SAN ANTONIO – Young women who were survivors of hematologic cancer were more likely to have a diagnosis of infertility than cancer-free women, according to a large population-based study.
Using Ontario, Canada, universal health care databases, Maria Velez, MD, and her colleagues compared young female hematologic cancer survivors with age-matched women who were cancer-free, finding that 20.4% of the cancer survivors and 15% of the cancer-free women had an infertility diagnosis (P less than .001).
The matched cohort study used the Ontario Cancer Registry and identified 1,226 women aged 16-34 years who had been recurrence free for at least 5 years after a hematologic malignancy such that it captured cancer diagnoses made between 1992 and 2005. Each of these women was matched with four randomly selected, cancer-free women (n = 4,293) by the investigators, who took each woman’s age, location and socioeconomic status into account.
Then, the Ontario Health Insurance Plan database was queried to see which women in each group had claims billed under a diagnosis of infertility, denoted by ICD-9 code 628. Dr. Velez said that, for the survivor group, the investigators began tallying infertility diagnoses a full year after treatment was completed.
Pooling all types of hematologic cancer and adjusting for socioeconomic status, the overall relative risk for infertility was 1.35 for hematologic cancer survivors (95% confidence interval, 1.19-1.54; P less than .001).*
Dr. Velez and her colleagues also compared relative risk by type of hematologic cancer. The relative risk for infertility was 1.35 for survivors of non-Hodgkin lymphoma (n = 371); 1.30 for Hodgkin lymphoma (n = 731); and 1.71 for leukemia (n = 124). These were all statistically significant elevations in RR.
In the survivor group, the mean age at cancer diagnosis was 25.7 years, and patients were followed for a median 16.2 years. The mean age of infertility diagnosis for cancer survivors – 33 years – was not significantly different from that of the cancer-free group (32.8 years).
Dr. Velez and her colleagues also examined whether parity at the time of diagnosis was a factor. Cancer survivors who were nulliparous had a pooled relative risk of 1.35 for infertility, compared with the cancer-free women (P less than .001)*. A significantly elevated relative risk was seen for each individual cancer, except for leukemia. Dr. Velez said that this was likely a statistical artifact of the relatively small number of women who had this diagnosis.
The relative risk of an infertility diagnosis for women who were parous at the time of diagnosis was 1.21, a nonsignificant difference (95% CI, 0.80-1.83; P = .37). No individual diagnosis in this group carried a significantly elevated relative risk for infertility.
It’s difficult to know why parity might make a difference in risk of an infertility diagnosis, Dr. Velez said. There might be “nonbiologic” reasons, such as a difference in motivation to seek care for infertility or in desire for pregnancy, she said.
Strengths of the study included the large sample size and the population-based cohort design. The study was the first to use the ICD-9 code of infertility in cancer research, Dr. Velez said. Also, the relatively recent study period meant that patients received more modern cancer treatment regimens, making the data more relevant than some older Scandinavian studies that reached back into the 1960s, said Dr. Velez of the department of obstetrics and gynecology, in the division of reproductive endocrinology and infertility at Queen’s University, Kingston, Ont.
The study did not track the treatment regimen patients received, so it does not shed light on which chemotherapy regimens might be less gonadotoxic over time. The results are a call to include “the effect of cancer treatment on ovarian reserve as a secondary outcome” in clinical trials for cancer therapies, Dr. Velez said.
The study was conducted through the Institute for Clinical Evaluative Sciences and funded by the Faculty of Health Sciences at Queen's University. Dr. Velez reported that she has no financial disclosures.
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*Correction 11/14/17: An earlier version of this article misstated the P values.