Cancer risk in children, adolescents, and young adults conceived by ART in 1983–2011
Author:
Spaan Mandy1234ORCID, Pontesilli Martina3, van den Belt-Dusebout Alexandra W1, Burger Curt W5, van den Heuvel-Eibrink Marry M6, Ravelli Anita C J347, Goddijn Mariëtte8ORCID, Lambalk Cornelis B4910ORCID, Roseboom Tessa J234, van Leeuwen Flora E1ORCID, Kostelijk E H, Schats R, Kortman M, Broekmans F J M, Laven J S E, Moolenaar L M, van Santbrink E J P, Rijnders P M, van der Westerlaken L A J, Cohlen B J, Curfs M H J M, Braat D D M, Ramos L, Smeenk J M J, Consten D, Cantineau A E P, Goddijn M, van Golde R J T, Dumoulin J C M, van Rumste M M E, van Inzen W, Hamilton C J C M, Meeuwissen P A M,
Affiliation:
1. Department of Epidemiology, Netherlands Cancer Institute , Amsterdam, The Netherlands 2. Department of Epidemiology and Data Science, Amsterdam UMC Location University of Amsterdam , Amsterdam, The Netherlands 3. Department of Obstetrics and Gynecology, Amsterdam UMC Location University of Amsterdam , Amsterdam, The Netherlands 4. Amsterdam Reproduction and Development , Amsterdam, The Netherlands 5. Department of Gynecologic Oncology, Erasmus Medical Center , Rotterdam, The Netherlands 6. Princess Máxima Center for Pediatric Oncology , Utrecht, The Netherlands 7. Department of Medical Informatics, Amsterdam UMC Location University of Amsterdam , Amsterdam, The Netherlands 8. Centre for Reproductive Medicine, Amsterdam UMC Location University of Amsterdam , Amsterdam, The Netherlands 9. Centre for Reproductive Medicine, Amsterdam UMC Location Vrije Universiteit Amsterdam , Amsterdam, The Netherlands 10. Department of Obstetrics and Gynecology, Amsterdam UMC Location Vrije Universiteit Amsterdam , Amsterdam, The Netherlands
Abstract
Abstract
STUDY QUESTION
Do children, adolescents, and young adults born after ART, including IVF, ICSI and frozen–thawed embryo transfer (FET), have an increased risk of cancer compared with children born to subfertile couples not conceived by ART and children from the general population?
SUMMARY ANSWER
After a median follow-up of 18 years, the overall cancer risk was not increased in children conceived by ART, but a slight risk increase was observed in children conceived after ICSI.
WHAT IS KNOWN ALREADY
There is growing evidence that ART procedures could perturb epigenetic processes during the pre-implantation period and influence long-term health. Recent studies showed (non-)significantly increased cancer risks after ICSI and FET, but not after IVF.
STUDY DESIGN, SIZE, DURATION
A nationwide historical cohort study with prospective follow-up was carried out, including all live-born offspring from women treated with ART between 1983 and 2011 and subfertile women not treated with ART in one of the 13 Dutch IVF clinics and two fertility centers.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Children were identified through the mothers’ records in the Personal Records Database. Information on the conception method of each child was collected through the mother’s medical record. In total, the cohort comprises 89 249 live-born children of subfertile couples, of whom 51 417 were conceived using ART and 37 832 were not (i.e. conceived naturally, through ovulation induction, or after IUI). Cancer incidence was ascertained through linkage with the Netherlands Cancer Registry for the period 1989–2019. Cancer risk in children conceived using ART was compared with risk in children born to subfertile couples but not conceived by ART (hazard ratio (HR)) and children from the general population (standardized incidence ratios (SIRs)).
MAIN RESULTS AND THE ROLE OF CHANCE
In total, 358 cancers were observed after a median follow-up of 18 years. Overall cancer risk was not increased in children conceived using ART, when compared with the general population (SIR = 0.96, 95% CI = 0.81–1.12) or with children from subfertile couples not conceived by ART (HR = 1.06, 95% CI = 0.84–1.33). Compared with children from subfertile couples not conceived by ART, the use of IVF or FET was not associated with increased cancer risk, but ICSI was associated with a slight risk increase (HR = 1.58, 95% CI = 1.08–2.31). Risk of cancer after ART did not increase at older ages (≥18 years, HR = 1.26, 95% CI = 0.88–1.81) compared to cancer risk in children not conceived by ART.
LIMITATIONS, REASONS FOR CAUTION
The observed increased risk among children conceived using ICSI must be interpreted with caution owing to the small number of cases.
WIDER IMPLICATIONS OF THE FINDINGS
After a median follow-up of 18 years, children conceived using ART do not have an increased overall cancer risk. Many large studies with prolonged follow-up are needed to investigate cancer risk in (young) adults conceived by different types of ART. In addition, international pooling of studies is recommended to provide sufficient power to study risk of specific cancer sites after ART.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by The Dutch Cancer Society (NKI 2006-3631) that funded the OMEGA-women’s cohort, Children Cancer Free (KIKA; 147) that funded the OMEGA-I–II offspring cohort. The OMEGA-III offspring cohort was supported by a Postdoc Stipend of Amsterdam Reproduction & Development, and the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award Number R01HD088393. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no competing interests.
TRIAL REGISTRATION NUMBER
N/A.
Funder
The Dutch Cancer Society OMEGA-women’s cohort, Children Cancer Free
Publisher
Oxford University Press (OUP)
Subject
Industrial and Manufacturing Engineering,Environmental Engineering
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