Association of platinum-based chemotherapy with live birth and infertility in female survivors of adolescent and young adult cancer

Abstract

Objective: To estimate the effect of platinum-based chemotherapy on live birth (LB) and infertility after cancer, in order to address a lack of treatment-specific fertility risks for female survivors of adolescent and young adult cancer, which limits counseling on fertility preservation decisions.

Design: Retrospective cohort study.

Setting: US administrative database.

Patients: We identified incident breast, colorectal, and ovarian cancer cases in females aged 15-39 years who received platinum-based chemotherapy or no chemotherapy and matched them to females without cancer.

Intervention: Platinum-based chemotherapy.

Main outcome measures: We estimated the effect of chemotherapy on the incidence of LB and infertility after cancer, overall, and after accounting for competing events (recurrence, death, and sterilizing surgeries).

Results: There were 1,287 survivors in the chemotherapy group, 3,192 in the no chemotherapy group, and 34,147 women in the no cancer group, with a mean age of 33 years. Accounting for competing events, the overall 5-year LB incidence was lower in the chemotherapy group (3.9%) vs. the no chemotherapy group (6.4%). Adjusted relative risks vs. no chemotherapy and no cancer groups were 0.61 (95% confidence interval [CI] 0.42-0.82) and 0.70 (95% CI 0.51-0.93), respectively. The overall 5-year infertility incidence was similar in the chemotherapy group (21.8%) compared with the no chemotherapy group (20.7%). The adjusted relative risks vs. no chemotherapy and no cancer groups were 1.05 (95% CI 0.97-1.15) and 1.42 (95% CI 1.31-1.53), respectively.

Conclusions: Cancer survivors treated with platinum-based chemotherapy experienced modestly increased adverse fertility outcomes. The estimated effects of platinum-based chemotherapy were affected by competing events, suggesting the importance of this analytic approach for interpretations that ultimately inform clinical fertility preservation decisions.

Keywords: Platinum chemotherapy; cancer; infertility; live birth.

Figure 1a:

Modeled 10-year cumulative incidence of live birth for the no cancer group (black), the no chemotherapy group (solid green), and direct effect of no chemotherapy if competing risks were set to be equal to the no cancer group (dashed green). 1b: Modeled 10-year cumulative incidence of live birth for no cancer (black), no chemotherapy (solid green), platinum chemotherapy (red), and direct effect of platinum chemotherapy if competing risks were set to be equal to the no chemotherapy group (dashed red)

Figure 2a:

Modeled 10-year cumulative incidence of infertility for the no cancer group (black), the no chemotherapy group (solid green), and direct effect of no chemotherapy if competing risks were set to be equal to the no cancer group (dashed green). 2b: Modeled 10-year cumulative incidence of infertility for no cancer (black), no chemotherapy (solid green), platinum chemotherapy (red), and direct effect of chemotherapy if competing risks were set to be equal to the no chemotherapy group (dashed red).