Assisted reproduction not tied to long-term ovarian cancer risk
Women who undergo assisted reproductive technology (ART) treatment for infertility appear to have an elevated risk of ovarian cancer, but the lack of long-term association suggests that detection bias as well as parity and cause of infertility may play roles and not ovarian stimulating hormones, according to a study from Denmark.
“ART treatment was not associated with a long-term increased risk of ovarian cancer which would be expected if caused by ovarian stimulating hormones,” said the researchers. “This pattern suggests an influence of detection bias while undergoing ART treatment,” they said.
“I would advise infertile women contemplating ART treatment to go ahead,” said study author Professor Anja Pinborg from Copenhagen University Hospital in Copenhagen, Denmark, who presented the findings at the annual meeting of the European Society of Human Reproduction and Embryology (ESHRE 2018).
Using the Danish National ART-Couple II (DANAC II) cohort which consists of all women who received ART treatment at fertility clinics between 1994 and 2015, researchers matched 58,472 women (mean age 33 years, 79.6 percent nulliparous) who had received ART treatment with 549,210 women (mean age 33.1 years, 42.3 percent nulliparous) who had never received ART treatment (background population). The women were followed up until end of study (December 2015), or primary cancer diagnosis, death, or migration, during which time 393 women (0.06 percent) were diagnosed with ovarian cancer, 64 (0.11 percent) and 329 (0.06 percent) in the ART and non-ART groups, respectively.
The risk of ovarian cancer was higher among women who had undergone ART treatment compared with women who had not (hazard ratio [HR], 1.20, 95 percent confidence interval [CI], 1.10–1.31). [ESHRE 2018, abstract O-193]
This elevated risk following ART treatment was demonstrated among parous women (HR, 1.34, 95 percent CI, 1.11–1.62). However, among nulliparous women, the risk of ovarian cancer was twofold, regardless of whether they had undergone ART treatment (HR, 2.38, 95 percent CI, 2.17–2.60) or had not (HR, 2.03, 95 percent CI, 1.89–2.19).
The elevated risk of ovarian cancer among women who received ART treatment was highest within the first 2 years of treatment initiation (HR, 1.24, 95 percent CI, 1.06–1.45), gradually decreasing until 12 years after treatment initiation when the risk was comparable with that of the background population (HR, 1.05, 95 percent CI, 0.87–1.27).
The elevated risk of ovarian cancer also only affected women who underwent ART treatment due to female factor infertility (HR, 1.36, 95 percent CI, 1.25–1.48) but not male factor or unexplained infertility where the risk was lower (HR, 0.87, 95 percent CI, 0.76–1.00).
“Some studies have found a positive association between ovarian cancer and ART treatment but whether there is a causal relationship is still a question,” said Pinborg.
“ART treatment was associated with ovarian cancer but the association was explained primarily by a higher prevalence of nulliparity. Nulliparity and female cause of infertility is associated with higher risk of ovarian cancer regardless of ART treatment,” said Pinborg.
“Female infertility is related to ovarian cancer and nulliparity is adding on this risk,” said Pinborg. “Whether it is the cause of infertility that is related to the risk of ovarian cancer or whether it is early stages of ovarian cancer that cause the infertility still needs to be explored,” she said.