Cancer Risk in Children and Young Adults (Offspring) Born after Medically Assisted Reproduction: A Systematic Review and Meta-Analysis

Chiavarini, Manuela; Ostorero, Andrea; Naldini, Giulia; Fabiani, Roberto

doi:10.3390/j2040028

Cited by 7 publications

(12 citation statements)

References 71 publications

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“…Studies on risk of childhood cancer after ART show conflicting results. Most large observational studies indicate similar overall cancer risk in children born after ART and in children in the general population [20][21][22][23], but a higher risk for both any cancer [24][25][26][27] and specific malignancies [20,21,[24][25][26] has also been reported. In a Danish populationbased registry study [22], a higher risk of any childhood cancer was found after FET compared to spontaneous conception, but the finding was based on a limited number of cases.…”

Section: Introductionmentioning

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: Introductionmentioning

confidence: 99%

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

et al. 2022

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“…If the in utero transfer of a pre-leukemic clone was the main causal pathway underlying the increased leukemia risk of twins, the risk among twins in this analysis should resemble that of singletons. Another possible explanation might be an adverse event of medical interventions associated with multiple birth such as fertility treatments, medically assisted reproduction (MAR) [53,55], and prelabour cesarean delivery [52]. In the FSO birth records, the proportion of multiple births among total births increased almost linearly with maternal age, from 1.6% among mothers aged 25 years or younger to 4.2% among those aged 40 years and above.…”

Section: Discussionmentioning

confidence: 99%

Birth characteristics and childhood leukemia in Switzerland: a register-based case–control study

Lupatsch

Kreis

Konstantinoudis

et al. 2021

Cancer Causes Control

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Purpose Initial genetic alterations in the development of childhood leukemia occur in utero or before conception; both genetic and environmental factors are suspected to play a role. We aimed to investigate the associations between childhood leukemia and perinatal characteristics including birth order, birth interval to older siblings, parental age, birth weight, and multiple birth. Methods We identified cases diagnosed between 1981 and 2015 and born in Switzerland between 1969 and 2015 from the Swiss Childhood Cancer Registry and randomly sampled five controls per case from national birth records matched on date of birth, sex, and municipality of residence at birth. We used conditional logistic regression to investigate associations between perinatal characteristics and leukemia at ages 0–15 and 0–4 years, and the subtypes acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Results The study included 1,403 cases of leukemia. We observed increased risks associated with high birth weight (adjusted OR 1.37, 95% CI 1.12–1.69) and multiple birth (1.89, 1.24–2.86). These associations were similar for ALL and stronger for leukemia at ages 0–4 years. For AML, we observed an increased risk for higher birth order (3.08, 0.43–22.03 for fourth or later born children). We found no associations with other perinatal characteristics. Conclusion This register-based case–control study adds to the existing evidence of a positive association between high birth weight and risk of childhood leukemia. Furthermore, it suggests children from multiple births are at an increased risk of leukemia.

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“…More than a century has passed since the pioneering work of Wesley Kingston Whitten (1956), the father of embryo culture medium [36], and signi cant progress has been made in culturing human and, to some extent, domestic species zygotes to blastocysts and then to embryos [37]. However, recent studies on humans have shown that culture media composition and assisted reproductive technology (ART) procedures affect parturition [38], the weight of children at birth, and even their health after ART procedure [39]. Despite these achievements in culturing human embryos, there is a need for further research, especially in culturing embryos from domestic species towards complete epigenetic patterns.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Two Embryo Culture Media, SOF and Commercial BO, on Pre- and Post-Implantation Development of Cloned Sannen Goat Embryos

Hajian

Jafarpour

Aghamiri

et al. 2020

Preprint

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Background: The ingredients of embryo culture media developed by different companies are disclosed. Thus, it is impossible to determine which ingredients might be responsible for differences in pre-and post-implantation embryo development. To address this gap, we performed an experiment to compare two embryo culture media, namely, SOF and commercial BO, on pre- and post-implantation development of cloned Sannen goat embryos. Cumulus oocyte complexes derived from slaughterhouse ovaries were used for in vitro embryo production . In vitro development of IVF, parthenogenetic and SCNT embryos were assessed in both BO and SOF media. The expression of 16 genes, including AKT , OCT4 , SOX2 , BMPR1 , FGFR4 , CDC25 , CDX2 , GCN5 , PCAF , FOXD3 , SMAD5 , FZD , LIFR1 , CTNNB , ERK1 , and IFNT , belonging to 7 important pathways, i.e. pluripotency, FGF, TGFβ, cell cycle and proliferation, histone transferase, trophectoderm, and WNT, were examined in the goat SCNT and IVF blastocysts from both BO and SOF media. Results: The blastocyst rate in BO medium was significantly higher than that of the SOF medium in SCNT embryos ( P < 0.05). All of the genes examined showed increased expression levels in SCNT embryos compared to IVF embryos. In the IVF group, OCT4 , BMPR1 , and GCN5 showed significantly higher expression in the SOF medium compared to the BO medium. In this group, AKT , FGFR4 , SOX2 showed significantly lower expression in the SOF medium compared to the BO medium. In the SCNT group, FGFR4 , GCN5 , FZD , CTNNB , BMPR1 , and FGFR4 showed significantly higher expression in SOF medium compared to BO medium. In vivo development did not differ significantly between the two groups. Conclusions: Based on these results, we concluded that the limited information available on the allocations of ICM and TE cells in SCNT embryos and embryo-specific gene expression may be the major drawback IVC medium and an impediment to successful animal cloning.

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Cancer Risk in Children and Young Adults (Offspring) Born after Medically Assisted Reproduction: A Systematic Review and Meta-Analysis

Cited by 7 publications

References 71 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

Birth characteristics and childhood leukemia in Switzerland: a register-based case–control study

The Impact of Two Embryo Culture Media, SOF and Commercial BO, on Pre- and Post-Implantation Development of Cloned Sannen Goat Embryos

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