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Study finds ovarian stimulation for IVF may increase risk of ovarian malignancies later in life

Oct. 27, 2011

By Maria Serraino

Women whose ovaries are stimulated into producing extra eggs for in vitro fertilization (IVF) may have an increased risk of ovarian malignancies later in life, according to a new study.

Lead researcher Professor Flora van Leeuwen and colleagues at The Netherlands Cancer Institute have found that the long-term risk for ovarian malignancies – including ovarian cancer and borderline ovarian tumours – is twice as high among women who undergo stimulation for IVF compared with subfertile women not treated with IVF.

In the study, subfertility refers to women who were unable to conceive after one or more years of frequent unprotected sexual intercourse. Unlike infertility, subfertility is not necessarily the complete inability to get pregnant, but rather is a condition of being less fertile than ‘normal’. Borderline ovarian tumours are defined in the study as tumours with a low malignancy potential, meaning they aren’t fatal, but require extensive surgery and cause substantial morbidity.

This study is the first to include a comparison group of subfertile women not treated with IVF. It is particularly significant because IVF treated women differ from the general population as they have difficulty conceiving and/or since they have never been pregnant, both of which are known risk factors for developing ovarian malignancies. 

The research was based on data from the OMEGA study - a large observational study in the Netherlands examining the effects of hormone stimulation in women diagnosed with subfertility problems. The researchers identified 19,146 subfertile women who received at least one IVF stimulation treatment between 1983 and 1995 and 6,006 subfertile women who were not treated with IVF. The risk of ovarian malignancies in the IVF group was compared with the risks in the general population and the subfertile group who were not treated with IVF.

After a median followup time of 15 years, researchers found that of the total number of subfertile women included (25,152), 77 had ovarian malignancies. Of those malignancies, 61 occurred in women who had IVF treatment (31 cases of borderline ovarian cancer and 30 cases of invasive ovarian cancer).

After adjusting for confounding factors including age, number of children (if any), and the cause of subfertility, the long-term risks for ovarian malignancies were significantly elevated in the IVF treatment group compared to those not treated. For ovarian malignancies overall there was a two-fold higher risk for the IVF treatment group, and for borderline ovarian cancer there was a four-fold higher risk. While the risk of invasive ovarian cancer was slightly increased in the IVF treatment group, this was not statistically significant.

The data from the study shows that ovarian stimulation for IVF is associated with an increased risk of borderline ovarian tumours and this risk remains elevated up to more than 15 years after the first cycle of treatment.

According to the study, in the Netherlands the cumulative risk of ovarian malignancies before the age of 55 is 0.45 per cent in the general population. The results of the study suggest that the risk increases to 0.71 per cent for women who undergo IVF.

The researchers found that ovarian stimulation for IVF may increase the risk of ovarian malignancies, especially borderline ovarian tumours. They suggest that women considering starting or continuing IVF treatment should be informed of the magnitude of these risks. While borderline ovarian tumours are not fatal, they often require extensive surgery and cause substantial morbidity. Ovarian cancer, however, is often fatal, and more research should be done to verify the study findings.

The study is published in the online issue of Human Reproduction on Oct. 27, 2011. 

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  • A publication of:
  • Women's College Hospital