Posted on February 11th, 2021by RMANY

Ep 49: The Frustrations of Unexplained Infertility with Dr. Rachel Gerber

Fertility Forward Episode 49:

Welcome back to another episode of Fertility Forward. Today’s guest is Dr. Rachel Gerber Gerber from RMA of New York. Dr. Gerber is a reproductive endocrinologist and infertility specialist and board-certified obstetrician and gynecologist who cares for patients at RMA of New York’s Eastside and Westchester offices. In addition to her medical expertise, Dr. Gerber prides herself on treating every patient with compassion, empathy, and respect. We dive into the topic of unexplained infertility, one of the most difficult things that some people face, and certainly a very tough and frustrating issue. Listening in, you’ll find out what it means and how it’s diagnosed, as well as the different types of treatment options, and so much more. So tune in today!

Transcript of Episode 49

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 from medical professionals, mental health specialists, wellness experts, and patients, because knowledge is power and you are your own best advocate.
Rena: So we are so excited to welcome back to Fertility Forward today another recurring guest, Dr. Rachel Gerber, from RMA New York. And we are so excited to have her back on today to talk about the really important topic of unexplained infertility. And I know that is one of the most difficult things that my patients face and certainly very, very tough. We're really excited to have you on to talk about this from a medical perspective and shed some light into what is really a very frustrating topic for so many people.
Dr. Gerber: Well, thanks for having me. I'm very happy to be back. And I think this is really an important topic that is so frustrating for everyone involved. I know as a REI physician, it's one of the most frustrating diagnosis as well, because we like to have answers, our patients like to have answers. We like to be able to give our patient, you know, answers. And so, you know, it really is one of those tough topics.
Dara: So what exactly is the definition? How do we define it? So I, it kind of sound self-explanatory, but I'm assuming medically there must be some sort of diagnosis to specifically say that someone has unexplained infertility.
Dr. Gerber: Yeah. So unexplained infertility, you know, it sounds, you know, it is what it sounds like, but let me go through what that really means. So what that means is that we've gone through our basic infertility work-up and we've, you know, checked all the boxes of different diagnoses that it could be. And we established that it's none of those traditional diagnoses and then you fall into the category of unexplained infertility. So let me just go through those things that we work up in your average fertility patient that we rule out as causes and in the case of unexplained fertility. So, you know, first thing is the patient has typically normal egg counts, right? So it's not an egg count issue. We want to make sure that they do in fact ovulate every month. So they're releasing an egg. This is typically, you know, just we can get this information really just by you saying you have regular periods and you get pre-menstrual symptoms, you know, that's 99% of the time you're ovulating. And in addition, we look at your fallopian tubes and your fallopian tubes look normal. So there's no sign of fallopian tube disease that, you know, is causing a blockage. That's not allowing the sperm to meet the egg. We also, you know, want to look at the semen analysis and make sure that there's no obvious cause, you know, on the male factor side. And finally, you know, we can look at the uterus as well and make sure there's nothing, quote unquote, uterine, you know, like a big fibroid or scar tissue in the uterus or something that is, you know, obvious there. So you've basically ruled out that it's the ovaries, the fallopian tubes, the uterus and the sperm. And you've said, it's none of these things that we can tell on our rudimentary, basic workup. And now you have a diagnosis of unexplained infertility.
Dara: Dr. Gerber, what about, is there any checkups or blood work on hormones to rule out whether that's an issue?
Dr. Gerber: Yes. So we will look at like thyroid function, for example, and you know, prolactin, the milk-producing hormone. And part of that often goes with the, you know, just typical day three blood work that you do. That is part of the workup to look at your egg counts.
Rena: You know what I think is interesting is how right at the beginning, you said the diagnosis of unexplained infertility. And I think that right there is exactly what my patients struggle with from the mental health perspective is they feel like unexplained infertility isn't a diagnosis.
