Charlotte Observer (NC)
Jan. 04--It was shocking enough that Shiela Johnston was diagnosed with Hodgkin's lymphoma in October 2012, and her 16-year-old daughter Hailey was diagnosed with the same disease two months later.
But as the Dallas, N.C., mother and daughter absorbed the news and made decisions about treatment, they faced another challenge they hadn't expected -- the possibility that chemotherapy and radiation would make them sterile.
It wasn't such a big deal for Shiela, 42, because she and her husband, Darell, have five children younger than Hailey. But for Hailey, then a high school sophomore, the thought of never being able to have children was frightening.
She was sitting on the sofa, holding her baby sister, Cecelia, when the idea really hit home: "I come from a big family. Of course I want to have kids."
When Hailey started asking questions, her oncologist referred her to Dr. Michelle Matthews, a specialist in fertility preservation at Carolinas HealthCare System.
Matthews advised the teenager that she could have her eggs frozen, in a process called cryopreservation, for potential use later. Or she could try a newer procedure that would freeze eggs along with tissue from one of her ovaries. The eggs alone or the tissue with eggs could be re-implanted in the future if Hailey has trouble getting pregnant naturally.
Worldwide, only 30 births have resulted from the latter, still-experimental technique called ovarian tissue cryopreservation. But Matthews thought it was the best option for Hailey because it could be done more quickly than freezing eggs alone, which would take at least two weeks and delay the start of her chemotherapy.
"I decided that day to have the surgery," said Hailey, now 17. "Hopefully I won't have to use it. But when the time is right, and if I can't get pregnant on my own, I'll have that to fall back on."
New field of oncofertility
Not that many years ago, oncologists rarely discussed potentially damaging effects of cancer treatment on reproduction because they were intent on trying for a cure. But as survival rates for young cancer patients have steadily increased, so has interest in quality of life.
The new field of cancer fertility -- or oncofertility -- blends the disciplines of oncology and reproductive medicine. Doctors in these specialties now agree that patients and their families should be counseled about fertility preservation at the time of a cancer diagnosis.
Women can have unfertilized eggs frozen, or they can have fertilized eggs, or embryos, frozen. Embryo freezing, available for more than 20 years, was until recently the more successful technique.
Freezing eggs alone had been problematic because eggs have significant water content that caused them to form ice crystals, leading to damage during the freezing process. With development of a more rapid cooling process, known as vitrification, egg freezing became more viable and is no longer considered experimental.
Both eggs and embryos are frozen in liquid nitrogen, where they can be preserved indefinitely. When the woman is ready to become pregnant, the frozen cells are thawed, eggs are fertilized with sperm, and embyros are implanted into the woman's uterus.
The newer ovarian tissue freezing, although still experimental, has been available for several years in Europe. The first baby born to a former cancer patient after transplanting previously frozen ovarian tissue was in 2004 in Belgium by Dr. Jacques Donnez.
Compared to traditional egg or embryo banking, tissue freezing preserves more eggs in a shorter time period. Part or all of an ovary is removed to protect it from damage during treatment. Thin strips of tissue are taken from the outside of the ovary, where the eggs are located, and the strips are then frozen.
One of the advantages of the new technique is that it can be used to help patients who need to begin cancer treatment immediately instead of waiting to undergo weeks of hormone stimulation to mature the eggs before retrieving them from the woman's body to freeze. It is also an option for women who don't want to take hormones because of the risk those drugs could accelerate growth of the cancer. Ovarian tissue freezing is the only option for girls who have not gone through puberty.
"Oncologists are talking more to patients about it," Matthews said. "If we don't offer this, they may not have any other option" to have a baby.
Discussing side effects
About 70,000 adolescents and young adults, age 15-39, are diagnosed with cancer each year in the United States, according to the National Cancer Institute. Yet the leading NCI-designated comprehensive cancer centers, which should be leaders in fertility preservation, aren't doing an adequate job of helping patients protect their fertility, according to a study in last month's Journal of the National Comprehensive Cancer Network.
Most of these centers don't have policies to consistently identify which patients may be at risk for fertility loss, to inform patients of this risk in a timely manner or refer them to fertility specialists, the study found.
