In vitro fertilization and risk of breast and gynecologic cancers: A retrospective cohort study within the Israeli Maccabi Healthcare Services

Objective: To assess long-term cancer risks associated with in vitro fertilization (IVF). Design: Record-linkage study. Setting: Health maintenance organization in Israel. Patient(s): A total of 87,403 women evaluated and/or treated for infertility on or after September 25, 1994, who were followed for cancer development through June 22, 2011: 522 breast, 41 endometrial, 45 ovarian, 311 in situ cervical, and 32 invasive cervical cancers were identified. Intervention(s): None. Main Outcome Measure(s): Hazard ratios (HRs) for specific cancers. Result(s): We found no significant relationships of IVF exposures to the risks of breast, endometrial, or ovarian cancers. However, compared with women with no fertility treatment, the HR for ovarian cancer associated with IVF was 1.58 (95% confidence interval [CI] 0.75-3.29), with higher risk among those receiving four or more cycles (HR 1.78, 95% CI 0.76-4.13). There was also a nonsignificantly elevated risk for endometrial cancer among women who received 1-3 IVF cycles (HR 1.94, 95% CI 0.73-5.12), but additional cycles were associated with less risk. In contrast, the risk of in situ cervical cancer was significantly reduced and invasive cervical cancer nonsignificantly reduced among women receiving IVF as well as other fertility treatments. Conclusion(s): Our results regarding long-term effects were largely reassuring, but women receiving IVF should continue to be monitored given that the procedures involve potent ovulation stimulators and repeated ovarian punctures.