Ovarian stimulation for in-vitro fertilization may increase the risk of ovarian malignancies, especially borderline ovarian tumors. The percentage of children born in the Western world by assisted reproductive technologies is increasing. Fertilized drugs used in in-vitro fertilization treatment temporarily raise hormones, and consequently increase the chances of multiple ovulations. The long-term effects of ovarian stimulation are unknown, and concerns have been raised that ovarian stimulation as used in in-vitro fertilization may increase the risk of ovarian malignancies. Invasive ovarian cancer accounts for 6% of female cancer deaths in the USA (Jemal et al., 2008).
Lots of confounders, such as cause of sub-fertility, have limited the conclusions from previous studies about the link between higher risk of ovarian cancer and ovarian stimulation. The study presented here (van Leeuwen et al., 2011) is the first one analyzing the risk of borderline ovarian tumours following in-vitro fertilization treatment.
This large study with a follow-up of 15 years (and more than 20 thousand women history were analyzed) shows that women treated with ovarian stimulation for in-vitro fertilization have a double increased risk of all ovarian malignancies compared with subfertile women not treated with in-vitro fertilization, and more than 4 times increased risk of borderline ovarian malignancies compared with subfertile women not treated with in-vitro fertilization. The study is also confirmed by the observation of a high proportion (46%) of all ovarian malignancies in the in-vitro fertilization group concerned borderline ovarian tumours, whereas in the general population borderline ovarian tumours account only for 15–30% of ovarian malignancies.
A concerning finding of this study is the increased rate of invasive ovarian cancer in the in-vitro fertilization group after more than 15 years of follow-up, which was not observed in the non-in-vitro fertilization group.
In conclusion, the results suggest that ovarian stimulation for in-vitro fertilization may increase the risk of ovarian malignancies, especially borderline ovarian tumours. Knowledge about the magnitude of the risks associated with ovarian stimulation is important for women considering starting or continuing in-vitro fertilization treatment, as well as their treating physicians. Clearly, the outcome of weighing a wish to conceive against the potential risks associated with in-vitro fertilization may differ among couples considering fertility treatment.
It should be explained to women opting for in-vitro fertilization 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.
This is a summary of the paper “Risk of borderline and invasive ovarian tumours after ovarian stimulation for in vitro fertilization in a large Dutch cohort” by F.E. van Leeuwen and collaborators: http://humrep.oxfordjournals.org/content/early/2011/10/19/humrep.der322.full.pdf