Cancer in children born after frozen-thawed embryo transfer: A cohort study
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Cancer in children born after frozen-thawed embryo transfer : A cohort study. / Sargisian, Nona; Lannering, Birgitta; Petzold, Max; Opdahl, Signe; Gissler, Mika; Pinborg, Anja; Henningsen, Anna Karina Aaris; Tiitinen, Aila; Romundstad, Liv Bente; Spangmose, Anne Lærke; Bergh, Christina; Wennerholm, Ulla Britt.
In: PLoS Medicine, Vol. 19, No. 9, e1004078, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Cancer in children born after frozen-thawed embryo transfer
T2 - A cohort study
AU - Sargisian, Nona
AU - Lannering, Birgitta
AU - Petzold, Max
AU - Opdahl, Signe
AU - Gissler, Mika
AU - Pinborg, Anja
AU - Henningsen, Anna Karina Aaris
AU - Tiitinen, Aila
AU - Romundstad, Liv Bente
AU - Spangmose, Anne Lærke
AU - Bergh, Christina
AU - Wennerholm, Ulla Britt
N1 - Publisher Copyright: © 2022 Sargisian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2022
Y1 - 2022
N2 - 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 personyears), 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.
AB - 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 personyears), 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.
U2 - 10.1371/journal.pmed.1004078
DO - 10.1371/journal.pmed.1004078
M3 - Journal article
C2 - 36048761
AN - SCOPUS:85137137525
VL - 19
JO - P L o S Medicine (Online)
JF - P L o S Medicine (Online)
SN - 1549-1277
IS - 9
M1 - e1004078
ER -
ID: 327075556