Transcription:
Fertility Preservation for Pediatric Cancer Patients

Melanie Cole (Host): The number of pediatric cancer survivors is growing rapidly as treatments become more effective. However, many current regimens can cause gonadotoxicity or permanent infertility significantly impacting the quality of life of these patients. My guests today are Dr. Kenan Omurtag, he’s a Washington University Reproductive Endocrinologist and Infertility Specialist, and Dr. Emily Jungheim, she’s a Washington University Reproductive Endocrinologist and Infertility Specialist. Welcome to the show, Doctors. Dr. Omurtag, I’ll start with you. Please, briefly explain you and Dr. Jungheim’s relationship to Saint Louis Children’s Hospital.

Dr. Kenan Omurtag (Guest): Dr. Jungheim – thanks again also, by the way, Melanie, for having us. Dr. Jungheim and I are board certified reproductive endocrinologists here at Wash U. with combined 15-plus years of experience in fertility preservation. Because of that experience and our relationship between Washington University and Saint Louis Children’s, we have a collaborative relationship with the pediatric oncology department that entails monthly meetings where we review pediatric oncology patients and their reproductive goals and desires – those undergoing current treatment, and those who might have completed treatment and are interested in the effects of their chemo later in life particularly as it relates to their reproduction. We serve as a consultation service to the pediatric oncology folks at Children’s to help patients preserve fertility and to reach their reproductive goals through whatever means necessary.

Melanie: And Dr. Jungheim, what are some possible complications that can arise in pediatric cancer patients in terms of fertility? What are some of the effects of chemotherapy and/or radiotherapy on male and female fertility?

Dr. Emily Jungheim (Guest): It really depends on what type of chemotherapy a child might be receiving, or where the radiotherapy might be directed. For the most part, chemotherapeutic agents that are attacking rapidly dividing cells are also going to attack oocytes for girls, or sperm for boys. Where someone is in their reproductive or pubertal development can also influence how negative these treatments might impact the ovaries and the testes. In any case, our concern is that if there is an insult early on to the eggs or the sperm for girls or boys, this can impact their ability to get pregnant down the road. In radiotherapy, the same thing, the more – some of the alkylating agents, for example, are going to be more damaging than some other agents, and the radiotherapy, that can leave permanent damage to the gonads.

Melanie: Dr. Omurtag, in your opinion, or in your experience, are patients with cancer interested in interventions to preserve fertility? When you speak to the families, what are you hearing?

Dr. Omurtag: Yeah, so this is a great question because cancer therapy has gotten significantly more focused and mortality rates have declined, and there are more survivors particularly in the pediatric population. More and more people are interested in what happens after cancer treatment, and fertility preservation is a big component of that as reproduction is a big element of one’s life post-chemo. This is something that families are very interested in. We want our families, and we want our pediatricians to be telling their patients to talk about future reproductive implications of the chemotherapy and talk about fertility preservation strategies. That is where we come in because we can counsel those patients about fertility preservation, whether it’s freezing sperm, banking sperm, or freezing eggs. Those things are the services we can provide those families. The one other thing I’ll add is when you talk to a cancer patient about reproduction, that gives that cancer patient additional hope that, “Look, there's a good prognosis here, that I’m going to survive this cancer diagnosis because they’re already talking to me about my future reproductive goals. I’m 15, and I haven’t even thought about that, but the fact that they want to at least address that with me means that they know that I have a good prognosis.” It’s part of the therapy to some extent.

Melanie: Dr. Omurtag, I’m sticking with you for a minute. Along the same line, what is the role of the oncologist in advising patients about fertility preservations, and when a specialist, such as yourself, might be brought in?

Dr. Omurtag: I think the role of the oncologist is critical because they are the first point in which the patient is going to talk about chemotherapy. Dr. Jungheim has been working – myself, we’ve been working to increase education with the oncologists to have that conversation about fertility preservation, and the uptake has been excellent. The oncologists are very good at saying, “Hey, this is part of –,” and incorporating in their counseling to the patient and then directing those patients to us to talk about their options for fertility preservation.

Melanie: Dr. Jungheim, if the child is prepubertal, how will this affect their ability to go through puberty, and will it affect – so the treatments obviously might affect some of their puberty, but where is fertility in that picture?

