Women who use assisted reproductive technology to help them conceive a child appear not to be at an increased risk of developing ovarian cancer, a nationwide study conducted in the Netherlands has found.
The study, “Long-Term Risk of Ovarian Cancer and Borderline Tumors After Assisted Reproductive Technology,” was published in the Journal of the National Cancer Institute.
Since the implementation of assisted reproductive technology (ART) 40 years ago, there have been concerns that these methods may raise a woman’s risk of developing ovarian cancer later in life.
This is because these strategies, which include in vitro fertilization, intracytoplasmic sperm injection, and embryo cryopreservation, use hormones to stimulate ovulation, which may also lead to the formation of tumors due to excessive ovary stimulation.
Additionally, there is also the concern that the repeated ovary punctures required during these procedures may disrupt ovary tissues and also promote tumor formation.
“Because of the worldwide increase in the use of ART and the poor prognosis of ovarian cancer, it is important from a public health perspective to examine the association between ART and long-term ovarian tumor incidence,” the researchers wrote.
Although several studies have attempted to shed light on the possible relationship between ART and ovarian cancer risk, their findings have been inconsistent. In 2013, two meta-analyses reported that women resorting to ART to conceive were 35–50% more likely to develop ovarian cancer than those in the general population.
However, it was still unclear if this increased ovarian cancer risk was a direct consequence of fertility treatments, or if it could be associated with other factors, such as infertility itself.
Conducted by researchers in the Netherlands who cross-linked data from nationwide cancer and ART databases, this study provides evidence that women who undergo these fertility treatments may not be at an increased risk of developing ovarian cancer.
The nationwide study included data from 30,625 women who received ovarian stimulation for ART from 1983 to 2000, and 9,988 infertile women who did not receive any fertility treatments.
The researchers then linked the women’s fertility data to that found on two national cancer registry databases — the Netherlands Cancer Registry and the Dutch Pathology Registry — to determine the incidence of invasive and borderline ovarian tumors.
After a median follow-up of 24 years, a total of 158 invasive and 100 borderline ovarian tumors were identified. The women were at a median age of 50.2 years at the time they were diagnosed with ovarian cancer.
Analyses showed that, compared with infertile women who did not receive any fertility treatments, those who underwent ART were not at a higher risk of developing ovarian cancer at any time over the course of more than 20 years of follow-up.
“Reassuringly, women who received ovarian stimulation for assisted reproductive technology do not have an increased risk of malignant ovarian cancer, not even in the long run,” Flora E. van Leeuwen, PhD, the study’s lead author, said in a press release.
“However, it is important to realize that even with the long follow-up in our study, the median age of the women at end of follow-up was only 56 years. As the incidence of ovarian cancer in the population increases at older ages, it is important to follow assisted reproductive technology-treated women even longer,” van Leeuwen said.
Yet, when compared with women from the general Dutch population, those who had fertility treatments were found to have a 43% higher risk of developing ovarian cancer at some point in their lives.
However, subsequent analyses indicated this increased ovarian cancer risk in women who received ART was likely because a larger proportion of women in this group remained childless, which has been shown to be a risk factor for ovarian cancer.
In fact, in women who had ART, the ovarian cancer risk tended to drop with a larger number of successful ART cycles — those resulting in childbirth — and a larger number of successful pregnancies.
Additional analyses found that women who used fertility treatments had an approximately two times higher risk of having borderline ovarian tumors than those in the Dutch general population and those who were infertile but did not receive ART.
Still, this increased risk did not rise any further after these women were followed for a longer period of time or had additional ART cycles. According to the researchers, these findings suggest the increased risk for borderline ovarian tumors in these women might be related to other clinical features and not to the fertility treatments themselves.
“Although lack of a dose-response relationship with ART-treatment cycles does not support a causal association, more research is warranted to examine the role of ART in the etiology of borderline ovarian tumors,” they wrote.
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