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Fertility treatments and pediatric neoplasms of the offspring: results of a population-based cohort with a median follow-up of 10 years

Published:January 29, 2017DOI:https://doi.org/10.1016/j.ajog.2017.01.015

      Objective

      Studies have questioned the long-term health effects of offspring conceived after fertility treatments.

      Methods

      We aimed to evaluate whether an association exists between mode of conception (in vitro fertilization, ovulation induction, or spontaneous pregnancy) and neoplasm risk (both benign and malignant tumors) among the offspring; we observed the offspring for up to 18 years.

      Study Design

      A population-based cohort analysis was performed that compared the risk for neoplasms among children (up to the age of 18 years) based on mode of conception. Neoplasm diagnoses were based on hospital records of the same single tertiary center in the region. All singletons born during from 1991–2013 and discharged alive were included in the study. Offspring with congenital malformations were excluded from the analysis. Kaplan-Meier survival curves were constructed to compare cumulative neoplasms incidence; multivariable survival analyses were used to control for confounders that included gestational age, pregnancy complications, and maternal factors.

      Results

      During the study period, 242,187 newborn infants met the inclusion criteria: 2603 (1.1%) were conceived after in vitro fertilization; 1721 (0.7%) were conceived after ovulation induction treatments, and 237,863 (98.3%) were conceived spontaneously. During the follow-up period (median, 10.55 years), 1498 neoplasms(0.6%) were diagnosed. Incidence density rate for neoplasms was higher among children conceived either after in vitro fertilization (1.5/1000 person years) or ovulation induction treatments (1.0/1000 person years), as compared with naturally conceived children (0.59/1000 person years; Kaplan-Meier log rank, P<.001). The association between in vitro fertilization and total pediatric neoplasms and the association between any fertility treatments and malignancies remained significant; we controlled for confounders such as gestational diabetes mellitus, hypertensive disorders, preterm birth, and maternal age (adjusted hazard ratio, 2.48; 95% confidence interval, 1.71–3.50; and adjusted hazard ratio, 1.96; 95% confidence interval, 1.14–3.36, for all neoplasms and all malignancies, respectively).

      Conclusion

      Children conceived after fertility treatments are at an increased risk for pediatric neoplasms.

