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BackTable / OBGYN / Podcast / Transcript #22
Podcast Transcript: Oncofertility
with Dr. Leslie Appiah
In this episode, Dr. Leslie Appiah, who is fellowship-trained in Pediatric and Adolescent Gynecology and is the Director of the Fertility Preservation Program at the University of Colorado, discusses oncofertility and fertility preservation. You can read the full transcript below and listen to this episode here on BackTable.com.
Table of Contents
(1) Oncofertility: A Critical Yet Overlooked Aspect of Cancer Care
(2) Counseling Patients on Fertility Preservation
(3) Approaches in Oncofertility: Egg, Ovarian Tissue, & Sperm Freezing
(4) Ovarian Tissue Cryopreservation: Extraction & Reimplantation
(5) Expanding Accessibility & Future Fertility Options
(6) Exploring Testicular Tissue Freezing
(7) The Landscape of Oncofertility: System Solutions and Advancements
(8) Future Frontiers in Oncofertility: A Path Toward Comprehensive Care
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[Dr. Mark Hoffman]
Hello, everyone, and welcome to the Back Table OBGYN Podcast, your source for all things obstetrics and gynecology. You can find all previous episodes of our podcast on Spotify, Apple Podcasts, and on Backtable.com. Welcome back to another episode of Back Table OBGYN. I'll be your host today. This is Mark Hoffman and I've got a good friend and mentor; Dr. Leslie Appiah is with us today. She is a pediatric, adolescent, and adult gynecologist. She's a professor and director of the Division of Academic Specialists in Obstetrics and Gynecology at the University of Colorado, and she's the director of the Fertility Preservation and Reproductive Late Effects Program. Dr. Leslie Appiah, welcome to the show.
[Dr. Leslie Appiah]
Hello, Mark. Thank you for having me. It's my pleasure to be here.
[Dr. Mark Hoffman]
Is it okay if I call you Leslie on the show?
[Dr. Leslie Appiah]
Absolutely, thank you.
[Dr. Mark Hoffman]
Leslie and I have known each other for a while. She was my boss, but she's not anymore, so I don't have to watch what I say quite as much as I used to. But she's a friend, but also a mentor, someone who's taught me a lot about the job that I have now, and I'm forever grateful for that. More than that, I think you have an incredible responsibility and job right now that I'm excited for you to talk about for our listeners because it's something that I certainly didn't get much training in, and I don't think most of us do along the way. That's Oncofertility. I'm really grateful that you're here today and I'm excited to hear you tell us all about it. Tell us about you, where you are, how you got there, and how you got to be doing what you're doing.
[Dr. Leslie Appiah]
Absolutely, thank you. I would love to. I do want your audience to know first that Mark has always told me what I needed to hear, even as his boss. [chuckles] It was a great partnership and we learned from each other. It was just as much my honor.
[Dr. Mark Hoffman]
Now, that means a great deal.
(1) Oncofertility: A Critical Yet Overlooked Aspect of Cancer Care
[Dr. Leslie Appiah]
I was recruited to the University of Colorado in 2019 for a few reasons, to help elevate the division's academic expertise to the national level and to build Oncofertility program. Oncofertility is my passion. It is an area of expertise that I began developing very early in my career as an assistant professor at Cincinnati Children's Hospital. I have been fortunate enough to help build now four fertility preservation programs across the country. It has been very beneficial and awe-inspiring work. I've had the opportunity to collaborate with experts across the world in improving care for this population.
A little bit about Oncofertility. Oncofertility is a multidisciplinary field that brings together clinicians, scientists, psychosocial experts, and patient stakeholders to improve fertility and reproductive health outcomes for patients with cancer diagnoses. This is an area that we do want all physicians to be familiar with because it touches primary care providers, specialists, everyone in medicine, and we want our patients to get the best care. The more we can advance knowledge across disciplines, the better it is for our patients.
[Dr. Mark Hoffman]
Well, it certainly doesn't sound simple. I mean, the list of folks you mentioned, and having seen what you are able to do in your time here at the University of Kentucky, it's a heavy lift. It's a big job. It's a lot of work, but you're dealing with one of the most vulnerable populations. Most of the patients you're dealing with or patients with cancer. Not all; most. This is something that in my years as a resident dealing with G1 Oncology in med school, I don't think it was mentioned once to me.
It was not something that came up in conversation, yet when you came and spoke to us about what it is that you do, it seemed like such an important thing that not a bright enough light or no light at all was being shone on it. Is that a sense you get from other places you've been as well where it's like, oh wait, we're not even doing this? Is that a common thing you do along the way?
[Dr. Leslie Appiah]
It is, and it's very common to hear physicians of all stages and degreed levels say that they've never heard of the term Oncofertility. The term was coined by Dr. Teresa Woodruff at Northwestern University in 2009. Teresa Woodruff is an ovarian biologist who really began the journey of preserving the fertility of patients with cancer. Since then, it has been our charge to increase knowledge around Oncofertility. At every institution that I've been employed, it tends to be a very novel idea or a novel discipline for individuals.
It is a huge lift. It takes a lot of heart and compassion and grit and determination and the ability to influence individuals to really take up the charge to care for this patient population. Fertility in this country only recently began to be understood or appreciated as a disease, and it's almost stigmatized to have infertility, and insurance providers don't cover fertility services for patients without cancer. You can imagine the challenge to begin to bring these services to patients who have this chronic illness.
[Dr. Mark Hoffman]
Why do you think that is that infertility is not considered a disease state? Is male infertility covered or not covered? In a way it's the same thing.