"It can be shocking for patients to find out their fertility was affected when there were potentially options that exist that were not offered to them," said lead author Marla Clayman, assistant professor of medicine at Northwestern University medical school.
Dr. Jennifer Pope, a pediatric oncologist at Levine Children's Hospital in Charlotte, said she and her colleagues work hard to make sure young patients and their parents are aware of the risks of cancer treatment, including potential harm to reproduction. "What methods we have for fertility preservation differ depending on your sex and your age," she said.
For example, she said a 3-year-old girl would "very likely go on to have full fertility" after treatment. "But if you're 16, the conversation is much different." Certain classes of drugs are more harmful to fertility than others, she said. For example, for children who receive high-dose chemotherapy and total-body radiation before receiving bone marrow transplants, the likelihood of infertility is 70 to 100 percent.
But most chemotherapy agents "will have no bearing on fertility," Pope said. And some children with aggressive cancers have to be treated quickly.
But "even when we act quickly, the family should always know the risks," Pope said. "We're all very aware of how strong our drugs are and what they do to someone's body."
Risks not well understood
Risks and success rates for ovarian tissue freezing are not yet well understood.
Although it has resulted in about 30 babies worldwide, experts don't know how many women and girls have had tissue frozen and not yet returned to have the preserved tissue re-implanted. It's also not clear how many women have returned for tissue implantation that did not work. In a recent article, Belgium's Donnez reported on 60 patients who had undergone the procedure. Of those, 11 conceived and six had delivered 12 healthy babies.
At Carolinas HealthCare, Matthews offers the procedure as part of research through a 50-center Oncofertility Consortium, based at Northwestern and funded by the National Institutes of Health.
Matthews has retrieved ovarian tissue from two patients, Hailey in December 2012, and a 29-year-old single woman who also had cancer in April. Neither has returned for the tissue. "It's probably going to be years," Matthews said.
At UNC Chapel Hill, Dr. Jennifer Mersereau, a reproductive endocrinologist, is also part of the Oncofertility Consortium and has performed ovarian tissue freezing for about five patients since 2008. None has returned for the tissue either.
Among the risks of re-implanting ovarian tissue, not just eggs, from cancer patients is the potential for re-introduction of cancer.
"In cancer patients, we don't love the idea of transferring that tissue back to the same person," Mersereau said. "There could be microscopic cancer (cells) in that tissue."
Currently, the procedure involves re-implanting ovarian tissue as well as eggs. But in the future, Mersereau said she hopes technology will have advanced so that the eggs can mature in the laboratory before they are fertilized and implanted, without the ovarian tissue.
The extent of the risk for cancer recurrence is unknown, but would appear to be highest for those with leukemias, or cancers of the blood, Matthews said. She said pathologists always examine ovarian tissue before it is re-implanted, and so far, there have been no reports of cancer recurring in patients who have completed the procedure.
Fertility experts at Reproductive Endocrinology Associates of Charlotte, a non-hospital-based fertility center, have offered egg and embryo freezing since 2009. They do not yet offer ovarian tissue freezing because of the "lack of well-documented outcomes" and the lack of insurance reimbursement, said Dr. Jack Crain, one of the REACH specialists.
Cost can be obstacle
Most fertility preservation procedures are not covered by insurance, and the cost can be an obstacle. Removing and freezing eggs can cost about $10,000, and the medicines cost about $4,000.
Matthews said she donates her time for the procedure and tries to combine the retrieval process with another planned operation to lower the cost. For example, she did Hailey's procedure after an operation to place a port in her chest for delivering medicine.
Hailey was still charged for extra operating room time, anesthesiology and use of equipment. But neither Matthews nor Hailey's mother could estimate the actual cost of the ovarian tissue freezing because they couldn't separate that charge from other surgical bills.
Matthews said she hopes the cost of ovarian tissue freezing will one day be covered by insurance as part of cancer treatment, just as some insurers now cover reconstructive surgery for breast cancer patients.
Price really wasn't a factor when Hailey and her mom made the decision to have the ovarian tissue freezing procedure. Depending on her response to cancer treatment, Hailey may be able to conceive without using the preserved tissue. But they wanted a backup, no matter what the cost.
As Shiela put it: "Those are my grandbabies."
(c)2014 The Charlotte Observer (Charlotte, N.C.)
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