On this episode of Cleveland Clinic’s Cancer Advances podcast, host Dale Shepard, MD, PhD, talks with Sarah Vij, MD, about Cleveland Clinic's Fertility Preservation Program for Male Cancer Patients. Listen as Vij discusses the different fertility-sparing techniques used for both pre-pubertal and post-pubertal male cancer patients.
Vij is Director of the Center for Male Fertility at Cleveland Clinic and Shephard is a medical oncologist at Cleveland Clinic who oversees the Taussig Phase I and Sarcoma Programs.
Shepard: Cancer Advances, a Cleveland Clinic podcast for medical professionals, exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a medical oncologist here at Cleveland Clinic overseeing our Taussig Phase I and Sarcoma Programs. Today, I'm happy to be joined by Dr. Sarah Vij, a urologist and director of the Center for Male Fertility at Cleveland Clinic. She's here today to talk about fertility preservation in male patients with cancer. Good morning, Sarah.
Vij: Good morning. Thank you for having me.
Shepard: Absolutely. So, maybe just to start off, maybe you could tell us a little bit about what your role is here at Cleveland Clinic.
Vij: I'm a urologist. I specialize in male infertility and sexual medicine and I'm the center director for our fertility center here. So, I see, the majority of my practice is male patients coming in with infertility. So, I do see a lot of fertility preservation patients for various reasons as well, most of whom have a cancer diagnosis. That's a very common scenario.
Shepard: So, maybe to start out, give us an overview. What are some of the fertility preservation techniques for males with cancer?
Vij: Fortunately, getting sperm from a male in most situations is relatively straightforward. So, if it's a post-pubertal patient and the male is able to provide an ejaculated sample with masturbation, then we're able to cryopreserve from the semen. So, for most of our patients, it's relatively straightforward and we'll get into, I'm sure, what to do in situations where patients are unable to do that. Yeah. In many situations, they'll collect more than one time.
We have a lab on site. They can collect in the lab. We can also make arrangements for them to collect at home if there's anxiety related to that, and we really try to work around their schedule, come in on the weekend if we have to make sure that this gets done in a timely fashion ahead of their treatment initiation.
Shepard: So, when you're talking about the timing part, tell me a little bit about that. What sort of timing do you typically need? If I see a patient in clinic and I need to start chemo, what kind of lead time do I need?
Vij: Really very little. We can get it done same day. Our andrology colleagues are very flexible around this issue because it's really, really important. A lot of patients don't bank for a lot of different reasons, and we certainly don't want access to be one of them. We can get it done same day. If the patient's starting their therapy the following day and there's really not much wiggle room there, we may not be able to get them to bank more than once. That's one thing to consider.
Then the other thing is when a male provides a semen specimen, to get an optimal sample, the abstinence interval, meaning time since their last ejaculation, should be about two to three days. So, we don't always have the luxury of timing that. But again, in this situation, we're trying to do the best we can. Fortunately, if we freeze just a small number of sperm, 10, 20, 30 sperm, these guys have options down the line to have a biological child.
Shepard: You mentioned something about trying to get a second collection. So, once someone has started chemo, is collection off the table, or is there a timeframe where if you really can try to sneak in a second, when you try to do that?
Vij: So, it's a little bit controversial, but in general, if the patient just started treatment, there's probably a small window of time where a second collection is totally reasonable. If they've been on chemotherapy for two, three, four, or five weeks, at that point, it's probably not advisable. But if the first sample looks poor, they got their first dose of chemotherapy that morning, I would probably have them try to collect a second time. The likelihood that it's impaired the quality of the sperm that quickly is pretty low. But there are some urologists who would say the moment that chemotherapy has started, we should not collect.
Shepard: So, we'll end up talking a little bit more about the finance part here in a bit. But certainly, as I try to start chemo, I have limitations in terms of coverage. But that's a little bit different with this, isn't it, in terms of the available coverages and how this is covered. So, can you talk a little bit about that?
