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Prakash Chandran: More than ever before, children treated for serious illnesses are living well into adulthood. This happy statistic means that there is increased awareness also of long-term quality of life concerns such as the risk of infertility. The comprehensive fertility and hormone preservation and restoration program at Lurie Children's offers solutions for those young patients, giving many their only chances to have biological children one day.

Today, we're talking with the directors of this remarkable program about the research and innovation happening to help preserve patients' fertility as part of their comprehensive care. Joining us is Dr. Erin Rowell, she's an attending pediatric surgeon at Lurie Children's; and Dr. Monica Laronda, Assistant Professor of Pediatrics at Northwestern University Feinberg School of Medicine and Stanley Manne Children's Research Institute. They're both directors of the Fertility and Hormone Preservation and Restoration Program, or FHPR, at Lurie Children's.

This is Precision: Perspectives on Children's Surgery. I'm your host, Prakash Chandran. So Dr. Rowell, Dr. Laronda, thank you so much for joining us today. I really appreciate your time. Now, Dr. Rowell, I wanted to start with you. At a high level, what exactly is the fertility and hormone preservation and restoration program at Lurie Children's.

Dr. Erin Rowell: Great. Thanks so much for having us. Yes, so our program, FHPR, is a comprehensive multidisciplinary program that really seeks to educate and counsel the patients and families, any of them, that have a diagnosis or treatment that places the child at risk of future infertility and to provide an assessment of what are the options for that child to preserve their fertility.

majority of the diagnoses that we see, so the majority of the patients that would fall into this category would be children who have a cancer diagnosis and who are going to have treatment that can affect their fertility. Other types of children that fall into that category would be children who need a stem cell transplant as part of their care. And sometimes children with other more rare conditions, such as those with differences of sexual development.

Prakash Chandran: Now, Dr. Laronda, I'd love to expand on something. You know, this is a very unique program. I think it's probably one of the only in the nation. How long has this program been around and why was it started in the first place?

Dr. Monica Laronda: Yeah, thank you so much. Our program started 10 years ago. And you're right, it's one of the only ones within a pediatric hospital. And so we're really tailored for our pediatric and adolescent patients when we're considering fertility preservation options. It was started really because Teresa Woodruff, who used to be at Northwestern University and is now at Michigan State University, started the Oncofertility Consortium. And she really brought awareness to this problem that physicians had been realizing would happen to their patients that had survived cancer. So there was a quality of life aspect of not being able to have their hormones or their family planning as others might have, as their siblings might have, due to their cancer treatments.

And so we were adjacent. So I started in 2016 with Dr. Rowell to kind of revamp and revitalize this program, expand the options that we have and to really put a large research component into fertility preservation at Lurie Children's.

Prakash Chandran: Now, Dr. Rowell, you started to touch on this, but I wanted to know who the ideal candidate for this program is. You know, I think you said any child with a cancer diagnosis or children that might need stem cells as part of their care. But can you expand on that a little bit more?

Dr. Erin Rowell: Yes. So we believe that any child whose medical diagnosis or treatment places them at risk of infertility ought to have education and counseling about what is the level of that risk. And that is really coming from guidance from multiple professional societies, such as the American Academy of Pediatrics, the American Society of Clinical Oncology and others that really advocate for patients to be aware of what that risk is, because it is so important. We know from data from long-term survivors of cancers, that it really becomes one of the most important long-term quality of life issues for people. And so we want to make sure that any patient and family that faces that from a childhood diagnosis understands what is the level of that risk and that they get proper education and counselling first of all.

So that doesn't mean that every child needs to have an operation or needs to have a procedure, but we try to provide the appropriate level of understanding of what is the risk. And we have a whole team that helps to do that. And we meet with patients and families after they've been diagnosed and we understand the treatment plan so that we can go over what will be the risk level for that child. And then based on that and on the age of the child and that child's sex, we can provide the appropriate option.

Prakash Chandran: Now, I do want to get into the team that works with this program, but I just want to ask some more basic questions first. So, Dr. Laronda, could you tell me a little bit more about, you know, how one becomes infertile? Like, is it the treatment that stunts hormone production? And if so, what is the hormone that actually makes someone fertile in the first place?

Dr. Monica Laronda: Yeah. So, one way that an individual could be infertile from their treatment is because those chemotherapy and radiation therapies, I think when we think about hair loss, for example, as a result or a side effect of a chemotherapy or radiation treatment with cancer, we can also think about the other types of cells that might be affected. So, unfortunately right now, a lot of our cancer treatments while extremely successful and we've had great increase in the number of patients who have survived their treatment and go on to live, you know, long, healthy lives, that treatment can affect some cells that we can't get back.