Dr. Jungheim: If the damage from chemotherapy or radiation is enough that it kills those cells that are making testosterone or estrogen, that can impact puberty. That’s something else that we keep in mind, and we work closely with other providers – pediatric endocrinologists – when thinking about these kinds of things. In regard to what options are available for preserving fertility, though, in these kids, those become experimental. Unfortunately, you can’t get a mature egg from a girl who hasn’t gone through puberty, yet. You can’t get a mature sperm cell from a boy who hasn’t gone through puberty, yet. One of the really neat things about working at an academic medical center like Washington University, is there are folks thinking about what types of – different research protocols, where we could potentially bank gonadal tissue from boys or girls. Down the road, hopefully, research will tell us how to utilize that tissue and then obtain mature gametes, mature eggs or sperm, from these tissues and use them for these folks as they enter their reproductive years and want to have their own genetically related children.

Melanie: Dr. Jungheim, what is the quality of evidence supporting current or forthcoming options for preservation of fertility in females?

Dr. Jungheim: For girls that are post-pubertal, and boys who are post-pubertal, the good news is we offer the same types of treatments that these folks are getting for fertility preservation -- we offer them in our general reproductive endocrinology and infertility practices. They are proven technologies that we can offer quite comfortably and say – and give a real option for having genetically-related children, so that’s the great news there. In regard to options for pre-pubertal kids, that’s where it’s a little less clear. Having said that, just tremendous progress has been made in learning how to get mature gametes from gonadal tissue in the last several years. While it might not be possible right now to use those tissues to get mature gametes, with the amount of progress that’s been made in the last five years, it’s pretty exciting to think that we probably will be there at the time – if a kid came in today, at age 11, and banked pre-pubertal tissue, twenty years from now, fifteen years from now, when these kids get to be reproductive ages and want to have their own genetically-related children, I suspect the technology will get there – will be there to offer them this chance.

Melanie: Is there any option now for after treatment how we’ll know if the child’s fertility has been affected?

Dr. Jungheim: Oh, that’s a great question. We’ve got markers that we can use to get an idea, and we can track these markers and see how they change over time, but there’s no clear answer to how an insult is going to impact someone’s long-term reproductive aging. As I mentioned earlier, it probably depends on what type of chemotherapy someone might receive, how much of it they received, where, in their reproductive process – pubertal process they received that chemo or radiation. There are all sorts of things that we need to take into account, so the answer is that we don’t have that answer yet, but there are people thinking about it. There’s a woman at University of California, San Diego, Dr. Irene Su, one of our colleagues in reproductive medicine, who’s doing a study looking at markers of ovarian reserve after chemotherapy to see how they change and how they might relate to reproductive aging, and eventually menopause, so that we can have better information to inform these kids and their parents of how the chemotherapy or radiation therapy might impact their long-term reproductive aging and options in the future.

Melanie: Dr. Omurtag, what about for males? Is there a quality of evidence supporting some forthcoming options or current options for the preservation of their fertility?

Dr. Omurtag: Yeah, historically – in regard to the standard of care. The standard of care for males for fertility preservation would be to bank sperm. That’s been the standard of care for a long time, and that’s proven. A lot of it has to do with how simple – at least compared to retrieving eggs -- retrieving sperm is. We just get a – typically it’s a masturbatory, ejaculatory sample, and you can freeze the sperm. For egg freezing, it’s a little more involved. This is for any male who is post-pubertal. The next question I’ll always get is, “Well, how do you know a boy has sperm in his ejaculate?” And that’s a very important question when I see these patients because I might see a twelve-year-old or a thirteen-year-old – Dr. Jungheim and I might see these patients, and we don’t know. We tell the parents at this point we just need to get a semen analysis to determine whether they have sperm in the ejaculate. One way we do this is to look at – do a physical exam. There are markers on physical exam that can give us a sense of where an adolescent boy is in pubertal development. That will help us predict whether or not – to some extent whether or not there will be sperm in the ejaculate. There is good evidence for sperm banking for fertility preservation. For pre-pubertal boys, extracting testicular tissue and getting immature sperm, where – these testicular islands may not – there are sperm cells, but they are not fully developed. Developing those sperm cells may have to be done in culture. Those efforts are being led across the world. They’re lagging a little bit behind the egg cryopreservation – the egg tissue – the ovarian tissue cryopreservation efforts, but they’re happening. Time will tell how beneficial those efforts would be for pre-pubertal boys. The good thing with adolescent cancer survivors, in general, is that many of them, due to their young age can withstand the chemotherapy that they get, but you can’t make such a broad statement because some people get more, some people get less. It just depends on the chemotherapeutic agent. Some of these patients will still be able to spontaneously conceive without fertility preservation. Again, the whole point is to be proactive and have an insurance policy so to speak, because there I a high chance, at least a greater than 50% chance that many of these people will need to use their preserved gametes after chemotherapy.