[Dr. Leslie Appiah]
I have pondered why infertility is not considered a disease state, whether it's a political reason, a religious reason. When we look at fertility services and fertility practices across religions, why variations in what is acceptable and what isn't in order to preserve fertility or to achieve biological children, I've always wondered if that has a role in it as our society tends to be heavily influenced by religious practices at times. No, infertility is not covered more for males or for females or any particular group. Infertility services across the board are not well funded or not well covered by insurance providers. I will say that that is changing.
There are now 13 states, including Colorado, with legislation that mandates that insurance providers cover fertility services, both for patients with cancer and without. Fertility preservation services for a woman or man who is going to undergo cancer treatments that are going to render them infertile, and then patients who actually meet the medical diagnosis of infertility.
[Dr. Mark Hoffman]
That's interesting. I've lived in states that do and lived in states that do not cover or that do not mandate coverage for infertility. I've never known whether a state that I've lived in had any specific coverage for things like fertility preservation. Is that something that's newer in terms of legislation? Illinois, where I trained, IVF was covered, it was all covered. Michigan, Kentucky was not. Would fertility preservation services be covered underneath that or does that typically take separate legislation?
[Dr. Leslie Appiah]
It typically takes separate legislation. You're very astute there as usual, Mark. In states where infertility services are covered, we have had to go back to the legislatures to add fertility preservation coverage. It's very specific language that needs to be placed into the bill in order to provide those services for individuals.
[Dr. Mark Hoffman]
You've been involved in some of that legislative work in Colorado. Is that right?
[Dr. Leslie Appiah]
I've been involved in several states, Kentucky, Ohio, and Colorado. Unfortunately, there are some political considerations to whether these bills are passed. Challenges in Kentucky and Ohio with passing these bills. We were successful in Colorado. We do have legislation as effective this January, January 2023.
[Dr. Mark Hoffman]
Wow, congratulations.
[Dr. Leslie Appiah]
Thank you.
(2) Counseling Patients on Fertility Preservation
[Dr. Mark Hoffman]
Talk about the patients that need Oncofertility treatment or care, I guess rather, because with cancer-- I'm reading The Emperor of all Maladies. I didn't want me to understand about cancer and those things, but I think one of the things that typically gets left out of these things is it's life or death, but there's a lot more to life than just living. I think that fertility preservation is something that we- again, that I haven't thought much about, but who are the patients that we should be discussing this with?
[Dr. Leslie Appiah]
Thankfully, the type of patient who would benefit from fertility preservation continues to grow. I say thankfully because initially the field was very focused on patients with cancer and that's our base. Patients with cancer, they're receiving highly toxic treatments and their fertility is going to be impaired. Patients with cancer diagnosis have historically been the primary population. However, we are now able to provide fertility preservation services for patients with sickle cell anemia who are undergoing bone marrow transplants, patients with systemic lupus erythematosus who are receiving alkylator therapies, cytoxan cyclophosphamide, transgender populations who are going to undergo gender-affirming surgeries and are receiving gender-affirming treatments are at risk of infertility, and patients born with genetic conditions that result in infertility such as Turner's syndrome, or those with differences in sexual differentiation. All of those patient populations are at risk of infertility, either from their diagnosis or from the treatments that we give them. These patients should be counselled about their options.
[Dr. Mark Hoffman]
You mentioned talking to other physicians and engaging other physicians, and this is a conversation that having worked alongside you, not in this endeavor, but having worked alongside you over the years when you were doing this, understanding that sometimes these conversations happen too late. Having to convince or having to educate people seems to be such a big part of this job. Because if I'm a cancer doctor and someone comes to see me and I'm taking care of the cancer, I don't have that conversation before we treat. We've done the damage. What are the chemotherapeutic agents or what are the treatments that you most commonly see as being the most negatively affecting fertility that have the most harmful impact on fertility?
[Dr. Leslie Appiah]
Before I answer that question, I do want to acknowledge your comment about the education piece. It does require consistent and persistent messaging about the risk of these treatments to fertility. We have a 13-member team at the University of Colorado, which again spans all disciplines. That is required to really ingrain the idea of Oncofertility across the institution, that every department is affected by, whether it's surgery, endocrinology, pediatrics, every physician will encounter a patient who has had a cancer diagnosis or is diagnosed with cancer. It's really important that this becomes a part of our culture, that we address this well for our patients.
Thankfully, not all chemotherapeutic agents will negatively affect fertility. The agents we worry about the most fall under a category called alkylator therapies. These therapies destroy both rapidly dividing cells as well as cells at rest. While these therapies are great for treating the tumor burden, they also destroy healthy tissues such as skin, ovaries, and testicular tissue. The higher the dose of alkylator the more harm. We want to be cognizant about how we counsel patients. We don't want to incite fear and trepidation in all patients because not all chemotherapeutic agents cause the same level of harm. We want to be sure that we message that appropriately. Another treatment that is highly toxic for the gonads is radiation. That is also dose dependent. The more radiation a patient receives, the more harm that may occur. Also, the location. Cranial spinal radiation, total body radiation, pelvic and abdominal radiation, and direct radiation to the groin, that is going to confer a high risk of infertility. Depending on the dose, it may be irreversible. I will say that men, there are many great attributes to being male.
