Fertility Preservation Innovations for Children with Monica Laronda, PhD

August 27, 2024

Pediatric and adolescent patients at risk of losing their fertility due to medical conditions and treatments have more options than ever before to preserve their fertility for the future. In this episode, Dr. Monica Laronda, an expert in the field of reproductive biology, shares many new projects she is leading alongside surgeons in Lurie Children’s Fertility & Hormone Preservation & Restoration Program.

“It takes a lot of us, as part of someone's care team, to make sure that the whole individual is considered and their future life after this diagnosis is considered … to understand where an individual patient is in their diagnosis, in their treatment plan, and how that treatment might affect their future fertility.”

Monica Laronda, PhD
Director of Basic and Translational Research, Fertility and Hormone Preservation and Restoration Program
Gesualdo Family Research Scholar
Assistant Professor of Pediatrics, Northwestern University Feinberg School of Medicine

Show Notes

Dr. Laronda has a unique role within Lurie Children’s Department of Surgery because she is a basic scientist who works alongside surgeons and other specialists in pediatric fertility preservation. She brings expertise in reproductive biology with a special interest in the field of fertility preservation.
Early on in her career, Dr. Laronda was mentored by Dr. Teresa Woodruff, Founder of the Oncofertility Consortium which “addresses the complex health care and quality-of-life issues that concern young cancer patients whose fertility may be threatened by their disease or its treatment.”
Dr. Laronda’s role in Lurie Children’s Fertility & Hormone Preservation & Restoration Program, includes collaborating with surgeon Dr. Erin Rowell and a diverse team of healthcare professionals to help children facing conditions, such as cancer and genetic disorders, that put them at risk of infertility.
For example, when Dr. Rowell performs a surgery to remove a whole ovary from a patient that has opted to cryopreserve reproductive tissue; Dr. Laronda can then take that tissue into that lab and process it and cryopreserve that tissue for future use.
Not only does the program team perform these procedures, they record information, track outcomes and to follow up with our patients who might want to use it to help inform the scientific and patient communities.
There are particular challenges in preserving fertility for prepubescent children and this is where Dr. LaRonda is focusing on some of her work. She and her colleagues want to establish best practices in young patients for surgically removing ovarian and testicular tissue, freezing it and then when the child is at an age to start a family, thawing it out and then transplanting it back.
Aside from offering expertise for procedures such as ovarian tissue cryopreservation and testicular tissue cryopreservation, Dr. LaRonda is leading cutting-edge research involving 3D printed bio-scaffolds and bioprosthetic ovaries. The goal is to create a technology that allows patients with cancer, for example, to develop eggs in vitro, to avoid the risk of transplanting cancerous tissue back into a patient.

Transcript

[00:00:00] Erin Spain, MS: This is Precision Perspectives on Children's Surgery from Ann & Robert H. Lurie Children's Hospital of Chicago. I'm your host, Erin Spain. On this podcast, we introduce you to surgeons at one of the country's most renowned children's hospitals to find out how they're transforming pediatric medicine. The field of pediatric fertility preservation has expanded in recent years, offering a variety of options to help even prepubescent children have future attempts at becoming parents. Here at Lurie Children's, the fertility and hormone preservation and restoration program is dedicated to researching the latest advances in the field. Dr. Monica LaRonda is the director of basic and translational research for the program, and joins me today to talk about this rapidly evolving field and opportunities offered to patients at Lurie Children's. Welcome to the show.

[00:01:01] Monica Laronda, PhD: Thank you so much for having me.

[00:01:02] Erin Spain, MS: A little bit about you. You are a scientist with a PhD in reproductive biology. Tell me what is it about fertility preservation and specifically pediatric fertility preservation that has led you into building a career and really being on the leading edge of ongoing research technologies in this field?

