Ovulation Induction and Cancer Bilgin GÜRATEŞ, MD.

In the United States nearly doubling between 1973 and 1991. Further increases year 2025 between 5.4 and 7.7 million women aged 15–44 will be diagnosed with some form of infertility.

A number of investigations have attempted to address the long-term effects of ovulation- inducing drugs on cancer risk, but most have had shortcomings. small numbers of study subjects, short follow-up times, imprecise information on drug exposures and the indications for usage, absence of information on other correlates of drug exposure that could influence cancer risk.

BACKGROUND Three lines of evidence raise concern regarding potential effects of ovulation-inducing drugs on cancer risk. 1. most commonly used medications, clomiphene citrate and gonadotropins in the etiology of both breast and ovarian cancers 2. these drugs raise both E2 and P levels 3. Some clinical and epidemiological studies have linked use of these drugs with an increased incidence of various cancers.

OVARIAN CANCER

Brinton LA, Lamb EJ, Moghissi KS, Scoccia B, Althuis MD, Mabie JE, et al. Ovarian cancer risk after use of ovulation-stimulating drugs. Obstet Gynecol 2004;103:1194 –203. The results were largely reassuring, showing no increases in risk associated with ever use of either clomiphene or gonadotropins. There were nonsignificant increases in risk (range of RRs, 1.5–2.5) associated with the use of either clomiphene or gonadotropins among the subjects followed for the longest periods of time, that is, 15 or more years.

OVARIAN CANCER

We should emphasize that the association between borderline tumors and ovulationinducing drugs was not a consistent finding among different studies. The relation between subfertility treatment and the risk of non-epithelial ovarian malignancies is even less clear.

In summary, the findings to date on ovarian cancer (especially invasive epithelial carcinoma and non-epithelial neoplasia) risk associated with fertility drug treatment are reassuring, but not definitive. A stronger association has been observed between fertility drug use and borderline tumors of the ovary. This finding, however, is not consistent among the available studies to date.

BREAST CANCER

ENDOMETRIAL CANCER twofold increase Non significant increas (RR 1.8; 95% CI, 0.9 –3.3) Few studies have been undertaken to assess the relationship between ovulation induction and endometrial cancer. Based on the two largest studies that demonstrate somewhat increased risks (similar to what has been previously observed for another SERM, tamoxifen), further study of the relationships appears warranted.

MELANOMA The available evidence does not allow any conclusions regarding this association. Further study may be warranted.

OTHER CANCERS Cervical cancer Thyroid cancer Clomiphene was reduced relative to nonusers (RR 0.4; 95% CI, 0.2– 0.8), Thyroid cancer In a pooled analysis of 13 case-control studies from North America, Asia, and Europe, use of fertility drugs was found to be associated with a 60% increase in thyroid cancer risk (95% CI, 0.9 –2.9) [La Vecchia, 1999] A significant four-fold excess risk associated with use of fertility drugs [Kolonel LN, 1990] Persistent trophoblastic tumors no additional risk Colon cancer no relationship to fertility drugs

THANK YOU