The risk of female malignancies after fertility treatments: a cohort study with 25-year follow-up.
OBJECTIVE
To investigate whether an association exists between a history of fertility treatments and future risk of female malignancies.


METHODS
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).


CONCLUSIONS
IVF treatments pose a significant risk of subsequent long-term ovarian and uterine cancer.
Department of Obstetrics and Gynecology, Faculty of Health Sciences, Soroka University Medical Center, Ben-Gurion University of the Negev, POB 151, 84101, Beersheba, Israel. kessousr@bgu.ac.il.
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Kessous
Faculty of Health Sciences, Soroka University Medical Center, Clalit Health Services (Southern District), Ben-Gurion University of the Negev, Beersheba, Israel.
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Davidson
Department of Obstetrics and Gynecology, Faculty of Health Sciences, Soroka University Medical Center, Ben-Gurion University of the Negev, POB 151, 84101, Beersheba, Israel.
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Meirovitz
Department of Public Health, Ben-Gurion University of the Negev, Beersheba, Israel.
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Sergienko
Department of Obstetrics and Gynecology, Faculty of Health Sciences, Soroka University Medical Center, Ben-Gurion University of the Negev, POB 151, 84101, Beersheba, Israel. sheiner@bgu.ac.il.
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E
Sheiner
D000328:Adult; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005300:Fertility Agents, Female / Q000009:adverse effects*; D005307:Fertilization in Vitro / Q000009:adverse effects*; D005500:Follow-Up Studies; D005833:Genital Neoplasms, Female / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007557:Israel / Q000453:epidemiology; D009367:Neoplasm Staging; D010062:Ovulation Induction / Q000009:adverse effects*; D011247:Pregnancy; D015995:Prevalence; D011379:Prognosis; D012307:Risk Factors; D013997:Time Factors
D005300:Fertility Agents, Female
Female malignancies; In vitro fertilization; Ovarian cancer; Ovulation induction; Uterine cancer