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Pregnancy Options Expand For Women With Cancer By Charlie Schmidt

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Woodruff, PhD, a professor of obstetrics and gynecology at Northwestern’s Feinberg School of Medicine. “As long as they have information, patients can be empowered to take control of that part of their treatment.”

Surveying Methods

According to Christos Coutifaris, MD, PhD, a professor of obstetrics and gynecology at the University of Pennsylvania’s Perelman School of Medicine, the most established method for preserving fertility among both healthy women and women with cancer remains in vitro fertilization (IVF), which accounts for 1%–2% of all births in the Western world. Egg freezing is a newer option for women. Last September, citing preliminary but “reassuring” safety data, the American Society for Reproductive Medicine concluded that egg freezing is no longer experimental, enabling wider use.

“As long as they have information, patients can be empowered to take control of that part of their treatment.” Both egg freezing and IVF require ovarian stimulation, the nature of which depends on the cancer diagnosis. Women with non–hormonally dependent cancers, such as lymphoma, can be treated with standard drugs used in IVF, including follicle-stimulating hormone. Women with estrogen-dependent cancers, however, are generally treated with aromatase inhibitors, such as letrozole. The safety record for ovarian stimulation before cancer treatment is based almost exclusively on research conducted by Kutluk Oktay, MD, FACOG, director of reproductive medicine

and fertility at New York Medical College. In 2008, Oktay published a study in the Journal of Clinical Oncology that investigated outcomes in 79 women stimulated with letrozole and gonadotropins before they started breast cancer treatment. No increased risk of tumor recurrence was apparent, and according to Oktay, the findings still hold up today Theresa Woodruff, Ph.D. among the hundreds of patients treated with the protocol since establishing his laboratory in 2005. Most of these cancer patients underwent IVF. With the lack of data, the number of children born from frozen and then thawed eggs is unclear, regardless of whether their mothers had cancer. Sources at Northwestern University estimate fewer than 2,000. “There haven’t been any good studies published on pregnancy in cancer patients using cryopreserved oocytes—my guess is because it’s so new that many people haven’t come back around to use their frozen eggs,” said one source. “Here at Northwestern, we’ve had only one patient come back to use cryopreserved eggs, and she wasn’t even a cancer patient. Most of the patients who have frozen eggs are fairly young and newly treated.” The American Society for Reproductive Medicine’s decision to no longer consider egg freezing experimental was based on studies of healthy young women in their early 20s who donated eggs for IVF.

Experimental Alternatives

Meanwhile, healthy women trying to obtain as many eggs as possible to maximize their chances of pregnancy can undergo repeated JNCI | News 1589

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ancer survivorship is increasing, and with it the expectation that patients can resume normal lives after treatment. And for many young patients with cancer, few things matter more than the hope of raising a family. But life-saving cancer treatments often rob patients of fertility. Preserving fertility before cancer treatments begin is one solution, which for postpubertal males is straightforward: freezing sperm samples for later use. Females, however, can face more complicated prospects, such as weeks of controlled ovarian stimulation followed by invasive egg harvesting. These treatments, which insurance does not usually cover, delay cancer treatment. Now, more physicians and fertility specialists argue that female cancer patients should be informed of their reproductive options and that insurance should cover methods in assisted reproductive technology (ART) as a standard benefit in cancer treatment. In California, legislators recently introduced Assembly Bill 912, which would require insurance companies to cover fertility preservation before medical treatments that could cause sterility. The Oncofertility Consortium is a nexus for efforts to preserve fertility in oncology. Formed in 2007 at Northwestern University in Chicago, the consortium has since expanded to 63 health care facilities nationwide, where cancer patients can access fertility counseling and services. Accompanying the growing spotlight on oncofertility are disputes over which ART methods are most appropriate for cancer patients. And bioethical concerns have emerged, mainly about future uses of reproductive specimens—particularly those from minors—and whether society should pay for fertility preservation in oncology, with the existing strains on health care resources. But patients should have a range of options, said Theresa

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follicular maturation in vitro, which is still years away from the clinic. Moreover, according to Woodruff, ovarian tissue transplants could also reintroduce cancer cells into the patient.

