2004 Newsletter - Page One Of Four
Mark P. Trolice, M.D., FACOG, FACS
Milton McNichol, M.D, FACOG
Board Certified in Reproductive Endocrinology and Infertility
No Increase in Ovarian Cancer After Infertility Treatment
Do medications used to treat infertility increase the risk of ovarian cancer? This possibility was suggested by 2 reports published more than a decade ago that were widely criticized for their study design and various biases.
To answer the question more definitively, Kashyap et al from the University of Ottawa, Canada, performed a meta-analysis of available literature. They made a computerized search of 6 databases from 1966 to the present as well as a hand search of 10 years of 5 medical journals. Both case-control and cohort studies were retrieved for analysis.
The population the authors focused on was infertile women who had been treated by any of the following medications used in assisted reproduction technology: clomiphene citrate, gonadotropins, human chorionic gonadotropin and gonadotropin-releasing hormone agonists. The treated women were compared with untreated infertile women (controls). The primary outcome was a new diagnosis of primary ovarian cancer of any histologic type.
Despite the huge number of studies identified by the literature searches, after applying a relevance filter and strict inclusion/exclusion criteria, only 6 cohort studies and 11 case-control studies were found eligible for quantitative analysis. A primary reason for this was that most of the available studies compared treated infertile patients with general population controls, whereas the current authors wanted to compare treated and untreated infertile patients.
The case-control and cohort studies were analyzed separately. In line with the earlier studies, the case-control data showed that the women with ovarian cancer appeared to have a significantly higher risk of exposure to fertility drugs when compared with a control group of noninfertile women. However, exposure to fertility drugs was not higher in infertile women who developed ovarian cancer than in infertile controls. When the cohort data were considered, there was a trend for untreated infertile controls to have a higher incidence of ovarian cancer than the treated infertile women.
Conclusions and Clinical Implications
The cohort studies, however, strongly suggest that infertility drugs do not increase the risk of ovarian cancer when treated women are compared with untreated infertile controls
The authors point out that cohort studies are stronger methodologically than case-control studies for establishing an association between infertility treatment and ovarian cancer. In their meta-analysis the case-control data proved neutral, showing neither a negative nor positive effect of infertility drug treatment. The cohort studies, however, strongly suggest that infertility drugs do not increase the risk of ovarian cancer when treated women are compared with untreated infertile controls. In fact, the treated women appear to have a lower incidence of ovarian cancer, suggesting that infertility treatment may have a protective effect, possibly related to the achievement of pregnancy.
Kashyap S, Moher D, Fung MFK, Rosenwaks Z. Assisted reproductive technology and the incidence of ovarian cancer: a meta-analysis. Obstet Gynecol 2004;103:785-794.
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