© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com Human Reproduction, Vol.34, No.1, pp. 2290–2296, 2019 Advance Access Publication on October 10, 2019 doi:10.1093/humrep/dez165 ORIGINAL ARTICLE Reproductive epidemiology Assisted reproductive technology treatment and risk of ovarian cancer—a nationwide population-based cohort study D. Vassard 1, *, L. Schmidt 1 , C.H. Glazer 2 , J. Lyng Forman 3 , M. Kamper-Jørgensen 4 , and A. Pinborg 5 1 Department of Public Health, Section of Social Medicine, University of Copenhagen, DK-1014 Copenhagen K, Denmark 2 Department of Occupational and Environmental Medicine, Bispebjerg University Hospital, DK-2400 Copenhagen NV, Denmark 3 Department of Public Health, Section of Biostatistics, University of Copenhagen, DK-1014 Copenhagen K, Denmark 4 Department of Public Health, Section of Epidemiology, University of Copenhagen, DK-1014 Copenhagen K, Denmark 5 Fertility Clinic, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen Ø, Denmark *Correspondence address. Department of Public Health, Section of Social Medicine, University of Copenhagen, Øster Farimagsgade 5, PO Box 2099, DK-1014 Copenhagen K, Denmark. Tel: +45-42-40-05-33; E-mail: diva@sund.ku.dk Submitted on April 4, 2019; resubmitted on June 17, 2019; editorial decision on July 17, 2019 STUDY QUESTION: Does hormone stimulation during assisted reproductive technology (ART) treatment increase the risk of ovarian cancer? SUMMARY ANSWER: No increased risk of ovarian cancer was found among ART-treated women, with the exception of ART-treated women with endometriosis. WHAT IS KNOWN ALREADY: Previous studies on the association between ovarian stimulation during ART and ovarian cancer have shown conflicting results. The risk of ovarian cancer varies according to the cause of infertility, and only a few studies on ART treatment and risk of ovarian cancer have had sufcient data to address this issue. Endometriosis has been linked to an increased risk of ovarian cancer. STUDY DESIGN, SIZE, DURATION: Women undergoing ART treatment during 1994–2015 were registered in the Danish IVF register. Data were linked with data from the Danish Cancer Register and socio-demographic population registers using an individual person identification number assigned to people residing in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women undergoing ART treatment were age-matched with a random sample of the female background population and followed for up to 22 years. After relevant exclusions, the population consisted of 58472 ART- treated women and 625 330 untreated women, all with no previous malignancies. Ovarian cancer risk was assessed using multivariable cox regression analyses with adjustment for educational level, marital status, parity and treatment year. Results are shown as hazard ratios (HRs) with corresponding CIs. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 393 (0.06%) women were diagnosed with ovarian cancer during follow-up (mean 9.7 years). Women treated with ART had an increased risk of ovarian cancer (HR 1.20, 95% CI 1.10–1.31), which diminished over time. The increased risk was apparent among women with female factor infertility (HR 1.36, 95% CI 1.25–1.48), whereas no female factor infertility was associated with a lower risk (HR 0.87, 95% CI 0.76–1.00). The risk was increased among women with endometriosis (HR 3.78, 95% CI 2.45–5.84), whereas no increased risk was found among ART-treated women with polycystic ovary syndrome, other female causes of infertility and unexplained infertility. LIMITATIONS, REASONS FOR CAUTION: The association between ART treatment and ovarian cancer is likely influenced by increased detection due to multiple ultrasound scans during ART treatment. WIDER IMPLICATIONS OF THE FINDINGS: Undergoing ART treatment without the presence of endometriosis was not associated with an increased risk of ovarian cancer, which is reassuring. Whether ART treatment increases the risk of ovarian cancer among women with endometriosis needs further investigation. Downloaded from https://academic.oup.com/humrep/article/34/11/2290/5584449 by guest on 11 November 2022