 40, it's about a 50% chance. There's so many caveats to that. 


I'm talking about getting to the point where you can see something on ultrasound.  I'm talking about clinical miscarriages. If you include positive pregnancy tests and late period like a biochemical miscarriage, that number can be significantly higher. 


The ability for people to be able to test at home and to follow their cycles and do home pregnancy tests is really empowering, and people can learn what's going on with their body. I just don't think people realize just how common biochemical miscarriages are. It can actually be two or three times a year if people are having unprotected intercourse, and not necessarily tracking that they can have biochemical miscarriages. 


It doesn't mean that there's anything wrong with the person in that, of course, it feels awful. And emotionally, it's a loss and you're trying to start your family. Even a period without a positive pregnancy test is grieving and lost time. And I understand that emotional piece. 


Biologically, human reproduction is so inefficient.  We've learned so much from doing genetic testing on embryos for people who are doing IVF and doing genetic testing on pregnancy losses that do get to a point where we can contest things. If you really include early biochemical losses, it can be as high as you know, 70%. 


I say that as hopefully a positive thing. I do really try to educate my patients that when doctors do say, “Oh, just try again,” that really, you can say it in two different ways. You can say it in a dismissive way, like, “I'm not going to do any testing, you should just try again.” Or you could say, “You know what, it's so common to have miscarriages, it's probably most likely an issue with that particular embryo. The next time that you try, you have a much higher chance of having a totally healthy baby without any intervention.”  


For me, like, doesn't that sound a lot better, because that actually is the science. You know, it doesn't mean that we don't do testing.  It doesn't mean that we don't validate and really think through losses and comparable strategy for family planning. I want people to understand just how common it is. If I can get that information out, it doesn't take away the sadness or the grieving.  It doesn't mean that we shouldn't do testing and take care of everybody. 


When they were first trying to work on getting a home pregnancy test. The NIH was working on this in the 70s, and they were just getting random samples from women every single month around the time of their period from across the United States. When the researchers realized just how common biochemical miscarriages work, that was one of the arguments to not allow home pregnancy tests to be sold and drugstores because they didn't think women could handle that information.

Georgie Kovacs  21:55
I know we can't go through the whole laundry list because you have all sorts of things listed in your book. So for anyone who wants the details, I would encourage you to read Dr. Shahine's book because it's very easy to read. It's honestly a quick read.  During COVID, with a four year old as a single mom, I was able to read it. 

Maybe you can give us some highlights.

Dr Lora Shahine  22:17

There are certain tests that all professional medical societies really do agree on. And then there's a lot of controversial stuff when it comes to testing for miscarriage and recurrent loss. The things that most professional societies recommend testing for our number one, genetic issues as far as a balanced translocation in the people that are getting pregnant. 


Let me back up one second. I just want to clarify the most common cause with first trimester miscarriage is a chromosomal issue in the embryo. 


When you're doing testing and a couple, for recurrent loss, you're testing the people that are getting pregnant. At least 50% of the time or more, I would argue, but the steady state 50%, you don't find anything abnormal in the people that are getting pregnant. 


Before anybody does a single test, I just want to clarify there's a real chance that we're not going to find anything wrong, but I really want to make sure that we're not missing anything else. So it's kind of like setting that expectation. 


The balanced translocation is basically a genetic chromosomal rearrangement and one of the parents that does not impact their own health, but when they go to make eggs and sperm, some of the eggs and sperm are going to be missing big portions of DNA and will result in miscarriage. So it's a blood test. You’re  testing for carrier type. And what you're specifically looking for is a balanced translocation. If we only find it about 3% of the time, it's very rare, but when you do find it, it really does explain a lot of what's going on. 


We look at uterine issues or anatomic issues that can put someone at higher risk of miscarriage. So a uterine septum is a fibrous band of tissue that someone can be born with that can make it a higher risk of miscarriage if the embryos implanting on this a vascular not very supportive tissue within the uterus. Some fibroids put people at higher risk of miscarriage. A lot of people have fibroids and they're not all affecting infertility or miscarriage risk, but fibroids that are inside the uterine cavity, you know where an embryo would implant or significantly large fibroids like 8 or 10 centimeters, those might need to be addressed hormonal issues and look for diabetes, thyroid disease, elevated prolactin those are important things to rule out. 


