The risk of female malignancies after fertility treatments: a cohort study with 25-year follow-up

J Cancer Res Clin Oncol. 2016 Jan;142(1):287-93. doi: 10.1007/s00432-015-2035-x. Epub 2015 Sep 4.


Objective: To investigate whether an association exists between a history of fertility treatments and future risk of female malignancies.

Study design: A population-based study compared the incidence of long-term female malignancies in a cohort of women with and without a history of fertility treatments including in vitro fertilization (IVF) and ovulation induction (OI). Deliveries occurred between the years 1988-2013, with a mean follow-up duration of 12 years. Excluded from the study were women with known genetic predisposition for malignancies or known malignancies prior to the index pregnancy. Female malignancies were divided into specific types including ovarian, uterine, breast and cervix. Kaplan-Meier survival curve was used to estimate cumulative incidence of malignancies. Cox proportional hazard models were used to estimate the adjusted hazard ratios (HRs) for female malignancy.

Results: During the study period, 106,031 women met the inclusion criteria; 4.1 % (n = 4363) occurred in patients following fertility treatments. During the follow-up period, patients with a history of IVF treatments had a significantly increased risk of being diagnosed with ovarian and uterine cancer as compared to patients after OI and patients with no history of fertility treatments. Cox proportional hazard models were constructed for ovarian and uterine cancer separately, controlling for confounders such as maternal age and obesity. A history of IVF treatment remained independently associated with ovarian and uterine cancer (adjusted HR 3.9; 95 % CI 1.2-12.6; P = 0.022 and adjusted HR 4.6; 95 % CI 1.4-14.9; P = 0.011; respectively).

Conclusion: IVF treatments pose a significant risk of subsequent long-term ovarian and uterine cancer.

Keywords: Female malignancies; In vitro fertilization; Ovarian cancer; Ovulation induction; Uterine cancer.

MeSH terms

  • Adult
  • Breast Neoplasms / chemically induced*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / epidemiology
  • Cohort Studies
  • Female
  • Fertility / drug effects*
  • Fertility Agents, Female / adverse effects*
  • Fertilization in Vitro / adverse effects*
  • Follow-Up Studies
  • Genital Neoplasms, Female / chemically induced*
  • Genital Neoplasms, Female / diagnosis
  • Genital Neoplasms, Female / epidemiology
  • Hospitalization / statistics & numerical data*
  • Humans
  • Israel / epidemiology
  • Neoplasm Staging
  • Ovulation Induction / adverse effects*
  • Pregnancy
  • Prevalence
  • Prognosis
  • Risk Factors
  • Time Factors


  • Fertility Agents, Female