Dr. Gerber: Yes. Well, I guess you would call it a diagnosis of exclusion is one way we say that, you know, we've looked into all the other diagnoses that we know about and that we have clearly defined tests for and you don't fit into those categories. So you now fit into this other category called unexplained fertility where, you know, we know there's something going on. Our tests just aren't good enough to find it right off the bat. You know, that's the frustrating part. It's like people often with chronic pain syndrome where everyone says, Oh, you're fine. You're fine. You're fine. No, you have, something is wrong. Just similar to this. No, you've been trying for a year, you know, of unprotected regular intercourse. If you're under 35 and we want you to come in sooner. So if you're 35 or older, we say come in after six months, so you've been trying and your average couple, you know, 85% of couples will get pregnant in a year of trying. And you are in that category of people who's not. There is something going on, but our tests are only so good. So that's what, I find, I try and let patients know it's not them. It's still, I put it on us. We as physicians and as a medical professionals, we still have work to go in order to really find out what all these diagnoses are and what other things there are that we could be missing in the standard infertility workup. So, you know, the patients shouldn't feel like, Oh, they're telling me there's nothing wrong with me. That's not what I tell my patients. I don't say you're fine. You know, your body's working completely normally, and this isn't happening. No, our tests aren't good enough to fully understand exactly what's going on in this case.
Dara: I appreciate you saying that, that you know, that there is this unknown and it's not your fault. I think, you know, I'm sure a lot of patients and I'm sure Rena can attest this, automatically say, Oh, if there's nothing diagnosable at this moment, it must be me. It must be my stress. It must be, maybe I'm trying too hard. And you know, I'm assuming that's not the case fully, of course.
Dr. Gerber: Yes, that's definitely not the case. And that is, you know, one of the worst parts about this diagnosis is that we all want to place quote unquote blame or, you know, we want to be able to say there is a problem and I can fix that problem. So this really leaves you in a very like unsatisfied place where as a physician and as a patient, you say, okay, well, if there's nothing that we're finding that's wrong then there's nothing to fix. So what do we do now? And so patients definitely internalize that as saying, well, then, you know, it has something to do with my psychological state or stress level, but that's really not true. I mean, people, you know, there's, there's really no evidence behind that. Even people in like war time and in, you know, under just immense amounts of stress have still gotten pregnant, you know, and there's, there's really proof, you know. Aometimes occasionally stress, acute stress can be so bad, if something, again like a war time kind of situation like happens where you're, or you have a huge tragedy in your life, you know, and you could maybe skip a period. So yes, if you're not getting periods and stress is causing that in a really acute, stressful situation, you know, then yeah, if you don't get your period, you don't ovulate, you can't get pregnant. But in this case they are ovulating every month. So in this case, you know, the stress that, you know, women go through trying to get pregnant and what that means, and you know, how you deal with that and how it builds month by month. You know, I know that every month can increase stress, but you're still getting your periods regularly. And there's really no evidence that that stress is causing you to not get pregnant. So it's not helpful to anybody. It's not based in science. And, you know, it's something that we have to work with our patients to internalize that they are not doing anything wrong and that they are not causing this and that stress and, you know, is not worsening it. And of course the dreaded line of just relax and it'll happen, or, you know, if you just, you know, try and keep your mind off of it, you know, and obviously that makes it worse and you know, it's just not helpful and it's not true.
Rena: So what are, do you have any, you know, words of encouragement or anything you say to patients struggling with unexplained?
Dr. Gerber: So I do. You know, it's a really frustrating diagnosis as we've been discussing, but our treatments work quite well for it. The problem is you sometimes might need to go to more invasive treatments like IVF to get there. But typically, you know, with these invasive treatments, if necessary, they have a very good prognosis of coming home with a healthy baby. So the encouragement is, although it's frustrating, our treatments do work well for it. And you just have to, you might just need a little more help than you wanted, but the end goal of having a baby is very attainable.
Rena: I think that's important. I just want to repeat that again that if you have unexplained, you know, you have every chance of having success. And I think the most difficult thing is just sort of having faith and hanging on and having to go through this without some sort of diagnosis. You know, I think it comes down to kind of mind over matter and believing that this process will work, even though you aren't going, you know, with, okay, I have endometriosis or I have PCOS, or I have a blocked tube. You know, you may not have a concrete reason as to why you're not getting pregnant naturally, but it doesn't mean that you won't.
Dara: Yeah. And there's reassurance to know that, you know, whether it's through IVF or perhaps there's something else that there is a way to get through this, but I think it's, it's tough. Rena and I always speak on the podcast about the idea of control and, you know, feeling like you can attach to something and getting reassurance of, of knowing what you're going through and what perhaps is the issue and not having that really can add that other level of anxiety and stress, but knowing that there is support and that there is something that you can do can be great.
