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Fertility Preservation in Oncology: An Overview of Techniques & Advancements

Author Taylor Spurgeon-Hess covers Fertility Preservation in Oncology: An Overview of Techniques & Advancements on BackTable OBGYN

Taylor Spurgeon-Hess • Jun 25, 2023 • 38 hits

Fertility preservation has become a crucial component of care for reproductive-age patients facing cancer therapies that may impact their fertility. Fertility counseling has become standard of care for these patients, however, the landscape of oncofertility preservation techniques and advancements continues to evolve. Egg freezing provides a viable option for those with ovaries, while sperm banking remains the go-to choice for patients with testes. Additionally, ovarian tissue freezing, once an investigational technique, has now become a clinical care standard, leading to over 200 successful births worldwide. Due to the complexities within the field of oncofertility, clinicians underscore the importance of comprehensive institutional support and the role of dedicated teams in maintaining successful preservation programs.

This article features excerpts from the BackTable OBGYN Podcast. We’ve provided the highlight reel in this article, and you can listen to the full podcast below.

The BackTable OBGYN Brief

• Fertility counseling is standard of care for patients of reproductive age undergoing cancer therapies. Egg freezing and sperm banking are the standard fertility preservation options for patients with ovaries and testes, respectively.

• Patients from several months old to age 35 can opt for ovarian tissue freezing and The interval between ovarian tissue removal and transplantation can be up to ten years. Over 200 successful births worldwide attest to the effectiveness of ovarian tissue freezing.

• Testicular tissue freezing is an emerging investigational method for fertility preservation in pre-pubertal boys who cannot provide a semen sample. Despite being investigational, testicular tissue freezing has seen successful transplantation procedures in non-human primates.

• Strong institutional support and a dedicated team are integral to a successful fertility preservation program. It is vital to ensure that the expertise and infrastructure of a fertility preservation program are not dependent on a single individual.

• Experimentation is ongoing with transplanting ovarian tissue in the subcutaneous space for hormone replacement, though challenges persist in developing a robust vascular system in this space.

• Tools such as Fertility Scout, available on the Alliance for Fertility Preservation website, are being developed to help patients and physicians find fertility preservation specialists and understand what to expect from such interventions.

Fertility Preservation in Oncology: Techniques & Advancements

Table of Contents

(1) Fertility Preservation Techniques in Oncology

(2) Testicular Tissue Freezing & Ovarian Tissue Cryopreservation

(3) The Future of Fertility Preservation in Oncology: Advanced Processes, Insurance Coverage & Tissue Transplantation

Fertility Preservation Techniques in Oncology

Advocated by major reproductive and oncological associations, fertility counseling has become the standard of care for patients of reproductive age facing potentially fertility-impairing cancer therapies. Patients with ovaries can opt for egg freezing, a standard procedure that even applies to adolescents who have reached menarche. This approach offers a 50-60% success rate for patients under 35 years old. For patients with testes, sperm banking remains the go-to option. Notably, ovarian tissue freezing, a process involving ovary removal, preservation, and transplantation post-cancer therapy, has transitioned from an investigational technique to a clinical care standard. It has led to over 200 successful births worldwide and can help patients from several months old up to 35 years. This method provides a lifeline for individuals requiring early-life pelvic and abdominal radiation, showcasing the evolving capabilities and potentials in the field of oncofertility.

[Dr. Mark Hoffman]
For our patients with ovaries, what can be done for women who are undergoing therapies that can be injurious, that can injure, their ovaries, that can reduce their ovarian reserve? What are the options if someone comes in diagnosed with malignancy recommended treatment? Talk about the processes available to these patients for fertility preservation. I imagine there's not just one thing you can do for them.

[Dr. Leslie Appiah]
Absolutely. To start off with, we should counsel all patients of reproductive age about the risk to their fertility and about the options. When I say reproductive age, I mean birth through age 42 for females or patients with ovaries and birth through the 60s for patients with testes and the children have reproductive potential. We want to counsel them about the harm of these therapies to their reproductive potential first. That is mandated, or I should say it is a standard of care as depicted or as stated by the American Society for Reproductive Medicine and the American Society for Clinical Oncology.

Every reproductive governing body, every oncologic governing body has stated that as medical providers, it is our responsibility to counsel every one of these patients or to offer counselling to every one of these patients who may be at risk. That's number one. Once we identify risk and the patient wants to proceed with fertility preservation options, there are several. For patients with ovaries, egg freezing is a standard of care. It is available to adolescents. I think historically we think about egg freezing for adult patients 18 and over but we can't freeze eggs in girls who have experienced menarchy. Success rates range anywhere from 50% to 60% in patients under age 35 years of age.

Sperm banking is standard of care for adolescent and adult males. They should be offered this opportunity. Ovarian tissue freezing is near and dear to my heart. It is a process where we would remove an ovary and then freeze the ovarian tissue prior to cancer therapies. Then when the patient has completed chemotherapy or radiation, we will transplant the tissue back into the pelvis when they're ready to have a family. Prior to December 2019, ovarian tissue cryopreservation was considered investigational. There now have been over 200 births worldwide. This is now considered clinical care. We do offer it to patients from several months of age to age 35.

[Dr. Mark Hoffman]
From several months of age, is that what you said?

[Dr. Leslie Appiah]
Several months of age. When you have patients with diagnoses that require pelvic and abdominal radiation at a very early age, unfortunately, those individuals are going to experience infertility. We will remove one ovary prior to cancer therapies and then freeze the tissue for their future use.

