Assisted Reproductive Technology Does Not Increase Ovarian Cancer Risk

New findings in Journal of the National Cancer Institute contradict previous research indicating that assisted reproductive technology might lead to an increased risk of ovarian cancer.

Women who use assisted reproductive technology (ART) like in vitro fertilization are not at a higher risk of developing ovarian cancer, a study published in the Journal of the National Cancer Institute suggests.1 The findings are contrary to previous research indicating that ART might lead to an increased risk of ovarian cancer and non-malignant borderline ovarian tumors.

ART was introduced 4 decades ago, and some have voiced concerns that it might increase a patient’s risk of ovarian tumors due to overstimulation of the ovaries. But research has been inconsistent, the authors of the new study note.

They point to 2 meta-analyses from 2013 that showed an association between ART and ovarian cancer risk compared to the general population. But those results don’t rule out an association between ovarian cancer and other factors, including infertility in itself. Another analysis based on 2 studies found that ovarian cancer risk was no higher in subfertile women treated with ART than it was in untreated subfertile women. But many studies lack an untreated subfertile comparison group, and others are inconclusive due to short follow-up times.

“Because of the worldwide increase in the use of ART and the poor prognosis of ovarian cancer, it is important from a public health perspective to examine the association between ART and long-term ovarian tumor incidence,” the study authors wrote. The new study aimed to determine the long-term risk of ovarian cancer after ART.

Researchers assessed the risk of ovarian cancer in a nationwide cohort of women who received ART between 1983 and 2000 (n = 30,625) compared with women in the Dutch general population (n = 40,613) and a cohort of subfertile women who did not receive ART (n = 9988). They also examined the effect of unsuccessful ART cycles versus those that lad to childbirth.

Overall, there were 158 cases of ovarian cancer and 100 borderline tumors were observed in the study population after a median follow-up of 24 years. The ART group saw a higher risk of ovarian cancer compared with the general population (standardized incidence ratio [SIR], 1.43; 95% CI, 1.18-1.71). But when compared with the subfertile, non-ART cohort, there was not a significant risk increase (age- and parity-adjusted hazard ratio [HR], 1.02; 95% CI, 0.70-1.50), even after 20 years.

They did find that women in the ART-treated cohort were at a 1.8-fold higher risk of borderline ovarian tumors than non-ART women. But because there was no dose-response relationship with ART cycles, the findings do not point to a causal relationship in that regard, but they do warrant more research.

Overall, study authors concluded that the findings suggest that the increased risk seen in ART-treated women might be due to the higher proportion of women in the ART treatment cohort that did not have children—not the ART itself—since nulliparity has been associated with a higher risk of ovarian cancer.

"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," study author Flora E. van Leeuwen said in a statement.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."

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. J Natl Cancer Inst. Published online November 17, 2020. Accessed December 4, 2020. doi:10.1093/jnci/djaa163

2. In vitro fertilization does not increase the risk of ovarian cancer. News release. Oxford University Press USA; November 17, 2020. Accessed December 4, 2020. https://www.eurekalert.org/pub_releases/2020-11/oupu-ivf111320.php