Posted on June 18th, 2020by RMANY

Ep 24: Recurrent Pregnancy Loss: A Reproductive Endocrinologist’s Perspective with Dr. Daniel Stein

Fertility Forward Episode 24:

Recurrent pregnancy loss or multiple miscarriages can be particularly challenging because they frequently cannot be medically explained. While couples may begin to feel hopeless after going through this difficult infertility obstacle, our guest today, Dr. Daniel Stein, shares that it’s not all doom and gloom, and that hope is still certainly there. Dr. Stein is the Director of RMA of New York’s Westside office and is Chief of Reproductive Endocrinology at Mount Sinai Roosevelt Hospital. He has been recognized by New York Magazine and Castle Connolly as one of New York’s “Best Doctors” and has been named a “Top Doctor” by US News & World Report. We kick off the episode by learning more about how a personal experience prompted Dr. Stein to work in reproductive endocrinology.

Transcript of Episode 24

Rena: Hi everyone! We are Rena and Dara and welcome to Fertility Forward. We are part of the wellness team at RMA of New York, a fertility clinic affiliated with Mount Sinai Hospital in New York City. Our Fertility Forward podcast brings together advice for medical professionals, mental health specialists, wellness experts, and patients because knowledge is power and you are your own best advocate.
Rena: Dr. Daniel E. Stein is the director of RMA of New York's West side office, and is chief of reproductive endocrinology at Mount Sinai West Hospital. Dr. Stein has over 20 years of experience as a reproductive endocrinologist and fertility specialist and served for eight years as a medical director of the in vitro fertilization program of the former continuum reproductive center before joining RMA of New York. He is board certified in both obstetrics and gynecology and reproductive endocrinology and infertility. For the past several years, Dr. Stein has been recognized by New York magazine and Castle Connolly as one of New York's best doctors and a top doctor by US News and world report. He has also been included as one of the best doctors in America. He has received multiple awards from patient advocacy groups for his years of service in the fields of reproductive medicine and fertility. Dr. Stein completed his residency training in obstetrics and gynecology at Thomas Jefferson University Hospital in Philadelphia, and then completed his fellowship training in reproductive endocrinology and infertility at the UMDNJ, New Jersey medical school. His specialties include egg freezing and fertility, in vitro fertilization, recurrent implantation failure, and recurrent miscarriages. In this episode we speak with Dr. Stein about the challenges of unexplained infertility and recurrent miscarriage, how recurrent pregnancy loss is defined and possible causes of recurrent pregnancy loss. I am so excited to welcome today to our podcast, Dr. Daniel Stein of RMA, my esteemed colleague. To Stein vs Stein!
Stein: I'm very happy to be here and looking forward to answering questions and expounding upon some pretty serious topics.
Rena: Well, thank you so much for giving us your time. I know it's so precious. You're very busy. And so what I want to kind of do to start with is just ask you some basic questions just about being a reproductive endocrinologist. How did you get into the field?
Stein: You know, I was actually not in the field. When I came out of medical school, I was interested at that time in actually doing ophthalmology and I had a brother in the field and it seemed very interesting to me. So I actually did some rotations and I thought I liked it. And I went ahead and actually got a residency position in it. And during my first year, I said, I don't like this at all. And at the same time, a very close family member was going through some pretty significant fertility issues and was being seen at a clinic in Manhattan. And I got very interested in what she was going through and I made the fateful decision of reversing course and switching out of my ophthalmology residency and going into obstetrics and gynecology and then into reproductive endocrinology.
Rena: Wow. That's so fascinating, I think, you know, speaks to... so many people that come on here got into the field, whatever aspect they're in the infertility field they're involved in because of some personal experience, be it, they went through it themselves or a family member. And so I had no idea that you also got into this too because of a personal connection.
