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Double board-certified obstetrician-gynecologist and reproductive endocrinology and infertility specialist Erica Bove discusses her article, “Why do high-quality IVF embryos fail.” Erica explores the heartbreaking reality of recurrent implantation failure, challenging the assumption that it is a rare phenomenon. She analyzes the physical factors often missed in standard studies, such as chronic endometritis, silent endometriosis, and adenomyosis, while explaining why the endometrial receptivity analysis is losing favor in the field. The conversation also highlights a critical, often overlooked variable: the role of stress and mental health in fertility outcomes. Erica advocates for a holistic approach that combines rigorous medical guidelines with emotional support to help patients navigate the complex journey of IVF. Learn what to do when the science says it should work but the result is still negative.

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Transcript

Kevin Pho: Hi. Welcome to the show. Subscribe at KevinMD.com/podcast. Today, we welcome Erica Bove. She is a reproductive endocrinology and infertility specialist. Today’s KevinMD article is “Why do high-quality IVF embryos fail?” Erica, welcome to the show.

Erica Bove: Thank you, Dr. Pho. It is so great to be here.

Kevin Pho: All right. Let’s start by briefly sharing your story. Then we will jump right into your KevinMD article.

Erica Bove: Absolutely. I love to start by saying I went to med school to be a psychiatrist. This is interesting because I have always been motivated by the emotional side and the motivational side of people. But when I went to medical school, I fell in love with women’s health and OB/GYN, specifically infertility medicine, to help people build their families.

As I started to get out into practice, I was having these conversations with my patients and feeling like I was not connecting. I was going through all the data, but the patient on the other side of the conversation was struggling to assimilate the information and to make empowered choices. They were in a tailspin.

Around the same time, I was accessing coaching for my own personal reasons, and I started to connect the dots. I thought: “What my patients need to help them make these empowered choices is some of these coaching tools.” So I started experimenting in the clinic because we can bill based on time. All of a sudden, my patients were having these amazing breakthroughs. That is when I thought: “OK, there is something substantial here.” That is when I decided to form my own coaching practice called Love and Science, where I help professional women build their families.

Kevin Pho: All right. Your KevinMD article is titled “Why do high-quality IVF embryos fail?” For those who didn’t get a chance to read your article, tell us what it is about.

Erica Bove: Absolutely. I am a practicing REI physician. I help people very often to conceive with IVF. People think that our jobs are so happy, helping people with their families. But I will say what I do with most of my time in my consultations is help people assimilate bad news and help people understand why their last cycle didn’t work. It is devastating. People are often spending $15,000, $20,000, or $30,000 of their own money per cycle. Success is not guaranteed. When you sit with these patients and couples and try to help them understand, it is just so multilayered and complex.

There are a couple of papers that have been published in the last few years as we have gotten better and better about understanding the quality of our embryos. There is still a certain percentage of embryos that just don’t take. Trying to understand why is key. The papers that came out in the last couple of years said that this phenomenon called recurrent implantation failure is quite rare. They stated that 95 percent of people who have had three chromosomally tested embryo transfers should have had an implantation after three transfers. However, that has not been my experience.

I decided to do a webinar for people in this situation. When I sat down and looked into the data, I could not believe it. I don’t think that data is extrapolatable for most people because over 99.9 percent of the people weren’t even able to be included in the study. What I really wanted to do was say: “Hey, you are not a zebra. If you have had two or three euploid transfers and it is not taking, maybe there is more testing that can be done. Maybe there is something that hasn’t been figured out.” People start to think: “I am not going to be able to have kids. I am not going to be able to build my family.” They start to feel threatened, and then that starts this cycle of hypervigilance and worse outcomes. So that is what I wanted to do: say, “Don’t hang your hat on these studies because there is more to the story. There is more that can be done, and let’s figure out how we can help you build your family and not just get scared by these numbers.”

