SART Fertility Experts - Behind the Breakthroughs: Understanding Fertility Research

In this episode of the SART Fertility Experts podcast, Dr. Joseph Findley speaks with Dr. Rachel Weinerman about how research shapes the field of reproductive endocrinology and infertility. They explain what medical research involves, from forming a hypothesis and designing a study to analyzing data, undergoing peer review, and publishing results. The conversation also explores why objectivity, scientific rigor, and awareness of bias are essential when evaluating new treatments. Dr. Weinerman highlights major areas of current fertility research, including embryo quality, uterine receptivity, egg and sperm biology, artificial intelligence, fertility preservation, and emerging technologies such as stem-cell-derived eggs and sperm. They also discuss the ethical and funding challenges unique to reproductive research and the importance of distinguishing exciting early findings from treatments supported by strong evidence. The episode encourages patients to ask whether recommended tests and therapies are evidence-based and emphasizes that fertility care continues to evolve as better research becomes available to guide safer, more effective patient care decisions.

Find the #StartwithSART Fertility Experts series wherever you get your podcasts. Looking for advice on building a family? Ask the experts and #StartwithSART.

For more information about the Society for Assisted Reproductive Technology, visit our website at https://www.sart.org

Have a topic you'd like to hear? Tell Us!

Hello and welcome to this episode of the SART Fertility Experts podcast. My name is Joseph Findley and I'm a physician in reproductive endocrinology and infertility at University Hospitals Cleveland Medical Center. Today we're going to be talking about what is research in the field of reproductive endocrinology and infertility.

Today I'm joined by Dr. Rachel Weinerman from University Hospitals Cleveland Medical Center. She completed her undergraduate medical training and med school training at Harvard, OBGYN residency at New York University, fellowship in reproductive endocrinology and infertility in Pennsylvania, and is now an associate professor, REI fellowship director at University Hospitals Cleveland Medical Center. Welcome.

Thank you. Happy to be here. So we oftentimes colloquially hear about people saying they're conducting research by simply looking up articles online or looking on social media.

When we talk about research in the medical field, what does that actually mean? That's a great question and thank you for having me here. I think research is such an important topic in our field and I'm very happy that we're spending the time today drawing attention to it. I would say broadly speaking, research is the ability to ask a question, which we call a hypothesis, and then answer that question using sound scientific methods.

So to be more specific, if we have something that we are not sure, say, does a treatment work? We can make a hypothesis that that treatment does work and then design a study to determine if it actually does based on sound research methods and sound statistical methods. So some examples of how we might test a hypothesis is something called a randomized control trial, where we have two groups of patients who are given two different interventions to see what works better. We can do what are called retrospective studies, where we look backwards at treatment that's already been given and see how it compares to an alternative.

Or we can design research studies that happen in the scientific laboratory, whether that's on animal models, such as mice, or with human tissue outside of the body to determine how cells interact with various therapeutic agents. Excellent. So it really involves a rigorous method of asking a question and figuring out how to appropriately address that question.

Exactly. And I think that the important thing here is how do you actually test that question? Because there's so many different ways that you can look at whether something is effective, whether that's by personal experience or broad experience, say, among many doctors. But until it is rigorously tested in a scientific method, we don't know if that experience is just coincidence.

And that's one of the challenges of research is to understand when is something actually scientifically proven versus when is something maybe associated with an outcome but not actually causing it. And when folks ask these initial questions, are these things that they are leaning one direction or another regarding what the results may show? Are they going into things more open-minded with the idea of trying to see from an objective standpoint, does a certain intervention work or does a certain treatment provide the benefits they think that it will or will not? So in general, we often, as humans, are subject to something that's called bias. Bias is our tendency to answer questions with answers that we want the answer to be.

So for example, if you're testing, say, a new medication, like a new drug, you want it to work. That's why you're doing the trial. But as scientists or physician scientists, we have to understand what methods are objective so that we can reduce our natural biases so that when we're answering that question, we're not going to be, say, over-interpreting the data or even designing the study in a way that is meant to show that a medication works.