[00:01:21] Monica Laronda, PhD: Yeah, I think that I got really interested in reproductive biology when I was an undergraduate, so, So I was in college. I became a course assistant for the Marine Biological Labs in Woods Hole, which is close to kind of where I grew up in Massachusetts. And it was called the Frontiers in Reproduction. And I met a whole bunch of faculty members, a lot of them from Northwestern University. And I became very interested in that type of research. So when I was applying for PhD programs I was very interested in Northwestern. And I came here and joined a lab of Dr. Larry Jameson, he was chairman of the medical school and then Dean of the medical school at the time and he studied sex development, so gonadal development in animal models like mice. And I worked on spermatogonial stem cell differentiation, so I worked on the testis. Other people in the lab worked on ovaries or dysgenetic gonads, and I just became extremely interested in. How do germ cells form? What is their environment like and how does that environment support those germ cells? And so when I became a postdoc, I was very fortunate to have met Theresa Woodruff who established the Oncofertility Consortium in the area and really started this field of fertility preservation. Became the forefront of a lot of other conversations during the new cancer diagnosis. And she also collaborated with engineers, which I thought was really amazing and interesting and was going to help drive this field forward. So it's really her mentorship and kind of that spark that started when I was in, college with some amazing reproductive biologists that put me into this field of tissue engineering, of fertility preservation, and then really it was Lurie Children's being close by to Northwestern really understanding that there was a patient need. There's pediatric and adolescent patients who have not gone through puberty yet. Do not make those mature gametes, that is the traditional way of preserving the fertility prior to a cancer diagnosis. And so the field needed to change a little bit and think about what else can we do to save someone's potential fertility.

[00:03:48] Erin Spain, MS: And we will be getting into that and it's really incredible. I can't wait to talk more about it. But first I want you to explain your role because as you mentioned, you're a scientist. you have a PhD. What role do you play in the fertility and hormone preservation restoration program as far as interacting with patients and surgeons and the rest of the care team?

[00:04:07] Monica Laronda, PhD: That's a really great point. It takes a lot of us as part of someone's care team to make sure that the whole individual is considered and their future life after this diagnosis is considered. So I work with Dr. Erin Rowell, who's a pediatric surgeon. She's the medical director of the Fertility Preservation Program. And her and I work with other individuals from urology, from hematology and oncology from stem cell transplant departments, and endocrinology. Really to understand where an individual patient is in their diagnosis, in their treatment plan, and how that treatment might affect their future fertility. We're extremely fortunate at Lurie Children's to have developed a clinical lab. So when Dr. Rowell performs the surgery to remove, for example, a whole ovary from a patient that is opted to cryopreserve their tissue for future, I can then take it into that lab and process it and cryopreserve that tissue for future use. The other role that I have, which is extremely exciting, where, my scientific background comes in is that as part of our research, we're always looking for ways to improve and advance what we can do to not just cryopreserve the tissue today, but how are we gonna be able to restore that tissue's function tomorrow, that fertility or that hormone production for these patients. And so it does take a lot of research team members and clinical team members for this program to work as well as it does.

[00:05:44] Erin Spain, MS: I want to talk more about these children, these patients, and you've mentioned cancer is a diagnosis that often these kids are coming before treatment to have these procedures done. But there are other reasons why a child may be at risk of infertility. Can you walk me through some of the most common that you see?

[00:06:02] Monica Laronda, PhD: Yeah, so some of the diagnoses that we see are brain tumors such as Wilms tumor, some sarcomas, some leukemias or lymphomas. There's also children that have a genetic variant or mutation that would result in either sickle cell anemia or differences in sex development. So they're at increased risk for developing premature gonadal insufficiency due to their genetic disease. Or like the cancer diagnosis it's the treatment itself that might put them into that premature gonadal insufficiency and I say gonadal to be including the ovary, the testis, and any dysgenetic, ovotestis, different type of gonad that exists within our patient.

[00:06:52] Erin Spain, MS: Tell me about the ages of these children that you are seeing, and you mentioned that there's this new area that you're exploring as far as kids who are prepubescent and finding ways to perhaps give them a chance to be parents one day. Explain to me some of the biological issues that your team is navigating when you're trying to help these children preserve their fertility.

[00:07:11] Monica Laronda, PhD: Yeah, so I think when someone thinks about fertility, they think about probably eggs and sperm. And maybe even a uterus. But the children that we see most of them actually have not gone through puberty yet, and so they do not produce eggs or sperm. What they do have is gonads that have immature cells. So the cells that will eventually become eggs which are called the oocytes or cells that will eventually become sperm called the spermatogonial stem cells. And then especially in the case of individuals that have ovaries, their oocytes are actually a finite resource. So there's a limited number of those cells. They're associated also with those hormone producing cells. So that's another aspect of that organ that we must think about because it's systemically important for a healthy body. And so, we're able to isolate out one whole ovary or a biopsy from a testicular tissue and process it in a way that preserves those cells, kind of freezes those cells in time. We put them into a cryoprotectant, we slow down the freezing process. It's stored in liquid nitrogen long term, and so we can ship those tissues to University of Pittsburgh Medical Center for the testicular tissue processing and cryopreservation. They are experts in testicular tissue. We are experts for the ovarian and the dysgenetic gonadal tissue. And we can have them in long-term storage with a third party to keep them until they're ready to be used. So if this individual wants to expand their family and do that with biological children they can transplant that tissue back and have children that way.