The one immune issue that's been associated with recurrent miscarriages, antiphospholipid syndrome, and it's a collection of risk factors you can see clinically and then certain antibodies that you can test for in the blood of the mom, that if they're present at the time of the embryo trying to implant, they can really impact implantation. And simple treatments can be aspirin, and heparin, which is a blood thinning medication. 


Other tests that are sometimes done are a semen analysis, just to get a good baseline.   If someone's taking a long time to conceive, sometimes you can find a sperm issue and it can really help with planning. 


Some people will check for antibodies to the thyroid. That's pretty controversial. But if you have antibodies to your thyroid, that might signal that you're not able to keep up as well in pregnancy. 


I have a whole chapter on sort of controversial tests and treatment and pros and cons. So I'm really trying to focus on your question, which is sort of what is recommended and, and so everybody agrees on that. 


But individual doctors will sometimes order different things, and that's honestly, that's why I wrote that book. I wanted patients to be able to advocate for their care and understand it in really simple terms. All the medical references are there including ASRM guidelines, and studies to support why these tests should be done. And so sometimes, people might be able to have a really fulfilling conversation with their physician.  I don't want to ever be tense situation between doctor and patient, but it's okay to learn and have that conversation.

Georgie Kovacs  27:11
The septate uterus. I've heard that it does impact being able to carry a child and that it doesn't. I attended the ASRM conference last year.  It was a US doctor and a European doctor comparing ASRM and ESHRE guidelines around a septate uterus. And what was fascinating is they took several different images, and they said, “Okay, if we compared ASRM guidelines versus ESHRE, would a given patient be diagnosed with it or not? They couldn't even agree on whether or not someone had it! And then it was still unclear if it impacted pregnancy! 

Can you shed light on this because as a woman, I'm observing that the doctors don't even agree on whether or not it matters. Most women probably wouldn't even know what a septate uterus is to even ask their doctor, “Do I have this?”

Dr Lora Shahine  28:16

Absolutely. That is one of the hardest parts about this field. Number one, there are not a lot of really strong, consistent, well-done clinical trials. That's the best way to really get definitive answers and science. They're just not a lot of them there, and that leaves a void. And then patients get stuck in the middle. 


There are absolutely women that have septate uteruses that have their families, so there isn't a complete, “If you have a septate uterus, you're never going to have a baby.” The way I think about it is there's lots of places in the uterine cavity for an embryo to implant. And so if the embryo implants on a wonderful, vascular, healthy uterine lining away from the septum, probably that person is going to have a full-term delivery. If the embryo implants on the septum and it's not very vascular, and it can't really support a pregnancy for very long, they might have a higher chance of miscarriage. 


There are definitely studies that show that if septums are removed, which is a very simple procedure, it's called a hysteroscopy. It's taking a little camera through the cervix, no incisions on the belly, just through the cervix when someone's asleep.  The doctor snips that little fibrous tissue. It's a very low risk procedure that if it has a high yield, it might be beneficial. 


You have to weigh everything. But there are studies that show if someone is having miscarriages, and they have a septum resected, the very next time that they get pregnant, they have a lower miscarriage rate than you would expect for what their history had been to date. Okay, so it's not a perfect test, the perfect scientific clinical trial would be with 200 women. They all have the same number of miscarriages, they all have the same exact diagnosis and image of a separate uterus. Half of them get it fixed, half of them don't. And let's see what happens in the next pregnancy. And that study just doesn't exist. And so it leaves room for doctors to think about things in different ways.

Georgie Kovacs  30:54
The other one I wanted to bring up is the thyroid antibodies. What I hear over and over is the most common test is TSH, yet there is disagreement on what a normal TSH is. I heard at Yale they test the full thyroid panel because they've seen so many Hashimoto’s cases that they're shocked.  They have decided to use a full thyroid panel. So maybe you can talk a little bit about that TSH test versus the thyroid antibodies and why it's so important just so people understand why you had brought that up in the controversy.