Stein: Absolutely. Absolutely. That's, that's probably one of the most emotionally compelling times because you want to do something with your life that you feel value with. Not that being an ophthalmologist wouldn't have been high value to. It would have been extremely valuable, but my personal satisfaction was increased by going into a field where I really thought I can help people get pregnant who are having such, such difficulty and it's a very painful process.
Rena: Sure. And I know, you know, your patients, you know, alllove you and it can certainly speak to your dedication and compassion to your patients. I think it comes across so much in your work. And I think we're so lucky to have you in the field.
Stein: Thank you.
Rena: So what would you say are kind of the hardest parts of your job?
Stein: The hardest part of the job is not knowing to me.
Rena: So similar to what patients would say.
Stein: Yeah, I would say that that's absolutely true. It's not knowing it's taking the couple that goes through so much, often multitude of cycles with insemination or in vitro fertilization. Things seem to be going very well. They can make decent embryos and the transfer of the embryos back to the uterus seems normal, but they don't get pregnant time and time again. And there's that black box in reproductive endocrinology that is essentially all the things that we don't know and all the cases that we desperately want to know in order to give people what they actually want to have. And that's very hard for people who have been in the sciences, as long as we have as, as reproductive specialists. We’re used to prior to this having sort of definitive diagnoses and a lot of medical fields, that there are definitive diagnoses that you then have a very clear treatment for. And the best example would be a surgical field where you have an inflamed appendix.Very easy. You go in, you remove the appendix, problem solved. It's not so easy in reproductive endocrinology because there is a great deal of that black box of, of not knowing what the diagnosis always is. And certainly not always knowing which treatment is going to be the best.
Rena: That's what I mean, I'm sitting here, you know, I never really sort of switched and thought from your perspective, you know, I have patients come to my office all the time, you know, unexplained infertility, and those are some of my toughest cases. And, you know, they say exactly what you said, but from the patient perspective, you know, I wish there was something the doctor could tell me, right. Some sort of diagnosis or reason. And so I never thought of it from your perspective, too, as someone who's in the medical field, you know, in science who wants to give that diagnosis, give a reason how difficult it must be for you too
Stein: No, absolutely. Absolutely. Yeah. I don't think there's any time I can imagine a doctor having the answer and not providing it. I think it's that we also don't know sometimes, but even when we don't know, we often achieve success usually through the tremendous dedication and strength of the patient who can sort of go through all these treatments with some faith and get it done. But sometimes we achieve great results and we don't even know exactly...we have a general idea of what's going on, but we don't know exactly what made it work this cycle versus last cycle. But it does, it often works
Rena: Well. I think that's a really good segue also into what sort of the main topic that I wanted you to talk about today, which is multiple miscarriage or recurrent pregnancy loss, which often is there's sort of no explanation.
Stein: Yeah, that's true. So recurrent pregnancy loss is defined differently in different sort of in different schools of thought and also in different countries. Sometimes there are different definitions, but we generally will say that anyone who has two pregnancy losses that occur with the absence of a live birth, the patient not having a live birth in the past, so two losses or three losses or more that occur. And we sometimes have an explanation sometimes we don't. I would say that we have an explanation in approximately 50% of cases. So, you know, 50 to 60% of cases, we can find a cause. In a good 40% of cases or more, you know, the cause eludes us.
Rena: So what could be some of the causes or explanations for recurrent pregnancy loss?