Vij: Sure. So, unfortunately all things related to fertility, our insurance companies are not kind to us. It's treated almost like cosmetic intervention, which of course, it's not. So, I have to say, the coverage seems to be getting better. We always use specific coding related to fertility testing and their cancer diagnosis to increase our likelihood of getting coverage. If you diagnose them with infertility, sometimes that alone, that's where it stops. So, we make sure we code it accurately.
Again, there is some coverage. We do have financial counselors that the patients can work with in real time to determine what their out of pocket payment is. But in general, the cash payment, if the patient has no coverage, looking at about $900 for the initial bank, about $700 for any subsequent banks, and then they pay an annual fee for as long as those samples are stored. Some young patients may have their samples stored for 10, 15 years. That's just another sort of financial thing for them to think about.
Shepard: Makes sense. You mentioned that there are other options for in other situations where someone can't necessarily collect sperm. What are some of those options?
Vij: So, sometimes, it's just a situational issue. They're having trouble collecting in the lab or maybe they're having difficulty getting an erection. We can use medications like Viagra, Cialis, have them collect at home. We actually have specialized condom collection devices so they can collect during intercourse. It's specialized condom that's not damaging to the sample, and then they just tie it up and bring it in. So, we do have some flexibility there.
Some of these patients are quite ill and so just being able to ejaculate is just not something that's going to happen. So, in those situations, we have a few different options. One is penile vibratory stimulation. So, this is an intervention that we use actually relatively commonly in our spinal cord injury patients, and it's essentially a vibrating device that's placed on the head of the penis and it can initiate the ejaculatory reflex arc. It works with a flacid penis. So, if the patient can't get an erection, it's still an option.
The problem with it is that it can be painful. So, that's why it suits well for the spinal cord injury patients because they're generally not sensate. But in a young cancer patient, it may not be successful. But that's something that we can try. We have a device that we own. So, if the patient's inpatient, we can bring it over to their room or they can come over to my office. Much less commonly, there is an option to do what's called electroejaculation.
We unfortunately don't have a machine here. So, patients have to travel for this, and given the timeline with cancer patients, can't say I've actually ever pursued this. But it is an option, and it's similar sort of physiology, except there's a probe that goes in the rectum to initiate the reflex arc through the rectum. So, again, we use this commonly in spinal cord injury patients. But in a sensate patient, they'd have to be put to sleep. So, really not very practical in this patient population, but it is an option.
Then maybe a little bit more commonly, what we will do is testicular biopsy for sperm extraction. So, if the patient cannot provide a specimen, we can take them to the operating room. It's a pretty minimally invasive operation, a small incision in the scrotum, open up the testicle, and take some seminiferous tubules, which are the tubules in which spermatogenesis occurs, and we send those to our andrology lab. They mechanically digest the tubes, release the sperm into the tissue, and freeze from the tissue.
So, we probably do that maybe four to five times a year. Patients who can't provide a specimen, often the CNS malignancy patients, it can be very difficult for them. Some patients are profoundly hypogonadal related to their cancer diagnosis. So, it can be very difficult for them to have normal sexual function. So, that's a scenario that comes up, and it was a nice backup option to have.
Shepard: So, when we think about a lot of the things you were talking about, I know those are readily available here on main campus. A lot of our cancer patients are treated out at our community sites. What sort of resources are there at those sites?
Vij: The penile vibratory stimulation is really something that would have to be done here. We just don't have the device elsewhere. But again, that's not utilized that much in this patient population. Testicular biopsy really can be done anywhere. I do go to several places. I have a partner who's down in the southern region, and really, the procedure itself can be done by any urologist, and if it needs to be done, we'll make it work.
The more limiting factor actually is the andrology piece, getting the specimen into the appropriate fluid, it's preserved in what's called human tubular fluid, and then getting it transported in a timely fashion down to main campus. But using couriers and again, the andrology lab is really willing to drop everything to make these things work. So, I can't say that those type of logistics have stopped us before. It does seem to be that these cases do tend to come up more commonly in main. But certainly, we can make it work if we need to.
Shepard: So, again, primarily focusing on sperm collection, what are the greatest access challenges? What keeps people from getting to you?
