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Preserving Fertility while Battling Cancer

When Dr. Neeraj Arora was treated for non-Hodgkin lymphoma in his 20s, his doctors never mentioned that the treatment could leave him infertile. Fortunately it didn’t; his daughter Shairee turned 6 years old in 2011.

Dr. Neeraj Arora was a 25-year-old graduate student when he was diagnosed with non-Hodgkin lymphoma (NHL). His oncologist recommended aggressive chemotherapy and radiation, beginning immediately, to stem the rapid growth of the cancer.

One day, waiting in the doctor’s office for his next round of chemotherapy, he happened to pick up a booklet about NHL treatment. Infertility, he read, was a common side effect of the regimen he was receiving.

“My doctors somehow forgot to mention that,” Dr. Arora recalled. Single at the time, he hadn’t given a lot of thought to becoming a father, but it upset him that no one had considered the risk to his fertility worth mentioning.

It was 1994, and the ability to have children after cancer treatment wasn’t even a blip on the radar screen for oncologists who were considering risks they should discuss with their patients. The concept of cancer survivorship—of a life beyond cancer—was still in its infancy.

Guidelines for Conversation

The estimated number of cancer survivors of reproductive age in the United States is now approaching half a million. Although cancer treatments have evolved to cause fewer harmful side effects in these patients, radiation therapy and many chemotherapy agents can still damage fertility.

The most frequent cause of impaired fertility in male cancer survivors is chemotherapy- or radiation-induced damage to sperm. The fertility of female survivors may be impaired by any treatment that damages immature eggs, affects the body’s hormonal balance, or injures the reproductive organs.

Fertility Issues for Adolescents and Young Adults with Cancer

Fertility Issues for Adolescents and Young Adults with Cancer

The effect of treatment on fertility is a special concern for young cancer patients.

In 2006 the American Society of Clinical Oncology published guidelines recommending that oncologists discuss with all patients of reproductive age the possibility of treatment-related infertility, as well as options for preserving fertility, and provide them with referrals to reproductive specialists. Several surveys, however, have found that fewer than half of oncologists in the United States are following these guidelines and that even oncologists who regularly discuss the risk of infertility with patients rarely refer them to reproductive specialists.

The potential impact of cancer treatment on fertility “has not been at the forefront of what oncologists think they need to discuss with patients and families up front,” said Dr. Peter H. Shaw, who directs the Adolescent and Young Adult Oncology Program at Children’s Hospital of Pittsburgh. “But it needs to be discussed right off the bat, once you have the diagnosis.”

Elissa Bantug was 23 years old when she was diagnosed with breast cancer in 2005. She had one child already and wanted a larger family. The doctors who she consulted dismissed her questions about the likely effects of treatment on her fertility. “One oncologist said to me, ‘Elissa, do you want to have kids or do you want to live? Because that’s what we’re dealing with,’” she recalled.

Bantug’s experience echoes survey findings that suggest oncologists may place a lower value than patients do on the risk of future infertility. In such surveys, many oncologists say they feel ill informed about fertility preservation and worry that discussing it will place an added burden on patients who are already stressed because of their cancer diagnosis.

But studies suggest that cancer patients are very concerned about risks to their fertility and want to know how these risks can be mitigated.

“To ensure quality of survivorship, informed dialogues about patients’ concerns and desires for their future need to be part of the initial treatment planning process,” said Dr. Julia Rowland, director of NCI’s Office of Cancer Survivorship. Moreover, she noted, if discussions about fertility do not happen until after cancer treatment has been completed, it “is generally too late to preserve reproductive options.”

Resources on Fertility Preservation for Cancer Patients

Oncofertility Consortium
NIH-supported interdisciplinary research consortium exploring relationships between health, disease, survivorship, and fertility preservation in young cancer patients
Patient education resource provided by the Oncofertility Consortium

Information and support for cancer patients and survivors at risk for infertility

American Society of Clinical Oncology
Recommendations on fertility preservation in people treated for cancer

Researching Options

Options for preserving cancer patients’ ability to have biological children depend on many factors, including the patient’s sex, age, type of cancer, and type of treatment. Most procedures remain experimental. Only two are well established and known to be effective: for men, freezing and banking sperm; for women, freezing and banking embryos.

Most options, whether established or experimental, are costly and unlikely to be covered by health insurance. And most of these options must be undertaken before or during cancer treatment. Patients who have just received a cancer diagnosis usually have a very brief window of time in which to decide whether to pursue fertility preservation—and, if so, to determine which procedure is most appropriate for their circumstances.

To help patients navigate the maze of fertility preservation options, NCI-supported researchers are developing Web-based decision aids that educate patients about cancer’s effects on fertility, explain the pros and cons of different fertility-preservation procedures, and help them clarify their values so that they can reach a decision they are comfortable with.