Stein: So the most common causes are really the same causes as single losses, which are chromosomal abnormalities. You know, abnormalities that occur in the chromosomes in an egg or sperm will lead to abnormal embryos, which oftentimes the body is a great filter and it stops that embryo from growing. So chromosomal loss is a very common and they're particularly increased in women as they age. So you start to see a lot more of those as women get older, but you can have multiple chromosomal losses in women who are younger and it's not just women. That's the important thing is, you know, it's a couple that we're treating because we also have to look at certain factors in the male and see if those are important as well. But I would say chromosome losses are the most common. Other things that are very common are abnormalities in the uterus or the uterine cavity. They could be things like fibroid tumors or polyps or scar tissue. There are also could be inherited abnormalities. Sometimes a uterus doesn't form properly during development. And you can have structural issues of uterus that prevent normal implantation, or you can have implantation, but it's short-lived. Besides those two, oftentimes we look to see if there are any circulating antibodies or immunologic factors that could be rejecting a pregnancy. We look to make sure that there are certain hormone levels that are not outside normal, particularly blood sugar levels or thyroid abnormalities. And we look at sometimes clotting factors depending on when these pregnancies occur, when these pregnancy losses occur. So there's a variety of different reasons, but the truth is in about 40% of the cases we don't really know, but even then sometimes we can help. But it's more empiric treatment because we don't know the actual cost.
Rena: So, okay. So a lot of things to go back on, I think, you know, for the reasons you discussed, a lot of them do have sort of okay it's because of this so we can treat it with them. I think probably the most hot button topic you touched upon in there was immunology. Um, you know, we get a lot of patients in here that are then asking about the specific immunology treatment. So what are your thoughts on that? And I know a study just came out touching upon that. So that's, you know, such a common topic among patients, especially in New York city area. What are your specific thoughts on that?
Stein: So the importance of immunology with regard to pregnancy and pregnancy loss is pretty significant. We know that a pregnancy can develop successfully because women become somewhat immunocompromised. They actually will recognize this tissue, this fetus that is developing in them that has half of its genetic material, for example, from the father. And they yet, they have this mechanism of recognizing it not as foreign, but as self. And that's what allows pregnancies to occur. So the mechanisms that allow that to happen are pretty incredible. So we know the immune system has a very significant effect in the success of pregnancy. One problem is that there are so many immunological tests and treatments out there that have no scientific basis and are often time-consuming, expensive, and frankly, I'm not sure that some of those treatments are being done by people who are as interested in the results as just giving the treatment. So I think that it is an area where people have to be very careful to really concentrate on evidence-based medicine. So one thing that I'm very interested in is making sure that we really test the immunologic factors that have been shown to very clearly A) be strongly associated with recurrent pregnancy loss and B) for which there is a treatment. And if it meets those two criteria, then it's worth testing. If they don't meet those criteria, it's not worth testing.
Rena: Okay. That seems pretty straightforward. And then in terms of the sort of empiric tests that you referred to for those cases, that lie in the other percentage of sort of unknown, what does that mean?
Stein: The unknown 40%, 40 to 50%? I don't know, frankly, because they're unknown. By the way, that's going back. That's one of the things that's so frustrating, right? Not knowing. In those cases, oftentimes it's perfectly reasonable and recommended that couples continue to try because they may very well conceive without any help at all. And there's a fairly high percentage of cases that can do well. But the problem is many couples at this point are older. And once they're older, the time to actually intervene with some medical treatment becomes shorter and shorter. So generally if I have younger couples who are having recurrent pregnancy loss, who are not finding the cause, I recommend that they continue to try maybe for another six months and see what happens. If it's an older couple, I generally, we will say, we should really begin to think about doing something in terms of a therapeutic option. And that could be for example, in vitro fertilization with testing of embryos, genetic testing of embryos. And we've had a lot of success in people having very successful pregnancies from that treatment, but there is some controversy out there about whether those treatments are always needed and whether those treatments are going to help everybody, or if they’ll only help a small subset of people and so forth. So we've had good success with that, but it doesn't mean that it's right for every couple.
Rena: And also just for our listeners, when you say older couple in the sort of fertility world, what does that mean to you?
Stein: So all fertility patients are young, but reproductively, I would certainly say that those who are over 35 have a lower success rate in general than those who are younger. Granted, not every 35 year old does the same. Some have an excellent supply of eggs. Some of the men who are older have very good sperm, sometimes even better than people who are younger. But in general age is not, is not a positive prognosticator for pregnancy. Certainly once you get above that, you know, the mid thirties. So we tend to be a little bit more aggressive in initiating therapy in couples that are older because our time to intervene is short.
