Fertility Preservation in Oncology: An Overview of Techniques & Advancements

[Dr. Leslie Appiah]
We actually tend to lead many fertility preservation programs and we tend to counsel the boys or the males or the individuals with testes about options. Testicular tissue freezing is an investigational option for pre-pubertal boys.

[Dr. Mark Hoffman]
That's what I was going to guess. Those who could not provide a semen sample-

[Dr. Leslie Appiah]
Exactly.

[Dr. Mark Hoffman]
-that would be your only option.

[Dr. Leslie Appiah]
That's right.

[Dr. Mark Hoffman]
Oh, interesting.

[Dr. Leslie Appiah]
There's only been one non-human primate birth with testicular tissue freezing and transplantation and that is why that is still considered investigational but Kyle Orwick's group AUPMC where this technology has been developed is now transplanting tissues into humans. We anticipate in the next year or two we will have more data about the feasibility and success but the technology is there. We're excited about that for boys. Right now boys with testes are the only group that we really don't have a good system for and we want to definitely not have disparities in care.

[Dr. Mark Hoffman]
No, that's interesting. Egg freezing, I keep having to think through all that but sperm making we know about. That seems like something that's pretty quick to do.

[Dr. Leslie Appiah]
Let's talk about that. Can we talk about this?

[Dr. Mark Hoffman]
Sure.

[Dr. Leslie Appiah]
How quick sperm banking is and [unintelligible 00:31:04]. I think that's one of the downfalls. Of all of this, we have these assumptions. We think sperm banking, easy to do, but these patients are sick, and it is difficult to produce an ejaculate when you are ill. When we come across or have a 17, 18, 20-year-old patient, we think, "Let's just have the person bank sperm and then we'll move on," and they can't. It's demoralizing and it's defeating, and they are-

[Dr. Mark Hoffman]
Oh, man, right.

[Dr. Leslie Appiah]
-so wanting to do this and something that they have done so easily, they can't. It's really important that we really operationalize male fertility preservation because we need to be able to say on Wednesday the male attempts to bank. If he's unable, then on Thursday or Friday we're going to do a testicular biopsy, extract testicular tissue and extract sperm from that tissue so that patient can undergo chemotherapy Friday afternoon. They don't have time for us to figure it out. We need to know who is at risk whether or not they can produce an ejaculate and whether or not there is sperm in the ejaculate and if not, then what is step two, and do that in a timely fashion. They need to start chemotherapy quickly and we need to operationalize this quickly. That is an area that we really need to focus on in terms of male fertility.

[Dr. Mark Hoffman]
Wow. How quickly are you guys getting to the OR for egg freezing?

[Dr. Leslie Appiah]
For egg freezing, the average time is 12 days. When we see a patient and the patient will need to undergo retrieval usually within 12 days. That may sound like a long time but it isn't because there are a lot of conversations when a patient first presents with a suspicion of cancer. If we called to see that patient immediately, we think this patient's going to have a cancer diagnosis, they are going to be a risk, can you talk to them? We should be seeing patients within 24 hours when they're in-house, and from that point on, we should be able to begin the process of ovarian stimulation and we can have that process started within 48 hours. REI specialists are ready to start this process immediately. Within 12 days, a patient can undergo retrieval from the point of contact with us and then undergo their treatment.

[Dr. Mark Hoffman]
It takes about 14 days to retrieve an egg from stimulation to--

[Dr. Leslie Appiah]
To retrieval. Correct.

