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Fady I. Sharara, MD, FACOG
Fertility Drugs and Ovarian Cancer
Virginia Center for Reproductive Medicine

Fertility Drugs and Ovarian Cancer

Ovarian cancer occurs in 1-2% of US women, with a mean age at diagnosis of 60. Some women with a family history of ovarian cancer, and especially those with special genetic mutations (such as BRAC1 and 2) have a higher incidence of ovarian cancer. There are also protective factors against developing ovarian cancer, such as using the birth control pill for five years or more, having a tubal ligation, and having four or more pregnancies. The increased awareness of infertility in the general population, better access to health care, and the vast improvements in fertility treatment, especially better success rates with IVF, have resulted in increased use of fertility medications.
A lot of media attention has been generated as to whether there is an association between ovarian cancer and fertility drugs. Some of the earlier studies have suggested such an association (these studies were based on a very small number of women with ovarian cancer and infertility), but nearly all of the newer (and larger) studies have failed to detect such an association.
In one large study conducted between 1989 and 1999 in eight centers in the US, Denmark, Canada, and New Zealand, 5,207 women with ovarian cancer were studied along with 7,705 matched controls. The study was adjusted for age, race, family history of ovarian cancer, duration of oral contraceptive use, tubal ligation, number of prior pregnancies, education, and research site (all factors that can affect ovarian cancer positively or negatively).
The results from that study showed that infertile women who have failed to get pregnant after five years of infertility are 2.7 times as likely to develop ovarian cancer compared to women who get pregnant in less than one year of trying to conceive. However, the investigators could not find any association between fertility drug use or duration of fertility drug use and ovarian cancer. In addition, fertility drug use in infertile women who never delivered a child was associated with a 2.5 times higher incidence of borderline serous ovarian cancer (these are non-invasive cancers with excellent chances for cure with surgery), but not with invasive ovarian cancer.
Are women willing to accept the theoretical risk of a higher chance of developing ovarian cancer if fertility treatment will result in a pregnancy? That question was posed to a group of 61 women at two fertility clinics in Toronto in 1997. Of the 52 who responded, 48 (79%) were willing to accept an increased risk of ovarian cancer (for some even if it meant increasing their risk five fold).
What are the current guidelines for use of fertility medications? Most clinicians recommend that women do not undergo more than three cycles of clomiphene citrate (Clomid), three cycles of injectable medications in conjunction with IUI, and if not pregnant, three cycles of IVF or IVF/ICSI. The women who fail to conceive after three cycles of IVF should consider donor egg or adoption.
In brief, the latest data on this subject are very reassuring and suggest that the use of fertility drugs, and the duration of fertility drug use, are not associated with a higher chance of developing invasive ovarian cancer.
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