So we have to be very objective in designing research studies so that we can minimize the bias and make sure that the answer that we get is scientifically sound and not the answer that we want. That's challenging. I would say, just to be real for a minute, as a researcher, that's really challenging because you really want the answer that you want.

But that is one of the challenges of scientific research is to remain objective about your hypothesis and make sure that you're the data as the data is and not how the data is that you want it to be. And certainly it seems like that's a pitfall that many can fall into when they don't necessarily go through this vigorous process to want to ask the question but then test their hypothesis. Would you agree? Definitely.

And I think it's something that researchers always need to be conscious of. That's why when we work as a research university, as I do at Case Western, every year I have to tell the university what my conflicts of interest are. You know, am I consulting for an outside company? Do I have stock or business interests? Because anything that I have, say, a business interest in, that could bias me in terms of the research that I'm performing.

So it's very important as researchers that we acknowledge our potential biases, confounding interests, so that way we can make sure that our research is being done as objectively as possible. And so what does it mean to publish research, to take something from concept to going through the process of testing the concept and then going forth to publish it? What does that actually mean? What kind of process is involved there? So research is a long process and sometimes it takes a while, you know, years to go from hypothesis to publication. The general way that we perform research is we start with our hypothesis, we design a trial to try to answer that question, and then we perform the research.

As I mentioned, that could be a clinical study that might have to recruit patients, say over one to two years. It could be a study that's done in the laboratory that could take, you know, six months or a year or several years, depending on the study. Once the study is performed, the data is collected.

The data then has to be analyzed using statistical methods. And the reason that we use statistical methods is to ensure that the findings that we see in the research are not just due to chance. So we have statistical tests that are based on probabilities that help us determine if the differences we're seeing in our study are likely to be true differences or that is likely to be due to chance.

Now, if we have a finding that we think is statistically sound, clinically meaningful, and we want to share it with the scientific community, then we can publish it. And what that means is that we would write up the findings in a scientifically standardized way. So every scientific research paper has a hypothesis, it has the methods.

It's very important that we publish the methods so that other people can replicate the study and hopefully get the same findings. We publish the findings and the discussion, which is the interpretation. That paper is then sent to a medical journal and undergoes what's called a peer review process.

So peer review means that other people in the field who would understand the scientific research have to read it and decide if the findings are scientifically sound. And that can be challenging because as a researcher, you inherently, as I mentioned, have some bias about the research. And so to have that paper reviewed by someone totally outside of the actual research team who understands the methods is crucial.

And they can point out where the flaws are in the study design, where the flaws are in the data interpretation, and hopefully allow the researchers to improve the study so that by the time it reaches publication, the whole scientific community can agree that this is scientifically evidence-based research that we think should be published and therefore utilized by future scientists and physicians. Excellent. So it sounds like the peer review process is pretty important and key to making sure that the data that we're looking at and trying to interpret and then apply to practice is something that's objective and as unbiased as possible.

Would you agree with that? Correct. And most papers do not get accepted on the first submission to a journal. All scientists will tell you, you know, sometimes papers are just simply rejected.

That can be challenging if you've worked on a study for a long time. But ultimately, if it's rejected, that means that you need to improve the study. So a lot of times, the process of peer review actually makes the study better.

So let's say it's not rejected. Let's say they send it back to the researcher with revisions. That means that some person, there's usually two or three reviewers, has said, you know, we think that the kernel idea here is good.

We think that the overall study, you know, has some potential, but it needs to be improved in these ways in order for the paper to be accepted by the scientific community. And that process typically improves studies significantly. So the time they're published, they are more scientifically sound.

The results are interpreted in a way that is consistent with what the data actually says. So what does that mean for interesting articles or pieces of data that we may see online or in magazines that appear, at least on the surface, to have a great impact on our field of medicine or in patients' lives, but that have not gone through that rigorous peer review process? That's an excellent question. And I think as in the, you know, non-scientific community, we're often being told of scientific findings or medical findings without really understanding what is the science behind those.