Dr. Gerber: And just going back to, you know, there are definitely hypothesis out there of different things that can be causing unexplained infertility. So there are, there's definitely thoughts about what it is. And so for example, and we know it's not everyone with unexplained infertility has one thing, it's a, probably a whole list of things that we don't have good concrete tests for. But you did mention endometriosis, right? So endometriosis is something that can cause blocked fallopian tubes. There can cause you to have cysts on your ovaries or, you know, have the traditional symptoms of endometriosis have severe pain with periods. And, and in those cases, you know, people can get a clear diagnosis, but there is also people who just have subtle endometriosis that you wouldn't necessarily find, unless you actually did a surgery, put, you know, a telescope in someone's belly button and actually looked. So it used to be, you know, years ago that everyone with unexplained infertility would get a surgery to rule out endometriosis. Right? But we ended up seeing that it didn't really change our treatment. And there were surgical complications that came with having to undergo, you know, a laparoscopic surgery. And so the current recommendations are really not to do that. But people still think that a lot of unexplained infertility is related to endometriosis that is not at the level that we are seeing really obvious signs at it, but it might be like more subtle and if we actually did look it's there, but you know, it's the risk-benefit of looking does not fall in favor of doing the surgery.
Dara: Oh, interesting.
Dr. Gerber: Yeah. So that is one, you know, people really think that that could be a whole chunk of what unexplained infertility really is. Aome other things you actually find out by doing IVF. So IVF can actually be diagnostic to some extent in unexplained infertility. So sometimes there could be for example, an issue with the sperm binding to the egg, right? This is not something we can really test for. Or just the whole fertilization process can be, you know, compromised in some way. So but we can’t tell that, you know, when it's happening inside your fallopian tube, but when we do IVF, we can actually, we look at it in real time. So, you know, we can do things like inject a sperm directly into the egg so it doesn't need to actually go through the binding and maybe get around that factor if it is a sperm binding issue. And we also now can really see, is there a fertilization issue? Is it an embryo development issue, you know, or is it, you know, that maybe a high proportion of the eggs are genetically more abnormal compared to someone else your age? And all that can be tested through IVF and I find that sometimes people get answers by doing IVF. So again, you would never use it as a diagnosis. You know, you wouldn't use IVF for the sake of diagnosis, but in the process of doing it, we sometimes do end up finding out, you know, that, Oh, maybe this is why you are having trouble getting pregnant.
Dara: I feel like we need to do more research on this. I feel that there is definitely, hopefully, for more answers, if we're able to do research on these types of patients to see if there happens to be any type of trend.
Dr. Gerber: Right. I agree. And I think that, you know, this is all stuff that is underway. And so that's why I always tell patients, you know, we're still looking, we're still studying, like, we're only as good as our science and as, like, our research and, you know, hopefully one day we will have better answers, but at least for now we know generally how treatments will, you know, end up what the prognosis is with different treatments. And again, they tend to be pretty good.
Rena: Well, I love how you said that IVF can often be diagnostic. You know, something I say to patients a lot is that remember that nothing you've ever done in this process is a waste, you know, starting from the day you walked into this clinic, even before, you know, when you picked up the phone because maybe you had been trying to conceive for six months or a year. And I think nothing was happening. Everything is always data leading you to where you want to go. I know that it can be a really hard because as the patient, you can feel like the pin cushion or the guinea pig and that's very difficult, but nothing is ever a waste. Everything you do, every IUI, every test, every cycle is data points and medicine is all about collecting data. And as you said, you know, the more you progress, you know, if you do get to something a little bit more invasive, such as IVF, it's all data that hopefully will lead you to where you want to go which is to having a healthy live birth and conceiving. So I think that's a really important point to emphasize. And I said, I love that you said that.
