with clomiphene use, but there were not enough subjects for the results to be statistically significant.

Looking more closely at the data, Dr. Ness said, there does seem to be some reason for concern. The numbers of women in the analyses are very small, so it is difficult to attain statistical significance for the results, but there are trends that deserve a closer look. With increased dosage, with a greater number of cycles of using the fertility drugs, and with more years since first use, the number of uterine cancer cases seemed to be going up. One study in particular focused just on women who had taken clomiphene and looked at the rates of various cancers. It found that as time elapsed since the treatment, there did seem to be an increase in risk for breast, ovarian, and endometrial cancers, with the highest risks for the endometrial cancers. This is of particular concern, Dr. Ness said, because it raises the possibility that many studies have missed the increased cancer risk because they haven’t followed their subjects for enough years.

Dr. Ness summarized what is known about fertility drugs and cancer risk this way: “There's no evidence that fertility drugs elevate the risk of breast cancer. There are a couple of little signals in maybe one study, but if we look overall at the literature, it is not terribly convincing. Infertility, not the assisted reproduction therapy, certainly increases the risk of ovarian cancer. There is no systematic evidence at this point that fertility drugs elevate the risk for invasive ovarian cancer. But for uterine cancer, where the data are too sparse to lead to any conclusion, I think that there's a greater concern. And the final concern is that these effects may not be evident until a longer period of time has elapsed between the exposure, the assisted reproduction therapy, and the cancer.”

POTENTIAL LONG-TERM FERTILITY EFFECTS

One of the major concerns that has been raised about the possible risks involved with hormone treatment is that the treatment may have some effect on a woman’s long-term fertility. “We've heard a lot about ovarian stimulation as a route to achieving more eggs,” Dr. Cataldo said. “The question exists whether this results in a depletion of the woman's egg supply. This is an important question, because if this were true, the retrieval of 20 eggs instead of the ovulation of 1 per cycle for 5 or 10 donation cycles might imply a considerable number of oocytes lost. And one might also worry that this could hasten the onset of age-related infer-



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