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Impaired fertility linked to radiation dose in survivors of childhood cancer

Issue: July 10, 2008

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Ovarian radiation dose and increasing alkylating agent exposure may be contributors to impaired fertility in women who have survived childhood cancer.

“Doses greater than 1,500 centigrade were associated with a greater than fivefold increased risk of not having been pregnant,” Daniel M. Green, MD, department of epidemiology and cancer control at St. Jude Children’s Research Hospital, said during his presentation.

Using data from the Childhood Cancer Survivor Study, Green and colleagues assessed 5,665 participants and 1,735 siblings who were surgically sterile, had impaired fecundity or were fecund to estimate the relative risk of pregnancy for survivors vs. siblings. Survivors were aged 15 to 44 years at the time of the study.

Compared to fecund siblings, the risk ratio for pregnancy among fecund survivors (n=4,734) was 0.9 (P=.0004). Among those with impaired fecundity, RR was 0.8 (P=.12).

Ovarian radiation dose ,250 cGy with pituitary dose .4,000 cGy (RR=0.4; P=.0005), ovarian dose .250 cGy with pituitary dose .4,000 cGy (RR=0.2; P=.04) and increasing alkylating agent exposure were all related to impaired fertility.

“We found that there was a lower risk of fertility significantly associated with the dose of radiation to the ovaries,” Green said. – by Stacey L. Adams

The critical need right now is not only to minimize the gonadotoxic effect of cancer treatments, but also preserve fertility in women. The current options, while being actively researched, are still in their embryonic stages. The viable options for fertility preservation in women include cryopreservation of embryos, gametes and gonads. However, most of these are not applicable to prepubertal girls, and require a window of opportunity that spans at least 6 to 8 weeks — an option that is not available in most childhood cancer patients.

We have a critical need to develop fertility preservation options. We need to have options which are applicable in pre-pubertal female patients, and we need to have an option which does not require a window of six to eight weeks.

Furthermore, while we are doing that, we need to be able to make sure that we can counsel the young girls with cancer adequately. The research that has been performed by Green et al describes the prevalence of impaired fertility and identifies those at highest risk, and this should form the basis for counseling the girls (and their parents) with newly diagnosed cancer regarding the various options.

– Smita Bhatia, MD, MPH

Associate Director for Population Research, Comprehensive Cancer Center,

City of Hope in Duarte, Calif.

For more information:

• Green DM. #10008. Presented at: 2008 ASCO Annual Meeting; May 30-June 2, 2008; Chicago.