[00:09:10] Erin Spain, MS: So these procedures you're describing, is this standard practice or is this more experimental and part of research studies that you're conducting?

[00:09:18] Monica Laronda, PhD: We're right on the forefront of some of these things. So the testicular tissue cryopreservation process itself is still considered experimental. The ovarian tissue cryopreservation is no longer considered experimental because there's been up to 200 reported live births around 150 reported live births around the world that's after, freezing that ovarian tissue, thawing it out and then transplanting it back. So it's, really a phenomenal technique. We do still perform these procedures under an IRB, so with the Institutional Review Board approvals, and really that's because the pediatric and adolescent population really hasn't been studied that much. Most of those live births have happened in individuals that were approximately 30 years old or late 20s when they froze their tissue. We do have a few examples of where it's worked in the younger individuals, but we really want to establish best practices here. We are definitely one of the institutions in the US that see an extremely high volume in comparison to other sites of these pediatric patients that want to do fertility preservation. And so we feel obligated, you know, on many levels to record this information, to track outcomes and to follow up with our patients who might want to use it.

[00:10:45] Erin Spain, MS: So, yeah, just explain to me what happens. It's frozen, it goes into storage, and then what happens from there?

[00:10:52] Monica Laronda, PhD: Yeah, so for the ovarian tissue when that individual has gone through an early menopause so that their other ovary that remains was then exposed to that gonadotoxic treatment and therefore was affected and those cells were depleted and they go through a menopause like state. They are able to request their tissue to be transplanted and we'll be able to support that. Dr. Rowell is a surgeon. But they can go wherever they like, where there's that type of expertise, thaw that tissue and transplant it back. It's often transplanted back on the other remaining ovary. They could have offspring either naturally or through other assisted reproductive technologies that are very commonplace now.

[00:11:38] Erin Spain, MS: Attempts to produce eggs from this preserved ovarian tissue is not yet efficient or really reliable. Is that right? But you're working on something that's so fascinating that we want to talk about today. Tell me about the work that you're doing, creating bioprosthetic ovaries and 3D printed bio scaffolds that could really help these eggs grow.

[00:11:59] Monica Laronda, PhD: Yeah, so this work is really inspired by our patients. So some of our patients will have cancer cells within their ovarian tissue. And so that process that I just described is likely not available to them. So we would definitely go through additional checks with the pathology department, their oncology team to determine how safe that tissue that is stored for them is for those individuals where we would want to isolate the cells that we want, so the oocytes and the hormone producing cells, away from any potential cancer cells. They would need some sort of scaffolding or environment to be able to grow like they normally do and to be able to be transplanted in. So, you can't just have like a massive amount of cells in an injected if the ovary just doesn't work that way. And so my lab in collaboration with Dimension Inx, which is some of my collaborators from this bioprosthetic ovary paper that was published in 2017 and, kind of started my lab. We are considering different ways that we might use some of these technologies both as a transplant and as something that could assist the assisted reproductive technologies or the reproductive endocrinology infertility clinics that already support this process. So can we take their early oocytes and grow them and mature them in vitro and then be able to use them to fertilize and implant and build their families that way.

[00:13:33] Erin Spain, MS: Explain what this looks like for people. Paint a picture.

[00:13:37] Monica Laronda, PhD: Yeah, so, much like, a scaffolding that helps support a building that's being built or a high rise, we use 3D printing. And we have a variety of different materials that we're testing to establish the right environment to then put these cells into. And so it has multi-pore structures. It might have some biological proteins that these cells can interact with and really that's critical because these oocytes when they develop into eggs or large follicles, which is a term that we use for the oocyte that's in the center, surrounded by those nurse cells, granulosa and theca that produce hormones. They grow approximately 600 times in size. So when we ovulate an egg from our ovary in our body, it's the size of a penny. So it grows quite large. The scaffold needs to be adaptable to that. It needs to support the oocyte when it's small, but also when it's big. And so because we can use different materials and create different scaffold designs within the same engineered piece with 3D printing, this is one of the reasons why we've used that technology.