Dr. Gerber: Yeah. And just to maybe go into a little bit of kind of how we treat these patients. So despite again, it being this group of patients where we don't have a lot of answers in terms of the diagnosis, we actually, they're a very well-studied group in terms of how they do with treatment. So we really know as a group, and again, it's clearly not a one diagnosis fits all. There's probably a lot of different things going on here, but in general, you know, with everything, all the tests coming out fairly normal, you know, and us still not having a reason, we've put all these patients into studies and have really solid information about how they do with different treatment options that we can counsel them really well. So at least on that side, you know, we have a lot of information. So, you know, once someone has been trying for a year and hasn't gotten pregnant and has a diagnosis of unexplained infertility, we know that their chances of getting pregnant each month without doing any intervention is about 4%. So that's lower than your average patient who has not, doesn't have infertility diagnosis where you're looking at a 15 to 20% chance each month, right? So once you have this diagnosis, you really do have a lower chance going forward because clearly there's something going on that unfortunately we don't have the right test for now, but you know, we now know that this is kind of what your prognosis looks like. So, you know, there've been studies to see, you know, does giving them a pill to help them ovulate, like Clomid for example, the most famous one, or doing an IUI which is putting the sperm directly into the uterus instead of formally during intercourse where the sperm goes into the vagina. You know, does either one of those seem to help get you pregnant? So studies are pretty clear that just doing Clomid alone, doesn't seem to be helpful. You're still at about 4%, 5% chance each month and doing IUI alone also doesn't seem to be helpful. But when you combine the two, so when you put Clomid or other oral medications with the IUI, you now increase your chance to about eight to 10%.
Dara: Oh wow. That's a doubling and doubling. What about Letrozole? Would that be another option?
Dr. Gerber: Letrozole would be in that category too, but studies have more, you know, focused on Clomid and Clomid does seem to do a little better in this population while in the PCOS patients, Letrozole seems to do a little bit better. That being said often Clomid can sometimes cause a thin endometrial lining or a thin lining. So often I'll start with Clomid and if in that patient, it looks like they have a thin lining, you know, I would potentially switch to Letrazole. I, you know, Clomid is really first line based on the information that we have in these patients. And the goal with Clomid is actually to have the patient ovulate two to three follicles. So I sometimes think of it as like buying tickets to the lottery, like you're ovulating one each month when you're trying on your own, right. So how do we increase the chances, right? So if you, obviously more than one you're now basically like each egg is like another chance to have a healthy, you know, egg that gets fertilized and grows into a healthy embryo. So it's like you're buying more tickets to the lottery. Yeah. So, you know, the problem is, is that you have to balance the fact that whenever you ovulate more than one egg, you have a risk of having, you know, multiple pregnancy. So the way it works is by increasing the number of eggs you ovulate and our goal is to have you ovulate two to three, but that also does slightly increase your risk of twins if you do get pregnant. So that's something important to understand because, again our goal is one healthy baby, but you know, we have to balance that with this actually working and actually improving your chances, right? So it seems like two to three follicles is a sweet spot. If you're growing four or five or six follicles that could ovulate, you know, then the doctor will often take a step back and say, you know what, this is actually too dangerous for having more than twins. And we need to, you know, cancel the cycle and try again with a lower dose or, you know, move to IVF because this is too risky.
Dara: That's interesting. At least there is some mounting research on a combination between Clomid and IUIs. And I'm assuming we'll, there'll be more research out there, whether it's with Letrozole or perhaps even more research on Clomid and IUI to really get more data points to see how people with unexplained infertility can have more success. That's I mean, double 8 to 10%, you said, as opposed to the 4%.
Dr. Gerber: And then, you know, the next thing you could do is do injectable medications with an IUI, but, you know, and that can actually increase your chances more about 15%. You know, the problem with using injectable medications is we really, you can end up growing really a lot more follicles, like I said, 4 or more. And we don't really have a lot of control in that case because, you know, you release all the eggs and however many fertilize, fertilize, and, you know, however many implant I,mplants. So doctors in our field, once we started to realize how much, you know, we were contributing to issues of having multiple pregnancies and even triplets and above and how, you know, the kind of complications that can come from that, we've really in a way taken a step back from using injectable medications with IUIs, you know, except in very specific situations and, you know, sometimes based on insurance or something like that, but you know, here at RMA we don't typically do a lot of that because it really puts you at risk of what we call higher order multiples, which is really, you know, something that is very scary to us and we are not, we're trying to avoid that at all costs.
