Does IVF treatment increase the risk of ovarian, uterine and breast cancer?

There has been a suggested link between the use of fertility drugs and the risk of ovarian, breast and endometrial cancer. Many studies lack control for possible confounding factors such as age, type of infertility, have relatively short follow-up periods. Furthermore, an increased risk may be due to an increased surveillance. In general, women are at significantly high risk of cancer due to their infertility and other confounding factors such as age, and family history of cancer, and previous pregnancy. Current studies have suggested the following with regards to each respective cancer.

Ovarian cancer

There are controversial studies linking ovarian stimulation drugs to ovarian cancer. The evidence is observational and there are significant problems in many of these studies, particularly in subgroup analysis, and by inability to control for other cancer confounding factors. Some studies have shown that infertile women who use infertility drugs but still never achieve pregnancy had a significantly increased risk of ovarian cancer compared to women who had no infertility problem. Currently, a small increased risk of borderline ovarian tumours cannot be excluded.

Jensen and colleagues analysed 54362 infertile women who were referred to Danish Fertility Centers from 1963 to 1998. They reported that the use of gonadotropins, clomifene, human chorionic gondaotrophin, and gonadotrophin releasing hormone were not associated with an overall increase in the risk of ovarian cancer. Furthermore, they found no increased risk of ovarian cancer in women who had 10 or more IVF cycles or in those who did not conceive after IVF treatments

Breast cancer

The exposure of the breasts to high concentration of estrogen during ovarian stimulation has raised concerns that IVF may add further risk. . There are controversial studies linking ovarian stimulation drugs to breast cancer. The evidence is observational and there are significant problems in many of these studies, particularly in subgroup analysis, and by inability to control for other cancer confounding factors. In a large study involving 10,358 women and followed up to 15 years, there was no increased risk compared with the expected risk in general population. A recent study from Netherland reported no significant difference in breast cancer among women undergoing fertility treatment and control after a median follow up of 21 years.

Endometrial cancer

The risk of endometrial cancer is increased in the infertile population. Venn and colleague compared 20,656 women who received fertility drugs with 9,044 control and reported only a transient increase in the risk of endometrial cancer. Multiple treatment cycles and high doses of Clomiphene (clomid) may be associated with an increase of endometrial cancer but the evidence fir this is inconclusive.

Fertility treatment and childhood cancer

Several case reports highlighted a possible link between IVF and childhood cancer. However, there is no strong eidence linking infertility treatment with childhood cancer.

Sources:

Rossing MA et al. 1994 N Engl J Med
Shushan A et al. 1996 Fertil Steril
Whittemore AS et al 1992 Am J Epidemiol
Lerner-Geva et al 2000 Cancer
Brinton LA et al. 2005 Obstet Gynecol
Allan Jensen et al. 2009, BMJ.
2016, JAMA.
Venn A et al.1999.Lancet.

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