November 2, 2012

Ovarian Stimulation for IVF is Not Associated with New Ovarian Tumors

Aggressive stimulation of the ovary concerns some for the inadvertent creation of ovarian cancer. To address this concern, the OMEGA study was established. This study is a large cohort study that evaluated the effects of fertility drug usage and its potential relation to ovarian cancer risk. Approximately 20,000 women were studied with a follow up time of at least 15 years. These women underwent at least one cycle of IVF; the control group (6000 participants) of women also demonstrated infertility but was not exposed to medications. Both groups were compared to fertile women in the general population. Compared to the general population, the risk of ovarian cancer was increased in the IVF group compared to the non-exposed, infertile group. However, when these data were analyzed separately, the risk of invasive cancer was no different in comparing any of the three groups.

This data may seem confusing. Initially there seemed to be a difference in the two groups but further data suggests none – how does one resolve this seeming conflict? Firstly, not all ovarian cancers are alike similar to that fact that all women who demonstrate subfertility are not alike. The overwhelming type of ovarian cancer was the “borderline” cancer. Like its name, it is an oddity. It has molecular features of a malignant cancer, however, it is not invasive acting more like a benign growth. Furthermore, the increase in diagnosis of these cases tended to be within one year of IVF. Cancers are many years in the making. Thus, it is more likely that the women who underwent IVF and then were diagnosed with borderline ovarian cancer already had the disease; it just had not been detected yet. Corroborating these findings is the fact that the number of IVF attempts and the doses of stimulatory medications did not appear to increase the risk of diagnosis. If, indeed, these medications solely were responsible for stimulating new malignancies, then it should be expected that increased and sustained doses should greatly increase the number of detectable cancers. Such was not the case.

The conclusions suggest that stimulation may increase the growth of tumors already seeded. There are confounders (other factors that can influence outcomes). For instance, those women with infertility, if not pregnant, were less likely to return to using oral contraceptives (which lowers the risk). Lastly, the investigators pointed out that the overall risk is minimal. Additionally, there are many risk factors for ovarian cancers: early menarche, nulliparity, later first birth, lack of oral contraceptives, endometriosis and ovulatory defect. These risk factors are shared by many, but not all women who have subfertility and it is implausible to tease out one from the other.

There exists a low incidence of ovarian cancer and with ovarian stimulation the overall risk remains low. Obviously, continued gynecologic care is an essential for all women regardless of fertility history. Fertility medications and gonadotropins are efficacious and safe. With these data and the accruing of future data, confirmation of these data are to be anticipated. It is plausible that limited exposure to such influences may further decrease the chances of developing invasive cancers. IVF success rates increase as technologies are improved. So, perhaps finding the most efficient modicums to pregnancy reduces the time of exposure and overall risks.

 

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Danielle Vitiello, Ph.D., M.D.

Danielle Vitiello, Ph.D., M.D. Board-Certified in Obstetrics and Gynecology, Reproductive Endocrinology and Infertility