Abstract PR05: Utilizing electronic fertility clinic records and registry linkage to establish a retrospective population-based cohort study to evaluate the association between in vitro fertilization (IVF) and subsequent cancer risk in women
Authors: Trabert Britton , Hirsh-Yechezkel Galit , Farhi Adel , Zaslavsky Inna , Elizur Shai E. , Kahana Arik , Orvieto Raoul , Holzer Hananel , Calderon Ilan , Friedler Shevach , Shalom-Paz Einat , Ron-El Raphael , Raziel Arie , Brinton Louise A. , Lerner-Geva Liat 
Published: June 2022

Abstract
Background: Since the introduction of in vitro fertilization (IVF) in 1978, the use of assisted reproduction technology (ART) has increased annually with an estimated 240,000 ART-conceived children born each year worldwide. Despite its widespread use, the impact on subsequent maternal and child health is not well understood. Specifically, cancer risk in women receiving IVF treatment has not been adequately evaluated, in part due to the complex nature of the research question and the need for large numbers of exposed women with long follow-up to evaluate rare cancer outcomes.
Methods: To address this research question, we designed a country-wide retrospective medical record linkage study that utilizes electronic records from all IVF units in operation in Israel between 1997 and 2014. Linkage to cancer registry is facilitated via unique national identification numbers. We selected Israel for this study because it has the highest rate of ART/IVF exposure in the world, with 24 IVF units in the country that perform more than 45,000 ART cycles annually. Fertility treatment is fully covered by national health insurance with no restriction on the number of cycles or type of procedure, thus reducing potential selection issues related to access to care that may exist in other populations. We are currently collecting medically documented and detailed exposure information from the IVF units, including causes of infertility, hormonal treatments, procedures (e.g., IVF), and important covariates (e.g., parity, body mass index, etc.). To date we have collected exposure and covariate information from 18,470 women receiving treatment at 9 IVF clinics and conducted an interim linkage with the cancer registry through December 2014, providing on average 15 years of follow-up. We calculated standardized incidence ratios (SIRs) for all cancers combined and separately for breast cancer and further evaluated breast cancer risk with number of treatment cycles using Cox proportional hazards regression.
Results: Based on interim registry linkage we identified 611 invasive cancers including 272 breast cancers among 18,470 women with more than 236,000 woman-years of follow-up. The incidence of cancer [SIR (95% confidence interval (CI)): 0.96 (0.88-1.04)] or breast cancer [0.98 (0.87-1.11)] was not elevated compared to the general population. Further, breast cancer risk was not associated with increased number of IVF treatment cycles [adjusted hazard rate ratio (RR) (95% CI) per IVF cycle: 1.01 (0.96-1.09)].
Conclusions: With this data we have demonstrated the feasibility of linking IVF clinic data with the nationwide cancer registry to evaluate cancer risk. In our preliminary analyses, IVF treatment was not associated with risk of incident invasive cancer or breast cancer. Given that continued linkage with the cancer registry is feasible, we will be able to monitor long-term cancer risks associated with IVF treatment using the enumerated data.
This abstract is also being presented as Poster A15.
Citation Format: Britton Trabert, Galit Hirsh-Yechezkel, Adel Farhi, Inna Zaslavsky, Shai E. Elizur, Arik Kahana, Raoul Orvieto, Hananel Holzer, Ilan Calderon, Shevach Friedler, Einat Shalom-Paz, Raphael Ron-El, Arie Raziel, Louise A. Brinton, Liat Lerner-Geva. Utilizing electronic fertility clinic records and registry linkage to establish a retrospective population-based cohort study to evaluate the association between in vitro fertilization (IVF) and subsequent cancer risk in women [abstract]. In: Proceedings of the AACR Special Conference on Modernizing Population Sciences in the Digital Age; 2019 Feb 19-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(9 Suppl):Abstract nr PR05.