Dr Lora Shahine  31:25

Sure, it's important to realize just physiologically that the baby or the pregnancy doesn't make its own thyroid hormone until after 10 weeks of pregnancy. For the first 10 weeks of pregnancy or about the first trimester, the maternal thyroid gland has to work about 30% harder in order to support the thyroid and the baby. If someone has overt hypothyroidism, or overt hyperthyroidism, if they really have active disease, they're definitely at higher risk of miscarriage. 


What's controversial is if someone's thyroid is working fine outside of pregnancy, what level should we be treating if the woman is fine? Is this a cause of miscarriage? There's something called subclinical hyperthyroidism, also where the TSH (thyroid stimulating hormone) and it comes from the hypothalamus to tell the thyroid to do what it needs to do. 


It makes sense that we should just be testing the hormones to understand what the thyroid is doing to figure out whether we need medication or not. The tests are kind of hard to do, actually. They're pretty finicky. And so the TSH has been the standard of what to check. It’s like pressing on the gas pedal. If the TSH is high, that means the thyroid is needing more bribery or more gas to go and get what it needs to get done. 


The controversy really lies in what TSH level is normal and what's abnormal. How are people at risk? What if the panel the thyroid seems to be working just fine? The hypothalamus is working just fine, but someone has antibodies in their system to the thyroid. The theory is that that's a warning sign that if these people have those antibodies, when they get pregnant, their own thyroid isn't going to keep up. The hard part is that it really takes about four to six weeks for our bodies to really reflect a change in TSH level that's reflective of a medication. So the worry is it if you just wait and test in pregnancy and somebody that's high risk or might be showing signs of not being able to keep up to just waiting until they're pregnant, it might be too late to make that difference. 


The controversies are just all over the map. The American Thyroid Association says something a little bit different from the European Society of Endocrinology. The American Board of Obstetrics and Gynecologists says something a little bit different than the Royal College of Obstetricians and Gynecologists. You know, the studies are kind of all over the place. 


Even in the most updated essary guidelines that came out in 2017, for recurrent miscarriage, they basically said, “Here are the studies. Everybody says something a little bit different. There's no definitive or absolute for treating subclinical hypothyroidism or thyroid antibodies, but it's really not unreasonable to focus and get a TSH level under 2.5.” When someone's trying to conceive, it's very low risk, and it really might help. 


There's so many things that hypothyroidism has been associated with in pregnancy. Hypothyroidism is associated not only with miscarriage, but pre-term delivery, lower birth weight for babies, higher risk of gestational diabetes, and even lower IQ points. 


And so there's a difference between studies that are really actively proving that you need to do an intervention versus an intervention that has no evidence of harm, and it might really improve options. It really is individualized, but everybody should look for thyroid disorders.  All the professional medical societies agree on that you should definitely test for it. They just sometimes disagree on which tests to do, and then they disagree a little bit on what level we should be shooting for.

Georgie Kovacs  36:22
Okay. I appreciate your explanation. We want answers, but the studies aren't there. But then there's so much logic around how the body works when you really break it down. I can assure you that anyone who's struggling with miscarriages or recurrent pregnancy loss, PCOS, endometriosis, you name it, they will stand on their head for three days, if you tell them that it will change what they're going through. I'm not at all saying doctors scrapped clinical trials. But I think women need to understand there are some levels of logic, and when you weigh the risks and the benefits, it's really important to understand and be educated on how the body works. 

Speaking of testing, we have become a society that, because of all the technology and data and Google, what would you give someone as guidance?

Dr Lora Shahine  37:52

I want people to hear that every pregnancy is a new opportunity, and that it's very unlikely that there's something that people are dramatically missing. Most people will go on to have a baby, if they are having miscarriages.  Every pregnancy is a new opportunity because it's a new set of genetics for that embryo. 


I would advise that when people are reading things on the internet, to be very cautious.  You can write whatever you want on the internet, and even when people have the most, you know, altruistic or generous feelings, and they're really trying to help other people.  When they write, “I ate pepperoni pizza every day for a month, and I finally got pregnant and had my baby!” To that person, it was the pepperoni pizza, and they want to share that with the world.


If something really sounds too good to be true, there's a real chance that it is, but it's okay to bring it up and have those conversations with your doctor; somebody that can help filter Dr. Google.