“It’s a complicated decision,” said Dr. Christine M. Duffy of Brown University and Rhode Island Hospital in Providence, who is developing a fertility preservation decision aid for women with breast cancer. “Often there is no obvious best choice. It depends on your values, on how important it is for you to have children, on how much you’re willing to go through.”

These factors are incorporated in a decision-aid tool on sperm banking that Dr. Leslie R. Schover of the University of Texas M. D. Anderson Cancer Center in Houston has pilot tested. The decision aid is part of a comprehensive educational tool about sperm banking for patients, families, and health care professionals.

Through a series of questions, patients are encouraged to think about things they may never have considered, Dr. Schover explained, such as whether they would feel sad if they never had a child or whether their family would accept a child born from donor insemination. In pilot testing, patients who used the decision aid were less conflicted about the decisions they made on sperm banking than patients who did not use it.

Health Outcomes in Children of Cancer Survivors

Cancer survivors may have a strong desire for children, but they may worry that their cancer treatment could lead to health problems, such as birth defects or genetic abnormalities, for their offspring.

Research findings to date suggest, however, that although infants born to survivors of childhood cancer may be at higher risk for premature birth and low birth weight, they are no more likely than other children to suffer from birth defects, genetic disorders, or chromosomal abnormalities.

Against the Odds

Patrick McArthur can attest to the benefits of an informed, carefully considered decision about fertility in the wake of cancer. Diagnosed with locally advanced lymphoblastic lymphoma (a type of NHL) in 2005 when he was 25 years old, he was counseled by a nurse about the possible effects of his treatment on fertility and about the option of freezing and banking sperm. “I knew immediately that I wanted that insurance policy,” he said.

An attorney in San Antonio, TX, McArthur is now the father of a baby girl, who was conceived naturally and born in June 2010. “My wife and I decided to try for a natural conception, knowing that if it didn’t happen we had the banked sperm as a backup,” he said.

Four years after her initial breast cancer diagnosis (and following treatment for a recurrence in 2007), Elissa Bantug and her husband consulted fertility specialists to see if it would be possible for her to get pregnant. “They warned me that it would be very difficult,” she recalled. But against the odds, she conceived right away. Her baby daughter turned 1 in October 2010. Bantug is now project coordinator of the Breast Cancer Survivorship Program at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore.

Dr. Arora, now a program director in NCI’s Division of Cancer Control and Population Sciences, is the father of a little girl who turned 6 in February 2011. “Given what I now know about the toxicity of the intense chemotherapy I received,” he said, “I consider the birth of my daughter to be a miracle.”

To help address some of the issues related to fertility preservation decisions and other areas relevant to young survivors, NCI, with support from the Lance Armstrong Foundation, has sponsored the Adolescent and Young Adult Health Outcomes and Patient Experience (AYA HOPE) Study. Data are forthcoming from this population-based cohort of young survivors identified through SEER cancer registries.

Additional Options for Preserving Fertility in Children

Children who are diagnosed with cancer before they reach puberty now have extremely good odds of surviving their cancer. But the treatments that save their lives may destroy their ability to have their own children. Currently no standard fertility preservation options exist for these children.

Adolescent boys and young men can opt to have their semen frozen and preserved in a sperm bank. Younger boys, however, do not yet produce sperm, although their testicular tissue contains immature cells that will eventually produce sperm.

Prepubescent girls’ ovaries contain immature eggs, or follicles, that are not yet capable of being fertilized, so egg freezing—a rapidly developing but still experimental fertility preservation option for adolescent girls and young women—isn’t feasible for younger girls.

Researchers at the Children’s Hospital of Philadelphia, led by Dr. Jill Ginsberg, are studying testicular tissue banking as a fertility preservation option for prepubescent boys. A biopsy is performed to remove a small piece of one testicle. Half of the specimen is frozen for possible future use by the patient. The other half is sent to the lab of Dr. Ralph Brinster at the University of Pennsylvania School of Veterinary Medicine, who has successfully developed a method of growing sperm stem cells in culture, reimplanting them, and restoring fertility in male rats. Dr. Brinster is now attempting to apply this technology to human sperm stem cells.

Biopsies have been performed on 23 boys so far, said Dr. Ginsberg. “In most cases, the parents of prepubescent boys are willing to agree to the procedure and are grateful for the opportunity,” she said, “even though there is no certainty that the preserved tissue will be useful to their sons in the future.”

Nine centers participating in the NIH-funded Oncofertility Consortium are offering ovarian tissue banking to prepubescent girls in an experimental protocol. One of the patients’ ovaries, or a section of one ovary, is removed. As in the testicular tissue banking study, most of the specimen is frozen for the patient’s possible future use, while a portion is used for research on optimizing techniques for freezing and thawing ovarian tissue for use in transplantation or in vitro follicle maturation.

“Although it is still at an experimental stage, in vitro follicle maturation may provide an important new option for preserving fertility in young women and girls with cancer,” said Dr. Teresa Woodruff, director of the Oncofertility Consortium.

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