So, you know, somebody can, for example, claim to have a new treatment that works, but how do we know that that treatment has actually been scientifically tested? So a lot of times journalists will understandably want to report on the newest thing. Well, the newest thing may not necessarily be scientifically based. And I think that's one of the key things as a reader that people can do who are not necessarily physicians or scientists is try to understand when something is being reported, is this actually based on scientific data that has been published or is this based on maybe someone's personal experience, which is not to say that it's not valid, but it's not scientifically tested and therefore not able to be applied to the general population with the same rigor that a true scientific study can.

Fantastic. Thank you. And so moving on, what are some broad areas of research that are happening right now in the field of reproductive endocrinology and infertility? Well, we have a very exciting field, I have to say.

One of the reasons I went into REI was because of the types of research being done in the community. It is a young field. You know, we have started to do what's called IVF or in vitro fertilization only in 1978.

So the scope of the field and the rapid change of the technology is really impressive and something that I love about our field. Currently, I would say the broad areas of research focus are in understanding in the context of in vitro fertilization what makes a good quality embryo. So we know that in order to get pregnant, we have to have eggs and sperm.

They come together to form an embryo. That embryo has to implant in the uterus. So what makes that embryo have the potential to become a baby? Now there are ways of testing embryos, for example, with something called pre-implantation genetic testing.

So that is a very interesting area of research. There are other non-invasive ways of assessing embryos. For example, embryomorphology may be assisted with artificial intelligence.

And are there ways that we can assess the quality embryo based on the culture media that the embryo is sitting in? So I think understanding embryobiology is one large area for our field. Another is that second piece that is necessary for pregnancy, which is the uterus. What allows the uterus to be receptive for an embryo to implant and then establish a pregnancy? We think we know some of the basics, but there's a lot more to be understood.

We know, for example, that there are some differences in the birth weight of babies that are born following different IVF treatments. Why? We think it might have to do with the uterine environment that the embryo implants in. And that's another area of research that I'm very excited about for the future.

There's also another area that just looks at clinical outcomes in our field. You know, we're very good at helping patients achieve pregnancy with IVF, but we could be better. There are at this point ways that we think we could improve, but we don't know exactly how.

And that's where research can really help us see how can we improve life-birth outcomes? What can we do in the scope of an IVF practice to improve the success rates for our patients? And that also involves not only embryo quality and the uterus, but also ovarian biology and testicular biology. What can we do to help create the best quality egg, the best quality sperm, to be able to help people conceive? And then finally, I mentioned before, but I think that artificial intelligence is a very broad area that is being explored currently in our field. How can we use new emerging technology to improve our understanding of, say, egg, sperm, embryo, and uterus? And how can we use it on a clinical level to help us choose the best egg, sperm, and embryo, or otherwise help ensure the success of IVF? So those are some of the areas that I think are very exciting right now in our field.

Excellent. Absolutely. Sounds interesting.

And so in your mind, what challenges exist? I know we talked about the process that goes into conducting research, but above that, what challenges exist for researchers trying to conduct these studies? We do face challenges in the world of reproductive endocrinology and infertility in research. And a lot of those challenges are unique to the fact that we are studying embryo biology in pregnancy. So it is very challenging to test things out on women who are trying to be pregnant or women who are pregnant.

We have a very high bar ethically, which is, I think, good in experimenting or trying experimental treatments on somebody who's pregnant. Because if we don't know what that impact is for the developing fetus, then that's something that we need to be taking very, very seriously. So that does limit to some extent what we can do in a clinical trial level.

And then the funding from the national government is limited as well because the federal government often does not fund studies that involve embryo research. So we do have some limitations there, which are challenging. I would say industry funding can also be challenging just because of the structure of our field.