Vij: I think one of the biggest barriers to getting this done more commonly is finances. So, patients are given those numbers and it's just not something that they can afford, and that's sort of the end. I always try to tell people, reach out to me, reach out to our department. We sometimes, we do have some grant funding for our pediatric patients and young adults. So, patients under the age of 25. We have some funding to help cover that, and our department sometimes is able to write it off because it's the right thing to do. We don't always like to promise that.
But I always do encourage the oncologists reach out to me directly. We may be able to work something out in a scenario where that's the major limiting factor. I get the sense that oncologists are doing a lot better than maybe 10, 20 years ago about bringing up fertility preservation. I'm getting more and more consults every month. So, I do think that it is being brought to the attention of the patients. The other thing that I try to make clear, at least to our oncologists, is the visit with me is not actually the most critical piece unless the patient's really undecided and doesn't understand how the sperm can be used down the line and wants to know a lot more about that.
It's really just getting them to the andrology lab and getting them to collect. That's the time sensitive piece. So, if they're going through the call center and trying to get on my schedule and that kind of thing, we don't want to do that. Getting them over to andrology is really a priority, and again, if they do need to have a discussion with me, I just do always encourage their referring team just contact me directly because again, these are time sensitive issues and I'm always happy to help. We have a fellowship here. So, I do have support and people who are boots on the ground at all times.
Shepard: So, it's good to hear that there is an increase in awareness perhaps and more of my colleagues are sending people to have collections. Does that still suggest there are educational opportunities to spread the word and let us know what's going on?
Vij: There is. There's definitely been publications that have come out within the last few years in doing surveys of patients and asking them, did your provider discuss fertility preservation with you? There's definitely still room for improvement. It's still not 100%, which it really should be. I'm sure, I'm not an oncologist, but I know there's a lot that you guys are balancing in these initial discussions, but the more that we can educate patients on really, well, for most of the time, really how simple it is, and even if they're not sure they want a family, apart from the cost, there's no risk in keeping that option open.
I just saw a patient yesterday, he was a leukemia patient who did not bank. I don't recall the reasons, but he's azoospermic now. He has no sperm in his ejaculate and he's absolutely devastated, and those are just hard situations to handle when it's after the fact. He's had a STEM cell transplant. There's really no hope for return. Again, I don't know the reasons why he didn't, but always better to just be on the safe side in this situation.
Shepard: Those are certainly tough things, and we can certainly send them to you to discuss some of those issues. But do you have any other support within your program, any psychologists or anything that can help people work through pros and cons of fertility preservation?
Vij: We don't have a psychology team that's focused specifically on this. There is a therapist that I work with commonly for a lot of my patients with concerns related to lack of fertility or sexual dysfunction, and that would be more in the survivorship setting. Again, I have a fellow, there's myself and Neel Parekh, who's a staff in the southern region who's trained in fertility.
So, we do have enough support, I think, on the physician side to have these conversations. Then again, my andrology colleagues are very experienced. Our lab's been up and running for over 20 years. They can certainly provide counseling and they actually do go over the cryopreservation reports with some of our patients just so they understand what the numbers mean. So, having enough personnel on our end is not a problem.
Shepard: So, we focused primarily on adult males. What are you doing on the prepubertal side?
Vij: Yeah. So, that's a timely question. So, we have been working hard for a couple years now to try to initiate a protocol that's active at several other major children's hospitals to cryopreserve prepubertal testicular tissue because prepubertal patients, their spermatogenesis has not been initiated. That occurs at puberty, and they're not masturbating, ejaculating.
So, you have a six year old patient with a cancer diagnosis who's going to get a very gonadotoxic regimen. The only option for fertility preservation for that patient would be to cryopreserve testicular tissue the same way I mentioned in an adult male. It's still sort of experimental. It's still in the research realm. It's been done in primates where the prepubertal tissue has been obtained and they've been able to, in vitro, generate mature sperm down the line from that tissue from the STEM cells and create a baby. So, that was in the lay press.
