**3.3 The risk for cancer development after IVF treatment**

The impact of infertility and fertility treatments on cancer risk has become more and more prevalent since the increasing need to use IVF treatment in current society. Relatively low number of studies has been published to investigate the relation between IVF treatment and developing cancer risk. The administration of high doses of gonadotrophin analogues during the induction of the ovaries and synthetic E2 and P4 preparations in order to support the endometrium has raised the question of a possible contribution of supraphysiological levels of hormones to the development of breast or other cancer types. Previous studies have demonstrated a possible association between infertility treatments and breast cancer for women treated with at least six cycles with clomiphene citrate, or within the first year after starting IVF (Venn et al., 1995, 2001). Also women who start IVF after the age of 30 appear to be at increased risk of developing breast cancer (Katz et al., 2008; Pappo et al., 2008). Other

the effects of prostaglandins are neutralized (Brogden et al., 1993). Most research and clinical experience with Mifepristone involves its use as an aborted material. Several studies reported its effectiveness in softening and dilation of the cervix prior to surgical abortion, decrease of pain in women with diagnosed endometriosis and in labour inducement (Goldberg et al., 1998). In the absence of P4, however, Mifepristone can act as a partial agonist (Spitz et al., 1993) and upregulate P4-responsive genes, such as p53, and through

Fig. 5. **The opposite effect of SERM on breast and uterine cell proliferation.** SERM might inhibit the ER found in breast cancer cells but activate the ER present in uterine endometrial cells. A SERM of this type would inhibit cell proliferation in breast cells, but stimulate the

http://www.cancer.gov/cancertopics/understandingcancer/estrogenreceptors/page14)

The impact of infertility and fertility treatments on cancer risk has become more and more prevalent since the increasing need to use IVF treatment in current society. Relatively low number of studies has been published to investigate the relation between IVF treatment and developing cancer risk. The administration of high doses of gonadotrophin analogues during the induction of the ovaries and synthetic E2 and P4 preparations in order to support the endometrium has raised the question of a possible contribution of supraphysiological levels of hormones to the development of breast or other cancer types. Previous studies have demonstrated a possible association between infertility treatments and breast cancer for women treated with at least six cycles with clomiphene citrate, or within the first year after starting IVF (Venn et al., 1995, 2001). Also women who start IVF after the age of 30 appear to be at increased risk of developing breast cancer (Katz et al., 2008; Pappo et al., 2008). Other

proliferation of uterine endometrial cells. (Figure adapted from internet:

**3.3 The risk for cancer development after IVF treatment** 

this possesses a slight anticarcinogenic effect.

studies have found elevated risk for ovarian cancer too but probably the risk was already higher prior to the first IVF (Källen et al., 2005; Kristiansson et al., 2007). However, there are publications, which have not found a relation between infertility treatments and any cancer development (Potashnik et al., 1999, Doyle et al., 2002; Dor et al., 2002; Lerner-Geva et al., 2010; Brinton et al., 2004). For example, a case-control study (1380 pairs) showed no risk for IVF treatment even among women who carry mutations in breast cancer susceptibility gene 1 (BRCA1) or BRCA2 gene (Kotsopoulos et al., 2008). The common opinion today is that the use of fertility medications does not increase the risk of breast cancer among those with family history of BRCA mutations.

A more recent study, published by Källen and colleagues using Swedish cancer register, showed that there was no or significantly low cancer risk among women udergoing IVF treatment compared to general population. The study included 24 058 women who had been treated with IVF where 1279 women later appeared in the cancer register. For comparison, total of 1 394 061 women in the general population were studied as a control group where 95 775 women had registered cancer (Källen et al., 2011).

The phrase "healthy patient effect" has emerged saying that women who choose IVF treatment might be more aware of risks or more health conscious at the time of conception compared to non-IVF women (Venn et al., 2001). In addition, there are numerous confounding factors which could influence the outcome of the study like the age at the time of the first IVF cycle or the first delivery, the number of the unsuccessful cycles and the follow up time after last IVF treatment. It is obvious that the question needs to be studied in more detail involving large number of women and with attention to precise subgroups.
