Hormonal stimulation during treatment of infertility and risk of breat cancer

Introduction an Aim: Over the past decades, the use of ovulation inducing drugs has been increasing. A possible causal link between fertility treatments (especially clomiphene citrate and gonadotrophins) and various types of malignancies, including cancers of female reproductive system, thyroid cancer and melanoma, has been postulated. A possible correlation between hormonal stimulation during treatment of infertility and the risk of cancer of the breast, the ovaries, the cervix or the uterus has been investigated in a number of epidemiological studies. Breast cancer is the most frequent cancer in reproductive age women. Although well known causal link between estrogen and breast cancer, the impact of ovulation induction on the risk of breast cancer still remains to be clarified. Breast cancer is a classic model of a hormone-dependent malignancy. Since the drugs used for ovulation induction as part of in vitro fertilization (IVF) treatment increase the levels of endogenous gonadal hormones, concerns have arisen regarding a possible association between IVF and the risk of developing breast cancer. The aim of this review is to determine the potential link between the use of fertility drugs and the risk of developing breast cancer in women treated for infertility.Methods: This review article is based on literature searches in the databases MEDLINE, Cochrane and EMBASE.Results: No studies showed a specific general correlation between hormonal ovulatory stimulation used as pre-treatment to assisted fertilisation and an increased risk of cancer of the breast, the ovaries, the cervix or the uterus. Most studies detected no increased risk. Some studies, however, showed an increased risk of cancer among certain sub-groups, such as women who have received repeated treatment with clomiphene citrate. An increased risk was recently observed in women giving birth after in vitro fertilization (IVF), but it appeared to be consequential to the infertile status rather than the effect of fertility drugs. More controversial are the results concerning breast cancer with some investigations suggesting an increased risk after exposure to ovulation inducing agents, especially clomiphene citrate, whereas others not supporting this concept. A possible trend towards an increased risk has been reported by some authors for endometrial cancer. results for increased risk for breast cancer and endometrial cancer following exposure to ovarian stimulation medications are inconclusive. Larger population studies with longer periods of follow-up and better adjustment for confounding factors are needed. However, one study showed that infertility treatment was associated with an increased risk of breast cancer of borderline significance among women with a family history of the disease. Another study showed that the incidence of breast cancer within the first year of exposure to fertility drugs was higher than expected, possibly due to the promotion of preexisting cancer lesions caused by superovulation or due to the early diagnosis made in the course of IVF treatment. Conflicting results were reported regarding the type of fertility treatment and breast cancer risk.Conclusion: Based on the reviewed studies, the conclusions are ambiguous. It is therefore necessary to monitor the long-term effects of infertility treatment on women s health. Further good-quality large-scale population studies are necessary, with longer follow-up periods and better adjustment for confounding factors.

Keywords:

Ovarian stimulation , agents , Breast cancer , Infertility