Childhood cancer survivors face, often overcome, infertility

Women who survived childhood cancer face a 50 percent higher risk of infertility than their siblings. However, the ultimate rate of conception among cancer survivors who are unsuccessful in becoming pregnant after one year of trying is nearly two-thirds, on par with eventual pregnancy among all clinically infertile women.

The study, published July 13 in Lancet Oncology, is the first large-scale study of female childhood cancer survivors that examines outcomes for women who experienced infertility.  

Sara E. Barton, MD, from the department of obstetrics and gynecology at Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues investigated infertility rates and time to conception among female childhood cancer survivors.

The researchers found survival rates exceeding 80 percent for childhood cancers; however, many of these women are at risk of unrecognized infertility. They mined data from the Childhood Cancer Survivor Study, and identified 3,531 female cancer survivors and 1,366 female sibling controls who enrolled between Nov. 3, 1992, and April 4, 2004.

They relied on two definitions of infertility: clinical infertility (women who were unsuccessful in achieving pregnancy after one year of trying) and total infertility, which expands the pool to women who reported ovarian failure.

Barton and colleagues constructed two models. The first assessed risk of total infertility and clinical infertility among survivors and siblings. The second model assessed the effects of disease and treatment factors.

The researchers found that cancer survivors had an increased risk of clinical and total infertility compared with siblings. Overall, 15.9 percent of women who survived childhood cancer were affected by infertility, with 12.9 percent trying to conceive for at least one year without success. The remainder of survivors included in the infertile group had ovarian failure and may not have even attempted pregnancy. In the sibling group, 10.8 percent experienced infertility.

Approximately 70 percent of women in both groups who reported clinical infertility visited a physician for the condition. However, 42 percent of cancer survivors were prescribed drugs to help them become pregnant compared with 75 percent of siblings, a finding the researchers characterized as “cause for concern.”

As far as treatment effects, “Cancer survivors with a history of lymphoma or who received any radiotherapy, total body irradiation, or radiotherapy to the abdomen or pelvis had an increased risk of infertility.” Other risks included increasing doses of uterine radiotherapy, exposure to high cumulative doses of alkylating agents and pituitary radiation doses of 1-30 Gy.

A total of 13 percent of survivors took more than 12 months to become pregnant, compared with 8 percent of siblings. “When survivors were grouped by cancer treatment, survivors who had received abdominal radiotherapy took significantly longer to become pregnant than those who did not.”

Barton et al noted the need for improved understanding of infertility after childhood cancer, which could inform counseling and decision making about conception attempts and fertility preservation. “Treatment for childhood cancer has variable effects on reproductive function, and counseling about the likelihood of fertility in survivors remains challenging.”

"What we found delivers a really nice message to clinicians," Lisa Diller, MD, chief medical officer of Dana-Farber/Boston Children's Hospital, said in a press release. "If you have a patient who is a childhood cancer survivor and is self-reporting clinical infertility, the chances are good that she will become pregnant. Women who have a history of childhood cancer treatment should consider themselves likely to be fertile. However, it might be important to see an expert sooner rather than later if a desired pregnancy doesn't happen within the first six months."

In an accompany editorial, Richard A. Anderson, MD, of the MRC Centre for Reproductive Health in Edinburgh, Scotland, wrote, “Barton and colleagues’ data highlight the risk of infertility in childhood cancer survivors beyond the risk of ovarian failure and the need for this risk to be addressed by oncologists at the time of diagnosis and during follow-up as a key part of long-term care.”