Kevin Pho: Now, before talking more about recurrent implantation failure, for those who aren’t familiar with IVF and what it entails, you mentioned the monetary cost (tens of thousands of dollars), but for these families that have implantation failure, let’s talk about some of the emotional experiences that they go through after this unfortunate event.

Erica Bove: I just got chills when you said that because it is profoundly devastating. First of all, they have gone through IVF. They have spent all this time preparing to do this. The IVF process itself takes about two weeks coming into the clinic every other day, getting blood draws and ultrasounds that culminate in an egg retrieval. The person has egg retrieval under anesthesia, wakes up, and we tell them how many eggs they have. Those eggs are fertilized later that day with sperm. Then people either will have a fresh embryo transfer in that same cycle, or they will return a month or two later to do a frozen embryo transfer. You can see this has already spanned three or four months at least of somebody’s life.

So then they do the embryo transfer, which is either immediate within a few days after the egg retrieval or a couple of months after the egg retrieval. Then they still have to wait nine to ten days to see if they are pregnant. That “two-week wait” is a really hard time because it is like: “Is this beautiful ball of cells that everyone says looks so great under the microscope going to become my child?”

If there is a connection and we are able to share the news, “Good news, you are pregnant,” people still aren’t out of the woods. But at least that step has worked. If we call somebody and say: “I am so sorry.” Sometimes, Dr. Pho, it is their only embryo. Sometimes we call them and say (and again, I am tearing up saying this because it is so emotional): “I am so sorry this didn’t work.” There is silence. Just like anytime we get devastating bad news, it takes the rug right out from under us. So there is that day, and then the days that come where there is a lot of processing of emotions.

I think the more bad news people get, the less hope they have about the process and the more they start to think it isn’t going to work for them. This doesn’t just affect an individual and their sense of self and their identity. It affects relationships. I have seen so many divorces happen in the context of these treatments. Sometimes the mental load is just so great that people even drop out; the dropout rate from treatment is so high. That is part of why I do this work as well. If people can stay in the game, if people can understand their options, their bodies, and all those things, people are truly likely to be successful if they stick with it. But when people drop out because it is so emotionally intolerable, that is when it is really hard. My goal is to make this a more holistic experience so people don’t have to suffer so much and we can say: “OK, let’s zoom out. Let’s look at the big picture and help people navigate the storm.”

Kevin Pho: Now, what does the data say in terms of the frequency of recurrent implantation failure? And do you think that the frequency is more common than that data suggests?

Erica Bove: Yes. There is a study (it was a retrospective study, but still a study) that showed that after three euploid, which means chromosome-tested, embryos, 95 percent of patients had had an implantation, and 92 percent of patients had had a live birth. There was another study, a follow-up study that brought that out to five euploid transfers and showed that approximately 98 percent had achieved their goal. That is where people say: “Why am I in the 5 percent? Why am I in the 2 percent? Why isn’t this happening for me?”

Sometimes it is even very simple, Dr. Pho. It is like: “Oh, you have chronic endometritis. We can treat that with antibiotics.” Then we clear it, and then their next transfer is a live birth. I think that is what the data suggests. But when you look at the fine print of the study, they excluded a lot of people. They excluded people with adenomyosis, which is very common for women. They excluded donor egg cycles. They excluded all sorts of severe male factors in the second study. So when you start going down the list, you ask: “OK, the patient in front of me, does this apply to them, or is there more that we can do?” And I will tell you, there is usually more we can do.

Kevin Pho: And before talking about what more we can do, what would you say are some of the more common reasons why women have recurrent implantation failure?

Erica Bove: Sure. It is twofold. When I am sitting in my clinic thinking about this with couples and families, I think: “OK, is it the embryo or is it the uterus? Or is it both?” We now are able to test embryos. But what we are realizing is that sometimes our testing is inaccurate, so sometimes it is better to not test the embryos. There is all the complexity: Just because it says that this is a euploid embryo doesn’t necessarily mean it is competent. It doesn’t necessarily mean that that is the truth. There are test characteristics where that may not be true, and so sometimes less is more. So embryo issues is one of the things.