So an individual would be born with the most number of potential egg cells, that they will ever have in their entire life. And so once those cells are destroyed and affected, those will not grow back. Those that have testes or young boys, then they have spermatogonial stem cell stem cells. Those cells can be still affected, but often some of those cells can regenerate and develop sperm later in life much later after their treatment. So this is why a comprehensive team and an understanding of certain treatments can affect those cells is really important.

Prakash Chandran: Okay. I understand. And I was just going to ask about whether this affects both girls and boys. But Dr. Rowell, it sounds like for girls, it's the egg cells that might be destroyed. And for young boys, it's that spermatogonial stem cell that, while it can develop much later in life, that's something that in the immediate term maybe stops working. Is that more or less correct?

Dr. Erin Rowell: Yes, that is, although I do think one thing that's important, and we've touched on this a little bit, is that it really does depend on the child's age. And as a surgeon one of my main areas of focus for our research has been on the pre-pubertal children. And those would be children that we think of that are under about the age of 10, who haven't yet shown any signs of puberty. So they are girls that haven't yet had a period and they're boys that haven't really begun any mature growth spurt development. And so the options for that group of children is different than for those that have gone through puberty and who are having functioning of their reproductive organs. And we can understand that, because if you have a period and your body is functioning more like an adult female or if you're a boy who's gone through puberty and your body's making sperm, then there are more options available.

So we do have to, when we do this counseling, help families to remember back to biology class, you know, and understand these things about how their child's body is functioning at that time, and then how the treatment might affect that. And then that helps us to explain what the options are.

Prakash Chandran: So Dr. Rowell, just at a high level, could you talk to us a little bit about when you get involved with the families?

Dr. Erin Rowell: Sure. We love to get involved when the patient has been diagnosed, so receives a new diagnosis and before treatment starts, but during the planning stages of what the treatment will be. And the reason for that is that we prefer if possible, if the child is in what we term a high level of significant risk, which generally puts the child at around a 75% to 80% risk of infertility long-term, that if that was the situation that the child was facing and the family were choosing to go forward with a surgical option to preserve fertility, we want to do that before the child receives any treatment for, number one, the best possible tissue to save for the future and also because we know many children will have other procedures as part of their regular care that require trips to the operating room. And some of those are other types of surgeries that I do where we put in special types of IVs called central lines so that the child can get their therapy. Sometimes they need to have a surgery to remove perhaps some or all of a tumor or they need to have a biopsy or they need to have some other types of procedures scheduled such as imagings like CTS and MRIs. And so we try to be mindful of that and put the child to sleep only one time if we can and coordinate these things together. So our team really like leaps into action and provides the education and counseling that the family needs. And then we quickly organize the steps that we need to do to do the operation safely under one anesthesia, if possible. And the surgery itself is not a long surgery. Some children go home the very same day that the surgery happens.

Other situations happen not at diagnosis because if the child was in a lower risk category, they could be candidates for a procedure to preserve fertility later on, for example, if they had a relapse that needs treatment again, and sometimes the decision-making about a stem cell transplant happens over weeks to months. And so we have more time. So I think there's kind of a variety of situations. Sometimes it's very urgent and it's happening quickly. And other times, we have more time for planning.

Prakash Chandran: So Dr. Laronda, I was reading on the website. It says that each patient is unique, so fertility preservation must be tailored and carefully integrated with a patient's treatment. Can you talk broadly about what that means and the team approach that you use to assess the unique treatment for each patient?

Dr. Monica Laronda: Yeah. So I think that Dr. Rowell had mentioned rightly before that we must consider the age as well as the diagnosis and treatment options for the patients. We also of course have to consider if they have testes or ovaries or dysgenetic gonads, which gets into another population that has a genetic variant that might have caused their gonads to form abnormally. And we have to consider the age specifically for options of whether or not to use mature gametes, so those eggs are sperm after they've gone through puberty, or if we will be collecting tissue. And so there'll be immature gametes prior to puberty and that would be, you know, ovarian or testicular.

I think the team approach is important with some of these procedures and what makes us a little unique for what we do is because we do have research protocols for the ovarian tissue cryopreservation, for the testicular tissue cryopreservation and for the dysgenetic gonad cryopreservation options. And this involves, you know, institutional review board protocols and processes that require, you know, additional moving parts and the support of good research staff as well.

Prakash Chandran: So Dr. Rowell, because we are talking about hormone and fertility preservation, one might conclude that at some point later in the child's life, they may come back to get those hormones re-injected. So can you talk at a high level about that process when the child, you know, develops a little bit and is interested in having a child, would they just contact you later in their life?

Dr. Erin Rowell: Yeah, that's a great question. So we do maintain contact with our families as the child grows up and we try to contact them once a year, just to find out where the child is in their treatment and in their life. Of course, we have children that if they were under around age 10, as I mentioned earlier, if they were in that very young age group, as they become older and they turn 12, we typically ask for the child's assent to continue to contact the family. And then, when the child turns 18 and becomes of adult decision-making capacity, we reconsent the family again. So we do keep mindful of the child's own evolving role on their own body as they grow and develop.