Rena: Well it sounds like there’s certainly plenty of options and plenty of treatment plans. And I think sometimes, you know, it, it's really important to have the conversation with your doctor to get a blueprint and get a timeline when, okay, you know, here's my plan. We're going to start you with doing this. And then if it doesn't work, we're going to move to this. And then here's another option. You know, I think laying it out and helping people understand that there really are multiple treatment bands and multiple paths to follow is really helpful.
Dr. Gerber: Right. And then ultimately, you know, the thing with the highest success rate for unexplained is going to be IVF where really, first of all, like you said, you get a lot of information from it, but it does seem that, you know, whatever these causes are, we are able to get around them, you know, through IVF, you know, with injecting the sperm directly into the egg, we can optimize the uterine lining with, have it be at the right time to accept an embryo. We can also sometimes test the embryos to make sure they're genetically normal and kind of optimize every step of it. And, you know, people with unexplained infertility really have excellent prognosis, the same as patients with other diagnoses. Once you have a nice embryo or a genetically normal embryo, you know, they really do extremely well. So, ultimately, you know, it's just, unfortunately these patients some things takes that extra work or extra invasiveness to get them pregnant. But like I said, you know, they have a really excellent chance of bringing home a healthy baby at the end of it. It's just kind of a long stressful road and, you know, something, we have to really work with our patients to get through.
Rena: Well, I think that this has been really helpful and I really, you know, think you've broken it down so well and explained it both medically and also given, you know, a message of hope and help people understand, you know, unexplained infertility is a diagnosis. And I think if you frame it like that and say, this is my diagnosis, this is a concrete diagnosis that hopefully that will help people who have been given this feel as though there is a light at the end of the tunnel, that this is an answer and it's not just a question. And that you're not going to be kind of shoved in this category off to the side and, you know, your doctor has given up on you, you know, this unexplained is a diagnosis and there are treatment plans and a lot of options.
Dr. Gerber: Exactly.
Dara: Well, thank you so much for being here and how we always like to end our sessions, I'm sure as you're already aware, we like to discuss gratitude. So on this day, what are you grateful for Dr. Gerber?
Dr. Gerber: I'm most grateful that I am one week out from getting my second dose of the Pfizer vaccine. So I am in theory at my full immunity and I'm just so happy. I can't wait for this to become available to everyone so that we can hopefully feel comfortable moving a little more towards normalcy and maybe even go on vacations and start to maybe eat in restaurants and do all the things that I know I love and miss so much. So that is by far what I'm most grateful for that I've had the ability to get the vaccine, you know, in this first group. And I just can't wait for everyone else to get it as well.
Dara:Lots to be hopeful for. Rena?
Rena: I love that. Well, I am grateful for your, you know, your message of hope. I'm really grateful for that and that you're able to see the future and vacations and health. So I'm going to piggy back on that because I love that and really get on your train and believe in that I'm sort of having a frustrating day myself just dealing with my own unexplained issues of sort of long haul COVID symptoms. And it's really frustrating. So I can definitely empathize with people dealing with unexplained health diagnoses, especially right now. It's extremely frustrating. So I just love this and this has been so helpful. So I hope other people listen to this and feel like there is a light at the end of the tunnel. Dara?
Dara: Referencing a couple episodes ago, I was grateful for receiving my air fryer, but I wanted to update our listeners because I have used my air fryer for a number of things. I made chicken. I made chicken a bunch of times. I actually made dried mango for my kids. And tonight I am making salmon which that's the main reason why I got in the first place, so I can have crispy salmon. And then I'm just grateful because I'm still cooking at home so much more so because you know, who's really going to restaurants these days? So I'm just grateful for something so simple, but what a great invention and it's brought me a lot of happiness.
Dr. Gerber: Maybe I have to go get one?
Dara: It’s brilliant. It's really simplified my life. You use a lot less oil, it speeds up a lot of the cooking and it makes food taste really good. So yeah, it's definitely something that I put my stamp of approval on. Next is the Instapot. So once I get the Instapot I’ll report back on that.
Rena: I’m very inspired
Dara: Well, thanks again, Dr. Gerber, no problem. And we'll definitely have you on again soon.
Dr. Gerber: All right. Thanks for having me have a great day.
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.

The First Step Towards Your Future

Every journey begins with a first step. Attend a free seminar, speak with
a patient concierge, or schedule a consultation.

Get Started

Stay Connected

Sep 14th - Virtual Egg Freezing 101 Seminar. Sep 14th - Virtual Egg Freezing 101 Semin…. Learn More