Georgie Kovacs  40:01
What about testing progesterone? I wanted to get your thoughts on it only because it seems to be a hot topic, or at least in the circles that I've been dealing with, like the Proov test. You pee on a stick for several days, and it'll tell you what's going on. I think you even said in your book, a one-shot test on day 21-ish of your cycle isn't necessarily sufficient. 

Then there was the PROMISE trial  that recently came out with its results. At the ASRM conference last year, they were quite hopeful about the results. Yet when the results officially came out, they were devastated. The website indicated that results did not show adding progesterone helped. 

Then there's data saying it depends on the day that you give someone progesterone, and that's why the PROMISE trial didn't work. 

Given that so many people are starting to talk about progesterone, can you educate us on what we do know what we don't know, just so that women can figure out how it fits into their ability to get pregnant? 

Dr Lora Shahine  41:05

Progesterone is very important. It's the dominant hormone after ovulation, when the embryo is implanting, and in early pregnancy. It is an immune modulator in that it helps shift the immune system to a more receptive state. 


We know from studies that were done in the 1960’s that if someone loses their source of progesterone before six or eight weeks of pregnancy, that the pregnancy will stop developing. So for the first six to eight weeks of pregnancy, the only source of progesterone is coming from the ovary - from the follicle that released the egg.  It's called a corpus luteum. And then, after 6 to 8  weeks of pregnancy, the pregnancy itself starts making its own progesterone. 


Knowing that the theory is, oh, maybe someone's progesterone is low. Maybe that's why the pregnancy is stopping early and not continuing. And so can we figure out, you know, what progesterone level is right? If we are going to treat, how do we treat the problem with testing progesterone, and a blood test is, physiologically the way it is produced by the corpus luteum is very sporadic. So it will, you know, be 20 at 10am. And then it'll be 10 at 2pm. And so trying to decide whether someone needs progesterone based on blood levels is really faulty based on physiology.  You can either be overly reassured by the levels that you get or overly nervous. 


People have tried testing multiple different times in the luteal phase to try to have an average.  I think the only real reason to test progesterone is just to confirm that somebody had ovulated because that's very black and white.  But using it as a way to dictate whether or not someone should take supplemental progesterone has its real faults. 


I do give a lot of progesterone because I feel that it's very low harm and very low risk, and I can't necessarily prove who needs it or not. And I'm very honest, when I give it to patients, I say, “This is not an end all be all. I'm way over prescribing this.”  I could be giving it to 100 women and helping three. And there's 97 women out there taking something they don't need. I offer it to a lot of my miscarriage patients, and I typically start it with a positive pregnancy test for a lot of different reasons. There are definitely some times where I started a little bit early. 


The problem with the PROMISE trial is that they started it as late as six weeks of pregnancy. So it just didn't make sense. If you're trying to do it to treat a deficiency in the corpus luteum if you're already starting close to when pregnancy begins and starting to do it anyway, the pregnancy is already really well established. Right? 


One thing that's really important to understand is if you start it before ovulation, it can actually decrease the chances of someone getting pregnant. So you really have to have pretty predictable regular menstrual cycles and know when you're ovulating if you're going to start it before a positive pregnancy test, because the uterine lining and the embryo have to fit together like a jigsaw puzzle. If that progesterone has been there way too long, it could throw off that match. 

Progesterone has side effects. It is the pregnancy hormone, and it will delay the onset of a period, whether someone's pregnant or not. Or if someone's not pregnant or delayed starting a period, not forever, but for enough days, and enough negative pregnancy tests, it can be really emotionally challenging. It makes people feel pregnant. So more tender breasts and mood swings and GI issues. So already, you're so excited and ready to start or complete your family and then you're having a delayed period on top of all of these symptoms. And then to find out you're not pregnant, it's just emotionally really hard. So there's lots of pros and cons, but it is something that that I do use in my practice

Georgie Kovacs  46:06
Two things there. One is progesterone in oil and the suppositories are going to be the best mode versus over the counter types of pills. Correct?

Dr Lora Shahine  46:18

The studies that did show a benefit for decreasing miscarriage did use vaginal progesterone. And so that that is encouraging because those progesterone shots, the progesterone in oil that you mentioned, can be uncomfortable. So I really do usually offer vaginal suppositories.