And so for many children, as they proceed through their treatment and hopefully cure and into long-term followup care and there are well established clinics at Lurie for the long-term followup of our patients, who've survived cancer. So as they go through those and are having just regular checks, when the child is progressing normally through their own development, for example, if they had been eight years old at the time that they had their ovary removed and preserved, for example, and then they go through and become turn 12 to 13 and get a period and are being seen regularly for checkups, if their body is continuing to function as it should, they go through puberty, they get a regular period, then we just keep watching. We don't rush to do anything. As long as their own body is continuing to function, which many do, then we just consider that tissue to be, you know, in reserve or in the tissue bank, if you will, the tissue bank freezer.

And then, many situations happen where with the ovary, the ovary doesn't just stop all of a sudden, it works for a while for many years. But then we expect that a young adult might go through what we would term early menopause, where they do start to have hormone dysfunction and feelings that would suggest menopause such as hot flashes and other things that would be familiar to an adult woman going through menopause. But it could happen really early, like for example, in the twenties. And that would be different for different patients and different types of treatment regimens. But if that were happening, then the question would be, is this the time to think about using some of the frozen tissue? And if the adult survivor was at a position that, you know, needed to start thinking about that, yes, we would wanna maintain contact and help facilitate here at Northwestern, the way that that unthawing would happen. But it could also be done if the patient had moved, it could be done in conjunction with their local hospital or clinic having contact with us.

The tissue is frozen at the time that it's frozen, and we'll maybe get into this in a little bit with Monica, you know, we really have focused a lot on the tissue processing aspect and being really thoughtful about a pediatric patient's ovary and how that might be different from an adult woman's ovary. But the ovary is not frozen as one solid ovary. It's processed carefully into individual small strips of tissue, and those are individually frozen into different vials so that they can be thawed one by one. And we could think about that as like chances or numbers of times that a patient could have some tissue thawed and put back in to work for a period of time.

That's based on today's technology, and we could talk some more about what we think might be in the pipeline for the future, but the idea would be that you would take it on a case by case basis when a child, now adult survivor, would need the tissue and trying to think about you know, thawing things at the right time and reimplanting them at the right time.

Prakash Chandran: Well, Dr. Rowell and Dr. Laronda, this has been a fascinating conversation. It's amazing that you are being so forward thinking about this to really give these children a chance at that long-term quality of life, right? Like cancer survivorship has increased, which is amazing. But I think oftentimes maybe people have felt before that it's an exchange, like "I can survive cancer, but I'm not able to have children if I do." But I really feel like you're opening up that opportunity now and giving hope to a lot of children that, you know, are maybe in this position. So just as we start to close, I'd love some final thoughts. And Dr. Laronda, we'll start with you.

Dr. Monica Laronda: Yes. I think that our program at Lurie Children's is just one example about how you can gain inspiration from the people and the patients around you. Those childhood cancer survivors who, you know, have come and told us as a group of physicians and researchers that they wanted a better quality of life and that they really value the ability to have children later on is really an inspiration for a lot of what we do. And we just hope that we can, in the future, give them even more restorative options for their fertility and hormone production.

Prakash Chandran: And Dr. Rowell, I'll give you the last word.

Dr. Erin Rowell: Okay. Thank you. I think, you know, I consider it really like one of the best honors in my life that I get to work with Monica and that we have had this opportunity to research and explore the clinical goals of this program together. And we really have many many years ahead to continue to do that. I'm so excited to work with her. I think it's the patients and families, the children that are at the center of this that really do inspire us to continue this work, which when you use the word translational research, many people use that term, but I think this program actually truly embodies that. It is true work that goes from the lab research bench to the patient's bedside and back again. And it has the ability to impact a child in his or her lifetime. This work is happening at such a rapid pace that for some of our youngest patients that are only a few years old, they very well may be able to have restoration of their fertility in ways that we can't even imagine today. And it's because of this type of program and this type of research collaborative.

So I do feel like it's truly meaningful work. And we do try to tailor the approach to the unique needs of the child in front of us and that family and what they're going through. But I would agree with Monica and what you said earlier, that it does provide hope that, with survival, there can be the ability for the child to flourish as an adult.

Prakash Chandran: Well, Dr. Rowell and Dr. Laronda, thank you so much for the education and everything that you do.

Dr. Monica Laronda: Thank you so much.

Dr. Erin Rowell: Thanks so much.

Prakash Chandran: Thanks for listening to Precision: Perspectives on Children's Surgery. You can visit luriechildrens.org/fertility for more information, including how to make an appointment. My name's Prakash Chandran. Thanks again for listening and we'll talk next time.