Cancer risk among parous women following assisted reproductive technology

Abstract

Study question: Do women who give birth after assisted reproductive technology (ART) have an increased risk of cancer compared with women who give birth without ART?

Summary answer: Without 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 already: Studies 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, duration: A 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, methods: Of 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 chance: A 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 caution: The 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 findings: In 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 remain nulliparous after ART remains to be assessed.

Study funding/competing interest: The study was funded by the Norwegian National Advisory Unit on Women's Health. All authors claim no competing interests.

Keywords: IVF; assisted reproductive technology; brain tumor; cancer; neoplasm of the central nervous system.

Figure 1

Number of women constituting the study cohort. ^aWomen registered in the MBRN as having given birth between 1 January 1984 and 31 December 2010. ^bWomen with a cancer at any site were excluded from the study population in analysis of overall cancer. ^cThe number of subjects in the study population in the analysis of overall cancer. MBRN: Medical Birth Registry of Norway; ART: assisted reproductive technology; ART women: those with at least one ART delivery as registered in the MBRN; Non-ART women: those without a registered ART delivery in the MBRN.

Figure 2

Hazard ratios for cancer by site for ART women compared with non-ART women. The right column displays numerically hazard ratios (HR) and 95% confidence intervals (CI). Adjustments have been made for attained age, age at start of follow-up, parity, region of residence and calendar period. N denotes the number of cancers occurring after the start of follow-up in the non-ART group. N* denotes the number of cancers in the ART group. CMM: cutaneous malignant melanoma; CNS: cancer of the central nervous system; CRC, colorectal cancer. Hazard rates which were statistically significant between ART and non-ART women, lost statistical significance after adjustments for multiple analyses using the Benjamini-Hochberg method.