Assisted reproductive technology treatment and risk of ovarian cancer—a nationwide population-based cohort study
Authors: Vassard D , Schmidt L , Glazer C H , Lyng Forman J , Kamper-Jørgensen M , Pinborg A 
Published: July 2019

Abstract

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 sufficient 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 58 472 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.

STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by a PhD grant to D.V. from the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Funding for establishing the Danish National ART-couple II cohort was achieved from Ebba Rosa Hansen Foundation. The funders had no influence on data collection, analyses or results presented. The authors have no conflicts of interest to declare.