Seven years ago, Teresa K. Woodruff, PhD, coined the term “oncofertility” to describe the melding of two medical specialties, oncology and reproductive endocrinology, with the goal of maximizing the reproductive potential of patients with cancer. Today, with Dr. Woodruff’s establishment of the Oncofertility Consortium—an interdisciplinary initiative designed to explore the reproductive future of cancer survivors—there are more than 60 cancer centers nationwide dedicated to incorporating fertility preservation strategies into oncology treatment.
More effective and targeted chemotherapeutics, which has led to improved survival rates for patients with cancer, has also presented more opportunities for oncologists to offer patients fertility preservation options at the time of diagnosis. For male adolescents and men, such options include cryopreservation of sperm or testicular tissue. Although fertility preservation in female adolescents and women is more complicated, advancements in cryopreservation of oocytes, embryos, and ovarian tissue are resulting in more successful pregnancies.
The ASCO Post recently spoke with Dr. Woodruff, Chief of the Division of Fertility Preservation, Department of Obstetrics and Gynecology, and Thomas J. Watkins Professor of Obstetrics & Gynecology at Northwestern University Feinberg School of Medicine in Chicago, about the progress being made in fertility preservation.
Please talk about the progress that has been made in fertility preservation in oncology patients, especially in young adults.
Over the past 5 years, we have seen tremendous progress. Advancements in cryopreservation of ovarian tissue, for example, have led to more than 25 babies born to women who had a cancer that threatened their fertility. In addition, many more young patients are now being referred to fertility specialists by their oncologists soon after their diagnosis, which has resulted in a rise in the number of young women who have gone through traditional fertility-sparing options like in vitro fertilization (IVF).
For young women who aren’t eligible for an ovarian tissue transplant or IVF, we are making continual progress on in vitro grown ovarian follicles and in building artificial ovaries to develop oocytes into mature eggs. Using these methods, we have had live births in mice and we now have embryos implanted in monkeys.
For young men, sperm can be collected before cancer treatment begins and then frozen and stored. For patients with low sperm counts, a procedure known as Onco-TESE (oncologic testicular sperm extraction), in which testicular tissue is removed and sperm extracted, frozen, and then stored, is also effective in preserving male fertility.
So I think both the present and future are looking very bright for fertility interventions for patients with cancer.
Is fertility preservation more achievable in younger cancer patients than older cancer patients?
It depends. For prepubertal boys and girls, it is a matter of removing testicular or ovarian tissue and we do not have much experience with that method in such young boys. For pubertal boys and young men, sperm banking is very easy and effective. For girls of pubertal age to age 18, the procedure is to remove ovarian tissue, which at that age is filled with large numbers of ovarian follicles, so maintaining reproductive potential is better.
For women approaching their late 30s, although their ovarian potential is already declining, it is not gone, and in many cases we can remove tissue and isolate the eggs, which can then be cryopreserved for implantation following cancer therapy and remission.
We don’t understand everything about the reproductive potential of cancer patients, but we do have options now for all these age ranges.
We have also developed a strategy for cancer survivors to have nonbiologic options as well—for example, adoption. When we started the oncofertility program, we didn’t realize how hard it was for women with a cancer diagnosis to adopt a child. We investigated the adoption process and found that adoption organizations weren’t familiar with the increasing number of cancer survivors due to more effective therapies. Now we have a group of 12 adoptive services that are oncofertility friendly, so more survivors have both biologic and nonbiologic options for having children.
Novel Strategy for Chemotherapy Delivery
Please talk about the research you and your husband [Thomas V. O’Halloran, PhD, Morrison Professor of Chemistry and Director of the Chemistry of Life Processes Institute at Northwestern University] are conducting with a new chemotherapy delivery system.
The system administers drugs to tumors in microscopic bubbles, or nanobins, sparing the reproductive organs.1 Our goal is to eliminate the need for oncofertility. One way to do that would be to deliver existing or new chemotherapeutics so that they don’t produce off-target effects on hair and ovarian follicles, so you don’t lose your hair and you don’t lose ovarian function.
We tested delivering a nanoscale formulation of arsenic trioxide in a murine lymphoma model in the hope that the drug would be delivered to the vascular cancer tissue and not have toxic effects on other organs, including the reproductive organs. It turned out that the nanobins really did target just the cancer cells, and we were thrilled because the study suggests that nanobin techniques could be used not just for new-generation chemotherapeutics but for existing chemotherapeutics as well.
How will the field of oncofertility change over the next decade?
First, we are going to be able to diagnose the disease earlier, and we are going to have smarter drugs that target the disease more effectively and have fewer off-target effects. As those advances develop, we will have less need for the field of oncofertility, which is our goal.
Second, there will be continued increases in the rate of fertility referrals by oncologists. They will become as commonplace as the rate of referrals to other specialists such as genetic counselors. Over the next 10 years, I can see fertility referrals from oncologists rising to between 85% and 90%, and fertility referrals will become nearly automatic for anyone under age 40.
Third, the progress we have seen over the past 5 years—including the birth of 25 babies through ovarian tissue transplants in patients after cancer treatment—will continue to grow.
The next step is to have live births from isolating the immature eggs housed within ovarian tissue follicles, maturing them in the laboratory, freezing the eggs until they are ready for in vitro fertilization, and then implanting them following cancer treatment. If successful, this method would provide a new option for women who have too much disease within their ovary because it would eliminate the chance of transferring cancer cells from the transplanted tissue back into the patient. ■
Disclosure: Dr. Woodruff reported no potential conflicts of interest.
1. Ahn RW, Barrett SL, Raja MR, et al: PLoS One, 8(3):e58491, 2013.