Rena: But I feel like what you said also is that every 35 year old still is not the same. And I think so many of my patients go on dr. Google and I say, stay off the internet because they go and they say, Oh, well, this person sounds like me. And this happened for them. And I always say, look, every person is individual. Every case is individual. And just because the internet says that, or you found another person out there, it seems like you, you're still your own case. You're your own body. Your partner is bringing their own stuff to the table. And so it's really important to trust your doctor, consult with them because every case still is very different.
Stein: Yeah. That's true. That's so true. And there's a lot of different possible treatments out there which are not necessarily evidence-based that people kind of jump to. And everyone has an anecdote about, you know, Oh my friend's sister, you know, had two miscarriages and then she, uh, ate two cans of spinach and she then had a successful pregnancy. I mean, I don't think anyone's ever said that, but it's sometimes to that level where people oftentimes they want answers so much that they'll provide their own.
Rena: I was so desperate that I spent one New Year's Eve driving around to the Lower East Side, trying to find herring row because I read that my aunt's dog sitter’s dog walker’s manicurist ate that and got pregnant. So I did that.
Stein: That's funny.
Rena: True story. It is not tasty.
Stein: No, I can't imagine it is. So there's so much, we still don't know. But as I said, sometimes people want answers so much that they'll accept something that's not at all evidence-based as being an answer. And it's also the responsibility of the physicians to be ethical and to very clearly state when the data isn't there. So you mentioned a study that came out recently, and I'm not sure if you're talking about what I'm talking about, but there was very recently within the last six months, a an excellent, excellent publication that was a review of all of the immunologic treatments for recurrent pregnancy loss and really looked at all the studies and graded the studies and looked at the size of the studies and their power to be able to detect differences in one group versus another. And I found in fact that a vast majority of immunologic tests and treatments had very poor support to do them. So I think there's a lot of excessive testing out there and a lot of excessive treatments, which can be quite costly, very costly for, for couples. And none of this stuff is cheap, but that can add thousands or tens of thousands.
Rena: I mean, I think, unfortunately I see a lot, this is an industry where people, patients are desperate. You know, this is family building, this is personal. People will do anything and unfortunately, there are a lot of people out there who realize that and they prey upon those people. And I think it's so important to go to an ethical practice, like where we are, where a doctor is going to tell you straight, they're not going to string you along and to make sure you're at a practice that's going to do that and tell you when it's appropriate to stop or maybe perhaps switch your treatment. Because I think there are a lot of people out there doing practices and promising things that may or may not be accurate in terms of helping you get where you want to go. And as you said, they're extremely expensive.
Stein: Yeah. I think that's definitely true. I think it's true. I'm not, you know, it's probably not only true in our field, but it's also true in other fields.
Rena: I think any healthcare thing, you know, people, it's desperate people wanting answers and wanting certainty and to feel that they're in control of, you know, our health. Loss of health is extremely, it's one of those difficult things to go through. Right?
Stein: Yeah. I think one advantage that we have here in RMA is we also contribute a lot to the literature and because we do contribute a lot to the literature because we are one of the most prolific contributors to the literature, it allows us to be more critical of ourselves, of our own data and we can also look at other data very critically and be able to kind of analyze how strong is the evidence and how valuable is it and what can we do about it?
Rena: Exactly. I think that's really powerful. And I think something patients really should consider when looking for a practice again, make sure you're at a practice where you trust your doctor. You can always ask to look at statistics of a practice. It's very important. And then I guess going back to sort of recurrent pregnancy loss and the uncertainty, I mean, what would you say to a couple of who, you know, has had multiple miscarriages and they're really losing hope? How do you kind of approach that? What do you say to them to give them hope or to counsel them?
