Female survivors of childhood cancer experience high rates of infertility, but most of those who try to conceive eventually succeed, researchers found.
Cancer survivors were 48% more likely to report infertility than their siblings (RR 1.48, 95% CI 1.23-1.78, P<0.0001), with the biggest difference in risk seen in the youngest survivors and siblings, according to a study published online in The Lancet Oncology.
These women took longer to get pregnant than their siblings (P=0.032), but a large proportion (64%) of those who reported infertility -- defined as the inability to achieve a desired pregnancy within a year -- eventually became pregnant, Elizabeth S. Ginsburg, MD, and colleagues from Boston's Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Brigham and Women's Hospital reported.
The study is among the largest and most comprehensive investigations of infertility in childhood cancer survivors ever conducted.
It is also among the few to focus on cancer survivors who were actively trying to get pregnant.
"Clinicians caring for survivors who request information about the likelihood of pregnancy or success of treatment for infertility have a paucity of data on which to base their recommendations," Ginsburg and colleagues wrote.
"To our knowledge, ours is the first large study of female childhood cancer survivors to quantify the risk of infertility that is based on a clinical definition and characterizes the use and success of infertility treatments in this setting."
The study included 3,531 female participants in the Childhood Cancer Survivor Study (CCSS), which tracks survivors of childhood cancer living in Canada and the U.S.
The women, who were treated between 1992 and 2004, were compared with 1,366 female siblings with no history of cancer. Women with known ovarian failure were excluded from the study.
Survivors under the age of 25 were nearly three times more likely to experience infertility as siblings with no cancer history (RR 2.92, 95% CI 1.18-7.20, P=0.029).
But the infertility gap between survivors and their siblings was less pronounced as the women got older, with survivors in their mid- to late 20s having a 61% greater infertility risk than siblings (95% CI 1.05-2.48, P=0.029) and survivors in their 30s having a 37% greater risk (95% CI 1.11-1.69, P=0.0035).
In an editorial published with the study, reproductive specialist Richard A. Anderson, MD, of the University of Edinburgh wrote that these findings seem to implicate specific cancer treatment effects, which become less pronounced as survivors age.
"Treatment-related risk factors for infertility were similar to those for ovarian failure -- notably exposure to alkylating agents, pelvic radiotherapy, and total body radiation," he wrote.
The study revealed that cancer survivors were as likely as their siblings who had trouble conceiving to seek treatment for infertility, but they were only half as likely to be prescribed infertility drugs.
"We really don't understand the reason for this," researcher Ginsburg told 51˶. "It may be that doctors have concerns about giving fertility drugs to women who are cancer survivors or that the women have concerns about taking these drugs. We just don't know."
Ginsburg is an associate professor of ob/gyn and reproductive biology at Harvard Medical School and the Medical Director of the In Vitro Fertilization Program at Brigham and Women's Hospital.
She added that young girls being treated for cancer today have more options to preserve fertility than the women included in the study, who were treated between 10 and 20 ago.
Over that time period, egg and embryo freezing has become the norm in some settings before cancer treatment. Ovarian tissue cryopreservation is still considered experimental, but it is increasingly being used in very young girls.
"There are now very good protocols for preparing and freezing ovarian tissue," Ginsburg said. "But there have been very few pregnancies at this point, so we really don't know how successful this procedure will be."
Disclosures
This study was funded by the National Cancer Institute, the American Lebanese Syrian Associated Charities, and Swim Across America. The study sponsors had no role in the study design, collection of data, data analysis, or interpretation of data.
The authors declared that they had no conflict of interest.
Primary Source
The Lancet Oncology
Barton SE, et al "Infetility, infertility treatment, and achievement of pregnancy in female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort" Lancet Oncol 2013; DOI: 10.101016/S1470-2045(13)70278-X.