Background and objectives An increasing number of children are born after assisted reproductive technology (ART) and monitoring their long-term health effects is of interest. This study compares cancer risk in children conceived by ART to that in children conceived without. Method The Medical Birth Registry of Norway (MBRN) contains individual information on all children born in Norway (including information of ART conceptions). All children born between 1984 and 2011 constituted the study cohort, and cancer data were obtained from the Cancer Registry of Norway (CRN). Follow-up started at date of birth, and ended on the date of the first cancer diagnosis, death, emigration, or 31st December 2011. A Cox proportional hazards model was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) of overall cancer risk between children conceived by ART and those not. Cancer risk was also assessed separately for all childhood cancer types. Results The study cohort comprised 1 628 658 children, of which 25 782 were conceived by ART. Of the total 4554 cancers, 51 occurred in ART conceived children. Risk of overall cancer was not significantly elevated, HR 1.21 (95% CI 0.90–1.63). However, increased risk of leukemia was observed for children conceived by ART compared to those who were not, HR 1.67 (95% CI 1.02–2.73). Based on small numbers, an elevated risk of Hodgkin lymphoma was found for ART conceived children, HR 3.63 (95% CI 1.12–11.72). Conclusion This population-based cohort study found elevated risks of leukemia and Hodgkin lymphoma in children conceived by ART.

Background Long-term safety of assisted reproductive techniques (ART) is of interest as use is increasing. Cancer risk is known to be affected by parity. This study examined risk of cancer after fertility treatment, stratified by women’s parity. Methods Data was obtained on all women (n=1 353 724) born in Norway between 1960–1996. Drug exposure data (2004–2014) was obtained from the Norwegian Prescription Database [drugs used in ART and clomiphene citrate (CC)]. The Medical Birth Registry of Norway provided parity status. Hazard ratios were calculated for all site cancer, breast, cervical, endometrial, ovarian, colorectal, central nervous system, thyroid cancer and malignant melanoma. Results In 12 354 392 person-years of follow-up, 20 128 women were diagnosed with cancer. All-site cancer risk was (1.14, 1.03–1.26) and (1.10, 0.98–1.23) following CC and ART exposure respectively. For ovarian cancer, a stronger association was observed for both exposures in nulliparous (HR 2.49, 1.30–4.78, and HR 1.62, 0.78–3.35) versus parous women (HR 1.37, 0.64–2.96, and HR 0.87, 0.33–2.27). Elevated risk of endometrial cancers was observed for CC exposure in nulliparous women (4.59, 2.68–7.84 vs. 1.44, 0.63–3.31). Risk was elevated for breast cancer in parous women exposed to CC (1.26, 1.03–1.54) and among nulliparous women after ART treatment (2.19, 1.08–4.44). Conclusion CC appears associated with increased risk of ovarian and endometrial cancer. Elevations in risks of breast and thyroid cancer were less consistent across type of drug exposure and parity. Impact Continued monitoring of fertility treatments is warranted.

Despite increasing numbers of women availing themselves of assisted reproductive technology (ART), effects on cancer risk remain unresolved. Given hormonal exposures, breast cancer risk is of particular concern. The aim of this study is to investigate breast cancer risk amongst women giving birth following ART as compared to that amongst women who gave birth without ART. Data on all women who gave birth in Norway with or without ART, between 1984 and 2010 was obtained from the Medical Birth Registry of Norway (MBRN). 808 834 women eligible for study were linked to the Cancer Registry of Norway. Cox proportional hazards model computed relative risk of breast cancer between the two groups, adjusting for age, parity, age at first birth, calendar period and region of residence. A total of 8037 women were diagnosed with breast cancer during the study period, 138 ART women and 7899 unexposed. Total follow-up time was 12 401 121 person-years (median 16.0), median age at entry was 32.5 years (range18.6-49.9) for ART women and 26.3 (range 10.5-54.6) for women without ART. Women exposed to ART had an elevated risk of breast cancer (adjusted HR 1.20, 95% CI 1.01-1.42). Subgroup analyses resulted in an HR of 1.30 (95% CI 1.07-1.57) for women treated with IVF and 1.35 (95 % CI 1.07-1.71) for women with follow-up >10 years, compared with controls. Our findings of increased risk in the study population, warrant continued monitoring of women treated with ART as this population advances into more typical cancer age ranges.

STUDY QUESTIONDo women who give birth after assisted reproductive technology (ART) have an increased risk of cancer compared with women who give birth without ART?SUMMARY ANSWERWithout correction, the results indicate an increase in overall cancer risk, as well as a 50% increase in risk of CNS cancer for women giving birth after ART, however the results were not significant after correcting for multiple analyses.WHAT IS KNOWN ALREADYStudies regarding the effects of hormonal treatments involved with ART on subsequent cancer risk have provided inconsistent results, and it has also been suggested that infertility itself could be a contributory factor.STUDY DESIGN, SIZE, DURATIONA population-based cohort consisting of all women registered in the Medical Birth Registry of Norway as having given birth between 1 January 1984 and 31 December 2010 was assembled (n = 812 986). Cancers were identified by linkage to the Cancer Registry of Norway. Study subjects were followed from start of first pregnancy during the observational period until the first cancer, death, emigration, or 31 December 2010.PARTICIPANTS/MATERIALS, SETTING, METHODSOf the total study population (n = 806 248), 16 525 gave birth to a child following ART. Cox regression analysis computed hazard ratios (HR) and 95% confidence intervals (CI) comparing cancer risk between ART women and non-ART women; for overall cancer, and for cervical, ovarian, uterine, central nervous system (CNS), colorectal and thyroid cancers, and for malignant melanoma.MAIN RESULTS AND THE ROLE OF CHANCEA total of 22 282 cohort members were diagnosed with cancer, of which 338 were ART women and 21 944 non-ART women. The results showed an elevated risk in one out of seven sites for ART women. The HR for cancer of the CNS was 1.50 (95% CI 1.03– 2.18), and among those specifically subjected to IVF (without ICSI) the HR was 1.83 (95% CI 1.22–2.73). Analysis of risk of overall cancer gave an HR of 1.16 (95% CI 1.04–1.29). Among those who had delivered only one child by the end of follow-up, the HR for ovarian cancer was 2.00 (95% CI 1.08–3.65), and for those nulliparous at entry the HR was 1.80 (95% CI 1.04–3.11). However, all findings became non-significant after correcting for multiple analyses.LIMITATIONS, REASONS FOR CAUTIONThe results of elevated risk of overall cancer and CNS cancer lost significance when adjusting for multiple analyses, implying an important limitation of the study. The follow-up time was relatively short, especially for ART women. In addition, as the cohort was relatively young, there were few incident cancers, especially for some rarer cancer forms, such as uterine cancer. Risk assessments according to different causes of infertility could not be done.WIDER IMPLICATIONS OF THE FINDINGSIn light of the findings in the present study, further studies should be made on risk of CNS and ovarian cancer, and continued monitoring of all those treated with ART is encouraged. Our findings may only be generalizable to women who give birth after ART, and the risk for women who r...