But we're not quite there yet in humans, but I think we will be. The science is moving really quickly. So, we are hoping that we're going to be able to open this to our prepubertal population soon. I'd say within the next three to six months. We did just receive a VeloSano impact order to support this, that it's not at cost to our patients, given that it's experimental and not cheap. So, we're really excited about this and again hope that we can offer it soon. Then the other thing is a lot of peripubertal and postpubertal patients are able to provide an ejaculate and have usable sperm. It may not be at the adult concentrations, but there is usable sperm. So, the older children, we have more options.
Shepard: Are there any other approaches that are in the research phase that are particularly promising?
Vij: There's a lot of talk about how best to use that prepubertal tissue to generate mature sperm. So, there's a lot of different things that are being tried as in a laboratory setting in a prepubertal realm. Then in the adult population, we're always trying to do better on cryopreserving really, really impaired samples. So, either an ejaculate or a testicular biopsy with very, very, very poor numbers, poor morphology, poor motility, low concentration. How can we improve our cryopreservation process to be less hostile for the sperm and to have those samples be usable if that's all we have?
Then back to that leukemia patient who I mentioned who didn't bank who now has nothing in the ejaculate, we can go in and do a microsurgical testicular biopsy on that patient population. Some patients do actually do okay in terms of their success rate. Testicular cancer patients tend to do the best. We're always trying to do better in terms of how we can identify seminiferous tubules where there may be still microscopic islands of spermatogenesis occurring that we can target.
Right now, all we have is our microscope and our eye to try to identify dilated tubules, but people are looking into ultrasound stains to identify tubules that may have active spermatogenesis occurring that we can harvest after the fact, after they've already had their gonadotoxic therapy to give those patients some hope.
Shepard: So, as people might be listening, in terms of resources, you mentioned the co-op program for the prepubertal patients. Is this something that's fairly widely available right now, or limited to some well-defined centers? How likely is it someone listening might be able to find a location for this for their patients?
Vij: Anything related to fertility preservation, we really will go far to make things work. So, again, everything's easier at main campus, but we can make this work really at any of our Northeast Ohio hospitals. There are protocols to offer this at several major children's hospitals. So, not every single one, obviously, but the major centers that do a lot of pediatric oncology are trying to get these protocols up and running because it's really, we feel the right thing to do to at least be able to offer it to patients.
Shepard: So, what's next for the program? How would you like to see this grow in the next few years?
Vij: So, we're still working through, given how large we are, the Cleveland Clinic, and as you mentioned, there's cancer care occurring all over the region now. We're still working on logistics to be able to offer these services in a timely fashion, and easily. So, we've looked into using Epic orders to get their fertility preservation consult over to me as fast as possible. We realized that that was sometimes causing a delay because it would need to get an appointment with me, which again, is not the most critical piece.
So, just trying to streamline how we can get these patients in so that a logistical issue is not ever what's preventing these patients from being unable to bank. So, if anyone has any ideas on that, I'm happy to take them. What I always say is I'm always available. So, if you don't know how to place the banking order and they're over there, again, just call me because these are the kind of things that we don't want to not be able to pursue because, again, because of logistical problem.
Then we always obviously are trying to grow. So, the more we can have this discussion with patients, the better. The pediatric side is actually hiring a fertility preservation social worker to be the point person to make sure that all of these patients are put in contact with her. She can help navigate with andrology with myself, with the patients, with the families. That may be something to consider on the adult side as well. So, for the great majority of patients on the male side, banking is really quite simple. So, anything we can do to sort of remove barriers to it.
Shepard: Excellent. Well, Sarah, thank you for your insight. You've provided some great information and quite honestly, I think probably reminders to people to get in contact and have the right discussions with patients. So, appreciate that.
Vij: Thank you for having me.
Shepard: This concludes this episode of Cancer Advances. You will find additional podcast episodes on our website, clevelandclinic.org/canceradvancespodcast. Subscribe to the podcast on iTunes, Google Play, Spotify, SoundCloud, or wherever you listen to podcasts. And don't forget, you can access real time updates from Cleveland Clinic's Cancer Center experts on our Consult QD website at consultqd.clevelandclinic.org/cancer. Thank you for listening. Please join us again soon.