One of the great attributes is that men can produce sperm into their 60s. The cells can regenerate. A young boy who is 15 and experiences a receives chemotherapy may recover their fertility in 5 to 10 years. For females, we're born with all of the eggs we're going to have. If there's injury in adolescence, we're only going to shorten the time to menopause. It's important that we counsel patients about the chemotherapeutic agents and the radiation they're experiencing, what that harm is, and then what we can do to mitigate that harm.
(3) Approaches in Oncofertility: Egg, Ovarian Tissue, & Sperm Freezing
[Dr. Mark Hoffman]
For our patients with ovaries, what can be done for women who are undergoing therapies that can be injurious, that can injure, their ovaries, that can reduce their ovarian reserve? What are the options if someone comes in diagnosed with malignancy recommended treatment? Talk about the processes available to these patients for fertility preservation. I imagine there's not just one thing you can do for them.
[Dr. Leslie Appiah]
Absolutely. To start off with, we should counsel all patients of reproductive age about the risk to their fertility and about the options. When I say reproductive age, I mean birth through age 42 for females or patients with ovaries and birth through the 60s for patients with testes and the children have reproductive potential. We want to counsel them about the harm of these therapies to their reproductive potential first. That is mandated, or I should say it is a standard of care as depicted or as stated by the American Society for Reproductive Medicine and the American Society for Clinical Oncology.
Every reproductive governing body, every oncologic governing body has stated that as medical providers, it is our responsibility to counsel every one of these patients or to offer counselling to every one of these patients who may be at risk. That's number one. Once we identify risk and the patient wants to proceed with fertility preservation options, there are several. For patients with ovaries, egg freezing is a standard of care. It is available to adolescents. I think historically we think about egg freezing for adult patients 18 and over but we can't freeze eggs in girls who have experienced menarchy. Success rates range anywhere from 50% to 60% in patients under age 35 years of age.
Sperm banking is standard of care for adolescent and adult males. They should be offered this opportunity. Ovarian tissue freezing is near and dear to my heart. It is a process where we would remove an ovary and then freeze the ovarian tissue prior to cancer therapies. Then when the patient has completed chemotherapy or radiation, we will transplant the tissue back into the pelvis when they're ready to have a family. Prior to December 2019, ovarian tissue cryopreservation was considered investigational. There now have been over 200 births worldwide. This is now considered clinical care. We do offer it to patients from several months of age to age 35.
[Dr. Mark Hoffman]
From several months of age, is that what you said?
[Dr. Leslie Appiah]
Several months of age. When you have patients with diagnoses that require pelvic and abdominal radiation at a very early age, unfortunately, those individuals are going to experience infertility. We will remove one ovary prior to cancer therapies and then freeze the tissue for their future use.
[Dr. Mark Hoffman]
What's the longest time between removal and replacement?
[Dr. Leslie Appiah]
I can imagine that we're still looking at somewhere from probably 10. We're probably looking at 10 years at this point, yes, because we've been doing this for a while.
(4) Ovarian Tissue Cryopreservation: Extraction & Reimplantation
[Dr. Mark Hoffman]
Talk us through that procedure when you remove the ovary or remove ovarian tissue to replacement. Talk us through that.
[Dr. Leslie Appiah]
I'm glad you asked, Mark. One of my favorite topics. When we remove an ovary, we are not able to freeze an entire ovary as it is because of the diameter and the width of the ovary. Our cryoprotectants or our freezing agents can't traverse the width of the ovary. We bivalve the ovary in half.
[Dr. Mark Hoffman]
You take out the entire ovary.
[Dr. Leslie Appiah]
We take out the entire ovary and that is actually a subject of debate. We may potentially remove strips of the ovary, and that's called taking cortical biopsies, or we may remove an entire ovary. There are some investigators who recommend removing just strips of the ovary for patients who are not at the highest risk of infertility. Some of us feel differently and we feel that perhaps we should only be doing ovarian tissue cryopreservation for those patients who are at the highest risk. In that case, we know that they have an 80% to 90% chance of infertility. It would behoove us to obtain as much tissue as possible. That means remove an entire ovary.
At the University of Colorado, we are of the school of thought of removing an entire ovary for patients who are at the highest risk. When we remove the ovary, we bivalve the ovary, we remove the medullas, the inner part of the ovary, because follicles are not contained there or so we believe. The follicles are primarily contained in the cortex. We then cut the cortex into strips of a very specific diameter; half a centimeter wide to a centimeter long to two millimeters wide.
[Dr. Mark Hoffman]
Done in the OR or this is all done after?
[Dr. Leslie Appiah]
Done after retrieval. The ovary is removed in the OR and then the ovary is transported to reproductive endocrinology and infertility specialists or pathologists who are trained in this technique. The procedure then happens there.
[Dr. Mark Hoffman]
Are you using energy, removing the ovaries like you normally would for an ectomy for anybody else?
[Dr. Leslie Appiah]
We are, because these patients, as you can imagine, have pancytopenia, they're anemic, they have thrombocytopenia. We want to make sure that we don't cause any additional bleeding and so we do use a heat source. We are getting better and better at using sources that have minimal spread so that we don't harm the fallopian tube or the blood vessels to the fallopian tube because we do leave the fallopian tube in place.
[Dr. Mark Hoffman]
Oh, interesting. I'm trying to figure out.
[Dr. Leslie Appiah]
This is the surgeon in Mark. He's thinking this through. Then we also don't want to harm the cortex of the ovary when we're transecting. This is far easier to do in adult patients where there's enough distance in the mesosalpinx. Pediatric patients, there've been some suggestion that maybe in pediatric patients we should remove the tube and the ovary together because we may end up damaging the tube if left behind, so why leave behind a damaged tube?
