IVF Linked to Ovarian Tumors. Should Women Worry?

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When TV host Giuliana Rancic was recently diagnosed with breast cancer after two rounds of in-vitro fertilization (IVF), cancer specialists were widely quoted as saying that there’s no evidence that the large hormone doses involved in fertility treatment contribute to breast cancer. The link between IVF and ovarian cancer, however, was muddier.

Part of the problem when studying IVF and ovarian cancer risk is that infertile women already have a slightly higher risk of ovarian cancer than women who are able to conceive naturally, so it’s difficult to figure out whether it’s the infertility or the IVF that may raise ovarian cancer risk.

MORE: The Case of Giuliana Rancic: Is There a Link Between IVF and Cancer?

Now a study of 25,152 Dutch women with fertility problems — 19,146 of whom underwent IVF, while the rest did not — is the first to try to get around that problem. The researchers found that after about 15 years of follow-up, women who had undergone IVF, which requires hormones to stimulate the ovaries, were twice as likely to have developed an ovarian malignancy, compared with the non-IVF group.

Most of that increase in risk was driven by “borderline” ovarian tumors, however. These are tumors that may turn into cancer and require surgery to remove the ovary, but are rarely life threatening. The IVF group was nearly twice as likely to have a borderline tumor as the general population, and more than four times as likely as the subfertile comparison group.

“Our data clearly show that ovarian stimulation for IVF is associated with an increased risk of borderline ovarian tumors and this risk remains elevated up to more than 15 years after the first cycle of treatment,” study author Flora van Leeuwen, head of the department of epidemiology at The Netherlands Cancer Institute, said in a statement.

So, how worried should women be? Not terribly. The absolute risk of ovarian tumors was very low. Researchers found just 61 ovarian malignancies in the IVF group, 31 of which were borderline tumors. In the Netherlands, the researchers note, the cumulative risk of ovarian malignancy, including borderline tumors, is 0.45% in women aged 55. “If our results are true, we would estimate a 0.71% risk for women who underwent IVF,” they write — a less than 1% chance.

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The other 30 malignancies in the IVF group were invasive cancer. Although the women receiving fertility treatment had more invasive cancers than the comparison group, the difference was not statistically significant, the study found.

Further, the overall rate of ovarian malignancies did not rise with increasing numbers of IVF cycles, suggesting that ovarian stimulation is not causally linked to cancer.

“The main message is that women who have had IVF shouldn’t be alarmed. The incidence of ovarian cancer was extremely low,” Curt Burger, a co-author of the study published in the medical journal Human Reproduction, told the BBC.

Meredith Melnick is a reporter at TIME. Find her on Twitter at @MeredithCM. You can also continue the discussion on TIME’s Facebook page and on Twitter at @TIME.