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Cancer risk among children conceived by fertility treatment.

ABSTRACT: 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.

SUBMITTER: Wang T

PROVIDER: S-EPMC6590158 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Cancer risk among children conceived by fertility treatment.

Wang Tingting T Chen Lizhang L Yang Tubao T Wang Lesan L Zhao Lijuan L Zhang Senmao S Ye Ziwei Z Chen Letao L Zheng Zan Z Qin Jiabi J

International journal of cancer 20190103 12

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 t ...[more]

PMID: 30548591

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Project description:Importance:An increasing number of children worldwide are born after the use of fertility treatment, although it remains unclear whether the treatment affects the risk of childhood cancer and whether any associations observed are due to the use of specific drugs, the use of specific procedures, or the underlying infertility. Objective:To examine the association between different types of fertility treatments and cancer risk in children. Design, Setting, and Participants:A retrospective cohort study based on Danish population-based registry data and the Danish Infertility Cohort (individual record linkage) that included 1 085 172 children born in Denmark between January 1, 1996, and December 31, 2012, linked with parental information. There were a total of 2217 children diagnosed with cancer (follow-up occurred during 1996-2015). Exposures:Maternal fertility treatment during the index pregnancy, including the use of fertility drugs (clomiphene [n = 33 835], gonadotropins [n = 57 136], gonadotropin-releasing hormone analogs [n = 38 653], human chorionic gonadotropin [n = 68 181], progesterone [n = 41 628], and estrogen [n = 16 948]) and assisted reproductive technology (in vitro fertilization [n = 19 448], intracytoplasmic sperm injection [n = 13 417], and frozen embryo transfer [n = 3356]). Each exposure was examined separately and compared with children born to fertile women. Main Outcomes and Measures:Hazard ratios and incidence rate differences for childhood cancer. Results:After 12.2 million person-years of follow-up (mean, 11.3 years), the incidence rate of childhood cancer was 17.5 per 100 000 for children born to fertile women (n = 910 291) and 44.4 per 100 000 for children born after the use of frozen embryo transfer (n = 3356). Compared with children born to fertile women, the use of frozen embryo transfer was associated with an elevated risk of childhood cancer (14 cancer cases; hazard ratio, 2.43 [95% CI, 1.44 to 4.11]; incidence rate difference, 26.9 [95% CI, 2.8 to 51.0] per 100 000), mainly due to an increased risk of leukemia (5 cancer cases; incidence rate, 14.4 per 100 000; hazard ratio, 2.87 [95% CI, 1.19 to 6.93]; incidence rate difference, 10.1 [95% CI, -4.0 to 24.2] per 100 000) and sympathetic nervous system tumors (<5 cancer cases; hazard ratio, 7.82 [95% CI, 2.47 to 24.70]). There were no statistically significant associations with the use of the other types of fertility treatment examined. Conclusions and Relevance:Among children born in Denmark, the use of frozen embryo transfer, compared with children born to fertile women, was associated with a small but statistically significant increased risk of childhood cancer; this association was not found for the use of other types of fertility treatment examined.

Project description:STUDY QUESTION:Do children conceived by ART have an increased risk of cancer? SUMMARY ANSWER:Overall, ART-conceived children do not appear to have an increased risk of cancer. WHAT IS KNOWN ALREADY:Despite the increasing use of ART, i.e. IVF or ICSI worldwide, information about possible long-term health risks for children conceived by these techniques is scarce. STUDY DESIGN, SIZE, DURATION:A nationwide historical cohort study with prospective follow-up (median 21 years), including all live-born offspring from women treated with subfertility treatments between 1980 and 2001. PARTICIPANTS/MATERIALS, SETTING, METHODS:All offspring of a nationwide cohort of subfertile women (OMEGA study) treated in one of the 12 Dutch IVF clinics or two fertility clinics. Of 47 690 live-born children, 24 269 were ART-conceived, 13 761 naturally conceived and 9660 were conceived naturally or through fertility drugs, but not by ART. Information on the conception method of each child and potential confounders were collected through the mothers' questionnaires and medical records. Cancer incidence was ascertained through linkage with The Netherlands Cancer Registry from 1 January 1989 until 1 November 2016. Cancer risk in ART-conceived children was compared with risks in naturally conceived children from subfertile women (hazard ratios [HRs]) and with the general population (standardized incidence ratios [SIRs]). MAIN RESULTS AND THE ROLE OF CHANCE:The median follow-up was 21 years (interquartile range (IQR): 17-25) and was shorter in ART-conceived children (20 years, IQR: 17-23) compared with naturally conceived children (24 years, IQR: 20-30). In total, 231 cancers were observed. Overall cancer risk was not increased in ART-conceived children, neither compared with naturally conceived children from subfertile women (HR: 1.00, 95% CI 0.72-1.38) nor compared with the general population (SIR = 1.11, 95% CI: 0.90-1.36). From 18 years of age onwards, the HR of cancer in ART-conceived versus naturally conceived individuals was 1.25 (95% CI: 0.73-2.13). Slightly but non-significantly increased risks were observed in children conceived by ICSI or cryopreservation (HR = 1.52, 95% CI: 0.81-2.85; 1.80, 95% CI: 0.65-4.95, respectively). Risks of lymphoblastic leukemia (HR = 2.44, 95% CI: 0.81-7.37) and melanoma (HR = 1.86, 95% CI: 0.66-5.27) were non-significantly increased for ART-conceived compared with naturally conceived children. LIMITATIONS, REASONS FOR CAUTION:Despite the large size and long follow-up of the cohort, the number of cancers was rather small for subgroup analyses as cancer in children and young adults is rare. WIDER IMPLICATIONS OF THE FINDINGS:Overall, ART-conceived children do not appear to have an increased cancer risk after a median follow-up of 21 years. This large study provides important results, enabling physicians to better inform couples considering ART about the long-term safety of ART for their children. However, larger studies with prolonged follow-up are needed to investigate cancer risk in adults and in children conceived by ICSI and/or from cryopreserved embryos. STUDY FUNDING/COMPETING INTEREST(S):This work was supported by The Dutch Cancer Society (NKI 2006-3631) which funded the OMEGA-women's cohort and Children Cancer Free (KIKA;147) which funded the OMEGA-offspring cohort. We declare no competing interests.