[Dr. Mark Hoffman]
What's the longest time between removal and replacement?

[Dr. Leslie Appiah]
I can imagine that we're still looking at somewhere from probably 10. We're probably looking at 10 years at this point, yes, because we've been doing this for a while.

Listen to the Full Podcast

Oncofertility with Dr. Leslie Appiah on the BackTable OBGYN Podcast)
Ep 22 Oncofertility with Dr. Leslie Appiah
00:00 / 01:04

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Testicular Tissue Freezing & Ovarian Tissue Cryopreservation

Despite ongoing advancements, experts highlight the need for more focus on fertility preservation strategies, especially for male patients. One promising investigational method is testicular tissue freezing, which targets pre-pubertal boys unable to provide a semen sample. While it's still under refinement, successful transplantation in non-human primates underscores its potential. On the flip side, ovarian tissue cryopreservation and transplantation offer well-established solutions that can be implemented within 24 to 48 hours and have proven effective at maintaining fertility post-chemotherapy. Dr. Appiah also mentions the impressive success rates of their fertility preservation program, acknowledging the vital role of a dedicated team and comprehensive institutional support in maintaining such a robust system.

[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.



[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.

The Future of Fertility Preservation in Oncology: Advanced Processes, Insurance Coverage & Tissue Transplantation

The future of oncofertility encompasses a holistic approach toward addressing patient needs, including streamlining processes for males, advocating for insurance coverage of fertility preservation services, and perfecting ovarian tissue transplantation techniques. The focus is on elevating ovarian tissue transplantation success rates beyond the current 29% to 41% and exploring ways to utilize the tissue for hormone replacement. Researchers are innovating with transplanting ovarian tissue in the subcutaneous space, a process that could potentially provide patients with long-term access to their own hormonal reserves. Challenges, such as developing a robust vascular system in the subcutaneous space, still need to be addressed. However, these patient-driven advancements underscore the need for medical professionals to keep pace with patient expectations and evolving industry standards. This forward-thinking approach is reflected in organizations like the Oncofertility Consortium and the Alliance for Fertility Preservation, which work to improve patient care and support the careers of upcoming researchers in the field.

[Dr. Mark Hoffman]
I'll find out. I'll look into it. What's the future? I know you're busy. I know we don't want to keep you here all night and I could talk to you forever, but what's on the horizon for Oncofertility?

[Dr. Leslie Appiah]
On the horizon is, again, streamlining these processes for males so that we can do things very quickly. Really getting every state to provide fertility preservation services through the insurance companies. Really finding out the best way to transplant ovarian tissue. We want that to become more efficient than just a 29% to 41% success rate. Quite frankly, patients are asking to use the tissue for hormone replacement.

[Dr. Mark Hoffman]
Actually, I thought about that while you were talking. You said it didn't last very long.

[Dr. Leslie Appiah]
So far it doesn't because we haven't really identified the best mileau for the tissue. Ideally, we will be able to transplant that tissue in the subcutaneous space. A patient instead of appellate, which we don't approve of, the patient may have ovarian tissue transplanted underneath the subcutaneous tissue and then have that tissue for as long as it's there and have not only their estrogen, progesterone, testosterone inhibit, all the things that may contribute to wellbeing.

[Dr. Mark Hoffman]
Whose ovary?

[Dr. Leslie Appiah]
Their ovary.



[Dr. Mark Hoffman]
They just keep getting their own ovary back.

[Dr. Leslie Appiah]
They just keep getting their own ovary back. Right now, the subcutaneous space does not have a robust vascular system so it's not panned out just yet, but we're getting there. Patients will push the envelope. This is what they are asking for, and to your point, if we don't do this in the medical realm, then industry will.



[Dr. Leslie Appiah]
Absolutely. I will do. I want to put out a plug to the Oncofertility Consortium which has really led the charge in developing this expertise. There are about 4,000 international members of the consortium. This was, again, started by Dr. Teresa Woodruff. This organization has been instrumental in providing care for patients and really building the careers of a lot of talented scientists and researchers. I also want to put out a plug for the Alliance for Fertility Preservation. I am going to send this link to you especially, Mark. If individuals go to www.allianceforfertilitypreservation.org, and this is for patients, there is a fertility scout button on their website.

You can push that or select that and it will allow you to find a fertility preservation specialist in your area anywhere in the country. It will also educate the patient about what they should be expecting from their oncology team and what they can expect from fertility preservation interventions. Physicians and patients can use that. I think that fertility scout is really important for patients to know about even in survivorship.

Podcast Contributors

Dr. Leslie Appiah discusses Oncofertility on the BackTable 22 Podcast

Dr. Leslie Appiah

Dr. Leslie Appiah is the director of the fertility preservation program and the chief of the division of academic specialists in OBGYN at the University of Colorado Anschutz.

Dr. Amy Park discusses Oncofertility on the BackTable 22 Podcast

Dr. Amy Park

Dr. Amy Park is the Section Head of Female Pelvic Medicine & Reconstructive Surgery at the Cleveland Clinic, and a co-host of the BackTable OBGYN Podcast.

Dr. Mark Hoffman discusses Oncofertility on the BackTable 22 Podcast

Dr. Mark Hoffman

Dr. Mark Hoffman is a minimally invasive gynecologic surgeon at the University of Kentucky.

Cite This Podcast

BackTable, LLC (Producer). (2023, May 4). Ep. 22 – Oncofertility [Audio podcast]. Retrieved from https://www.backtable.com

Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.

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