Well, the reason we should leave behind a tube is because we prefer to transplant the tissue back into the pelvis near the fallopian tube where we removed the ovary because half of the pregnancies, or half of the live births, the singleton live births have been in patients who have conceived spontaneously. If we leave the tube in place, then patients can have intercourse and conceive.
[Dr. Mark Hoffman]
Ovary comes out, chopped up, frozen, freezer, cancer treated, patient's ready to start a family. How do you reverse that?
[Dr. Leslie Appiah]
Exactly. We will use the same incisions typically, so laparoscopic procedure ideally and create a pouch or pocket in the peritoneum of the pelvis, so near the fallopian tube in the ovarian fossa. We just place two or three strips. In an adolescent or an adult female, you may have 15 to 20 strips depending on the age. We don't want to put all the strips back in one time because there's just a finite duration of viability for the tissue. That duration is anywhere from 6 months to 11 years based on the data. We'll place two or three strips into that pocket or that pouch. You can suture the pouch closed, put [unintelligible 00:22:02], use surgical glue, and then within 30 to 90 days, angiogenesis occurs, and the ovary begins to produce hormone and begins to ovulate. It is amazing.
[Dr. Mark Hoffman]
No way. Wait, you're just sewing it inside the pelvic sidewall?
[Dr. Leslie Appiah]
Yes, pelvic sidewall.
[Dr. Mark Hoffman]
Just stick it in there, close it over.
[Dr. Leslie Appiah]
Yes. Get it in there anywhere you can. There are some other techniques that are a little bit more sophisticated where we always try to leave one ovary behind in the event that there's spontaneous recovery. There is a technique that is described where one could create slits within the ovarian cortex of the remaining ovary, undermine the cortex, and then just slide each strip of thawed cortical tissue beneath the surface. The idea is that that blood supply may be more robust and that you may have success there. There is also a third technique where a surgeon may decorticate, so remove the cortex of the remaining in situ ovary completely to allow exposure to that vascular bed and then suture ligate these thawed strips of--
[Dr. Mark Hoffman]
It's like a face transplant.
[Dr. Leslie Appiah]
Exactly. Just like that.
[Dr. Mark Hoffman]
You're just skinning the ovary-
[Dr. Leslie Appiah]
That's right.
[Dr. Mark Hoffman]
-and putting the new cortex on top of it.
[Dr. Leslie Appiah]
Yes. Now, when they look at all three approaches, the success rates are similar. Now, you have 200 patients born worldwide, you have to say, do we have the power to really say that they're equivalent? Thus far it does not seem that any procedure is superior to the other. I will say that the face plant for the ovary and the pockets requires a big rescission and microsurgical dissection and technique and so you really need someone who has a surgical expertise. The rest of us Average Joe Schmos surgeons, can do a laparoscopic procedure where we create the pouch and place the tissue there.
[Dr. Mark Hoffman]
We had Dr. Elliott Richards from Cleveland Clinic come and talk to us about uterine transplant. That was a whole other series of problems trying to figure out what needed to happen to get all of that going, but this is fascinating. The idea that you can just throw it back in there and it comes back alive, putting that tissue in the pelvic sidewall, how does it ovulate? Does it just pop through the peritoneum?
[Dr. Leslie Appiah]
It pops through the peritoneum.
[Dr. Mark Hoffman]
Finds a way.
[Dr. Leslie Appiah]
You got it. It pops right through the peritoneum. They've done some sophisticated ultrasound studies to see that occurring. Very early on there was a debate, oh, is it really the tissue transplanted or is it the remaining ovary? They've shown that. They've shown ovulation coming from that tissue.
[Dr. Mark Hoffman]
I guess if you have somebody with no ovaries, can you put a--
[Dr. Leslie Appiah]
Yes. They've done that. They've done those studies. The success rate is 29% of 41% depending on the age of the patient at the time of retrieval, because there's more tissue for an older patient, but there are more eggs, so in a younger patient. Even though children have really small ovaries, there are millions of follicles there. The success rate depends on size of the tissue and then the center that is performing the transplantation. I think that's important for me to say because I would recommend that surgeons not do this procedure to transplant the tissue if they have not developed the expertise.
Most gynecologic surgeons and general surgeons can remove an ovary, but transplanting the tissue is going to require more than just putting the tissue back. We may need to look at the vascular bed. We are trying to identify agents such as anti-Müllerian hormone to place the tissue in prior to transplantation. How do we support the tissue when it's transplanted into the pelvis? Because the follicular atresia and the loss of follicles is pretty rapid once the tissue is transplanted, if the vasculature is not robust. We don't want surgeons to take this on because they want to help patients. We want to make sure that this happens at centers of excellence and places where there is a team to do this well.
[Dr. Mark Hoffman]
Well, I'm not looking to put any ovarian strips in the sidewall without you there, so don't worry about it.
[Dr. Leslie Appiah]
That's great.
[Dr. Mark Hoffman]
Also, you got to have the frozen ovary strips too. You can't just do part of the program. You got to do it all. Colorado is lucky to have you.
(5) Expanding Accessibility & Future Fertility Options
[Dr. Leslie Appiah]
Yes, and I want to comment on that because we do want to make ovarian tissue cryopreservation accessible to smaller institutions or institutions that don't have the resources to have the Cadillac version of things as we do here in Colorado. It is possible to remove an ovary, place the ovary in holding media and transport the ovary to another center. Actually, at the moment, we transport our tissue to University of Pittsburgh, to Kyle Warwick's Group, and they process the tissue there and then they send the tissue to a long-term storage facility. Typically, we use an organization called ReproTech, and I'm going to call them out because they are an amazing partner and do amazing things for these patients. That's our long-term storage facility. At the University of Kentucky, where we started the program and things have been in transition for a while, you, Mark, can remove an ovary.
