A researcher prepares a sample of testicular tissue for further processing, including freezing and banking. The sample could one day be used to restore fertility of a young male cancer patient who has become infertile due to cancer treatment. Download this photo in high resolution.
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.”
Preserving Fertility in Males
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.
Preserving Fertility in Females
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.
About the University of Pittsburgh School of Medicine
As one of the nation’s leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1997 and now ranks fifth in the nation, according to NIH data for 2008 (the most recent year for which the data are final).
Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region’s economy. For more information about the School of Medicine, see www.medschool.pitt.edu.
About Magee-Womens Research Institute
Magee-Womens Research Institute (MWRI), established in 1992, is devoted exclusively to reproductive biology and the health concerns of women and their infants. Today, the Institute is the largest women’s health research facility in the country, conducting research that spans a woman’s entire life cycle – from the formation of cells and embryos through pregnancy, menopause and late life. Since its inception, the Institute has become a well-recognized and respected center for its research, both nationally and internationally.
Now in its second decade, it has grown from approximately 20 faculty members to more than 90 faculty members who have broad experience in numerous aspects of reproductive physiology and biology. Dedicated to basic, translational, and clinical research in women and infants’ health, this diverse group of basic and clinical scientists collaborates on research studies and the practical application of their findings. MWRI’s interactive approach to research, affiliation with the University of Pittsburgh, and location (only steps away from Magee-Womens Hospital of UPMC’s large clinical patient volume) uniquely positions MWRI as an ideal center for reproductive sciences research.
About Magee-Womens Hospital of UPMC
Magee-Womens Hospital of UPMC is a full-service women’s hospital and includes a range of services for women and men: diagnostic imaging including CT and MRI, a Heart Center, bariatric surgery, orthopaedics, digestive disorders, comprehensive breast and gynecologic cancer services, pulmonology, thoracic surgery, minimally invasive abdominal surgery, vascular surgery, and a full-service emergency department.
About Children’s Hospital of Pittsburgh of UPMC
Renowned for its outstanding clinical services, research programs and medical education, Children’s Hospital of Pittsburgh of UPMC has helped establish the standards of excellence in pediatric care. From ambulatory care to transplantation and cardiac care, talented and committed pediatric experts care for infants, children and adolescents who make more than 500,000 visits to Children’s and its many neighborhood locations each year.
Children’s also has been named consistently to several elite lists of pediatric health care facilities, including ranking eighth among children’s hospitals (FY 2006) in funding provided by the National Institutes of Health, and is named one of the top pediatric hospitals in the United States by U.S. News & World Report.