Stein: Well, first thing I'd say is that for many of our couples who have recurrent losses, even three or four losses, many of them do very, very well with treatment. And some of them will do well despite us. You know, they will get pregnant as we're doing our evaluation. So having a few losses as devastating as it is for many, many couples in reality, isn't always a death sentence by any means when it comes to fertility and successful reproduction. And so what we try to do is approach it in a logical fashion. What we do is we look at the various factors, the anatomical factors, the genetic factors, hormonal factors, the immunologic factors. We look at all these different things. We try to do it in an organized way. We try to create a good evidence based approach. And when we don't have sufficient evidence, I'll say to a couple, I don't have sufficient evidence for this particular treatment, but it has been described before. It has been used a lot. We've had good success with it. I don't know if this one, this particular treatment will work for you but I think it's worth trying. And so it is not necessarily all doom and gloom. It's a lot of pain, anguish, and frustration for couples and for the doctors, but it is not all doom and gloom. I did, having a diagnosis of recurrent pregnancy loss does not mean you're not going to go on and have a perfectly healthy pregnancy.
Rena: I think that's so important for people to hear. I think sometimes they, you know, get in a place of just feeling hopeless, but you know, the reality is too that, you know, the percentage of miscarriage is really high. And I think oftentimes people don't realize that or they don't kind of hear it until it happens to them. And then of course they are, Oh yeah. You know, it's unfortunately really common and it happens. And it doesn't mean that you can't go on to have a successful sustainable pregnancy. And sometimes it might take, you know, multiple times as difficult as that is.
Stein: That's definitely true. I think that the greatest success in our field is what comes from couples that are persistent, persistent, that don't give up because, and there's so many reasons to give up, right? The fear of failure, the, you know, the, the continued pain that comes each time you get a negative pregnancy test, the, the expense, the, uh, side effects of medications, all that stuff. There's a lot of reasons to give up. I understand when people feel that they don't want to do more. But those who do persist often are rewarded for their persistence.
Rena: I like that. And that's true here and sort of in life in general.
Stein: Yeah that’s true.
Rena: So, I mean, is there anything else you would want to tell patients struggling? You know, it seems like you really have such a great empathy and understanding for the patient side of this.
Stein: Oh, absolutely. I mean, when my wife and I had been trying to have a child, we experienced a miscarriage that was very devastating. We then were able to succeed and we did have children, but, and it was only one miscarriage. And I know how disappointing that was having multiple miscarriages. I can only imagine how hard it is. And often people tend to blame themselves, even when it is completely nothing to do with anything that they're doing. They figure maybe I did this. Maybe I did that. Maybe I ran too fast when I was going down the subway stairs. Or I lifted that six six pound bag of flour. I don’t even know if they make 6 pound bags of flour. Or I was in a train and this person had a cough, you know, so people tend to blame themselves, but it's often just something that happens and we try to find causes and we try to be very diligent about being organized. And in a whole lot of cases, we're able to succeed. My advice to couples would be, as soon as you have two losses and you don't have a history of a prior child, but you have two losses, seek the help of a reproductive endocrinologist who is at a very well established and highly reputable practice, don't run around necessarily to the person on the internet who has the most links to treatments that aren't offered anywhere else. If a treatment is offered only in one place, it's probably not evidence-based.
Rena: I think that's really, that's really solid advice. So two recurrent losses, seek out a reproductive endocrinologist.
Stein: Oh, absolutely. Because at the very worst you're going to hear, don't worry. Okay. At the very best you hear, you don't worry at the very worst, okay. So you'll find out something significant that is often treatable.
Rena: I think that's great. And not the reproductive endocrinologist with the best Instagram or website, you know, really ask around, you can look at stats, you can seek those out.
Stein: I don’t even know how to get on Instagram.
Rena: We can't find you on Instagram. You're not over there tweeting?
Stein: I don't even know. I don't know the difference between that and Snapchat or all these things my kids talk about. So I don't know.
