The OMEGA cohort

We recently completed a very large cohort study examining whether women who underwent ovarian stimulation for IVF have an increased risk of ovarian tumors later in life.  The OMEGA cohort included over 40,000 subfertile women, 30,625 women who received ovarian stimulation for IVF in 1983-2000 and 9,988 subfertile women not treated with IVF.

After a median follow-up of 24 years, 158 invasive and 100 borderline ovarian tumors were observed. Ovarian cancer risk was increased in the IVF group compared with ovarian cancer incidence in the Dutch population (Standardized Incidence Rate (SIR)=1.43) but not when directly compared with the non-IVF group (Hazard Ratio (HR)=1.02). Compared with the non-IVF group no trend was observed with more IVF treatment cycles. In women with a follow-up period of ≥20 years, ART did not increase the risk of ovarian cancer compared to the risk in non-IVF women (≥20 years HR=1.07; 95%CI=0.57-2.02). Ovarian cancer risk decreased with higher parity (number of children) and with a larger number of successful ART cycles (resulting in childbirth), but was not associated with the number of unsuccessful ART cycles.

Risk of borderline ovarian tumors was significantly increased in IVF-treated women compared with the general population (SIR=2.20) and compared with women in the non-IVF group (HR=1.84). However, no trend was observed with more IVF cycles or longer follow-up.

We conclude that, reassuringly, IVF-treated women do not have an increased risk of invasive ovarian cancer compared with subfertile women not treated with IVF. The higher risk of ovarian cancer compared with the general population is likely due to the higher prevalence of nulliparity in IVF-treated women. Our study is the first to examine whether unsuccessful IVF cycles carry a different risk of ovarian tumors than successful cycles, hypothesizing that childbirth after IVF might counteract any risk increase from IVF. Analyses incorporating numbers of successful and unsuccessful cycles showed that IVF-treated women with more successful cycles had a significantly reduced risk of ovarian cancer, whereas a larger number of unsuccessful cycles did not increase the risk. This supports our findings that IVF does not increase ovarian cancer risk and that parity also reduces risk in IVF-treated women.

However, IVF-treated women had a significantly 1.8-fold higher risk of borderline ovarian tumors than non-IVF women. Although lack of a dose-response relationship with IVF-treatment cycles does not support a causal association, more research is warranted to examine the role of IVF in the etiology of borderline ovarian tumors.