In a lot of other fields, for example, let's say cardiology, there are a lot of medications that are being developed to help manage, say, acute disease or chronic disease. And so an industry might be interested in funding, say, the development of a drug. And then you can develop clinical trials that will enroll patients in testing out that drug.

The research that's being done in reproductive endocrinology and infertility, a lot of it is more scientific on a basic level, you know, understanding, say, for example, embryo biology, or it's more of a clinical technology adaptation, you know, understanding how we test embryos, for example, or maybe looking at cultural media. So a lot of it is not as straightforward as a drug that could be funded by a drug company. So I think there are ways that industry can fund studies in our field, but it's not as straightforward because a lot of the research that we do doesn't fit into some of the categories that are traditionally funded by industry.

So I think those are some two broad challenges that we have in research funding. But the good news is that we have a lot of very scientifically curious and very driven reproductive endocrinology physician scientists on our field who are pushing forward and finding interesting ways to fund their research. So despite the challenges, I'm very optimistic about the research being done in our field.

Excellent. What future directions do you see for research within our field? So I think there's a lot of excitement happening in our field because of the advances that we're making in general, in genomic and biologic research. So for example, we know that in order to use an egg today, we have to mature the egg.

That means that a woman has to undergo two weeks of injections in order to get an egg to get to the mature stage. And then we can remove it and what's called an egg retrieval and hopefully fertilize that egg. There is current research being done and I think will be done into can we use those eggs at an earlier developmental stage or called immature that would remove the necessity to do these injections.

Some of that research is already being done. I see that as being an area for the future. I think that the way that we do IVF will look very different if we can optimize egg maturation and understanding of egg biology outside of the ovary.

In the same vein, there's a lot of research being done now in animals translating into humans on can we actually create eggs and sperm from stem cells. Now, when you hear about this research, it may sound like science fiction, but I actually think it's something that will happen maybe in our lifetimes where you can actually take say saliva sample from a person and turn those cells into eggs and sperm. Now the opportunity there for future treatment in some ways is limitless because if you have the ability to create eggs and sperm, there's so much more that we can do to treat infertility and to help people in their family building.

And that lends to another area that I think is very exciting in our field, which is fertility preservation. Now we know that there are a lot of people who want to be able to preserve their fertility for the future. For example, before they undergo cancer therapy or other therapy that might prevent them from having children in the future or people who just want to be able to combat age-related fertility decline.

And there are a lot of technologies already being developed such as ovarian tissue freezing and transplantation that are helping to improve this concept of fertility preservation. We also now have the ability to transplant uteruses from one woman to another. And so I think that this area of how can we expand fertility by preserving it, by thinking of creative ways, that is another area that I'm very excited about for the future.

That all sounds amazing. And so with all of this new research coming out, obviously there is going to be varying levels of evidence to support particular intervention. So when this new info comes out, how is it kind of implemented into today's practice for patients who need help now? That's a great question.

And I think that a lot of times, like we were talking about before, journalism can pick up on some of these very exciting developments in the field. And patients might think that that's happening today. So I think it's very important to understand that there's a lot of research being done that's very exciting, but it's not necessarily ready for implementation.

The research that actually translates into clinical care often takes longer because of the very rigorous peer review process that we mentioned. And so I think as a patient who's thinking about what research opportunities are available to me, one of the challenges is that a lot of what we hear about as cutting-edge breakthroughs in the fertility world are not yet evidence-based. And that's something that I would caution patients about.

Sometimes they'll go to a doctor and be given some options that might not yet have the evidence behind it to be ready to be implemented. And this is one of the challenges of our field. Because of some of the inherent limitations of doing research in women who are trying to get pregnant or who are pregnant, a lot of times we will implement changes in clinical practice that make sense, see if we see them working for our own patients, maybe spread to other physicians starting that same practice, and only then go back and do the rigorous testing that would be needed to show if that treatment is actually evidence-based.

And sometimes it isn't. I think it's one of the challenges of our field. So I'll give you an example of where I think this can happen.

