Study Finds Assisted Reproductive Technology Does Not Lead to Increased Risk of Ovarian Cancer

An article published in the Journal of the National Cancer Institute suggested that the increased risk of ovarian cancer in women treated with assisted reproductive technology (ART) compared with the general population can likely be explained by nulliparity rather than ART treatment.¹

However, the researchers indicated that though a lack of dose-response relationship with ART-treatment cycles did not support a causal association, more research is still warranted to determine the role of ART in the etiology of borderline ovarian tumors.

“Reassuringly, women who received ovarian stimulation for assisted reproductive technology do not have an increased risk of malignant ovarian cancer, not even in the long run,” lead author, Flora E. van Leeuwen, PhD, of the Department of Epidemiology at the Netherlands Cancer Institute in Amsterdam, said in a press release.² “However, it is important to realize that even with the long follow-up in our study, the median age of the women at end of follow-up was only 56 years. As the incidence of ovarian cancer in the population increases at older ages, it is important to follow assisted reproductive technology-treated women even longer.”

This nationwide cohort study consisted of 30,625 women who received ovarian stimulation for ART from 1983 to 2000 and 9988 subfertile women who were not treated with ART. The investigators obtained incident invasive and borderline ovarian tumors through linkage with the Netherlands Cancer Registry and the Dutch Pathology Registry until July 2018.

With a median follow-up of 24 years, a total of 158 invasive and 100 borderline ovarian tumors were observed. In the cohort of patients who received ART, ovarian tumor risk was found to be increased compared with the general population (standardized incidence ratio [SIR], 1.43; 95% CI, 1.18-1.71) but not when compared with the non-ART group (age- and parity-adjusted HR, 1.02; 95% CI, 0.70-1.50). However, risk decreased with higher parity and with a larger number of successful ART cycles (resulting in childbirth, P_trend = .001) but was not associated with the number of unsuccessful ART cycles.

Moreover, borderline ovarian tumor risk was found to be increased in women treated with ART compared with the general population (SIR, 2.20; 95% CI, 1.66-2.86) and with non-ART women (HR, 1.84; 95% CI, 1.08-3.14). Risk did not increase with more ART cycles or longer follow-up time though.

“Results suggested that the increased risks observed for ovarian tumors might be due to underlying patient characteristics rather than ART treatment because increased risks were restricted to women with endometriosis, low parity, or both and were not observed in women treated because of male factor only or unexplained infertility,” the study authors explained. “However, in the absence of a subfertile comparison group not treated with ART, the authors could not determine whether the increased risks were due to ART, subfertility, or parity.”

Importantly, incidence of ovarian cancer is low before age 50 years and rises exponentially thereafter according to the researchers. Thus, even with the long-term follow-up within this study, relatively few women had reached the sixth or seventh decade of life and the number of cases in this large cohort was still relatively small, making it difficult to draw definitive conclusions. Further, detection bias could have occurred due to diagnostic procedures for subfertility. However, results from analyses including the first year of follow-up showed comparable results, which the investigators explained makes such bias unlikely.

References:

1. Spaan M, van den Belt-Dusebout AW, Lambalk CB, et al. Long-Term Risk of Ovarian Cancer and Borderline Tumors After Assisted Reproductive Technology. Journal of the National Cancer Institute. doi: 10.1093/jnci/djaa163

2. Study finds in vitro fertilization does not increase the risk of ovarian cancer [news release]. Published November 17, 2020. Accessed November 17, 2020.