Transcription:

Melanie Cole: Welcome to Better Edge, a Northwestern Medicine podcast for Physicians. I'm Melanie Cole and today we're discussing emerging therapeutic strategies and technologies for male infertility. Joining me is Dr. Robert Brannigan. He's the Vice Chair of Clinical Urology, Chief of Male Reproductive Medicine and Men's Health, and a Professor of Urology at Northwestern Medicine. Dr. Brannigan, it's a pleasure to have you join us today. Let's start with onco-fertility. We know cancer and cancer treatments can threaten reproductive health speak about some of the options for fertility preservation in cancer patients. And when that is discussed, when somebody is diagnosed with cancer?

Dr. Brannigan: Well thank you for the opportunity to talk about this very important issue. So fertility preservation in the past was really not undertaken as a routine part of cancer treatment and the problem or the issue with that is that about half of men over the course of their lifetime will get cancer. And certainly men of reproductive age and even younger men are not immune to cancer. And so the problem was that for the longest time the focus was on cancer and cancer alone, to the detriment of fertility. The very treatments, as we all know, that are used to cure cancer can also have a permanent effect on fertility causing permanent and lingering asospermium. So back in 2006 the American Society of Clinical Oncology released guidelines calling for providers to offer fertility preservation services to patients at the time of cancer diagnosis. And that's important because obviously we want to freeze sperm in the case of men prior to the administration of any chemotherapy or radiation treatment. And I think that the good news is, is that, you know, centers such as ours and other centers around the country that have an interest in this, we really have gotten good at providing the care in parallel with ongoing cancer treatment. So I think it's an exciting time because we've definitely seen an improvement in quality of life in the survivorship issues, such as reproduction. We've seen big improvements as we've gotten better delivering this care alongside oncologic care.

Host: It's so important. And thank you for telling us about that. Tell us a little bit before we get into what's unique and what you're doing at Northwestern, tell us a little bit about how radiation chemotherapy, whatever cancer treatments can affect male fertility, what exactly is going on?

Dr. Brannigan: So let's start with radiation treatments. So the thing is that while lining cells, as we all know the cells in the testicles that make testosterone, are relatively immune to the effects of testicular radiation, the germ cells are not. In doses as low as two gray, which is a really low dosage can cause permanent asospermia. And so again, you know, the lining cells typically are, are much more resistant. They can experience 20 gray radiation exposure before testosterone production is negatively impacted. And then when we look at the effects of chemotherapy, I think it's important for providers to keep in mind this, that we know that we can look up the particular profile of a chemotherapeutic regimen, and typically there'll be rated as high risk, intermediate risk, or low risk for their prospects for causing negative effects on fertility. But you know, there are a couple of issues that the prior providers also need to keep in mind.

And one of these is that we really don't know in the end, even if a patient is exposed to a low risk chemotherapeutic regimen, that patient may progress on over the course of his treatment to intermediate or high risk agents or regimens. And also at the end of the day, we don't know how a specific patient might react in terms of what their reproductive potential might be, even if they are exposed to more favorable regimen. We see this all the time where, you know, providers say, well, we didn't bang firm cause the regimen was low risk. And you know, that particular patient you know, had an adverse outcome with permanent oligospermia or asospermia meaning, you know, low sperm counter, or absence of sperm all together after the chemotherapy is completed. So banking sperm on the front end is really important. And that's, that's the approach that's recommended by ASCA when we're looking at these patients.

Host: So then tell us about what your team is doing at Northwestern Medicine and what makes this program so unique.

Dr. Brannigan: So the program has really evolved substantially since it was formed in 2005, 2006. And I really have to, you know, tip my cap to a colleague here at Northwestern, Dr. Teresa Woodruff, who interestingly just left Northwestern is become the provost of Michigan State University. But, you know, she really was the person who coined the term onco-fertility. And she's the person who really, you know, helped to set the stage for a truly multidisciplinary effort to establish this field and promote fertility preservation as a routine part of oncologic care. And so we work closely with her. She's not a clinician, she's a basic scientist, but had huge clinical impact here at Northwestern and really around the globe with the work that she's done here at Northwestern. You know, one of the things that we really focused on was trying to be able to implement our care without disrupting the routine course of routine oncologic care. And one of the things that we learned was that, you know, obviously in addition to having a lab with flexibility, to be able to freeze sperm on short notice. Also having a patient who is there watching, seeing what else is going on with the patient's care and being able to leap at the opportunity for us to insinuate ourselves clinically and provide that fertility preservation care, without disrupting the rest of cancer care, that was an important maneuver of the patient navigator. And it's really a key to our program right now,

Host: Such an exciting time to be in your field. And as you say, it's such a burgeoning field. Now, the field of onco-fertility and fertility preservation, tell us about some of the recent advances in assisted reproductive technologies or techniques such as IVF and intracytoplasmic sperm injection, and some of the exciting technologies going on to help male infertility.

