Risk of cancer after use of fertility drugs with in-vitro fertilisation

Lancet. 1999 Nov 6;354(9190):1586-90. doi: 10.1016/S0140-6736(99)05203-4.


Background: We investigated the incidence of invasive cancer of the breast, ovary, and uterus in a cohort of patients who had undergone in-vitro-fertilisation (IVF) treatment and examined whether cause of infertility or exposure to fertility drugs to induce superovulation was associated with an increased cancer risk.

Method: Ten Australian IVF clinics provided data for women who had been referred for IVF before Jan 1, 1994. The frequencies of invasive breast, ovarian, and uterine cancer were assessed by record linkage to population-based cancer registries and the national death index. The observed number of cancers was compared with the expected number calculated by application of age-standardised general-population cancer rates to the cohort. Standardised incidence ratios (SIRs) were derived from the ratio of observed to expected cases.

Findings: The cohort consisted of 29,700 women: 20,656 were exposed to fertility drugs and 9044 were not. 143 breast cancers, 13 ovarian cancers, and 12 cancers of the uterus occurred among these women. For breast and ovarian cancer the incidence was no greater than expected (SIR 0.91 [95% CI 0.74-1.13] for breast cancer and 0.88 [0.42-1.84] for ovarian cancer in the exposed group and 0.95 [0.73-1.23] for breast cancer and 1.16 [0.52-2.59] for ovarian cancer in the unexposed group). The incidence of uterine cancer was no higher than expected in the exposed group (1.09 [0.45-2.61]) but was significantly higher in the unexposed group (2.47 [1.18-5.18]). Women with unexplained infertility had significantly more cancers of the ovary and uterus than expected (2.64 [1.10-6.35] and 4.59 [1.91-11.0], whole cohort). Analysis of cancer incidence within 12 months of exposure to fertility drugs with IVF showed that incidence was significantly higher than expected for breast and uterine cancer (1.96 [1.22-3.15] and 4.96 [1.24-19.8]).

Interpretation: Women who have been exposed to fertility drugs with IVF seem to have a transient increase in the risk of having breast or uterine cancer diagnosed in the first year after treatment, though the incidence overall is no greater than expected. Unexplained infertility was associated with an increased risk of a diagnosis of ovarian or uterine cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Australia / epidemiology
  • Breast Neoplasms / chemically induced*
  • Breast Neoplasms / epidemiology
  • Cohort Studies
  • Data Interpretation, Statistical
  • Female
  • Fertility Agents / adverse effects*
  • Fertilization in Vitro / adverse effects*
  • Humans
  • Incidence
  • Infertility, Female / drug therapy
  • Middle Aged
  • Ovarian Neoplasms / chemically induced*
  • Ovarian Neoplasms / epidemiology
  • Ovulation Induction / adverse effects*
  • Population Surveillance
  • Risk Factors
  • Uterine Neoplasms / chemically induced*
  • Uterine Neoplasms / epidemiology


  • Fertility Agents