[00:14:52] Erin Spain, MS: So tell me, this 3D printed bio scaffolding, is this being used outside of fertility preservation? Is there precedent for this approach working well with human tissue?

[00:15:03] Monica Laronda, PhD: So there's a very large, and I think growing bioengineering tissue, regenerative medicine type of field. There's very limited use of it in the clinic today. There's some tissue engineering that maybe doesn't include 3D printing quite yet with either artificial skin transplants or cartilage development, things like that. That is kind of early bioengineering tissue technologies. But 3D printing, just in the last few years, has really expanded to use more biologically relevant biocompatible materials. One thing that I can think of is, fresh printing tech techniques where there's a support bath that supports these challenging materials to print and develops a whole heart or a cardiac valve or other large organs. There's also ones that are used for pieces of livers or pieces of the pancreas that would help with regenerating those injured tissues.

[00:16:06] Erin Spain, MS: So you've actually been awarded an NIH grant to work on this project. Tell me how the research is progressing.

[00:16:13] Monica Laronda, PhD: Yeah, so I think there's a few grants that we were fortunate to be rewarded. So one of those grants is the collaboration with Dimension Inx to develop the 3D printed scaffolds that will be used to both isolate and activate those early quiescent follicles that are present within the cryopreserved tissue that we save for our patients. So to gap onto that first activation step in a very high throughput way has been challenging in the field. And we think that some of the engineering and materials based technologies that my collaborators are great at and have developed would be the key to that. And then the next step for that process would of course to be grow those then initiated follicles and have them ovulate through our system. So we're working right now with bovine ovaries as a model for human ovaries to kind of test this out. We've seen that there's migration through the scaffolds like we want, and so kind of release of those follicles. But we're really looking forward to how this research is going to be progressing within the lab. I'm really excited about it.

[00:17:25] Erin Spain, MS: So what could we see maybe in the next decade? What could happen for these patients using these techniques?

[00:17:32] Monica Laronda, PhD: We really hope that this would be something that would benefit future patients. We are definitely considering when we're designing our experiments, how this might fit into the clinical process that already exists. And so we're hoping that something like this would be available in the future for an assisted reproductive technology where patients can then utilize some of their tissue that's been cryopreserved and have an egg develop in a dish. So it would reduce that risk of transplanting any cancer that might be within their tissue for a certain number of cancers. And just be able to use that in vitro fertilization pipeline that already exists within the REI clinic.

[00:18:16] Erin Spain, MS: Do you talk to your young patients' families about the research that you're doing, and what do they say if you do? What is their response when they hear about these 3D printed organs, basically?

[00:18:28] Monica Laronda, PhD: Some patients and families are extremely excited about this and really do see it as something that they hope we can develop within the next 10, 20 years, when those children grow up and might want to utilize their tissue. So I think it really does add a level of hope for the future once they've survived their cancer and can think about family building and that they've really taken the steps that they think are important for their own lives and their quality of life. We've had patient/ family luncheons, and get togethers and there have been a few families that have reached out to me knowing that I'm the research side of the program and just have questions. And so those that are interested are definitely very interested in and do like to talk about it.

[00:19:12] Erin Spain, MS: The program has really grown in recent years. How successful has it been?

[00:19:17] Monica Laronda, PhD: In the last several years when we were able to open our lab so our clinical lab that processes tissue and is able to coordinate fertility preservation for those with ovaries, those with testes, those with dysgenetic gonads. Just being able to offer that service and have, our collaborating physicians know that this service is available. We have the flexibility to offer it at the time that is most convenient and appropriate for the patient. It has definitely grown. We have also seen consistently approximately 20% of the patients that we offer fertility preservation to, our come from other hospitals. So we've had patients come from as far as Seattle or Florida, or Arizona to come and utilize this service that is not available at other hospitals. And I really think that both the successes from the research program and the ability for us to be flexible for our patients, it's just much more well known within Lurie and outside of Lurie. It's really been a joy to be able to increase the number of patients that we can offer this service to.

[00:20:34] Erin Spain, MS: Well, we are very excited to see what all of your research holds in the future, and I'm sure we will be talking with you again as you have more results. Thank you Dr. Monica Laronda for being on the show.

[00:20:46] Monica Laronda, PhD: Thank you.

[00:20:46] Erin Spain, MS: For more information, including how to make a referral or an appointment, visit LurieChildrens.org.