But I will say when somebody has had several tested or high-quality embryos that aren’t implanting, there is usually something either with the uterus or something systemic that we need to address. One of the common things is adenomyosis or endometriosis, which can be suppressed by a GnRH agonist for two or three months, sometimes even with an aromatase inhibitor as well. Once you can calm that hormonally responsive tissue (the endometriosis, the endometrial adenomyosis, which are often comorbid), you will see an increase in people’s chance of success.

Then it is like: “OK, well how do you diagnose it? Do you do surgery? Do you do this receptive testing?” So there are some nuances to it. But even empiric treatment with the GnRH agonist has been shown to largely improve outcomes. Same thing with chronic endometritis. We can diagnose that either histologically on an endometrial biopsy or visually with the hysteroscope. I like to do both myself. But when we treat it and clear it and then we do another transfer, success rates are higher.

Those are a couple of things. I have seen people with fibroids. We also think about the structure of the uterus. I saw one woman; she had had three or four euploid embryos that had been transferred and it wasn’t working. She was a physician as well, a radiologist. I said to her: “I know you have had all this treatment and we haven’t talked to you about this.” (I was joining the practice; I hadn’t been taking care of her all along.) I said: “But I think you need a myomectomy.” She had a myomectomy, and then her second transfer after the myomectomy took. She ended up having twins.

So it is one of those things where you really have to be thorough and curious. Also, from a patient advocacy perspective, make sure that the relationship with your fertility specialist is a solid one. I think most fertility specialists have a vested interest in you and want to use this thorough and curious approach. Sometimes it is not a good fit, and I think people really do need to tune into that voice and sometimes seek a second opinion because there is a doctor who will figure this out for you. It just might take a little more time and a little more openness.

Kevin Pho: In terms of standard of care, like what you are suggesting in terms of the workup and potential treatment approaches, is that part of standard of care? Or is that something that is more cutting-edge, or something that is not currently being done?

Erica Bove: That is such a great question. A couple of years ago, ESHRE, one of the European societies, came out with a recommendation for recurrent implantation failure. I think it is tricky because nobody agrees on the definition of what that is. You can put it at two or three euploid embryos. What they say in their study and their guideline is that when you expect that somebody “should have conceived by now,” it is time to look into it. They have a whole equation of when you start this.

But they divide it into three tiers, which I love. They say: “We recommend these few things: lifestyle, and interestingly, antiphospholipid antibody testing because it has been shown that if people’s blood flow is better, outcomes improve.” The embryo is truly looking for blood flow to survive. So if somebody has an impairment in their blood flow, you can give Lovenox and baby aspirin with improvement in outcomes. So there are a couple of things that have been shown to be beneficial, and then there are a few things that are in the gray zone, and then there are a lot of things that are not recommended.

The ESHRE guideline is how I practice. I will say most of the time I am doing what is recommended and then exploring the gray to try and understand the full picture, like thyroid testing and endometrial testing and those sorts of things. But a lot of the stuff that sounds like it has promise, like natural killer cells and HLA markers and this whole field of reproductive immunology, has not been shown to be effective, though there may be promise in the future. So I usually counsel patients regarding what I think is evidence-based, what I think is not evidence-based, and provide the best-tailored plan moving forward.

Kevin Pho: If someone comes to you with recurrent implantation failure and you do a thorough diagnostic workup and implement some therapeutics, what is your success rate in terms of improving that outcome?

Erica Bove: It is very high. I would say fewer than 10 percent of my patients are unable to meet their goal eventually. Sometimes it means a different frozen embryo transfer protocol where we need to get the uterine lining thicker. That is one of the top things that the ESHRE guideline recommends: uterine thickness. Some people really struggle with that. But I think that success rates are generally quite high as long as we are able to meet certain criteria with endometrial thickness and quality embryos.