UPMC will send the shipping materials to you. You can send the ovary to UPMC. They will establish a relationship with the patient as will ReproTech. Then that patient has had their fertility preserved and when they're ready to have the tissue transplanted back, there are several centers that the patient will then be able to go to to say, "I would like to have my tissue transplanted here."
[Dr. Mark Hoffman]
That changes everything though, honestly. I think the idea that there are a small number of centers with a very finite number of surgeons and teams that are doing the incredible work that you're doing, but the idea that now that someone like me can just take an overview out and send it somewhere, now that person's got access to their future fertility.
[Dr. Leslie Appiah]
Exactly. It should be that simple. It should be the oncologist has a patient. The oncologists know the risk stratification, they know which patients are at harm and they can contact a surgeon and say, "This patient's at harm. We've talked about ovarian tissue, cryopreservation. They would like to participate," and then we can take it from there.
[Dr. Mark Hoffman]
Are there companies doing this or is this all academic?
[Dr. Leslie Appiah]
It's academic for now. For now, it's academic, but in medicine, when we don't do what we're supposed to do, industry will do it for us. I recommend that we do this as academicians so that we can follow the science around it. It would be my recommendation.
[Dr. Mark Hoffman]
How many places do you estimate are sending ovaries to a place like Pittsburgh? Or is there not a place like Pittsburgh? Is Pittsburgh yet? Are there other places you can send it?
[Dr. Leslie Appiah]
There are other places. One can send tissue to Northwestern. I believe University of Michigan is bringing their program up in a year. Colorado will be a regional center.
[Dr. Mark Hoffman]
Is Molly Moraveck doing that?
[Dr. Leslie Appiah]
Yes, and I do like good friend Molly.
[Dr. Mark Hoffman]
I've known Molly for a long time. She's great.
[Dr. Leslie Appiah]
Yes. Right now UPMC takes about, I would say it's probably over 25 centers across the world that utilize them for ovarian and testicular tissue freezing. That's the other option that we should talk a little bit about.
[Dr. Mark Hoffman]
It's an OBGYN show. Leave that for the urology show.
[Dr. Leslie Appiah]
Well, you know what, we OBGYNs, we step in when the work needs to be done.
[Dr. Mark Hoffman]
That's right. That's right.
(6) Exploring Testicular Tissue Freezing
[Dr. Leslie Appiah]
We actually tend to lead many fertility preservation programs and we tend to counsel the boys or the males or the individuals with testes about options. Testicular tissue freezing is an investigational option for pre-pubertal boys.
[Dr. Mark Hoffman]
That's what I was going to guess. Those who could not provide a semen sample-
[Dr. Leslie Appiah]
Exactly.
[Dr. Mark Hoffman]
-that would be your only option.
[Dr. Leslie Appiah]
That's right.
[Dr. Mark Hoffman]
Oh, interesting.
[Dr. Leslie Appiah]
There's only been one non-human primate birth with testicular tissue freezing and transplantation and that is why that is still considered investigational but Kyle Orwick's group AUPMC where this technology has been developed is now transplanting tissues into humans. We anticipate in the next year or two we will have more data about the feasibility and success but the technology is there. We're excited about that for boys. Right now boys with testes are the only group that we really don't have a good system for and we want to definitely not have disparities in care.
[Dr. Mark Hoffman]
No, that's interesting. Egg freezing, I keep having to think through all that but sperm making we know about. That seems like something that's pretty quick to do.
[Dr. Leslie Appiah]
Let's talk about that. Can we talk about this?
[Dr. Mark Hoffman]
Sure.
[Dr. Leslie Appiah]
How quick sperm banking is and [unintelligible 00:31:04]. I think that's one of the downfalls. Of all of this, we have these assumptions. We think sperm banking, easy to do, but these patients are sick, and it is difficult to produce an ejaculate when you are ill. When we come across or have a 17, 18, 20-year-old patient, we think, "Let's just have the person bank sperm and then we'll move on," and they can't. It's demoralizing and it's defeating, and they are-
[Dr. Mark Hoffman]
Oh, man, right.
[Dr. Leslie Appiah]
-so wanting to do this and something that they have done so easily, they can't. It's really important that we really operationalize male fertility preservation because we need to be able to say on Wednesday the male attempts to bank. If he's unable, then on Thursday or Friday we're going to do a testicular biopsy, extract testicular tissue and extract sperm from that tissue so that patient can undergo chemotherapy Friday afternoon. They don't have time for us to figure it out. We need to know who is at risk whether or not they can produce an ejaculate and whether or not there is sperm in the ejaculate and if not, then what is step two, and do that in a timely fashion. They need to start chemotherapy quickly and we need to operationalize this quickly. That is an area that we really need to focus on in terms of male fertility.
[Dr. Mark Hoffman]
Wow. How quickly are you guys getting to the OR for egg freezing?
