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.
The overall better outcome for the unexplained infertility group with respect to live birth rate, twin birth rate and early abortion rate compared to the minimal peritoneal endometriosis-associated and tubal factor infertility groups might be a guide to select diagnostic groups for single embryo transfer and be useful in patient counselling.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.