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One of the nation’s first comprehensive programs to help preserve or restore fertility after cancer treatment for not only adults, but also preadolescent girls and boys, has been established by a network of experts in reproductive medicine and cancer at Magee-Womens Research Institute (MWRI), Children’s Hospital of Pittsburgh of UPMC, Magee-Womens Hospital of UPMC and the University of Pittsburgh School of Medicine.
The Fertility Preservation Program in Pittsburgh aims to educate patients and their physicians about the long-term reproductive impact of cancer therapies and the options for preserving fertility – some investigative – that are available to them, explained Kyle Orwig, Ph.D., associate professor of obstetrics, gynecology and reproductive sciences at the School of Medicine, an MWRI researcher and one of the program leaders.
Studies show that up to 90 percent of cancer patients are not informed about the risks cancer treatment can pose to fertility, a statistic that physicians and researchers in Pittsburgh hope to change by offering counseling and services seamlessly coordinated with patient care.
“This is a discussion that needs to happen before toxic therapies are initiated and fertility is irreversibly destroyed,” said Dr. Orwig.
While adult men and women can freeze eggs, sperm or embryos prior to treatment, there currently are no options to preserve the fertility of boys and girls who are not yet producing mature eggs or sperm. “For these young patients, we will freeze testicular or ovarian tissue that might be used in the future to restore fertility when experimental techniques emerge from the research pipeline,” said Dr. Orwig. “In conjunction with pediatric oncologists at Children’s Hospital and the Center for Fertility and Reproductive Endocrinology at Magee, we are poised to provide standard as well as experimental options for preserving fertility.”
Surviving cancer is much more likely than it has been in the past, but patients who hope to eventually have biological children might face a new set of challenges because some treatments, particularly bone marrow transplant, can impair or destroy natural fertility.
“Many chemotherapies and radiation therapies work by killing rapidly dividing cells, which includes both cancer cells and innocent bystanders, such as the gonadal cells that make eggs and sperm,” Dr. Orwig said. “For example, leukemia could be treated with drugs to destroy the blood system, which is then restored with a bone marrow transplant. The cancer will be eradicated, but there is a significant risk that fertility will be wiped out, too, as a side effect.”
In the Fertility Preservation Program, Dr. Orwig and his team will cryopreserve, or freeze, testicular tissue from prepubescent boys with the hope that special precursor cells called spermatogonial stem cells can be obtained from it and later be given back to the patient in an “auto-transplant” that will allow sperm production to resume after cancer treatment.
While scientists can’t yet say for certain that collecting, storing and putting back spermatogonial stem cells will make it possible for boys to grow up to father children, the technique does appear to work in extensive animal testing, Dr. Orwig said.
An outpatient surgical procedure through the scrotum is necessary to collect testicular tissue. Ideally, it will be done when a cancer patient is already sedated in the operating room to get a central line, which is a long-term catheter placed in a large blood vessel for the administration of drugs and to draw blood for tests.
A small portion of the testicular tissue would be used for research, although if a sample is very small, all of it would be saved for the patient’s future use. Dr. Orwig’s team has already established techniques to determine whether stem cells are present and how many there are.
“One focus of our research is to isolate the therapeutic stem cells and remove contaminating malignant cells, so we don’t run the risk of reintroducing cancer when cells are given back to the patient,” he said. Spermatogonial stem cell transplantation is still a work in progress. However, “a patient treated today who doesn’t cryopreserve his tissue will not be able to take advantage of this new technology when it becomes available,” Dr. Orwig added. “We are encouraged by successes in several animal models and believe this technique can be translated to the fertility clinic, possibly in the next decade.”
Men and boys who have gone through puberty could provide a semen sample that could be preserved for later use in an artificial insemination procedure, a simple and well-tested approach that would likely be the first choice for many male patients, Dr. Orwig said. But in some cases, the patient may be too ill from his cancer to provide a good quality sample, or he or his family may be uncomfortable with the act of producing one. Preservation of spermatogonial stem cells might be an option in such situations.
The Fertility Preservation Program also will endeavor to aid women and girls who are starting cancer treatment or preparing for a bone marrow transplant. Currently their choices are quite limited and, for many, biologically impossible or morally unacceptable, noted Joseph S. Sanfilippo, M.D., director of the Center for Fertility and Reproductive Endocrinology at Magee-Womens Hospital.
“Women can undergo ovarian stimulation to generate multiple mature eggs, which can then be fertilized with partner or donor sperm to produce embryos for later implantation and possible pregnancy,” he said. “These techniques are now well-established, and we will offer them to female patients who wish to pursue this option.” Another option is ovarian cryopreservation, where an ovary is removed before cancer therapy is initiated with the plan to replace ovarian tissue once the patient is cured.
Still, the stimulation technique takes time and could delay cancer treatment. It also produces high estrogen levels that could make some hormone-sensitive tumors worse, he noted. A component of the Fertility Preservation Program is to help individual patients understand the relevant issues to assist with decision-making.
For pre-adolescent girls, who don’t yet make eggs for fertilization, embryo freezing is not possible, said Peter Shaw, M.D., head of the Adolescent and Young Adult Oncology Program at Children’s Hospital and leader of the female side of the fertility preservation effort. He and his colleagues are working with National Physicians Cooperative of the Oncofertility Consortium, based at Northwestern University, to explore cryopreservation of mature eggs or ovarian tissue and other approaches to restore fertility after cancer.
Through the program, girls who have cancer and are at risk of losing their future fertility can have tissue samples stored. Conservative surgeries and other techniques can be used to try to preserve the reproductive system. Meanwhile, researchers around the country are trying to understand how the egg maturation process works to see if it is possible to rescue eggs or ovaries.
“We didn’t know until 33 years ago that a so-called ‘test tube baby’ was possible, so it’s very possible that we can find solutions for these problems in the near future,” Dr. Shaw said. “We have to try to preserve the tissue now or we will never succeed. We think the technology will be available in the future to use this frozen tissue to restore lost fertility.” Almost all of these options are experimental procedures, he acknowledged.
“We’re suggesting patients undergo an extra procedure while providing no guarantee that we can provide any help,” he said. “As always, it’s ultimately up to the patient and family. The most important thing we can do is provide them up-to-date information and resources.”
The Fertility Preservation Program has established a dedicated phone line that patients and their physicians can call to learn about the reproductive side effects of their treatments and options for preserving fertility. The number is 412-641-7475.
Marc Lukasiak, 412-692-7919, marc.lukasiak@chp.edu Gloria Kreps, 412 586-5764, KrepsGA@upmc.edu Anita Srikameswaran, 412 578-9193, SrikamAV@upmc.edu
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