So for anybody who's listening, they may have heard of a test called the endometrial receptivity array or the ERA test. Now, this test was developed to try to help patients time their embryo transfer better. So if we can do a test that says your endometrium will be receptive after a certain number of days of exposure to the hormone progesterone, we can then personalize your embryo transfer protocol and try to improve outcomes for you.

Now, on paper, this makes sense. And for a lot of physicians, it made sense. So a lot of people started doing this test, personalizing transfer timing for their patients based on this endometrial receptivity array test.

It wasn't until several years later that a randomized controlled trial was designed and performed to see, well, actually, does it improve outcomes when you do this test and time embryo transfer is based on that? And the study actually said, no, it doesn't actually change timing. And what happened was that there are now some physicians who are still doing that test, but a lot of doctors have said, no, if there's not good scientific evidence behind this test, we're not going to do it anymore. And so I think that's an example where a patient might come to their physician and say, I've read about this test, let's do it.

And then the physician might say, no, actually, we now have good scientific evidence saying that this test is not effective. So I'm not going to offer that to you because it's going to cost extra money and we don't see that it's actually going to improve your outcome. And I think that that unfortunately happens too much in our field.

But part of the reason why it happens is because of the nature of the treatment that we have. That instead of everything that we do being originally rigorously tested, sometimes we have to go backwards, try out new treatments, and then go back and test them. So I would say for a patient who's thinking about how this research affects their personal lives, they need to understand that some of the treatments being offered to them will not yet have that rigorous testing behind it.

And so I think that they need to ask the questions of their physician, this test that you're recommending to me, is this evidence-based or not? And if not, why is it being recommended to me? And I think that that's a very important point that you make in that sometimes folks will hear about one treatment or another will be offered some sort of intervention that later on they find that we no longer do in the field or we no longer offer that sort of intervention. And, you know, when that happens, the initial recommendations weren't necessarily a reflection of somebody trying to deceive a patient or necessarily having any kind of gain. It's just that more and better information regarding that specific subject became available.

And so all we can do as physicians and human beings, frankly, who are trying to provide the best care that we can, is follow the best recommendations, the best available evidence. And sometimes that means things are going to change or things that were seen once as a standard of care or as a highly recommended intervention, those are no longer recommended. Exactly.

And it's one of the good things about scientific research that our knowledge evolves. And I think that's one of the important aspects of being an RAI physician that I have learned as I've advanced in my career, is that I have to be humble enough to understand that what I do today and what I know today might look very different one, two, three, or five years down the line. And I try to be honest with my patients about that too, that I will do my very best as a physician to keep up with the medical literature, to keep up with evidence-based practice, and personally do research myself because I am a researcher so that we have the ability to provide our patients the best care that we can today, even if that looks different than what's going to happen in the future.

Well, excellent. Well, thank you very much. Any concluding statements that you would like to make for the audience today? Well, I would just say that I think that what we are discovering about reproductive biology in the field of reproductive endocrinology and infertility is so incredibly exciting.

You know, we are learning things about the way that life begins that we wouldn't have ever dreamed of knowing, you know, a hundred years ago. So I just am so inspired by the work that's being done in the research community. I am so honored to be a part of it, and I absolutely love that we can translate these findings into helping our patients overcome their own infertility challenges.

So I am very excited about the future of research in our field. I'm very realistic about the challenges that we face, and I'm hopeful that we will continue to be able to provide evidence-based care for our patients the more that we learn. And, you know, hopefully that will translate to more babies being born.

That's the ultimate goal of everything that we're doing. Well, excellent. Well, thank you very much for joining us today, Dr. Weinerman.

Thank you so much for having me. This was so much fun. Absolutely.

And with that, this concludes our episode of the SART Fertility Experts Podcast. Please tune in again next time. The information and opinions expressed in this podcast do not necessarily reflect those of ASRM and its affiliates.

These are provided as a source of general information and are not a substitute for consultation with a physician.