Pew Funds Genetics and Public Policy Center's New Consumer Genetics Project
The Pew Charitable Trust has awarded $750,000 to the Genetics and Public Policy Center for a new project focused on consumer protections for applications of genetic testing.
Gynecologic Cancer
Much of the discussion to date about ovulation induction drugs and cancer addresses the risks associated with the use of one drug in particular, clomiphene citrate. Clomiphene is used for ovulation induction among women who have stopped ovulating or those undergoing artificial insemination but which is not commonly used for oocyte donation or IVF. Some, but not all studies have identified a positive association between clomiphene and malignancies, both gynecologic and non-gynecologic. (Rossing et al., 1994; Whittemore et al., 1994). Concerns about clomiphene often have carried over to a similar concern about gonadoptropins, a separate set of drugs used to induce controlled ovarian hyperstimulation.
In 2005, a systematic review of nearly 100 studies examined the incidence of breast, ovarian, endometrial, melanoma, and other malignancies. (Brinton et al., 2005). In general, that review concluded that while some studies had shown a link between ovarian stimulation drugs (both those used to induce ovulation and those used to stimulate the ovaries for IVF purposes) and cancer risk, many of these studies had significant shortcomings. Two later studies similarly concluded that there is no clear evidence that infertility treatment causes cancer but that additional data are needed to thoroughly investigate this issue. (Salahab et al., 2005; Mohdavi et al., 2006)
Ovarian Cancer
The data concerning the link between infertility treatment and ovarian cancer are limited by several factors. First, sample groups in the studies have been small. Second, there has not been long-term follow-up with patients. Third, many of these investigations have been conducted as cohort studies, which are not considered as reliable as randomized controlled trials. (Gordis, 2004).
Brinton et al. (2005) concluded from a systematic review of multiple studies that there “is no conclusive link between fertility drug use and ovarian cancer.” A few trends did exist among the studies. First, ovarian cancer occurred predominantly among nulliparous women (women who have borne no children). However, this group already is at an increased baseline risk of malignancies because of their reproductive histories. Second, some studies found an increase in borderline ovarian tumors among women who underwent IVF. However, it has been proposed that the gonadotropins used might have induced the growth of already existing borderline tumors and that these women, because of their increased awareness of health issues, are more likely to be diagnosed at an earlier stage.
Breast Cancer
Studies addressing the risk of breast cancer from infertility treatment are somewhat conflicting. Some studies suggest an increased breast cancer risk while others do not. For instance, a study by Burkman noted that, in general, infertility drug use is not associated with an increased risk of breast cancer. However, those women who used a specific hormone, Human Menopausal gonadotropin (hMG), for at least six treatment cycles or months had a two to three-fold increased risk of breast cancer (Burkman et al, 2003). However, the investigators make note that these data should be approached with caution, given the number of limiting and confounding elements to the study. In another investigation, Brinton and collegues concluded that the data about the risk of breast cancer following infertility treatment are inconsistent. It is particularly difficult to tease out the effects of gonadotropins on breast cancer risk. Breast cancer is a malignancy often directly related to the hormonal environment of the women, an environment that can be temporarily increased by gonadotropin administration. In addition, many of the studies on this topic relied on thepatient to report her fertility drug dosage and duration many years after the initial treatment for infertility, raising questions about accuracy and utility of the data. Finally, as is the case with ovarian cancer, any increased incidence of breast cancer may be linked with the effects of fertility agents on an existing tumor that may be detected earlier because of the patient’s increased awareness of and attention to her health.
Endometrial Cancer
The data regarding endometrial cancer is not as robust as that for breast and ovarian cancer. In addition, the majority of research in this area pertains to the use of clomiphene and the risk of cancer. Though there is evidence that there is a twofold increase in relative risk of endometrial cancer among clomiphene users, this same trend was not noted among IVF patients (Althuis et al., 2005a). There have been very few studies that have looked directly at the effect of IVFspecific agents. Most cohort studies have not identified an increase risk of endometrial cancer specifically with IVF agents. However, some of the studies that have identified an increased risk of endometrial cancer interpret this more as a function of long-term unopposed estrogen exposure, a hormonal state associated with infertility and endometrial cancer, than the use of fertility drugs alone. At the same time, the investigators comment that more definitive evidence is required before dismissing this potential association (Modan et al., 1998).
