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

Yang

et al. 2019

Intl Journal of Cancer

Prior studies on the association between fertility treatment and childhood cancer risk have generated inconsistent results. We performed a systematic review and meta‐analysis of observation studies to summarize the evidence regarding the relation of fertility treatment with childhood cancer risk. A systematic literature search of several databases was conducted through April 2018 to identify relevant studies. The outcomes of interest included overall cancer, haematological malignancies, neural tumours, other solid tumours, and eight specific cancers. The overall risk estimates and corresponding 95% confidence intervals (CIs) were pooled using random‐effects meta‐analysis. Sixteen cohort and thirteen case–control studies were included. Results showed that children conceived by fertility treatment had significantly higher risk for developing overall cancer (relative risk [RR]: 1.16, 95% CI: 1.01, 1.32), haematological malignancies (RR: 1.39, 95% CI: 1.21, 1.60) and other solid tumours (RR: 1.57, 95% CI: 1.14, 2.16). For specific cancers, fertility treatment was associated with a significantly increased risk of leukaemia (RR: 1.31, 95% CI: 1.09, 1.57) and hepatic tumours (RR: 2.26, 95% CI: 1.32, 3.85). Sensitivity analysis validated evidence of the robustness of the findings. The results may demonstrate a possible association between fertility treatment and an increased risk of cancer among the offspring. However, the findings cannot say whether this increased risk is due to the subfertility itself or to the fertility treatment. Further research is needed to address the underlying mechanisms.

Section: Resultsmentioning

confidence: 99%

“…Of the 29 observation studies included here, 16 were cohort in design and 13 were case–control . The characteristics of the 16 cohort studies are shown in Table .…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Cancer risk among children conceived by fertility treatment

Yang

et al. 2019

Intl Journal of Cancer

Assisted Reproductive Technology and Risk of Childhood Cancers

Weng

Huang

et al. 2022

JAMA Netw Open

IMPORTANCEThe number of children born through the use of assisted reproductive technology (ART) has been increasing. These children may have higher risks for epigenetic alteration and adverse perinatal outcomes, which may be associated with childhood cancers. OBJECTIVETo determine the associations between different modes of conception and childhood cancers and potential mediation by preterm birth and low birth weight.

Medically Assisted Reproduction and Risk of Cancer Among Offspring

Rios,

Herlemont,

Fauque

et al. 2024

JAMA Netw Open

ImportanceCancer is a leading cause of death among children worldwide. Treatments used for medically assisted reproduction (MAR) are suspected risk factors because of their potential for epigenetic disturbance and associated congenital malformations.ObjectiveTo assess the risk of cancer, overall and by cancer type, among children born after MAR compared with children conceived naturally.Design, Setting, and ParticipantsFor this cohort study, the French National Mother-Child Register (EPI-MERES) was searched for all live births that occurred in France between January 1, 2010, and December 31, 2021 (and followed up until June 30, 2022). The EPI-MERES was built from comprehensive data of the French National Health Data System. Data analysis was performed from December 1, 2021, to June 30, 2023.ExposureUse of assisted reproduction technologies (ART), such as fresh embryo transfer (ET) or frozen ET (FET), and artificial insemination (AI).Main Outcomes and MeasuresThe risk of cancer was compared, overall and by cancer type, among children born after fresh ET, FET, or AI and children conceived naturally, using Cox proportional hazards regression models adjusted for maternal and child characteristics at birth.ResultsThis study included 8 526 306 children with a mean (SD) age of 6.4 (3.4) years; 51.2% were boys, 96.4% were singletons, 12.1% were small for gestational age at birth, and 3.1% had a congenital malformation. There were 260 236 children (3.1%) born after MAR, including 133 965 (1.6%) after fresh ET, 66 165 (0.8%) after FET, and 60 106 (0.7%) after AI. A total of 9256 case patients with cancer were identified over a median follow-up of 6.7 (IQR, 3.7-9.6) years; 165, 57, and 70 were born after fresh ET, FET, and AI, respectively. The overall risk of cancer did not differ between children conceived naturally and those born after fresh ET (hazard ratio [HR], 1.12 [95% CI, 0.96 to 1.31]), FET (HR, 1.02 [95% CI, 0.78 to 1.32]), or AI (HR, 1.09 [95% CI, 0.86 to 1.38]). However, the risk of acute lymphoblastic leukemia was higher among children born after FET (20 case patients; HR 1.61 [95% CI, 1.04 to 2.50]; risk difference [RD], 23.2 [95% CI, 1.5 to 57.0] per million person-years) compared with children conceived naturally. Moreover, among children born between 2010 and 2015, the risk of leukemia was higher among children born after fresh ET (45 case patients; HR, 1.42 [95% CI, 1.06 to 1.92]; adjusted RD, 19.7 [95% CI, 2.8 to 43.2] per million person-years).Conclusions and RelevanceThe findings of this cohort study suggest that children born after FET or fresh ET had an increased risk of leukemia compared with children conceived naturally. This risk, although resulting in a limited number of cases, needs to be monitored in view of the continuous increase in the use of ART.