      Key words

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      References

        • Boivin J.
        • Bunting L.
        • Collin J.A.
        • Nygren K.G.
        International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care.
        Hum Reprod. 2007; 22: 1506-1512
        • Zegers-Hochschild F.
        • Adamson G.D.
        • de Mouzon J.
        • et al.
        International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology, 2009.
        Fertil Steril. 2009; 92: 1520-1524
      1. Practice Committee of the American Society for Reproductive Medicine.
        Fertil Steril. Jan 2013;
        • De Mouzon J.
        • Goossens V.
        • Bhattacharya S.
        • et al.
        Assisted reproductive technology in Europe, 2006: results generated from European registers by ESHRE.
        Hum Reprod. 2010; 25: 1851-1862
        • Pinborg A.
        • Wennerholm U.B.
        • Romundstad L.B.
        • et al.
        Why do singletons conceived after assisted reproduction technology have adverse perinatal outcome? Systematic review and meta-analysis.
        Hum Reprod Update. 2013; 19: 87-104
        • Kallen B.
        • Finnstrom O.
        • Lindam A.
        • Nilsson E.
        • Nygren K.G.
        • Olausson P.O.
        Cancer risk in children and young adults conceived by in vitro fertilization.
        Pediatrics. 2010; 126: 270-276
        • Messerlian C.
        • MacLagan L.
        • Basso O.
        Infertility and the risk of adverse pregnancy outcomes: a systematic review and meta-analysis.
        Hum Reprod. 2013; 28: 125-137
        • McDonald S.D.
        • Han Z.
        • Mulla S.
        • Murphy K.E.
        • Beyene J.
        • Ohlsson A.
        Preterm birth and low birth weight among in vitro fertilization singletons: a systematic review and meta-analyses.
        Eur J Obstet Gynecol Reprod Biol. 2009; 2: 138-148
        • Lim D.
        • Maher E.R.
        Genomic imprinting syndromes and cancer.
        Adv Genet. 2010; 70: 145-175
        • Pinborg A.
        • Loft A.
        • Romundstad L.B.
        • et al.
        Epigenetics and assisted reproductive technologies.
        Acta Obstet Gynecol Scand. 2016; 95: 10-15
        • Lazaraviciute G.
        • Krauser M.
        • Bhattacharya S.
        • Haggarty P.
        • Bhattacharya S.
        A systematic review and meta analysis of DNA methylation levels and imprinting disorders in children conceived by IVF/ICSI compared with children conceived spontaneously.
        Hum Reprod Update. 2014; 20: 840-852
        • Tobi E.W.
        • Goeman J.J.
        • Monajemi R.
        • et al.
        DNA methylation signatures link prenatal famine exposure to growth and metabolism.
        Nat Commun. 2014; 26: 5592
        • Neelanjana M.
        • Sabaratnam A.
        Malignant conditions in children born after assisted reproductive technology.
        Obstet Gynecol Surv. 2008; 63: 669-676
        • Tournaire M.
        • Devouche E.
        • Espié M.
        • et al.
        Cancer risk in women exposed to diethylstilbestrol in utero.
        Therapie. 2015; 70: 433-441
        • Birnbaum L.S.
        • Fenton S.E.
        Cancer and developmental exposure to endocrine disruptors.
        Environ Health Perspect. 2003; 111: 389-394
        • Jordan S.J.
        • Green A.C.
        • Whiteman D.C.
        • Webb P.M.
        • for the Australian Cancer Study (Ovarian Cancer), and the Australian Ovarian Cancer Study Group
        Risk factors for benign, borderline and invasive mucinous ovarian tumors: epidemiological evidence of a neoplastic continuum?.
        Gynecol Oncol. 2007; 107: 223-230
        • Sadetzki S.
        • Chetrit A.
        • Jarus-Hakak A.
        • et al.
        Cellular phone use and risk of benign and malignant parotid gland tumors: a nationwide case-control study.
        Am J Epidemiol. 2008; 167: 457-467
        • Hansen M.
        • Kurinczuk J.J.
        • Milne E.
        • de Klerk N.
        • Bower C.
        Assisted reproductive technology and birth defects: a systematic review and meta-analysis.
        Hum Reprod Update. 2013; 19: 330-353
        • Van den Belt-Dusebout A.W.
        • Spaan M.
        • Lambalk C.B.
        • et al.
        Ovarian stimulation for in vitro fertilization and long-term risk of breast cancer.
        JAMA. 2016; 316: 300-312
        • Spaan M.
        • van den Belt-Dusebout A.W.
        • Burger C.W.
        • van Leeuwen F.E.
        • OMEGA-project group
        Risk of colorectal cancer after ovarian stimulation for in vitro fertilization.
        Clin Gastroenterol Hepatol. 2016; 4: 729-737.e5
        • Saso S.
        • Louis L.S.
        • Doctor F.
        • et al.
        Does fertility treatment increase the risk of uterine cancer? A meta-analysis.
        Eur J Obstet Gynecol Reprod Biol. 2015; 195: 52-60
        • Hargreave M.
        • Jensen A.
        • Toender A.
        • Andersen K.K.
        • Kjaer S.K.
        Fertility treatment and childhood cancer risk: a systematic meta-analysis.
        Fertil Steril. 2013; 100: 150-161
        • Williams C.
        • Constantine A.
        • Sutcliffe A.
        Systematic review and meta-analysis of cancer risk in children born after assisted reproduction.
        Arch Dis Child. 2011; 96: A6
        • Williams C.L.
        • Bunch K.J.
        • Stiller C.A.
        • et al.
        Cancer risk among children born after assisted conception.
        N Engl J Med. 2013; 369: 1819-1827
        • Brinton L.A.
        • Kruger Kjaer S.
        • Thomsen B.L.
        • et al.
        Childhood tumor risk after treatment with ovulation-stimulating drugs.
        Fertil Steril. 2004; 81: 1083-1091
        • Lerner-Geva L.
        • Toren A.
        • Chetrit A.
        • et al.
        The risk for cancer among children of women who underwent in vitro fertilization.
        Cancer. 2000; 88: 2845-2847
        • Reigstad M.M.
        • Larsen I.K.
        • Myklebust T.Å.
        • et al.
        Risk of cancer in children conceived by assisted reproductive technology.
        Pediatrics. 2016; 137: e20152061
        • Sundh K.J.
        • Henningsen A.A.
        • Källen K.
        • et al.
        Cancer in children and young adults born after assisted reproductive technology: a Nordic cohort study from the Committee of Nordic ART and Safety (CoNARTaS).
        Hum Reprod. 2014; 29: 2050-2057
        • Hargreave M.
        • Jensen A.
        • Nielsen T.S.
        • et al.
        Maternal use of fertility drugs and risk of cancer in children: a nationwide population-based cohort study in Denmark.
        Int J Cancer. 2015; 136: 1931-1939
        • Petridou E.T.
        • Sergentanis T.N.
        • Panagopoulou P.
        • et al.
        In vitro fertilization and risk of childhood leukemia in Greece and Sweden.
        Pediatr Blood Cancer. 2012; 58: 930-936
        • Bruinsma F.
        • Venn A.
        • Lancaster P.
        • Speirs A.
        • Healy D.
        Incidence of cancer in children born after in-vitro fertilization.
        Hum Reprod. 2000; 15: 604-607