Project description:ImportanceChildren with birth defects have a greater risk of developing cancer, but this association has not yet been evaluated in children conceived with in vitro fertilization (IVF).ObjectiveTo assess whether the association between birth defects and cancer is greater in children conceived via IVF compared with children conceived naturally.Design, setting, and participantsThis cohort study of live births, birth defects, and cancer from Massachusetts, New York, North Carolina, and Texas included 1 000 639 children born to fertile women and 52 776 children conceived via IVF (using autologous oocytes and fresh embryos) during 2004-2016 in Massachusetts and North Carolina, 2004-2015 in New York, and 2004-2013 in Texas. Children were followed up for an average of 5.7 years (6 008 985 total person-years of exposure). Data analysis was conducted from April 1 to August 31, 2020.ExposuresConception by IVF for state residents who gave birth to liveborn singletons during the study period. Birth defect diagnoses recorded by statewide registries.Main outcomes and measuresCancer diagnosis as recorded by state cancer registries. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs for birth defect-cancer associations separately in fertile and IVF groups.ResultsA total of 1 000 639 children (51.3% boys; 69.7% White; and 38.3% born between 2009-2012) were in the fertile group and 52 776 were in the IVF group (51.3% boys; 81.3% White; and 39.6% born between 2009-2012). Compared with children without birth defects, cancer risks were higher among children with a major birth defect in the fertile group (hazard ratio [HR], 3.15; 95% CI, 2.40-4.14) and IVF group (HR, 6.90; 95% CI, 3.73-12.74). The HR of cancer among children with a major nonchromosomal defect was 2.07 (95% CI, 1.47-2.91) among children in the fertile group and 4.04 (95% CI, 1.86-8.77) among children in the IVF group. The HR of cancer among children with a chromosomal defect was 15.45 (95% CI, 10.00-23.86) in the fertile group and 38.91 (95% CI, 15.56-97.33) in the IVF group.Conclusions and relevanceThis study found that among children with birth defects, those conceived via IVF were at greater risk of developing cancer compared with children conceived naturally.

Project description:BackgroundWomen with a new cancer diagnosis face complex decisions about interventions aiming to preserve their fertility. Decision aids are more effective in supporting decision making than traditional information provision. We describe the development and field testing of a novel patient decision aid designed to support women to make fertility preservation treatment decisions around cancer diagnosis.MethodsA prospective, mixed-method, three stage study involving: 1) co-development of the resource in collaboration with a multi-disciplinary group of key stakeholders including oncology and fertility healthcare professionals and patient partners (n=24), 2) alpha testing with a group of cancer patients who had faced a fertility preservation treatment decision in the past (n=11), and oncology and fertility healthcare professionals and stakeholders (n=14) and, 3) beta testing with women in routine care who had received a recent diagnosis of cancer and were facing a fertility preservation treatment decision (n=41) and their oncology and fertility healthcare professionals (n=3). Ten service users recruited from a closed Breast Cancer Now Facebook group and the support group Cancer and Fertility UK also provided feedback on CFM via an online survey.ResultsA 60-page paper prototype of the Cancer, Fertility and Me patient decision aid was initially developed. Alpha testing of the resource found that overall, it was acceptable to cancer patients, healthcare professionals and key stakeholders and it was considered a useful resource to support fertility preservation treatment decision-making. However, the healthcare professionals felt that the length of the patient decision aid, and elements of its content may be a barrier to its use. Subsequently, the prototype was reduced to 40 pages. During beta testing of the shortened version in routine care, women who received the resource described its positive impact on their ability to make fertility preservation decisions and support them at a stressful time. However, practical difficulties emerged which impacted upon its wider dissemination in clinical practice and limited some elements of the evaluation planned.DiscussionWomen receiving the decision aid within the cancer treatment pathway found it helped them engage with decisions about fertility preservation, and make better informed, values-based care plans with oncology and fertility teams. More work is needed to address access and implementation of this resource as part of routine oncology care pathways.

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Cancer risk among children conceived by fertility treatment.

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Cancer risk among children conceived by fertility treatment.

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