Importance: In vitro fertilization (IVF) is associated with birth defects and imprinting disorders. Because these conditions are associated with an increased risk of childhood cancer, many of which originate in utero, descriptions of cancers among children conceived via IVF are imperative. Objective: To compare the incidence of childhood cancers among children conceived in vitro with those conceived naturally. Design, Setting, and Participants: A retrospective, population-based cohort study linking cycles reported to the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System from January 1, 2004, to December 31, 2012, that resulted in live births from September 1, 2004, to December 31, 2013, to the birth and cancer registries of 14 states, comprising 66% of United States births and 75% of IVF-conceived births, with follow-up from September 1, 2004, to December 31, 2014. The study included 275686 children conceived via IVF and a cohort of 2266847 children, in which 10 births were randomly selected for each IVF birth. Statistical analysis was performed from April 1, 2017, to October 1, 2018. Exposure: In vitro fertilization. Main Outcomes and Measures: Cancer diagnosed in the first decade of life. Results: A total of 321 cancers were detected among the children conceived via IVF (49.1% girls and 50.9% boys; mean [SD] age, 4.6 [2.5] years for singleton births and 5.9 [2.4] years for multiple births), and a total of 2042 cancers were detected among the children not conceived via IVF (49.2% girls and 50.8% boys; mean [SD] age, 6.1 [2.6] years for singleton births and 4.7 [2.6] years for multiple births). The overall cancer rate (per 1000000 person-years) was 251.9 for the IVF group and 192.7 for the non-IVF group (hazard ratio, 1.17; 95% CI, 1.00-1.36). The rate of hepatic tumors was higher among the IVF group than the non-IVF group (hepatic tumor rate: 18.1 vs 5.7; hazard ratio, 2.46; 95% CI, 1.29-4.70); the rates of other cancers did not differ between the 2 groups. There were no associations with specific IVF treatment modalities or indication for IVF. Conclusions and Relevance: This study found a small association of IVF with overall cancers of early childhood, but it did observe an increased rate of embryonal cancers, particularly hepatic tumors, that could not be attributed to IVF rather than to underlying infertility. Continued follow-up for cancer occurrence among children conceived via IVF is warranted.
Bibliographical noteFunding Information:
Additional Contributions: We thank the Society for Assisted Reproductive Technology and all of its members for providing clinical information to the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System database for use by patients and researchers. Without the efforts of our members, this research would not have been possible. We also wish to acknowledge the help and expertise of each agency of participating states as follows. All analyses, interpretations, and conclusions are the authors’ and not those of data contributors. California: California birth data were supplied by the California Department of Public Health Office of Health Information and Research (CDPH/HIRS). California Cancer Registry data were obtained through the California Cancer Reporting and Epidemiologic Surveillance (CalCARES) Program, Institute for Population Health Improvement, University of California Davis Health. Technical descriptions of the data are consistent with those provided by CalCARES/HIRS. Colorado: Colorado birth and cancer data were supplied by the Colorado Department of Public Health and Environment. Connecticut: Connecticut birth and cancer data were supplied by the Office of Vital Records and the Connecticut Tumor Registry at the Connecticut Department of Public Health (DPH). This study was approved by the DPH Health Investigation Committee. Certain data used in this study were obtained from the DPH. Florida: Florida birth and cancer data were supplied by the Florida Department of Health. Illinois: Illinois birth and cancer data were provided by the Illinois DPH, Springfield, Illinois. Massachusetts: Massachusetts birth and cancer data were supplied by the Massachusetts Pregnancy to Early Life Longitudinal Data System and the Massachusetts Cancer Registry, Massachusetts DPH. Michigan: Michigan birth and cancer data were supplied by the Division for Vital Records and Health Statistics, Michigan Department of Health and Human Services. New York: New York state birth data were supplied by the Vital Statistics Unit, Bureau of Health Informatics, New York State Department of Health. Birth data for New York City were derived from data provided by the Bureau of Vital Statistics, New York City Department of Health and Mental Hygiene to the state. Cancer data were supplied by the New York State Cancer Registry, New York State Department of Health. New Jersey: New Jersey birth and cancer data were supplied by the Bureau of Vital Statistics and Registration, New Jersey Department of Health, and the New Jersey State Cancer Registry, The Cancer Institute of New Jersey, with linkage performed by Xiaoling Niu, MS. Cancer Epidemiology Services, including the New Jersey State Cancer Registry, receives support from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute under contract HHSN 261201300021I and control No. N01PC-2013-00021, the National Program of Cancer Registries, Centers for Disease Control and Prevention under cooperative agreement 5U58DP003931-02, the State of New Jersey, and the Rutgers Cancer Institute of New Jersey. Linkage was conducted by Ji Lie, MPH. North Carolina: Birth and cancer data were supplied by the Vital Statistics team and the Central Cancer Registry Branch of the State Center for Health Statistics. Linkage was conducted by Gary Y. Leung, PhD. We thank Dr Leung for sharing his linkage programming with other study states. Ohio: Ohio birth data were supplied by the Bureau of Vital Statistics, Ohio Department of Health. Ohio cancer data were supplied by the Ohio Cancer Incidence Surveillance System at the Ohio Department of Health, a cancer registry partially supported by the National Program of Cancer Registries at the Centers for Disease Control and Prevention. Use of these data does not imply that the Ohio Department of Health or Centers for Disease Control and Prevention agrees or disagrees with the analyses, interpretations, or conclusions in this publication. Pennsylvania: Pennsylvania birth and cancer data were supplied by the Bureau of Health Statistics & Registries, Pennsylvania Department of Health, Harrisburg, Pennsylvania. Texas: Texas birth and cancer data were supplied by the Center for Health Statistics and the Texas Cancer Registry of the Texas Department of State Health Services. Virginia: Virginia birth and cancer data were supplied by the Virginia Department of Health.
Author Contributions: Drs Brown and Luke had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Spector, Brown, Luke. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Spector, Brown, Letterie, Luke. Critical revision of the manuscript for important intellectual content: Brown, Wantman, Letterie, Toner, Doody, Ginsburg, Williams, Koch, Schymura, Luke. Statistical analysis: Spector, Brown, Luke. Obtained funding: Spector, Luke. Administrative, technical, or material support: Spector, Wantman, Letterie, Toner, Williams, Koch, Schymura, Luke. Supervision: Spector, Letterie. Conflict of Interest Disclosures: Dr Spector reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Brown reported receiving a grant from the National Institutes of Health. Dr Wantman reported serving as a contractor for the Society for Assisted Reproductive Technology outside the submitted work. Dr Luke reported receiving personal fees from the Society for Assisted Reproductive Technology outside the submitted work and reported receiving a grant from the National Institutes of Health. No other disclosures were reported.
© 2019 American Medical Association. All rights reserved.