Melanie: And Dr. Omurtag, sticking with you for a second, is sexual function relatively spared during some of these treatments, and is testicular dysfunction one of the more common, long-term, side effects of chemotherapy in males, and how does that affect what you tell the families?

Dr. Omurtag: That’s a great point because I’ll see adolescents with bone cancers who have undergone essentially sterilizing chemotherapy. They’ve banked sperm before, so their reproductive future is intact despite the fact that they are making no sperm in their testicles currently. What goes along with the sterilizing chemotherapy is their testicles’ ability to make testosterone. As a result, they may have problems with libido. They may also have problems – although not necessarily all of the time, they might have erectile dysfunction, they might have some other sexual dysfunctions. That is something that we talk about with these patients, and there are therapies like testosterone replacement that can help mitigate those concerns.

Melanie: Dr. Jungheim, what does current research indicate for future developments and treatments? Give us a little blueprint for future research.

Dr. Jungheim: We’re pretty good at providing fertility preservation services that work for kids that are post-pubertal – we talked about egg banking; we talked about sperm banking – but where there are a lot of gray zones are an opportunity to bank tissue from pre-pubertal girls and pre-pubertal boys, to obtain gametes that can actually result in a viable pregnancy. Dr. Omurtag alluded to that a little bit, and that’s really where the research lays right now. There’s a lot of progress being made. There’s also research being done on -- are there medications that can prevent gonadotoxicity from chemotherapy, so looking at different pathways in which eggs mature – and spermatocytes mature over time. Can you intervene there and prevent the effects of chemotherapy on those cells? There’s research being done there with medications to prevent gonadotoxicity of agents used to treat cancer and also, how can we bank tissues from these pre-pubertal kids and then get viable gametes that can be used down the road?

Melanie: And Dr. Jungheim, in summary, what can you tell other pediatricians that you would like them to know about advising their pediatric cancer patients on fertility preservation?

Dr. Jungheim: I would just like to let pediatricians know that there are viable options that are accessible and attainable for kids that are facing chemotherapy, for fertility preservation. It may not seem – things happen so quickly sometimes for these kids and needing them to get treatment, but at least at Wash U., we’re always available for consultation. If you’re out in a more rural practice and there aren’t quick options to get someone in to see someone, reach out to your close, nearby academic medical center in more of your metropolitan areas and get information for these folks. There are great online resources, too. MyOncofertility.org is one; the national physician’s cooperative through My OncoFertility has a listing of all of the different academic, medical, and private practices that provide these services, and if you look on there you might be able to find someone. Even if it doesn’t seem like there’s someone close providing these services, you might be able to find someone there. Things are changing rapidly in this field, so just stay tuned, and please, if you think you have somebody who may be impacted down the road -- or if you’re even wondering if they may be impacted down the road -- please reach out to a reproductive endocrinologist, or ob/gyn if you don’t have access to a reproductive endocrinologist, and we’ll do what we can to help these kids make sure they have options down the road.

Melanie: Thank you, so much, both of you, for being with us today. A physician can refer a patient by calling Children’s Direct Physician Access Line at 1-800-678-HELP, that’s 1-800-678-4357. You’re listening to Radio Rounds with Saint Louis Children’s Hospital. For more information on resources available at Saint Louis Children’s Hospital, you can go to SaintLouisChildrens.org, that’s SaintLouisChildrens.org. This is Melanie Cole. Thanks, so much for listening.