[Dr. Leslie Appiah]
For egg freezing, the average time is 12 days. When we see a patient and the patient will need to undergo retrieval usually within 12 days. That may sound like a long time but it isn't because there are a lot of conversations when a patient first presents with a suspicion of cancer. If we called to see that patient immediately, we think this patient's going to have a cancer diagnosis, they are going to be a risk, can you talk to them? We should be seeing patients within 24 hours when they're in-house, and from that point on, we should be able to begin the process of ovarian stimulation and we can have that process started within 48 hours. REI specialists are ready to start this process immediately. Within 12 days, a patient can undergo retrieval from the point of contact with us and then undergo their treatment.
[Dr. Mark Hoffman]
It takes about 14 days to retrieve an egg from stimulation to--
[Dr. Leslie Appiah]
To retrieval. Correct.
[Dr. Mark Hoffman]
What about ovarian tissue? How quickly are you guys--
[Dr. Leslie Appiah]
We can arrange that within 24 hours. We can see the patient today and logistically speaking we can get them into the or the next day but because we are sending tissue out of state, we need to coordinate. That's a probably another 12-hour process. I would say 24 to 48 hours for most individuals or most centers to be able to identify a patient who needs ovarian tissue cryopreservation, and then perform the nephrectomy. To your point, Mark, that is relevant in patients with leukemia, for example, or patients with lymphoma with mediastinal masses who do not have time, who don't have 12 to 14 days. No, they don't have it. But our sarcoma patients do, bone marrow transplant patients do, there are other patients. Thankfully, we have now identified the ability to freeze an ovary even after chemotherapy. We cannot freeze eggs once a patient has received chemotherapy because of the risk of DNA damage, malformations, and fetal wastage. We can however freeze ovarian tissue after one or two cycles of chemotherapy as long as that patient has not reached the threshold of harm. We know how much chemotherapy is too much chemotherapy for average patient and based on age, if they have not received that threshold, we can remove the ovary because in the ovary it's an all or non-phenomenon.
The chemotherapy is going to destroy the growing eggs and it's going to destroy some of the resting eggs. The resting eggs that are not destroyed do not incorporate DNA damage from the chemotherapy. They are safe. We can remove an ovary after one or two cycles, freeze the ovary, and when the patient is ready to conceive, transplant the tissue. [unintelligible 00:35:18] out of Israel has done some very sophisticated studies and [unintelligible 00:35:24] I would say as well, have done sophisticated studies to show that there is fertility after chemotherapy in patients who've used ovarian tissue cryopreservation and transplantation.
There's also the question of whether or not cancer cells may be found in the ovary and in some cancer diagnoses that is a concern, so leukemia and some lymphomas. Those investigators have also done some very sophisticated studies to do immunohistochemistry staining, fish analyses, to determine whether or not tumor cells are in the tissue that has been frozen and then transplanting the tissue if there has been no identification of tumor, and to date there have been no recurrences.
[Dr. Mark Hoffman]
There's no at least theoretical need to go back and remove that ovarian tissue after reimplantation. Not yet.
[Dr. Leslie Appiah]
Not to date.
[Dr. Mark Hoffman]
I would think putting it back on the ovary it would be easier to just take the other ovary. I don't know if you're worried about it but it looks like it would be more like an ovarian remnant on the side of reimplantation which is not the easiest surgery in the world to do but interesting. How many are you guys doing a year? Is this something you guys do once a month? Is this something you guys are doing?
[Dr. Leslie Appiah]
Probably two a month.
[Dr. Mark Hoffman]
Really?
[Dr. Leslie Appiah]
Yes.
[Dr. Mark Hoffman]
That's ovarian removal, ovarian preservation. What about egg freezing?
[Dr. Leslie Appiah]
Egg freezing, we are doing several a month because we have insurance coverage and prior to insurance coverage we have a philanthropic organization called Chick Mission who pay for egg freezing for all of our patients 18 years and older. I just want to give a shout-out to Chick Mission and their philanthropic efforts because they have been amazing to our patient population. We have the resources and so we've been able to offer that to patients. Our success rates for egg freezing are two times that of the national average because we are able to provide that for more patients and sperm banking, I think 89% success rate in some fertility preservation procedure for males, which is three times the national average. Because we have such a robust team, because it is ingrained in our culture, and because of insurance coverage, we're able to treat patients the way they deserve to be treated.
[Dr. Mark Hoffman]
You truly optimize the opportunity to really make every bit count. That's where having seen, unfortunately for Kentucky, you left before or when you leave, a lot of your expertise goes with you but seeing you in its early stages, the number of people it takes, it can't just be you. It can just be Leslie because you're Superwoman, but for the rest of us, it can't just be one person. It is got to be someone on call 24/7 or at least almost every day. It sounds like it has to be a program that's running on all cylinders, and you think NCIs, those centers where folks go to get cancer treatment, you would have that. How many NCI centers are there right now?
[Dr. Leslie Appiah]
I'm not sure how many NCIs. I'm actually not sure but I do want to comment on something you just said because I always say the one regret that I have had is exactly what you stated. I am very passionate about this, and I will just do what it takes to get it done but one person can't do it. Part of being a leader and part of developing a program is to put things in place so that when you are not there, there is longevity because the expertise shouldn't go with you. It should be within the institution.
I think for anyone who's interested in starting a program, it's really important to take the time to make sure you have all of the stakeholders at the table who are committed, you have a good business plan, you have buy-in, otherwise, yes, you may get the job done, but if you're recruited away or if you have to move for family reasons, then patients are at a loss. That's sometimes even worse because now people have been exposed to this opportunity, they agree that there's a need, some patients have had the opportunity and now some patients won't. It just creates confusion to be quite frank if you're not able to really make the program, have a strong foundation when you start. That is my one regret that I did not do that as best as I could have in my enthusiasm to get the program going.
