In vitro fertilization and risk of breast and gynecologic cancers: a retrospective cohort study within the Israeli Maccabi Healthcare Services

Abstract

Objective To assess long-term cancer risks associated with in vitro fertilization (IVF). Design Record-linkage study Setting Health maintenance organization in Israel Patients 87,403 women evaluated and/or treated for infertility on or after September 25, 1994 who were followed for cancer development through June 22, 2011: 522 breast, 41 endometrial, 45 ovarian, 311 in situ cervical and 32 invasive cervical cancers were identified. Intervention(s) None Main Outcome Measures Hazard ratios (HRs) for specific cancers Results We found no significant relationships of IVF exposures to the risks of breast, endometrial or ovarian cancers. Compared to women with no fertility treatment, the HR for ovarian cancer associated with IVF was 1.58 (95% CI 0.75–3.29), with higher risk among those receiving 4+ cycles (1.78, 95% CI 0.76–4.13). There was also a non-significantly elevated risk for endometrial cancer among women who received 1–3 IVF cycles (1.94, 0.73–5.12), but additional cycles were associated with lesser risk. In contrast, the risk of in situ cervical cancer was significantly reduced and invasive cervical cancer non-significantly reduced among women receiving IVF as well as other fertility treatments. Conclusions Our results regarding long-term effects were largely reassuring, but women receiving IVF should continue to be monitored given that the procedures involves potent ovulation stimulators and repeated ovarian punctures.

Environmental (nongenetic) factors in gynecological cancers: update and future perspectives

“…Initial concerns came from two small studies suggesting that women who had taken fertility drugs did indeed have an increased risk of ovarian cancer [16,40]. Subsequent studies have generally not shown significant associations between use of fertility drugs and risk of ovarian [41], endometrial [42,43] or cervical cancer [44] overall, but some have reported significant or nonsignificant increased risks for specific fertility drugs [42,43], women who have undergone a greater number of cycles of treatment [42,43] or with increasing duration of follow-up [43]. Most studies have, however, had limited power to detect an association, particularly in subgroup analyses.…”

The determination of possible genetic damage to women undergoing in vitro fertilization due to infertility caused by the male factor

“…If estrogen concentration exceeds the threshold value, then its risk occurs as genotoxicity (Metzler et al, 1998). However, the use of fertility medicine and various cancers is not found to be related in some studies (Brinton et al, 2013;Dor et al, 2002;Jensen et al, 2007;Lerner-Geva et al, 2003;Modan et al, 1998;Potashnik et al, 1999;Sergentanis et al, 2014). Some studies claimed that there is no significant relationship between the use of fertility medicine, or other medicine used to stimulate ovaries and breast, and ovarian or endometrium cancer (Jensen et al, 2007;Modan et al, 1998;Potashnik et al, 1999;Zreik et al, 2010).…”

“…Some studies claimed that there is no significant relationship between the use of fertility medicine, or other medicine used to stimulate ovaries and breast, and ovarian or endometrium cancer (Jensen et al, 2007;Modan et al, 1998;Potashnik et al, 1999;Zreik et al, 2010). Furthermore, no significant difference was found between women who took IVF treatment and the general population for the formation of breast cancer and ovarian cancer (Brinton et al, 2013;Dor et al, 2002;Lerner-Geva et al, 2003;Sergentanis et al, 2014;Venn et al, 1999Venn et al, , 2001. According to a study conducted on 29,700 IVF patients, ovarian, breast, and uterine cancer formation in patients is not higher than the general population's cancer incidence rates (Venn et al, 1999(Venn et al, , 2001.…”

“…The relationship between infertility and associated medications has been of widespread interest with regard to cancer risk (Brinton et al, 2013). Many studies in literature deal with the relationship between fertility medicine and the formation of cancer (Hannibal et al, 2008;Jensen et al, 2007;Lerner-Geva et al, 2003;Modan et al, 1998;Potashnik et al, 1999;Tonguc et al, 2011;Van Leeuwen et al, 2011).…”

“…Many studies in literature deal with the relationship between fertility medicine and the formation of cancer (Hannibal et al, 2008;Jensen et al, 2007;Lerner-Geva et al, 2003;Modan et al, 1998;Potashnik et al, 1999;Tonguc et al, 2011;Van Leeuwen et al, 2011). Some studies report an increase in cancer risk due to use of fertility medicine, whereas majority of the studies claim that use of fertility medicine does not increase cancer risk (Brinton et al, 2013;Jensen et al, 2007;Kashyap and Davis, 2003;Sergentanis et al, 2014;Zreik et al, 2010). Due to conflicting results, in our study, the possible genotoxic damage to women who were exposed to in vitro fertilization due to infertility with male factor was investigated with four different genotoxicity tests (CA, SCE, MN, and comet tests).…”