It is interesting; for most people, embryo generation seems to be the rate-limiting step of IVF. But once you are generating good embryos and they are not taking, then you really have to understand what is going on deeper. I will often give a couple of months of Lupron. I will make sure that they don’t have any endometritis causing inflammation of the uterine lining because those are low-hanging fruit and they really can make a big difference.

Kevin Pho: In your article, you talk about a statistic regarding female physicians having higher infertility rates, and that is certainly a striking statistic. So what does that tell us about the impact of things like lifestyle and high-stress careers on fertility?

Erica Bove: Yes. It is such a great point. I think that stress is really hard to measure, but I think we are getting better at it, especially as we all have these wearable devices and we are getting more real-time data. But it is undeniable that female physicians have worse fertility outcomes. It is not just childbearing either. People say: “Oh, it is because your surgery residency and fellowship took nine years combined, and you are 39.” If you even age-match people and look at a 35-year-old to 35-year-old female physician, they have worse outcomes.

I believe that is due to stress. Our jobs carry a big load. It is inherently stressful to take care of patients and families. Even though it is so rewarding, sometimes the care can be very stressful for many reasons. A lot of times our sleep cycles are dysregulated, so we are up for long periods. Especially if you are an attending and aren’t protected by these GME rules, we are working for 30 hours straight, sometimes even 72 hours straight if you are in certain fields. That is not good for the body.

Most of my people and my patients and my clients are eating well, they are exercising, they are doing all those things. But if we don’t acknowledge that physiologically stress increases cortisol levels, and we know that that has an effect on our basic physiology like our heart rate and our blood pressure, we miss the full picture. I truly believe, and we need to study this, that hypercortisolism negatively affects uterine receptivity.

This is part of what got me into this work: “Why are my female physician friends and colleagues at their fifth cycle and it is not working?” But I will tell you, Alice Domar has done a lot of this research, and I am finding it in my own coaching practice. When you help people connect their minds and their bodies, when you can decrease their stress levels, the success rates go up. We see higher implantation rates. We see higher ongoing pregnancy rates. There is data to show this. We need more, obviously. But that is really the thing.

If we are talking about uterine receptivity and why my high-quality embryos are not taking, we really do have to look at stress as the variable that people aren’t talking about to say: “This is, even though it is hard, modifiable.” There are well-documented studies and strategies in 2025 in terms of increasing parasympathetic tone and helping people connect with their breath. So we can look at stress, we can treat it. It does take maybe some hard choices and some boundaries. But if you are listening to this and this is your situation, really think about it because stress is negotiable and we have a lot more power than we think.

Kevin Pho: We are talking to Erica Bove. She is a reproductive endocrinology and infertility specialist. Today’s KevinMD article is “Why do high-quality IVF embryos fail?” Erica, let’s have some take-home messages that you want to leave with the KevinMD audience.

Erica Bove: Sure. What I would tell you, dear listener, is that you are never alone. I think part of what makes the fertility journey so hard is that it is incredibly isolating. Maybe everybody in your world is getting pregnant and we are approaching the holidays. What I would say is you are never alone. There are support groups that exist. There are therapists who understand. There are fertility coaches who are willing to bridge you through and grateful to do so. So find the support you need, find the community that you need, find the mental health support you need, because when you do that, not only will it feel better for you, but it will help your journey.

The second thing I would say is: Give yourself grace. One thing I have learned from doing this work over a decade is people blame themselves. They are like: “Oh, it is my fault. It is because I did X, Y, or Z, or because I waited too late, because I did all these different things.” Give yourself grace. Mindful self-compassion is a skill, but this is absolutely not your fault. We honor that, we nourish that, and we come together and we bridge people to parenthood. It is just what we do.

Kevin Pho: Erica, thank you so much for sharing your perspective and insight. Thanks again for coming on the show.

Erica Bove: Thanks, Dr. Pho.