JMIR Publications

ABSTRACT

Background:

The relationship between assisted reproductive technology (ART) and childhood cancer risk has been a topic of debate for several decades. Previous meta-analyses have not appropriately considered the impact of infertility, and the present study fills this gap.

Objective:

This study aimed to assess the relative risk (RR) of childhood cancer in infertile populations with different types of ART versus non-ART offspring.

Methods:

The literature review was conducted through PubMed, EMBASE, Cochrane, and Web of Science with a cut-off date of July 10, 2024. This study was registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) 202470119. Pooled estimates with corresponding 95% confidence intervals (CIs) were calculated and compared using random effects models.

Results:

A total of 18 studies were included, including 14 cohort studies and four case-control studies. The quality of the included studies was moderate or high. Specific types of ART include in vitro fertilization (IVF), Intracytoplasmic Sperm Injection (ICSI), frozen embryo transfer (FET), and fresh embryo transfer (ET). Compared with non-ART conception (subfertility), ART conception was not significantly associated with the risk of childhood overall cancer (RR, 0.95; 95% CI, 0.71-1.27). Meanwhile, separate analyses of IVF (RR, 0.86; 95% CI, 0.59-1.25) and ICSI (RR, 0.76; 95% CI, 0.26-2.20) showed similar results. Further analysis revealed no significant differences in other childhood-specific cancers, including leukemia (RR, 0.99; 95% CI, 0.79-1.24), lymphoma (RR, 1.22; 95% CI, 0.64-2.34), brain cancer (RR, 1.22; 95% CI, 0.73-2.05), embryonal tumors (RR, 1.00; 95% CI, 0.63-1.58), retinoblastoma ( RR, 1.30; 95% CI, 0.73-2.31), and neuroblastoma (RR, 1.02; 95% CI, 0.48-2.16). Moreover, Compared to non-ART conception(subfertility), neither FET nor fresh-ET conception was significantly associated with the risk of childhood overall cancer (RR FET, 0.98; 95% CI, 0.54-1.76; RR ET, 0.75; 95% CI, 0.49-1.15). Similar results were observed in a head-to-head comparison of FET versus fresh-ET (RR, 0.99; 95% CI, 0.86-1.14).

Conclusions:

Overall, there is no strong evidence that infertile parents who conceive using assisted reproductive technology have a significantly increased risk of childhood cancer in their offspring. Furthermore, we advocate additional research, particularly targeting individuals who are subfertility yet conceive naturally, to serve as a reference. Clinical Trial: INPLASY 202470119.