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Another factor that may explain some of the elevated cancer risk among children born by ART is infertility and the underlying causes of it, according to Barbara Luke, ScD, professor of obstetrics, gynecology and reproductive biology at Michigan State University in East Lansing.
Though the Nordic study and others have shown that the increased risk of childhood cancer persists after adjusting for parental age and other factors, there could be additional confounders that were not taken into account, Dr Luke said.
In the aforementioned US study, Dr Luke and colleagues found that children born by natural conception who had siblings born by ART had a 34% higher risk of all cancers, compared with other babies born by natural conception.4 The finding underscores the potential role of parental infertility or subfertility in pediatric cancer risk.
On the other hand, the Taiwan study showed that children born by ART had a 42% higher risk of childhood cancer, compared with children of subfertile parents who did not use ART.3 However, the authors of that study noted that “ART conception may be a proxy for more severe infertility.”
Determining the Risk
If there are certain aspects of ART that increase the risk of childhood cancer, researchers have not been able to identify what those may be. In addition to the aforementioned studies, other studies of FET or fresh embryo transfer have generally been mixed on whether either method is associated with more risk.10,11
“I don’t think we can say there is a higher risk of cancer in [the FET group], even though our study did show that,” said Christina Bergh, MD, PhD, professor of obstetrics and gynecology at the University of Gothenburg in Sweden, who co-led the Nordic study.
The inconsistency between studies may be due to the low sample sizes in many studies and how cancer cases, birth defects, and other outcomes are recorded in the various registries, she added. For example, some registries may require cancer cases to be reported, while others do not, so reporting may vary between the different ART and natural conception groups.
Nevertheless, experts suspect that certain aspects of ART may increase cancer risk. Dr Cedars speculated that “probably the greatest risk is the culturing of the embryo.” This involves letting the embryo grow in the lab to the blastocyst stage, instead of cleavage stage, before freezing or implantation.
There has been a trend toward increased culturing time, which is a “good thing because it has allowed us to select better embryos . . . to decrease multiples, but downstream effects may be increased risk of childhood cancers,” Dr Cedars said. Studies have not addressed whether there are actual differences in risks associated with blastocyst and cleavage-stage embryos.
Dr Bergh and colleagues are now carrying out larger cohort studies, with the ever-increasing number of children born by ART. The team is aiming to tease apart risks associated with FET, fresh embryos, and parental infertility, such as by comparing pairs of siblings in which one was born by FET and the other by fresh embryo.
Though such studies are needed to answer remaining questions, it is important for parents to know that the long-term health of children born by ART has been studied, and there do not seem to be major concerns, Dr Bergh said.
She noted that, at the individual level, the increase in cancer risk appears very limited with ART. “In absolute numbers, it is very low, and that should be reassuring for parents,” she said.
Some researchers have argued that the link between ART and childhood cancer suggests children born via ART should be monitored more closely or screened for cancer.3,4 Dr Cedars said she doesn’t think the data support this practice because cancers are still rare in this population.
Disclosures: Dr Cedars, Dr Luke, and Dr Bergh reported having no relevant disclosures.
References
1. Sundh KJ, Henningsen AK, Källen K, et al. Cancer in children and young adults born after assisted reproductive technology: A Nordic cohort study from the Committee of Nordic ART and Safety (CoNARTaS). Hum Reprod. 2014;29(9):2050-7. doi:10.1093/humrep/deu143
2. Reigstad MM, Larsen IK, Myklebust TÅ, et al. Risk of cancer in children conceived by assisted reproductive technology. Pediatrics. 2016;137(3):e20152061. doi:10.1542/peds.2015-2061
3. Weng S, Huang Y, Huang Y, et al. Assisted reproductive technology and risk of childhood cancers. JAMA Netw Open. 2022;5(8):e2230157. doi:10.1001/jamanetworkopen.2022.30157
4. Luke B, Brown MB, Wantman E, et al. The risks of birth defects and childhood cancer with conception by assisted reproductive technology. Hum Reprod. 2022;deac196. doi:10.1093/humrep/deac196
5. Sargisian N, Lannering B, Petzold M, et al. Cancer in children born after frozen-thawed embryo transfer: A cohort study. PLoS Med. 2022;19(9):e1004078. doi:10.1371/journal.pmed.1004078
6. 2019 assisted reproductive technology fertility clinic and national summary report. Centers for Disease Control and Prevention. Published 2021. Accessed March 27, 2023.
7. Magnusson A, Laivuori H, Loft A, et al. The association between high birth weight and long-term outcomes-implications for assisted reproductive technologies: A systematic review and meta-analysis. Front Pediatr. 2021;9:675775. doi:10.3389/fped.2021.675775.
8. Luke B, Brown MB, Wantman E, et al. The risk of birth defects with conception by ART. Hum Reprod. 2021; 36(1): 116–129. doi:10.1093/humrep/deaa272
9. Sazonova A, Kallen K, Thurin-Kjellberg A, et al. Obstetric outcome in singletons after in vitro fertilization with cryopreserved/thawed embryos. Hum Reprod. 2012;27(5):1343-50. doi:10.1093/humrep/des036
10. Hargreave M, Jensen A, Hansen MK, et al. Association between fertility treatment and cancer risk in children. JAMA. 2019;322(22):2203-2210. doi:10.1001/jama.2019.18037
11. Bal MH, Harlev A, Sergienko R, et al. Possible association between in vitro fertilization technologies and offspring neoplasm. Fertil Steril. 2021;116(1):105-113. doi:10.1016/j.fertnstert.2020.12.013
This article originally appeared on Cancer Therapy Advisor