Georgie Kovacs  46:40
I have heard that women asking their doctors to prescribe it, find that many of the clinicians refuse. So what do those poor women do? Because it has to be a prescription they cannot use the over-the-counter version. They need the help, as you mentioned.  You didn't say it directly, but my takeaway is it honestly could possibly do more help than harm. So what do women do when their doctor refuses to prescribe it?

Dr Lora Shahine  47:18

Yeah, I think it just takes a healthy conversation and it might take, honestly getting a second opinion.

Georgie Kovacs  47:27
Okay. Thank you for being straightforward with that. Last question is about, there's a new test out there, that's testing for the BCL6, and you talk so much about the uterine lining and how it needs to be healthy. And because you specialize in recurrent pregnancy loss and miscarriage, and I know they're really aiming to help such women. Share your thoughts.

Dr Lora Shahine  47:51

What you're talking about, that I'm familiar with, is doing an endometrial biopsy to test for a marker called BCL6, which is associated with endometriosis. Yep. And that's typically used in diagnosing or sort of looking into reasons why somebody is not conceiving, especially with embryo transfers, when they're doing IVF. It's not a typical test for recurrent miscarriage. I do know that the company that is now selling that product is looking into whether it's associated with recurrent loss, but that's really not standard. There really aren't studies to support that.  Part of my job as a physician is to really be very conservative before I start offering tests to my patients, because it's so easy to get tests out there to market. These days, the demands that the FDA has are just really very low right now, and this is such a vulnerable population and doing an endometrial biopsy is painful. You have to miss a month of trying because that test needs to be done in the luteal phase. So you don't want to disrupt a potential pregnancy. And so without a lot of evidence, that diagnosis is really going to change outcomes for my patients. 


You also have to think, what are you going to do with that information? There's not a lot of evidence that really supports that endometriosis is an independent risk factor for miscarriage. What's the treatment going to be if you have a positive BCL6 marker that is associated with and we chose this 90% of the time, but endometriosis isn't necessarily associated with recurrent miscarriage. The treatment for endometriosis is often surgical, or shutting the ovaries down for two to three months with Lupron and you're losing precious time and trying to conceive and for something that's not significantly supported in the literature. So I'm really not using that in my practice right now. But I'm always open to learning.

Georgie Kovacs  50:42
I know as a patient who has endometriosis, I definitely feel like it's a potential game changer. It's helpful to know where it fits in for the miscarriage and recurrent pregnancy loss versus something else. I like to make sure women have the opportunity to hear experts' opinions on both sides of the spectrum, making an effective decision. 

My last question is - what is your greatest hope for for women and especially those who are struggling with recurrent pregnancy loss and miscarriage?

Dr Lora Shahine  51:14

Yes, I hope that we have more research. I strongly believe that genetics is one of the most important things. As we learn more, it might drastically change the field of miscarriage. We know that 60 to 80% of pregnancies that end in miscarriage, if you test them, have a chromosome imbalance, but that leaves 20 to 40% that are undiagnosed. 


When we're looking at chromosome matching, it's matching 23 pairs of chromosomes and there's 10,000 to 25,000 genes on each chromosome.  There just has to be a gene that's required for an embryo to get from four to five weeks and another gene that's required to get from five to six weeks. 


There are some labs in the world that are trying to look for a needle in a haystack and find genetic mutations that lead to an increased risk of miscarriage, just like there's genetic mutations that lead to an increased risk of cystic fibrosis or sickle cell disease or muscular dystrophy.  We have to keep looking for that because it wouldn't be in every embryo that a couple has.  Just like we can screen embryos for a mutation to a certain disease, we could screen embryos for a mutation for a miscarriage. We can dramatically decrease the risk of miscarriage but of course, that would also require - which I know is a more costly intervention than trying naturally. I really do think that genetics are the future of miscarriage, learning and care.

Georgie Kovacs  53:14
And thank you for making time to educate us about such a very sad time that so many women and couples have to go through.

Dr Lora Shahine  53:23

I really appreciate your kind words. And thank you so much for this opportunity. 


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