New research shows that women who undergo ovarian stimulation to produce extra eggs for in-vitro fertilization (IVF) are at increased risk for a type of growth known as “borderline ovarian tumors”.
These borderline ovarian tumors are typically not aggressive, according to the U.S. National Cancer Institute. Even if the tumor does spread, the vast majority of women survive borderline ovarian tumors. However these do need extensive surgery, explained lead researcher Flora van Leeuwen, head of the epidemiology department in The Netherlands Cancer Institute.
The team of researchers examined data from over 19,000 infertile women in the Netherlands who underwent ovarian stimulation prior to IVF and about 6,000 infertile women who did not undergo IVF.
After following up the women for 15 years they noted that the women who underwent ovarian stimulation were four times more likely to develop a borderline ovarian tumor. Their findings are published in the Oct. 27 online edition of the journal Human Reproduction.
“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,” van Leeuwen explained. Overall, however, the number of women developing any sort of ovarian tumor was low. The cumulative risk in the general population of an ovarian malignancy for women under age 55 in the Netherlands is 0.45 percent. For women who undergo IVF, it's 0.71 percent, “with the increase being due to borderline tumors of the ovary,” van Leeuwen added.
“Borderline tumors have low malignant potential. They are not what patients consider ovarian cancer. They are very different from 'real' ovarian cancer. That's a really important distinguishing factor,” says Carolyn Runowicz, a gynecologic oncologist and past president of the American Cancer Society. Runowicz was not involved with the Dutch study.
Further research is planned to confirm the finding in a larger number of patients, and to look at whether some women are more at risk. At present, the numbers involved are small. There were 61 women with ovarian tumors in the IVF treatment group; 31 had borderline ovarian tumours and 30 had ovarian cancer. “If we find out that women who receive several IVF cycles or large doses of ovarian-stimulating drugs are at a greater risk of ovarian cancer, then these women would need to be informed about these risks when continuing IVF treatment and possibly advised to discontinue treatment after three to six cycles (depending on which number of cycles would be associated with the high risk of ovarian malignancies),” van Leeuwen noted.
The International Federation of Fertility Societies (IFFS) issued a statement in response to the new study findings. In it, general secretary of the IFFS, Richard Kennedy of Coventry, England, said, “Over the last decade, several reports have considered the long-term risks of ovarian stimulation practiced as part of the IVF process. These reports have been generally reassuring in terms of risk of ovarian cancer.”
“You could easily reason that the ovaries of the women in the IVF group are more resistant to pregnancy than the other subfertile [women with fertility problems] group. It could be that there is some connection between severity of infertility and risk for a tumor,” said Joe Leigh Simpson, a gynecologist and past president of the American Society for Reproductive Medicine.
Another co-author, Prof Curt Burger added, “The main message is that women who have had IVF shouldn't be alarmed. The incidence of ovarian cancer was extremely low.”
Commenting on the study, Prof Hani Gabra, of the Ovarian Cancer Action Research Centre at Imperial College London, said, “Reassuringly, and in keeping with lots of previous research in this area, this study shows that the risks of invasive ovarian cancer are small in populations of patients receiving ovarian stimulation for IVF. Although this study shows that ovarian stimulation may increase the risk of much less aggressive borderline ovarian tumors, it underlines the fact that ovarian stimulation for IVF is not a major risk factor for invasive ovarian cancer.”
Dr Claire Knight, senior health information officer at Cancer Research UK, said, “This interesting study suggests a possible link between ovarian stimulation for IVF and borderline ovarian tumors, but it certainly doesn't show that IVF causes invasive ovarian cancer. There were only a relatively small number of cases in this study, and the researchers didn't find that risk increased with the number of cycles a woman had, making conclusions hard to reach. Women can reduce their risk of ovarian cancer by being a non-smoker and keeping a healthy weight, and women who have taken the Pill or been pregnant are also at lower risk.”
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