Dr. Brannigan: Yeah. So I think that, you know, the point of these assisted reproductive techniques is, is really important. I think most clinicians are familiar with intrauterine insemination and invitro fertilization, IVF most commonly is done you know, with a partner being stimulated hormonally to produce a number of follicles. Each one contains an egg, those eggs were removed and they're in a lab dish. One by one sperm are injected into the eggs. And so that is typically how the sperm that's cryopreserved from fertility preservation is used in the setting of IVF. And what's amazing is that the fertilization and pregnancy rates are quite high pregnancy rates are about 50%, five, zero% for all commerce in this day and age. And so I think the, the key is looping this back to fertility preservation is that only very small numbers of sperm are required now to successfully help a couple conceive a pregnancy. If I could just look at the second part of your question there and look to you know, kind of future developments.

There's some very interesting work from the University of Pittsburgh, looking at a primate model where testicular tissue was removed from the animal, and then reimplanted back into the animal. And what was interesting was that this tissue that was replanted subsequently resulted in the development of sperm and actually that sperm was extracted and used through invitro fertilization to father an offspring through IVF. And so this is just one sort of maneuver where tissue could perhaps be removed from a patient before chemotherapy is being given, frozen, and then re reimplanted back into the patient with the host that's fermented Genesis will resume, and that the sperm can be harvested and used for for invitro fertilization. So this is research it's not being used in humans, but with sort of a proof of principle and a primate model that this may be something that could be applied to humans down the road.

Host: Well, while we're speaking about what can be applied, and it is fascinating, Dr. Brannigan, how can advances in big data analytics and insights into applied genetics impact patient care? How does this all work together and translate?

Dr. Brannigan: Well, you know, I think that this idea of, of, you know, big data and analytics is just so important in it. It's just untapped potential. I had one patient not long ago who works in this field. And it's interesting, he said that data and information is the petroleum of the future. It's really going to be the thing that drives or runs our society and our economy. Kind of an interesting observation. I think for us, the place that it's going to have, the biggest impact is in genetics and in particular reproductive genetics. Right now, our understanding about genetics and what causes infertility in patients is really you know, not well understood. And I think that there are lots of opportunities to characterize individuals who are hitting bumps in the road with their fertility and identifying what underlying genetic mechanisms might be at play. Now, how that would translate into therapeutics down the road, I think is a big question, but there may be opportunities there once a specific genetic issue is identified, truly target therapies at that issue, with the hope of improving overall health.

Host: So before we wrap up, what would you like other providers to take away from this and other urologists to learn from your studies, Dr. Brannigan, any exciting projects that you'd like to speak about and what would you like them to know about treating male infertility and referral to Northwestern Medicine?

Dr. Brannigan: Well, first of all, I think that, you know, other providers should realize that fertility preservation care can be effectively delivered parallel to, or concurrent to cancer care. It can be done well. And we know from work that we've done, that patients greatly appreciate when this is done by the providers and that there's significant regret down the road when they experienced fertility and fertility preservation care, wasn't considered an important aspect to pursue at the time of cancer treatment. I think that you know, providers should know that we really are patient centric and do our very best to try to get the patients through their care in an expedited fashion. We realize that time is of the essence for a lot of our patients who are grappling with a cancer diagnosis. And our aim is to really try to, you know, provide this care in step with the the oncologic care. We're very familiar with this process and regard ourselves as being you know, friendly to patients and providers. So we greatly welcome you know, providers or other individuals reaching out if there's any questions that they might have, or if they'd like to coordinate patient care. We're here and available.

Host: Thank you so much, Dr. Brannigan, what an exciting and fascinating topic. And thank you for joining us and sharing your expertise today. That concludes this episode of Better Edge, a Northwestern Medicine Podcast for Physicians. To refer your patient, please visit our website at NM.org. Please also remember to subscribe, rate, and review this podcast and all the other Northwestern Medicine Podcasts. I'm Melanie Cole.