[Dr. Mark Hoffman]
What about ovarian tissue? How quickly are you guys--

[Dr. Leslie Appiah]
We can arrange that within 24 hours. We can see the patient today and logistically speaking we can get them into the or the next day but because we are sending tissue out of state, we need to coordinate. That's a probably another 12-hour process. I would say 24 to 48 hours for most individuals or most centers to be able to identify a patient who needs ovarian tissue cryopreservation, and then perform the nephrectomy. To your point, Mark, that is relevant in patients with leukemia, for example, or patients with lymphoma with mediastinal masses who do not have time, who don't have 12 to 14 days. No, they don't have it. But our sarcoma patients do, bone marrow transplant patients do, there are other patients. Thankfully, we have now identified the ability to freeze an ovary even after chemotherapy. We cannot freeze eggs once a patient has received chemotherapy because of the risk of DNA damage, malformations, and fetal wastage. We can however freeze ovarian tissue after one or two cycles of chemotherapy as long as that patient has not reached the threshold of harm. We know how much chemotherapy is too much chemotherapy for average patient and based on age, if they have not received that threshold, we can remove the ovary because in the ovary it's an all or non-phenomenon.

The chemotherapy is going to destroy the growing eggs and it's going to destroy some of the resting eggs. The resting eggs that are not destroyed do not incorporate DNA damage from the chemotherapy. They are safe. We can remove an ovary after one or two cycles, freeze the ovary, and when the patient is ready to conceive, transplant the tissue. [unintelligible 00:35:18] out of Israel has done some very sophisticated studies and [unintelligible 00:35:24] I would say as well, have done sophisticated studies to show that there is fertility after chemotherapy in patients who've used ovarian tissue cryopreservation and transplantation.

There's also the question of whether or not cancer cells may be found in the ovary and in some cancer diagnoses that is a concern, so leukemia and some lymphomas. Those investigators have also done some very sophisticated studies to do immunohistochemistry staining, fish analyses, to determine whether or not tumor cells are in the tissue that has been frozen and then transplanting the tissue if there has been no identification of tumor, and to date there have been no recurrences.

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[Dr. Mark Hoffman]
That's ovarian removal, ovarian preservation. What about egg freezing?

[Dr. Leslie Appiah]
Egg freezing, we are doing several a month because we have insurance coverage and prior to insurance coverage we have a philanthropic organization called Chick Mission who pay for egg freezing for all of our patients 18 years and older. I just want to give a shout-out to Chick Mission and their philanthropic efforts because they have been amazing to our patient population. We have the resources and so we've been able to offer that to patients. Our success rates for egg freezing are two times that of the national average because we are able to provide that for more patients and sperm banking, I think 89% success rate in some fertility preservation procedure for males, which is three times the national average. Because we have such a robust team, because it is ingrained in our culture, and because of insurance coverage, we're able to treat patients the way they deserve to be treated.

[Dr. Mark Hoffman]
You truly optimize the opportunity to really make every bit count. That's where having seen, unfortunately for Kentucky, you left before or when you leave, a lot of your expertise goes with you but seeing you in its early stages, the number of people it takes, it can't just be you. It can just be Leslie because you're Superwoman, but for the rest of us, it can't just be one person. It is got to be someone on call 24/7 or at least almost every day. It sounds like it has to be a program that's running on all cylinders, and you think NCIs, those centers where folks go to get cancer treatment, you would have that. How many NCI centers are there right now?

[Dr. Leslie Appiah]
I'm not sure how many NCIs. I'm actually not sure but I do want to comment on something you just said because I always say the one regret that I have had is exactly what you stated. I am very passionate about this, and I will just do what it takes to get it done but one person can't do it. Part of being a leader and part of developing a program is to put things in place so that when you are not there, there is longevity because the expertise shouldn't go with you. It should be within the institution.

I think for anyone who's interested in starting a program, it's really important to take the time to make sure you have all of the stakeholders at the table who are committed, you have a good business plan, you have buy-in, otherwise, yes, you may get the job done, but if you're recruited away or if you have to move for family reasons, then patients are at a loss. That's sometimes even worse because now people have been exposed to this opportunity, they agree that there's a need, some patients have had the opportunity and now some patients won't. It just creates confusion to be quite frank if you're not able to really make the program, have a strong foundation when you start. That is my one regret that I did not do that as best as I could have in my enthusiasm to get the program going.