Ovarian cancer risk increases after IVF


Women who underwent at least one vitro fertilization cycle in an effort to become pregnant were almost twice as likely to develop ovarian cancer as women who experienced infertility but did not get such treatment, say the authors of a large Dutch study published this week.

The study is one of the largest conducted to date and tracked women for roughly 15 years after their first IVF cycle. Its findings appear to contradict those of an even larger Danish study published in 2009, which found no increase in cancer risk among women who had undergone infertility treatment. But the study’s design and its long tracking period allow the study to bring some clarity to a relationship between IVF and cancer that has been long feared but inconsistently proven by researchers.

It was published in the European journal Human Reproduction.

It found that for women who underwent at least one IVF cycle, the greatest increased risk was for “borderline ovarian tumors,” which are less aggressive than invasive ovarian cancer and are far more treatable, though still difficult to detect: Women who took medication to stimulate the growth of eggs and had them surgically removed for fertilization were almost three times more likely than infertile women who did not get such treatment to be diagnosed with a borderline ovarian tumor.

Borderline ovarian tumors are very slow growing and do not spread, or metastasize, in the way that invasive ovarian cancer does. And unlike invasive ovarian cancer, they are not likely to lead to death. They grow and must be surgically removed but are not generally treated with chemotherapy.

Averaged over the study period, rates of invasive ovarian cancer--a far more serious condition that typically kills four in five of women diagnosed-- were not significantly higher for women who had had IVF treatment than for those who had not. But the longer the two groups of women were tracked, the more evident differences became. Among women who were tracked for 15 years or more after their first IVF cycle, rates of invasive ovarian cancer were more than three times higher than invasive ovarian cancer rates among their long-tracked sisters who had not had IVF. Such cancer is rarely found early and is typically advanced when diagnosed.

Ovarian cancer is the fourth leading cause of deaths in women due to cancer, a number that appears to be rising. But it is rare: women’s risk for ovarian cancer increases with age, but even so, between the age of 50 and 70 years old, just .58% of women will get such a diagnosis. So increases in risk, even when they appear large, do not make ovarian cancer a high likelihood.

Dr. Khrishnansu Tewari, a gynecologic oncologist at Orange Coast Memorial Medical Center and associate professor at University of California Irvine, said the study’s findings are in some ways reassuring, in that invasive ovarian cancer rates did not, on average, go up for women who underwent IVF. He added that borderline ovarian tumors are highly treatable. And he said that the Dutch study is not more revealing than the 2009 study which came to an opposite conclusion. “I don’t think readers should make too much of this,” Tewari said.

The authors of the study, led by the Dutch Cancer Institute’s Flora van Leeuven, said that patients and physicians will likely vary in their interpretation of the findings, depending on the urgency with which they wish to produce a pregnancy. “It should be explained to women opting for IVF treatment that a borderline ovarian tumor does not constitute a lethal disease, although it may require extensive surgery and cause substantial morbidity,” the authors wrote.

At least one of the Dutch study’s findings raises more questions than it answers. The researchers found no increase in ovarian cancer rates when a woman had several cycles of IVF: Whether she had undergone one cycle or five in an effort to conceive a baby, the increase in ovarian cancer risk was the same. That absence of a “dose response relationship,” in addition to the finding that, overall, invasive ovarian cancer rates did not rise with IVF, mean there’s likely to be more research--and more twists and turns--to this line of research.