[Dr. Mark Hoffman]
You were more than enthusiastic enough. Your work ethic and your time spent and your energy and your effort, you should have no regrets about that. It takes a team, and it takes people to want to get things done. You've built the infrastructure and had there been someone, and it's not my area of expertise. Could I have stepped in and done what you've done? I don't think so, but I think there's always opportunities for folks to do things if they're interested. I think you have plenty to be proud of both at Kentucky and everywhere you've been. You've done a remarkable job, you've had a remarkable career, and you're young and you've got all this stuff you get to do for years in the future too.
[Dr. Leslie Appiah]
Well, I appreciate that, Mark. Thank you. That's fair. I appreciate it. I receive it, so thank you.
(7) The Landscape of Oncofertility: System Solutions and Advancements
[Dr. Mark Hoffman]
No, no, it's something that I think-- I ask how many NCI centers there are. It seems to me that that's where you would want to house a lot of these programs where you have a gathering of cancer patients and cancer experts where that conversation can be taught, where this can be a routine. This is not something that we have to pull strings for. You and I have talked about that and we are working here, certain things were hard every time. Why is this hard every time? This shouldn't be every time.
It's because the systems haven't been put in place. But once systems get put in place you don't have to think about things. Things can be systems-based that get done based on the way it's built, not just remembering to do something. We don't have to rely on our imperfect human brains. How many programs are there doing what you guys are doing, and not even necessarily to the level you're doing, but how many would you say true Oncofertility programs are out there across the country?
[Dr. Leslie Appiah]
I would say across the country intimately that I know probably 15 to 20 across the country, which isn't bad. That includes pediatric and adult institutions. I could probably start rallying them off of my fingers here.
[Dr. Mark Hoffman]
Some are adult only, some are adult and kids.
[Dr. Leslie Appiah]
Correct. Some are adult and kids. Yes.
[Dr. Mark Hoffman]
[unintelligible 00:41:47], is that a part of it, or depends on where the--
[Dr. Leslie Appiah]
[unintelligible 00:41:51] adolescent gynecology providers tend to lead a lot of the fertility preservation programs, interestingly enough. I think that's because we are adult-trained first and then pediatric and adolescent-trained second, and so we bridge both sides. We're able to take care of adults and children. We have the knowledge on both sides and so it makes us uniquely suited for this role. We take the role seriously and we're passionate about it and we love it and we're bringing more people into the fold every day. I want to comment on something you said about the comprehensive cancer centers.
It really is important to get buy-in from the NCI-designated centers because oncologists are the gateway to these patients. If we don't help our oncologists to understand that there are fertility preservation options for patients and that we can counsel patients in a timely fashion, then they're going to do what they think is best for their patient first. What they think is best is that their patient receive their cancer treatments in a timely fashion.We all agree that that is the most important thing. Our job is to make it easy for the oncologist and the patient and to get in there, counsel the patient, streamline the process and make the options available, and to educate everyone about the options. That's what we do as leaders in these programs. Our NCI-designated centers are critically important.
[Dr. Mark Hoffman]
Educating doctors is one thing. I imagine educating patients is a different challenge. I think like everything in healthcare, there's likely a few Reddit posts out there or Facebook groups that are doing this, but, unfortunately, it would seem that for Oncofertility, as you've already alluded to or spoken about, this is something that's really timely. You're in the hospital, you've got this diagnosis, your brain is not thinking about much but life and death, I would imagine. To rely on patient education, I would think it would be something people might find out more often than not after the fact. Is there a big patient education part of what you do? I would think it would mostly have to come from the doctor's side.
[Dr. Leslie Appiah]
I would say that we do spend most of our energies educating the physicians to make sure they make the patients aware. Then it's really important that we have written materials for the patients to have as well as audiovisual materials. Developing decision aids, giving them links to sites that really talk about fertility preservation is really important. My dream is that every patient who has a cancer diagnosis will automatically receive something through their EMR MyChart that says, you've been diagnosed with cancer. This is what you need to know about your fertility. These are links, these are resources. We really have to bypass physicians because we have our biases, we have our beliefs, so sometimes we don't always do the right thing for our patients despite what we feel about ourselves.
[Dr. Mark Hoffman]
With our best intentions, we forget.
[Dr. Leslie Appiah]
We forget. It's very busy. Cancer diagnosis, there's so much information coming to a patient. If they can just receive something that says this is an alert, here are the resources, or please ask these questions of your oncology provider, I think that that would do wonders.
[Dr. Mark Hoffman]
Or have an alert to the doc when you're prescribing a chemotherapeutic agent or a-
[Dr. Leslie Appiah]
I'm glad you mentioned that.
[Dr. Mark Hoffman]
-toxic agent. Hey, Dr. So-and-so, have you spoken to your patient about their fertility? [laughs]
[Dr. Leslie Appiah]
We have that. We have that. It's called--
[Dr. Mark Hoffman]
Do you?
[Dr. Leslie Appiah]
Yes. It's a best practice advisory. It comes up as soon as a patient has a treatment plan or when we're trying to decide when's the best time. Treatment plan seems a little bit too late, but the diagnosis comes up or we have a pathologic report, and it says, "Physician, your patient was diagnosed with this malignancy. Have you counselled them, or have you offered fertility preservation counselling?" If yes, then you are done. If no, it asks for a reason why not. Then it actually--
[Dr. Mark Hoffman]
Does a little person come up with their arms crossed saying, "Why not?"
