New study examines long-term health effects of fertility treatment

While women with infertility are increasingly seeking fertility therapy, little research has been done to examine its long-term health effects.

A new study, published Monday in the Canadian Medical Association Journal (CMAJ), aims to shed light on this topic, examining years of health data on women who received fertility treatment in Ontario.

It found women who received fertility treatment, but did not give birth, were 19 per cent more likely to experience a cardiovascular event, particularly heart failure, compared with those who gave birth within one year of fertility treatment. However, this increased relative risk was mostly seen within the first five years after therapy, and researchers emphasized the absolute risk was modest, amounting to 10 cardiovascular events for every 1,000 women for whom fertility treatment failed, compared with six events for every 1,000 women who gave birth after treatment.

Dr. Jacob Udell, lead author of the study and a scientist at the Institute for Clinical Evaluative Sciences, said the findings should not deter women from seeking fertility treatment.

"We don't suggest women who are in need of these therapies don't get them," he said.

Rather, he said, women for whom fertility treatments fail could benefit from additional measures to protect their cardiovascular health as they age. He suggested those who are middle-aged or older may wish to mention prior failed fertility therapy to their doctors.

"That may factor into how aggressive one should be in terms of reducing the risk for health disease, looking at healthy lifestyle, exercise, diet, smoking cessation as well as treating blood pressure and cholesterol," said Dr. Udell, a cardiologist at the Peter Munk Cardiac Centre at Toronto General Hospital and Women's College Hospital.

The study, funded by the Heart and Stroke Foundation of Canada and the Canada Research Chair in Medical Decision Science, analyzed data on 28,442 women, 50 and younger, who received fertility therapy in Ontario between 1993 and 2011. Of these, 32 per cent gave birth within one year after receiving their last fertility treatment, while 67 per cent did not. The median number of fertility treatments was three. Researchers found 2,686 cardiovascular events occurred over a median 8.4 years after receiving treatment.

Dr. Udell noted the study did not determine how the long-term health risks of women who receive fertility treatment compare with those who do not receive treatment. With the available data, researchers were also not certain of the type of fertility drugs that were used or the doses.

Dr. Udell suggested there are two possible explanations for the increased risk of heart disease and stroke found in women for whom fertility therapy failed. The first is that fertility treatment may act as a metabolic stress test; when it is unsuccessful, it unmasks or points out individuals who may have medical problems later in life, he said.

The other possibility is that exposure to fertility drugs could lead to a higher risk of heart failure and stroke.

"It's unclear which one [is the answer] and in this study, we can't tell the difference," he said.

This study provides a rare examination of fertility issues, which are often overlooked in large population studies, said Dr. Heather Shapiro, past-president of the Canadian Fertility and Andrology Society, who was not involved in the study.

However, she noted an unknown number of women who were categorized as having had successful fertility treatment in the study may, in fact, have had failed therapy. The study considered treatment to have failed if it was not followed by a birth within one year, but this would have more accurately been defined as not having a birth within the typical gestation period of nine months, said Dr. Shapiro, a reproductive specialist at Mount Sinai Fertility and vice-chair of education in the department of obstetrics and gynecology at University of Toronto.

Moreover, since the study relies on Ontario Health Insurance Plan data, it does not capture a significant number of individuals who used fertility treatment not covered by the provincial health plan, she said.

"When those two things are taken into consideration – people who maybe should have been in one group but were in the other and a whole swath of people who weren't even accounted for – it's very hard for me to take anything meaningful from this," she said.

Dr. Shapiro said this study may be helpful as an exploratory exercise to determine further research, but its findings should not influence clinical practice.

"If people came to me and said, 'I've read this [study]. How should it change the way I approach fertility?' My answer would be it should not change our practice at all," she said.