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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