The Link Between Fertility Drugs and Ovarian Cancer

Ever since January 1993 when a study was reported by researchers at Stanford University suggesting that the use of fertility agents increased the risk of ovarian cancer, there has been tremendous concern and anxiety among women who use fertility drugs. At first, the findings seemed well founded because intuitively it made biological sense that fertility drugs might promote cancer due to the increased the number of ovulations a woman has. And so, the studies received wide public attention. It subsequently turned out that this study which was based on, data compiled from 12 retrospective studies on ovarian cancer patients done in the late seventies and early eighties was seriously flawed for the following reasons:

  • While, retrospective (trohoc) studies have value in identifying an area of relevance for subsequent evaluation they are inadequate for reaching definitive conclusions. The only valid way to conclusively determine whether there is a link between prior use of fertility drugs and ovarian cancer would be through prospectively controlled statistical studies that compare the risk of ovarian cancer in infertile women who undergo ovarian stimulation with infertile women who do not.
  • Infertile women who spend more than five years trying to conceive have about a 3 times higher risk for ovarian cancer than do fertile women. This is especially true when the infertility is due to absent or dysfunctional ovulation. Prior to the 90’s when the era of ovulation induction for intrauterine insemination (IUI) and IVF began to take off , the commonest indication for the use of fertility drugs was to induce  ovulation in women who were not ovulating at all or normally. That all changed as more and more normally ovulating women started having IUI and IVF. Today, in 1st world countries, the number of normally ovulating women who receive fertility drugs exceeds those who receive such treatment because of absent or abnormal ovulation.  Thus the emphasis has changed dramatically and with it, the risk of ovarian cancer has declined commensurately.
  • Animal studies suggest that in contrast to gonadotropins, clomiphene citrate might after long and sustained usage, be carcinogenic. Since the 1993 Stanford University study data was derived at a time when most women undergoing COH were receiving clomiphene citrate (rather than gonadotropins), the possibility exists that the higher incidence of ovarian cancer might, at least in part, be due to this factor.
  • The 1993 report did not take into account that pregnancy itself has a protective effect against the development of ovarian cancer. This means that those women who in fact conceived following the use of fertility drugs might through the occurrence of pregnancy have reduced their risk of subsequently getting ovarian cancer.

Most important is the fact that several large prospective studies have now refuted the existence of a link between the use of gonadotropins and ovarian cancer. On the other hand, there does appear to be an association between ovarian cancer and certain causes of infertility itself, such as endometriosis.
While the case is still out with regard to whether or not in humans the prolonged and repeated use of clomiphene citrate increases the risk of ovarian cancer, when it comes to the use of gonadotropins for controlled ovarian stimulation (COS) women can in my opinion, breathe easy.

 

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