Rena: Well, maybe that's because you're out here helping get people pregnant and not, you know, on social media, right?
Stein: That’s true. I don’t have a lot of time for it.
Rena: Yeah. Yeah. I think that that's great and really, really wonderful advice. A sort of final question is how do you see the field changing in the next few years? Anything, you know, big you see coming up on the horizon in terms of, you know, assisted reproductive technology?
Stein: Yeah, I do genetics as it becomes more and more and more important. Well, actually it's always been very important. I don't think we realized how significant it is and not just the genetics of the embryos, looking at the genetics of the gene expression of the uterus, looking at another area where genetics will be very important is the ability to be able to assess the genetic competence of embryos without necessarily having to biopsy an embryo, remove cells from the embryo, which is not a difficult process to do. I mean, it's something we do very, very well here, but,
Rena: And you're referring to PGT testing?
Stein: Right. Preimplantation genetic testing. But you know, there are definitely studies now, which are looking into the potential value of doing a noninvasive assessment of the genetic competence of embryos. So there's a lot of different ways in which I think genetics will be the value of genetics and genetic testing will explode in our field. Other trends that I see are more and more people freezing eggs, which I think is a very smart thing to do when you're, when you still have good eggs particularly.
Rena: And that's also where sort of this 35 year old age comes into play. Correct? You would say before 35 if you can?
Stein: Yes. Best to do it before 35, but it doesn't mean it's not of value in the older people. It's just that you have to be able to understand that as you get older, there'll be less good eggs. So if you're gonna do egg freezing and you are under 35, do it when you're younger, don't, don't do it when you're older, when you'll get less good eggs. I mean, you can do it when you're older, but if you have a choice do it when you’re young. There's a lot of different, I think there's, you know, maybe eight years ago I would see a couple of patients a month who froze eggs. And now I see a couple a day.
Rena: Wow. Yeah.
Stein: Yeah. It’s tremendous. And I have two daughters and I have every intention if they'll allow me to, to freeze their eggs before they're 30.
Rena: I think it's the most empowering thing you can do as a female to take control of your fertility.
Stein: Oh definitely.
Rena: I tell everyone to do it for sure. I mean, I think it's, you know, hopefully in the future it becomes less costly and more accessible for people, it is still a hefty price tag, but, you know, hopefully it becomes something that insurance covers and people do. People start learning about it at a younger age, so they can do it and take control of their fertility in a way that's medically out there.
Stein: Hope so. Absolutely.
Rena: So I think this is all very sound advice and great information for our listeners. You know, and again, we're so appreciative to have you on.
Stein: Thank you so much for having me.
Rena: And your time.
Stein: Appreciate it.
Rena: And we like to wrap up our podcast by going and asking you to say a gratitude to end on a positive note. So something you are grateful for today and your life in general.
Stein: Well, I'm very grateful for a lot of things. I'm very grateful for the family that I have. And I'm very grateful to be working with amazing people. I would say that I'm particularly extremely grateful for the opportunity to do something in my life that leads to significant benefit to others. And it's a privilege that not everyone has the opportunity to have. And I always remember it's a privilege.
Rena: I love that. And I will say, I am also grateful for, I feel like I always steal other people's gratitudes, but they're so good. The family that I have and you know, the opportunity to work with such dedicated, compassionate, caring people. You know, I think this is a field where it's so important to have empathy and compassion towards the patient. You know, it's such a personal experience. It's a difficult journey. And I know because I see so many of your patients, you know, how much you treat everyone with such compassion and care and warmth. And I think it was wonderful and something to really be grateful for. So thank you.
Stein: Thank you.
Dara: Thank you so much for listening today. And always remember, practice gratitude. Give a little love to someone else and yourself. And remember, you are not alone. Find us on Instagram @fertility_forward. And if you're looking for more support, visit us at and tune in next week for more Fertility Forward.

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