Bioethical Concerns

Regardless of method, expense is a key factor in oncofertility. Hormonal stimulation and egg harvesting can run $10 000– $15 000 per cycle, which leads some critics to say that it’s available only to wealthier patients. Silber claims that the Fertility Center he directs offers ovarian tissue freezing for free. So far, 14 children have been born from treatments at the center— three to women with cancer (including one who had her ovaries frozen for more than 10  years)—and more than 140 ovarian tissue samples are now frozen and awaiting use. But the center’s free services are an exception. Arthur Caplan, PhD, who heads the division of bioethics at New York University Langone Medical Center,

questions whether, without insurance coverage, the poor could afford oncofertility. “And we’re grappling with questions about what to do with unclaimed or abandoned reproductive material left behind if a patient should die,” he said. Some experts question whether offering fertility preservation to patients who might be genetically predisposed to cancer is appropriate, whereas still others worry that the health status of children born through ART hasn’t been sufficiently assessed, since no international registry tracks them. Despite these issues, Jacqueline S.  Jeruss, MD, PhD, a breast cancer surgeon at Northwestern Memorial Hospital, said that oncofertility’s broader acceptance is long overdue. “I see many young patients, and for them, fertility preservation is an incredibly significant priority,” she said. “These people are being totally derailed by a cancer diagnosis, and sometimes more than anything this is a part of life that they want to keep on track.” © Oxford University Press 2013. DOI:10.1093/jnci/djt326 Advance Access publication October 18, 2013

Risks of PSA Screening Now Better Understood By Judy Peres

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fter more than two decades of widespread screening for prostate cancer, medical groups have largely agreed that men should not routinely undergo prostate-specific antigen (PSA) testing and should be informed that the test’s harms may outweigh its benefits. Nevertheless, disagreement over the value of screening remains intense, and how the evolving guidelines will translate into clinical practice is unclear. An educational session at the annual meeting of the American Society of Clinical Oncology in June illustrated the fundamental controversy over screening with the PSA blood test. Although conceding that too many men are being diagnosed and treated for low-risk 1590 News | JNCI

prostate cancer because of PSA screening, Peter Scardino, MD, of Memorial Sloan– Kettering Cancer Center in New York, said that going back to the era before PSA, when most patients presented with advanced prostate cancer, would be inconceivable. Doctors just need to screen smarter, he said, so that “the harm can be managed and the good can be retained.” To reduce the potential harm of prostate cancer screening, Scardino said, physicians should stop testing older men, set higher thresholds for biopsy, recommend more active surveillance, and refer patients who need immediate treatment to high-volume providers. Timothy Wilt, MD, of the University of Minnesota, represented the other side

of the argument. The smarter approach, he said, is to not screen with PSA at all. PSA screening is low-value care, Wilt said. “Physicians can provide high-quality, high-value care by recommending against it.” The main benefit of PSA screening is a potential reduction in risk of death from prostate cancer—a benefit that some, but not all, randomized clinical trials have shown. Harms of screening include falsepositive results, which cause anxiety and lead to unnecessary biopsies. Biopsies, in turn, carry risk of pain, fever, and urinary tract infections. But overdiagnosis and overtreatment are the most serious, and least understood, harms of screening. Vol. 105, Issue 21 | November 6, 2013

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stimulation, but cancer patients may have time for only one or two cycles, limiting the number of viable eggs they produce. Some patients might have no time for ovarian stimulation. For them, said Sherman Silber, MD, director of the Infertility Center of St. Louis, the best option is the less-often used and experimental ovarian tissue freezing, in which slices of ovarian tissues are frozen, stored, and then later sutured back into the patient. If the once-frozen tissues regain their normal functionality, then pregnancy can result as usual. Compared with IVF and egg freezing, the number of children born to mothers who had their ovarian tissues frozen remains exceedingly small—just 32 worldwide since 2004, according to Silber. Still, the technique has some advantages, he said. Eggs in frozen tissues can better resist freezing damage than aspirated eggs, he said, and the pregnancy doesn’t rely on IVF, which some patients find morally objectionable. Ovarian tissue freezing won’t work in younger patients whose eggs have yet to mature, however. Options for these patients are far more preliminary and depend on

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