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Grand Rounds

Are Children Born After use of ART and Fertility Drugs at a Higher Risk of Childhood Cancer?

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BACKGROUND AND PURPOSE:

  • Associations between ART, fertility drugs, and cancer in offspring remain uncertain
    • Where associations have been found, it is unclear if results are a result of the treatment plan or underlying infertility 
  • Hargreave et al. (JAMA, 2019) investigated the association between different types of fertility treatments and cancer risk in children

METHODS:

  • Retrospective cohort study
  • Data sources
    • Danish population-based registries and Danish Infertility Cohort (individual record linkage)
  • Participants
    • Children born between 1996 to 2012 (linked with parental information)
  • Exposures: Maternal fertility treatment during the index pregnancy including 
    • Fertility drugs: Clomiphene | Gonadotropins | GnRH analogs | Human chorionic gonadotropin | Progesterone | Estrogen
    • ART: IVF | ICSI | Frozen embryo transfer
  • Study design
    • Cohort follow up through to 2015
    • Each exposure was examined separately and compared with children born to fertile women
  • Primary outcomes
    • Hazard ratio (HR) and incidence rate differences for childhood cancer

RESULTS:

  • 1,085,172 children included
    • 2,217 children were diagnosed with cancer
    • 12.2 million person-years of follow-up (mean, 11.3 years)
  • Use of frozen embryo transfer was associated with an elevated risk of childhood cancer (14 cancers) based on the following incidence rates of childhood cancer
    • Fertile women (control): 17.5 per 100,000
    • Frozen embryo: 44.4 per 100,000 
    • HR 2.43 (95% CI, 1.44 to 4.11) | Incidence rate difference 26.9 (95% CI, 2.8 to 51.0) per 100,000
  • Elevated risk for frozen embryo was mainly due to an increased risk of
    • Leukemia (5 cancer cases)
      • Incidence rate, 14.4 per 100,000 | HR 2.87 (95% CI, 1.19 to 6.93) | Incidence rate difference 10.1 (95% CI, −4.0 to 24.2) per 100,000)
    • Sympathetic nervous system tumors (<5 cases)
      • HR 7.82 (95% CI, 2.47 to 24.70)
  • There were no statistically significant associations with the use of the other types of fertility treatment examined

CONCLUSION:

  • Authors acknowledge important limitations including
    • Rarity of childhood cancer cases
    • Confounding was assessed, however not all confounders can be accounted for and one important confounder – infertility diagnosis – was not available
  • Slight increased risk of childhood cancer associated with use of frozen embryo transfer
  • No other associations found between childhood cancer and the use of other types of fertility treatment examined

Learn More – Primary Sources:

Association Between Fertility Treatment and Cancer Risk in Children

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Related ObG Topics:

Children Conceived by ART and Cancer Risk: Results from the OMEGA Offspring Cohort
Does Assisted Reproduction Increase Risk of Breast, Ovarian, Uterine Cancer?
Are Adverse Birth Outcomes Following Medically Assisted Reproduction a Result of Treatment or Underlying Issues?

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