The association between fertility treatments and the incidence of paediatric cancer: A systematic review and meta-analysis

Zhang, Yaoyao; Gao, Rui; Chen, Hanxiao; Xu, Wei; Yang, Yihong; Zeng, Xun; Sun, Xiaochi; Zhang, Sirui; Hu, Xiao; Qin, Lei

doi:10.1016/j.ejca.2020.08.001

Cited by 11 publications

(8 citation statements)

References 31 publications

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“…In contrast, a Danish population-based registry study found higher risk of any childhood cancer after FET than after spontaneous conception, but the result was based on only 14 cases (HR 2.43, 95% CI 1.44 to 4.11) [ 22 ]. Studies on childhood cancer after ART were recently summarized in a systematic review [ 55 ], concluding that FET may be related to a higher risk of pediatric cancer. In an even more recent study from Israel, with a limited number of children, a higher risk of cancer was found in children born after fresh transfer [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Cancer in children born after frozen-thawed embryo transfer: A cohort study

et al. 2022

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Background The aim was to investigate whether children born after assisted reproduction technology (ART), particularly after frozen-thawed embryo transfer (FET), are at higher risk of childhood cancer than children born after fresh embryo transfer and spontaneous conception. Methods and findings We performed a registry-based cohort study using data from the 4 Nordic countries: Denmark, Finland, Norway, and Sweden. The study included 7,944,248 children, out of whom 171,774 children were born after use of ART (2.2%) and 7,772,474 children were born after spontaneous conception, representing all children born between the years 1994 to 2014 in Denmark, 1990 to 2014 in Finland, 1984 to 2015 in Norway, and 1985 to 2015 in Sweden. Rates for any cancer and specific cancer groups in children born after each conception method were determined by cross-linking national ART registry data with national cancer and health data registries and population registries. We used Cox proportional hazards models to estimate the risk of any cancer, with age as the time scale. After a mean follow-up of 9.9 and 12.5 years, the incidence rate (IR) of cancer before age 18 years was 19.3/100,000 person-years for children born after ART (329 cases) and 16.7/100,000 person-years for children born after spontaneous conception (16,184 cases). Adjusted hazard ratio (aHR) was 1.08, 95% confidence interval (CI) 0.96 to 1.21, p = 0.18. Adjustment was performed for sex, plurality, year of birth, country of birth, maternal age at birth, and parity. Children born after FET had a higher risk of cancer (48 cases; IR 30.1/100,000 person-years) compared to both fresh embryo transfer (IR 18.8/100,000 person-years), aHR 1.59, 95% CI 1.15 to 2.20, p = 0.005, and spontaneous conception, aHR 1.65, 95% CI 1.24 to 2.19, p = 0.001. Adjustment either for macrosomia, birth weight, or major birth defects attenuated the association marginally. Higher risks of epithelial tumors and melanoma after any assisted reproductive method and of leukemia after FET were observed. The main limitation of this study is the small number of children with cancer in the FET group. Conclusions Children born after FET had a higher risk of childhood cancer than children born after fresh embryo transfer and spontaneous conception. The results should be interpreted cautiously based on the small number of children with cancer, but the findings raise concerns considering the increasing use of FET, in particular freeze-all strategies without clear medical indications. Trial registration Trial registration number: ISRCTN 11780826.

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Section: Discussionmentioning

confidence: 99%

Cancer in children born after frozen-thawed embryo transfer: A cohort study

et al. 2022

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“…Some studies indicated that ART conception increases the risk of childhood cancers, [15][16][17][18][19] but others found no association. [20][21][22][23] This discrepancy may be due to several factors. First, different reference groups were used in these studies, and very few studies have differentiated children of parents who had an infertility diagnosis with or without fertility treatments from those who delivered after natural conception to provide an appropriate comparison.…”

Section: Introductionmentioning

confidence: 99%

“…Second, only a few studies adjusted for potential confounders or adjusted for very few confounders. [15][16][17][19][20][21][22][23] In circumstances in which both exposure and outcome are rare events, few studies used a nationwide or large population-based design to reduce selection bias and avoid the limited number of exposed cases. 15,17,18,21 Finally, to our knowledge, no previous study explored whether perinatal outcomes mediate the association between mode of conception and childhood cancers.…”

Section: Introductionmentioning

confidence: 99%

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Assisted Reproductive Technology and Risk of Childhood Cancers

Weng

Huang

et al. 2022

JAMA Netw Open

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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.

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“…The use of frozen embryo transfer, this cohort study includes slow freezing and cryopreservation, was significantly associated with an increased risk of cancer in children, mainly including leukemia and neurological tumors [ 37 ]. In 2020, the European Cancer Research Center also clarified that frozen embryo transfer was associated with an increased incidence of cancer in offspring [ 38 ]. Professor Huang Hefeng, a member of the Chinese Academy of Sciences, has long been concerned about the safety and genetic effects of human ART, and a recent study by this team found that male mouse offspring transferred after freezing–thawing showed impaired glucose metabolism, mainly manifesting as insulin resistance [ 39 ].…”

Section: Reflections On Fertility Preservation In Chinamentioning

confidence: 99%

Current status and reflections on fertility preservation in China

Zhang

Wei

Deng

et al. 2022

J Assist Reprod Genet

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Purpose With the progress of medical technology and renovated conception of fertility, the prospective studies and practice of fertility preservation are drawing more and more attention from medical workers. With the largest population of over 1.4 billion, China makes the experience accumulated in fertility preservation efforts even more relevant. This article summarizes China’s experience and shares it with the world to promote the healthy development of fertility preservation. Methods This study was based on multiple Chinese expert consensuses on fertility preservation issued in 2021 and the current national regulations and principles, compared with the latest advice and guidelines issued by global reproductive authorities such as the ASRM and ESHRE. Summarize the experience and reflection of Chinese scholars in the process of fertility preservation. Results This study reports on the current situation of fertility preservation in China, sharing the Chinese experience gained in the process of development, and offering Chinese reflections on worrying issues. Conclusion Fertility preservation is a medical and social issue of reproductive health security, which is conducive to the sound development of the world population and social production.

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The association between fertility treatments and the incidence of paediatric cancer: A systematic review and meta-analysis

Cited by 11 publications

References 31 publications

Cancer in children born after frozen-thawed embryo transfer: A cohort study

Cancer in children born after frozen-thawed embryo transfer: A cohort study

Assisted Reproductive Technology and Risk of Childhood Cancers

Current status and reflections on fertility preservation in China

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