[Dr. Leslie Appiah]
Why not? Are they too sick? Did they decline? What are the reasons? Then there's an automatic option for the referral. It's embedded also in the new--
[Dr. Mark Hoffman]
So you can just click the referral right from there?
[Dr. Leslie Appiah]
Yes.
[Dr. Mark Hoffman]
That's a system solution. That's awesome.
[Dr. Leslie Appiah]
It's awesome, yes. We have it also in the new patient order set. It just says, "Do you automatically default to social work?" It's automatically defaulted for fertility preservation consult and it is up to the physician to deselect, that's called opt-out. It has been shown to be most effective for any number of alerts. This is happening in centers and it's really changing the way.
[Dr. Mark Hoffman]
I'll have to find out if it's happening in my center.
[Dr. Leslie Appiah]
You will.
(8) Future Frontiers in Oncofertility: A Path Toward Comprehensive Care
[Dr. Mark Hoffman]
I'll find out. I'll look into it. What's the future? I know you're busy. I know we don't want to keep you here all night and I could talk to you forever, but what's on the horizon for Oncofertility?
[Dr. Leslie Appiah]
On the horizon is, again, streamlining these processes for males so that we can do things very quickly. Really getting every state to provide fertility preservation services through the insurance companies. Really finding out the best way to transplant ovarian tissue. We want that to become more efficient than just a 29% to 41% success rate. Quite frankly, patients are asking to use the tissue for hormone replacement.
[Dr. Mark Hoffman]
Actually, I thought about that while you were talking. You said it didn't last very long.
[Dr. Leslie Appiah]
So far it doesn't because we haven't really identified the best mileau for the tissue. Ideally, we will be able to transplant that tissue in the subcutaneous space. A patient instead of appellate, which we don't approve of, the patient may have ovarian tissue transplanted underneath the subcutaneous tissue and then have that tissue for as long as it's there and have not only their estrogen, progesterone, testosterone inhibit, all the things that may contribute to wellbeing.
[Dr. Mark Hoffman]
Whose ovary?
[Dr. Leslie Appiah]
Their ovary.
[Dr. Mark Hoffman]
Their own?
[Dr. Leslie Appiah]
Their own. I think--
[Dr. Mark Hoffman]
They just keep getting their own ovary back.
[Dr. Leslie Appiah]
They just keep getting their own ovary back. Right now, the subcutaneous space does not have a robust vascular system so it's not panned out just yet, but we're getting there. Patients will push the envelope. This is what they are asking for, and to your point, if we don't do this in the medical realm, then industry will.
[Dr. Mark Hoffman]
They talked about that with uterine transplant. It's very patient-driven. It's what they want, what they're asking for. Well, Dr. Leslie Appiah, it's good to see you. It's good to hear from you and I'm always fascinated by what you're doing and you're doing such important work.
[Dr. Leslie Appiah]
Thank you.
[Dr. Mark Hoffman]
I know you're busy. I'm so grateful you were able to share your time with me and our listeners. Send me whatever links you have so that you mention websites, patient information, physician information, send us all that and we can put that in our show notes for our listeners to be able to have access to all that stuff.
[Dr. Leslie Appiah]
Absolutely. I will do. I want to put out a plug to the Oncofertility Consortium which has really led the charge in developing this expertise. There are about 4,000 international members of the consortium. This was, again, started by Dr. Teresa Woodruff. This organization has been instrumental in providing care for patients and really building the careers of a lot of talented scientists and researchers. I also want to put out a plug for the Alliance for Fertility Preservation. I am going to send this link to you especially, Mark. If individuals go to www.allianceforfertilitypreservation.org, and this is for patients, there is a fertility scout button on their website.
You can push that or select that and it will allow you to find a fertility preservation specialist in your area anywhere in the country. It will also educate the patient about what they should be expecting from their oncology team and what they can expect from fertility preservation interventions. Physicians and patients can use that. I think that fertility scout is really important for patients to know about even in survivorship.
[Dr. Mark Hoffman]
Love it.
[Dr. Leslie Appiah]
Thank you so much. It's so great seeing you.
[Dr. Mark Hoffman]
It's great to see you. All the best to you and your family.
[Dr. Leslie Appiah]
Thank you so much, Mark. Same to yours.
[Dr. Mark Hoffman]
Take care. Thanks for coming on.
[Dr. Leslie Appiah]
Absolutely.
[Dr. Mark Hoffman]
Thank you so much for listening. If you haven't already, make sure to follow the podcast, rate it five stars and share with a friend. If you have any questions or comments, direct message us at _BacktableOBGYN on Instagram, Twitter, or LinkedIn.
The views and opinions expressed by the hosts and guests on Backtable OBGYN are their own, and do not reflect the views or positions of their employers or any entities they represent.
Podcast Contributors
Dr. Leslie Appiah
Dr. Leslie Appiah is the director of the fertility preservation program and the chief of the division of academic specialists in OBGYN at the University of Colorado Anschutz.
Dr. Amy Park
Dr. Amy Park is the Section Head of Female Pelvic Medicine & Reconstructive Surgery at the Cleveland Clinic, and a co-host of the BackTable OBGYN Podcast.
Dr. Mark Hoffman
Dr. Mark Hoffman is a minimally invasive gynecologic surgeon at the University of Kentucky.
Cite This Podcast
BackTable, LLC (Producer). (2023, May 4). Ep. 22 – Oncofertility [Audio podcast]. Retrieved from https://www.backtable.com
Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.
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