Childhood cancer risk after assisted reproduction

A large nationwide prospective cohort study (Danish registry data, n=1,086,136 live-born children, 1996–2012 with follow-up through 2023) evaluating childhood cancer incidence following assisted reproductive technology (ART) (1):

• overall finding: conception via ART is associated with a modest relative increase in childhood cancer risk compared to natural conception, though the absolute risk remains very low
• modality-specific risk: elevated risks were primarily driven by frozen embryo transfer (FET) and intracytoplasmic sperm injection (ICSI); standard in vitro fertilisation (IVF) showed no statistically significant increase in risk

Key Study Findings

Overall ART vs non-ART risk

• overall incidence rate: 23.6 per 100,000 person-years in the ART group vs 18.3 per 100,000 person-years in the non-ART group
• overall hazard ratio: HR 1.26 (95% CI 1.07 to 1.48)
• absolute risk: remains low across all treatment groups despite relative increases

Risk stratification by ART modality

• frozen embryo transfer (FET):
  • incidence rate: 41.1 per 100,000 person-years
  • hazard ratio: HR 2.18 (95% CI 1.45 to 3.29) compared to non-ART
• intracytoplasmic sperm injection (ICSI):
  • incidence rate: 27.9 per 100,000 person-years
  • hazard ratio: HR 1.48 (95% CI 1.16 to 1.89) compared to non-ART
• standard in vitro fertilisation (IVF):
  • incidence rate: 18.5 per 100,000 person-years
  • hazard ratio: HR 1.01 (95% CI 0.79 to 1.28) compared to non-ART (no significant increase in risk)

Specific childhood cancer subtypes

• frozen embryo transfer (FET) associations:
  • leukaemia: HR 2.36 (95% CI 1.06 to 5.28; incidence rate 11.1 per 100,000)
  • lymphomas: HR 3.03 (95% CI 1.13 to 8.12)
  • soft tissue sarcomas: HR 7.63 (95% CI 2.82 to 20.62)
• intracytoplasmic sperm injection (ICSI) associations:
  • lymphomas: HR 1.94 (95% CI 1.07 to 3.54; incidence rate 4.6 per 100,000)
  • soft tissue sarcomas: HR 3.28 (95% CI 1.54 to 7.00; incidence rate 3.3 per 100,000)
  • central nervous system (CNS) neoplasms: HR 1.63 (95% CI 1.04 to 2.57; incidence rate 8.2 per 100,000)
• standard IVF: no statistically significant associations observed for any specific cancer subtype

Clinical practice implications and etiology

• potential underlying cause: when researchers compared children conceived via FET or ICSI against children born to women with untreated subfertility or those conceived via standard IVF, the increased cancer risk remained unchanged; this indicates that the higher risk is likely linked to specific laboratory techniques (such as freezing embryos or injecting sperm directly into the egg) rather than parental fertility problems
• patient communication and counselling: clinicians should reassure prospective parents undergoing fertility treatment that while relative risks are elevated for certain specific modalities (FET and ICSI), the overall absolute risk of a child developing cancer remains extremely low

Reference

1. Mose K, Kjaer SK, Jensen A, et al. Childhood Cancer Risk After Assisted Reproductive Technology. JAMA. 2026 Oct 21:e2618862. doi: 10.1001/jama.2026.18862