As the use of assisted reproductive technologies has increased, so, too, has the concern over its effects on the female reproductive system. Specifically, the increased gonadotrophin levels in ovarian cancer pathogenesis coupled with the multiple ovarian punctures and repeated ovarian stimulation associated with in vitro fertilization have raised concerns that IVF may increase the risk of ovarian malignancies. To better understand this relationship, Dr Flora van Leeuwen, head of the division of Psychosocial Research and Epidemiology in the Netherlands Cancer Institute in Amsterdam, and colleagues conducted a large nationwide cohort study in the Netherlands to examine long-term risk of ovarian malignancies (both invasive ovarian cancer and borderline ovarian tumors) after ovarian stimulation for IVF.
Van Leeuwen et al. identified subfertile women (N=19,861) who received at least one IVF cycle with ovarian stimulation. For comparison purposes, the researchers identified women (N=6,604) who were diagnosed with fertility problems shortly before IVF became a routine procedure for subfertile patients. All women were sent a 23-page questionnaire that was designed to elicit reproductive histories, subfertility treatments, exogenous hormone use, lifestyle factors, and family history of cancer. Medical records were also obtained for the patients. The Dutch nationwide network and registry of histo- and cytopathology was used to determine ovarian malignancy incidence (including borderline ovarian tumors).
The researchers found 42 invasive ovarian cancers and 35 borderline ovarian tumors after a median follow-up time of 14.7 years, for a total of 77 ovarian malignancies. Van Leeuwen and colleagues found a majority of the malignancies (61) occurred in the group who had received IVF. When they compared these rates with the general population, van Leeuwen et al. found an increased risk for borderline ovarian tumors in the IVF group but not in the group that did not receive IVF treatment. Interestingly, standardized incidence ratios of ovarian malignancy did not increase with a greater number of IVF cycles or ampoules of gonadotrophins. While they did not find an association with fertility drug use prior to IVF treatment and increased standardized incidence ratios for all ovarian malignancies, the researchers found a non-significant increase for invasive ovarian cancer.
“This large nationwide cohort study with a median follow-up of 15 years shows that women treated with ovarian stimulation for IVF have a 2-fold increased risk of ovarian malignancies compared with subfertile women not treated with IVF,” van Leeuwen and colleagues concluded. “The excess risk was mostly due to borderline ovarian tumours, but 15 or more years after IVF treatment we also observed a [standardized incidence ratio] SIR of 3.5 for invasive ovarian cancer.”
Although they suggest further research is warranted, the authors note the risks should be presented to couples considering IVF treatment. “It should be explained to women opting for IVF treatment that a borderline ovarian tumour does not constitute a lethal disease, although it may require extensive surgery and cause substantial morbidity. Ovarian cancer, however, is a disease with a high case fatality rate, for which effective screening methods are not available,” they added. “Clearly, the outcome of weighing a wish to conceive against the potential risks associated with IVF may differ among couples considering fertility treatment.”
van Leeuwen FE, Klip H, Mooij TM, et al. Risk of borderline and invasive ovarian tumours after ovarian stimulation for in vitro fertilization in a large Dutch cohort. Hum Reprod. 2011 Oct 26 [Epub].