Childhood cancer survivors with clinical infertility have a good chance of achieving pregnancy, according to new findings from the Childhood Cancer Survivor Study (CCSS).
Study Background
As a group, women who survive childhood cancer are known to have lower fertility rates. This study, however, focused on survivors with functioning ovaries who wanted to get pregnant, comparing them to a control group of sisters of childhood cancer survivors.
The survivors were more likely to have clinical infertility, meaning they had tried to get pregnant for at least a year without success. However, 64% of the survivors with clinical infertility eventually conceived, about the same rate as women in the general population with clinical infertility. The results challenge the common view that childhood cancer survivors who have trouble getting pregnant are likely to be infertile. Moreover, these findings suggest strategies that may optimize a survivor’s chances of getting pregnant.
The survivors with clinical infertility were younger on the whole than those in the sibling control group with clinical infertility, and infertility increased with age as expected in both groups. Overall, 13% of survivors had clinical infertility compared to 8% of the sisters. The gap was especially wide at younger ages. That suggests survivors could benefit from infertility counseling and treatment in their 20s, rather than waiting as many women do until they are in their 30s or older, said Lisa R. Diller, MD, Chief Medical Officer of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and senior author of the study.
“It’s important to get infertility experts involved earlier rather than later,” she said. “That’s one important message from this study.”
Published recently in Lancet Oncology,1 the study included 3,531 women who had been diagnosed with cancer before age 21 and 1,366 sibling survivors, all participants in the ongoing, multicenter CCSS. The researchers used questionnaires to gather data on participants’ infertility, medical treatment for infertility, and time to first pregnancy.
Treatment Gap
A second important message from the study concerns infertility treatment. Among participants with clinical infertility, about the same proportion of survivors and controls (~70%) sought help from infertility specialists. However, significantly fewer survivors received drug treatments commonly prescribed for infertility; 42% of these survivors received drugs, compared to 75% of their siblings.
That finding came as a surprise. “We have no idea why…. It’s kind of a mystery,” said Elizabeth
Ginsburg, MD, Medical Director of Assisted Reproductive Technologies at Brigham and Women’s Hospital, Boston, and a coauthor of the study. Possibly the women themselves declined drugs because of past medical experiences, she conjectured. Or they and their doctors may have been concerned about comorbidities, such as the heart problems that can result from anthracycline use.
Dr. Ginsburg said that in the Brigham and Women’s survivorship clinic, patients ask two main questions about infertility treatments: Could their cancer treatments have put future offspring at risk of birth defects or other problems? And would the infertility treatment increase their own risk of cancer recurrence?
There’s no evidence to suggest that the answer is yes to either of these questions, she said, but it is still a common concern. “Whatever the specific reason, there seems to be generally more trepidation on the part of cancer survivors,” she said.
There is also the possibility of low expectations on the part of providers. “My guess is that people just think it’s not going to work,” said Dr. Diller. “Without this data in front of you, you might think there was no chance. The study gives you a cohort to which you can compare your individual patient.”
Dr. Ginsburg agreed: “We’re hoping that as more studies like this one appear, there will be greater awareness that it’s better to address fertility issues early and that survivors can benefit from treatment,” she said.
Perhaps the most important group to reach with the new data are the youngest adult survivors, those in their early 20s. In the survivorship clinic at Oregon Health and Science University (OHSU)/Doernbecher Children’s Hospital, providers routinely discuss fertility whether the patient brings it up or not, said
Susan Lindemulder, MD, who leads the clinic. Also routinely, they offer referrals to OHSU’s reproductive endocrinology department.
“But it’s a minority who choose to do that,” said Dr. Lindemulder. “One of the mental barriers is that these young survivors are not ready to have children. We have a very frank discussion and tell them not to follow societal norms [waiting until their 30s], but it’s still hard for them to get beyond their current priorities in life, especially the young 20s.”
Early Collaboration
The findings also highlight the importance of early collaboration between oncologists and reproductive medicine experts in order to preserve fertility, according to Richard A. Anderson, MD, PhD, Professor of Clinical Reproductive Science and Head of Obstetrics and Gynaecology at the MRC Center for Reproductive Health, University of Edinburgh, who wrote an editorial accompanying the study.2 “Fertility preservation is now part of mainstream fertility treatment,” he writes, “but requires seamless links between oncologists and reproductive medicine.”
For girls who have reached puberty, it is possible to collect and freeze oocytes. But for younger patients, the only option is collecting and freezing ovarian tissue for future implantation, a still experimental procedure performed only in the research setting.
The new findings also reinforce the importance of coordination between oncologists and physicians who provide follow-up care to cancer survivors. Many large cancer centers have follow-up programs for survivors, but eventually most patients transition as adults to a primary care physician. Some centers have transition programs that support both the primary care physician and the patient. Typically, a treatment summary and a survivorship care plan are prepared for each patient.
Still, many young adult survivors are lost to follow-up. “That is sort of a Pandora’s box,” said Dr. Lindemulder. “It’s the classic young adult thing—they feel indestructible. Later, around age 30, it’s different, they are finding us.” She and her colleagues talk with colleges and universities and local pediatricians to try to reach these youngest adults.
Another effort to help survivors get the care they need is the Children’s Oncology Group’s guidelines for the transition from childhood cancer follow-up care to adult primary care: www.survivorshipguidelines.org.
“If we can incorporate the data from the current study into the guidelines, it could help change practice no matter where the care is taking place,” Dr. Diller said. ■
Disclosure: The study was funded by the National Cancer Institute, American Lebanese Syrian Associated Charities, and Swim Across America.
Reference
1. Barton SE, Najita JS, Ginsburg ES, et al: Infertility, infertility treatment, and achievement of pregnancy in female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol 14:873-881, 2013.
2. Anderson RA: Infertility in women after childhood cancer. Lancet Oncol 14:797-798, 2013.
