A medication used to prevent infections in cancer patients shows promise of helping male cancer patients preserve their fertility and chance of having children, according to a new study led by an assistant professor at the University of Texas at San Antonio.
The study by Brian Hermann, an assistant professor of biology who has a doctorate in molecular and integrated biology, is another research study within the growing field of oncofertility, a medical specialty that brings together oncology and reproductive medicine with the goal of helping cancer patients and survivors protect their reproductive options and fertility.
The number of patients who survive cancer treatment is growing, but are they aware of their fertility risks and options?
“For certain cancers, treatments have become so successful that survivors can now focus on life after cancer,” said Dr. Alan E. Guttmacher, director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) in a 2014 issue of the National Institutes of Health’s MedlinePlus magazine, “and for many, the ability to have biological children is a major quality of life issue.”
Data from the National Cancer Institute (NCI) registry of cancer patients shows that there are about 10.5 million survivors of cancer, with 5% between 20 and 39 years old. That means there are at least 630,000 young cancer survivors, with the number increasing every year, according to Dr. Teresa Woodruff’s 2007 book “The Emergence of a New Interdiscipline: Oncofertility.” Woodruff, who coined the term oncofertility in 2006, is the director of the Oncofertility Consortium at Northwestern University.
“More than 25% of breast cancer patients are younger than 40 years old and more than 12,400 children and adolescents are diagnosed with cancer each year and the cure rate for all childhood cancers has reached 75%,” Woodruff states in her book.
This is in line with a 2013 estimate that there were more than 420,000 survivors of childhood cancer.
“We’re getting better at diagnosing cancer, we’re diagnosing it earlier, the treatment options are better, so patients are living,” said Dr. Terri Woodard, assistant professor in the department of Gynecologic Oncology and Reproductive Medicine and head of the Oncofertility Consult Service at The University of Texas MD Anderson Cancer Center in Houston.
There was a time when a cancer diagnosis was considered a death sentence, she said, but modern medicine has enabled people to live long, full lives after a history of cancer. Now, the option of reproducing after a cancer battle is no longer off the table.
“It’s highlighted fertility issues and thus the field of oncofertilty more so probably over the last 15 years,” Woodard said. “But our ability to freeze gametes like sperm or freeze embryos even has been around for some time. It’s just we’ve been a bit slower to adapt it to the population of patients with cancer.”
Cancer’s Effect on Fertility
There is a risk of infertility for cancer patients, and different treatments have different effects. The risk depends on many factors, including the patient’s age, type of treatment, type and dose of chemotherapy drugs used, amount and target area of radiation, type and extent of surgery, number of treatments used, and length of treatment, according to the UT MD Anderson Cancer Center. For men, the risk of infertility can come from the treatment itself.
“That’s because the cells that are in the testes responsible for making sperm – just like the cancer cells – are dividing. When they divide, they become susceptible to the chemotherapy,” Hermann said. “So unfortunately the effective nature of the chemotherapy itself is what causes the infertility, because the germ cells in the testes get killed off.”
Assessing infertility risk is a challenge for medical professionals, Hermann added, in part because there’s often a lag between the time patients are treated and the time they learn they’re infertile. In that time, the treatments may have changed.
“In general, there are some treatments that are more risky for sterilization,” Hermann said. Certain agents essentially create DNA damage that the cell can’t fix, causing it to die. These agents oftentimes cause infertility, depending on the dose, he added.
In his research on mice, Hermann said he used such an agent called busulfan, which can be used to treat people before they get bone marrow transplants, to reflect the kind of treatment that can cause long-term or permanent infertility in men. The study that he originally started on primates showed that the drug granulocyte colony-stimulating factor (G-CSF), given to stimulate white blood cell production in the bone marrow to fight off infections associated with a bone marrow transplant, also stimulated sperm cell production. By stimulating cell production, the drug helped replace the sperm cells killed during the busulfan treatment.
A 2013 study performed on female mice at the University of Pittsburgh School of Medicine found that the G-CSF drug decreased ovarian follicle loss and extended time until premature ovarian insufficiency, meaning that in the mice treated with the G-CSF drug the cancer treatment didn’t destroy as many follicles that contain egg cells and they were able to keep those follicles and egg cells longer than the mice who weren’t. Women are born with all of the egg cells they will have in their lifetime, and those egg cells are kept in small pockets called follicles. Cancer treatments can damage the follicles, leading to a decreased number of eggs and earlier onset of menopause.
“I would say the female fertility preservation field is maybe 10, 15 years ahead of male, so for sure there’s a need,” Hermann said. While infertility is not life-threatening, he believes it nonetheless warrants effort and attention, especially among people who might have the ability to have their own children despite a cancer diagnosis.
Cancer Patients and Fertility
“I think we do a bad job with everybody, honestly,” Woodard said. “The sad thing is for men we have a good option, which is sperm-banking, which can be done quickly, the same day before chemotherapy. And we still miss a lot of these men.”
A 2009 survey, published in the Journal of Clinical Oncology, found that less than half of U.S. physicians followed guidelines from the American Society of Clinical Oncology (ASCO), which suggests all patients of childbearing age should be informed of fertility preservation options. According to a 2011 article in Mayo Clinic Proceedings, 95% of oncologists reported that they routinely discuss the effect treatment may have on patients’ fertility, but only 39% routinely referred patients to a specialist in reproductive medicine. In sperm conservation, 91% of oncologists agreed it should be offered to eligible men, but only 10% reported actually offering it.
“For certain cancers, like breast cancer, lymphoma, gynecologic cancers, they do a really good job at referring, because they’re used to dealing with young patients,” Woodard said. But when it comes to types of cancer that are associated with older patients, many oncologists fail to thoroughly discuss fertility or refer younger patients to specialists, she added.
The goal is to lessen the oncologists’ burden, she said, by providing patients with pertinent information ahead of time to empower them to talk to their oncologists about their fertility options and get referrals to specialists.
“It’s hard to rely on already overworked oncologists to cover that in any significant depth or in a way that patients can understand,” she said.
Woodard ultimately sees the patient as the best source for improving fertility discussions about risks and options.
“They have to say what they want,” she said. “We’re starting to get patients advocating for themselves and saying, ‘Hey, what about my fertility? Is there anything I can do?’”
Some doctors struggle with the ethical decisions of discussing fertility options as it can mean delaying or decreasing treatment with less toxic chemotherapy regimens, but Woodard doesn’t see fertility concerns compromising care.
“I think most oncologists are still picking [treatment] regimens that are reasonable,” she said.
Woodard believes that just having the fertility discussion – whether the patient ultimately pursues any of the options or not – is valuable. Ideally, the conversation would move beyond the patients to insurers to make sure the options are covered by insurance.
Hermann’s study on male fertility shows promise of options for men beyond sperm banking, but he cautions that the study is still in its infancy and needs more follow-up research to see if the G-CSF drug can preserve fertility in humans.
“This is just the tip of the iceberg,” he said. “We still have a lot of work to do to understand whether this is something that will be effective in the clinic.”
