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Study Finds No Link Between Fertility Treatments and Breast Cancer Risk

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Medicines that stimulate the ovaries to release eggs as part of fertility treatment don’t seem to increase the risk of developing breast cancer, according to a meta-analysis.

Still, the researchers said the quality of the evidence was very low because many of the studies they reviewed were not randomized, so the results could have been biased.

The research was published online on June 21, 2021, by the journal Fertility and Sterility. Read the abstract of “Risk of breast cancer in women treated with ovarian stimulation drugs for infertility: a systematic review and meta-analysis.”

About medicines to stimulate the ovaries
About the study
What this means for you

About medicines to stimulate the ovaries

Medicines that stimulate the ovaries to release eggs have been used to treat infertility since the early 1960s. The medicines work much the same way the hormone estrogen does: they cause the ovaries to develop eggs and release them.

But doctors and women have had concerns that, because the medicines work similarly to estrogen, they also could make hormone-receptor-positive breast cancer develop and grow. Still, results from earlier studies on fertility drugs and breast cancer risk have been mixed.

There are two types of medicines that stimulate the ovaries to release eggs:

  • Clomiphene citrate (brand names: Clomid, Serophene) is a pill taken by mouth once a day for 5 days, starting on day 5 of a woman’s menstrual cycle.
  • Gonadotropins are hormones that regulate ovarian and testicular function. There are three human gonadotropins: follicle stimulating hormone (FSH), luteinizing hormone (LH), and chorionic gonadotropin (hCG). To stimulate the ovaries, doctors may give you an injection of FSH alone or combined with LH.

Sometimes doctors use a combination of clomiphene and gonadotropins for certain fertility procedures, such as in vitro fertilization.

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About the study

This study was a meta-analysis. A meta-analysis combines and analyzes the results of many earlier studies. In this case, the researchers reviewed 20 studies looking at medicines that stimulate the ovaries and breast cancer risk.

The researchers compared women undergoing fertility treatment with two groups of women who had not been exposed to ovary stimulating medicine: women in the general population who had no fertility issues and women diagnosed with infertility. When making this comparison, the researchers looked at clomiphene citrate, gonadotropins, and a combination of clomiphene citrate and gonadotropins.

In their comparison, the researchers separated women in the general population and women diagnosed with infertility because women who haven’t had a full-term pregnancy have a higher risk of breast cancer than women who have given birth.

For clomiphene citrate:

  • 19 of the studies looked at clomiphene citrate and breast cancer risk; the analysis found no increase in breast cancer risk in women taking clomiphene citrate compared with women not taking the medicine
  • 10 of the studies compared breast cancer risk in women taking clomiphene citrate versus women in the general population who hadn’t taken the medicine; the analysis found no increase in breast cancer risk between the two groups of women
  • nine of the studies compared breast risk in women taking clomiphene citrate versus women diagnosed with infertility who hadn’t taken the medicine; the analysis found no increase in breast cancer risk between the two groups of women

For gonadotropins:

  • 14 of the studies looked at gonadotropins and breast cancer risk; the analysis found no increase in breast cancer risk in women being treated with gonadotropins compared with women not being treated with the medicine
  • seven of the studies compared breast cancer risk in women being treated with gonadotropins versus women in the general population who hadn’t been treated with the medicine; the analysis found no increase in breast cancer risk between the two groups of women
  • seven of the studies compared breast cancer risk in women being treated with gonadotropins versus women diagnosed with infertility who weren’t treated with the medicine; the analysis found no increase in breast cancer risk between the two groups of women

For clomiphene citrate and gonadotropins combined:

  • eight of the studies looked at clomiphene and gonadotropins and breast cancer risk; the analysis found no increase in breast cancer risk in women being treated with clomiphene citrate and gonadotropins compared with women not being treated with the medicines
  • four of the studies compared breast cancer risk in women being treated with clomiphene citrate and gonadotropins versus women in the general population who hadn’t been treated with the medicines; the analysis found no increase in breast cancer risk between the two groups of women
  • four of the studies compared breast cancer risk in women being treated with clomiphene citrate and gonadotropins versus women diagnosed with infertility who hadn’t been treated with the medicines; the analysis found no increase in breast cancer risk between the two groups of women

The researchers pointed out that while there seemed to be no increase in breast cancer risk in women treated with ovary stimulating medicines compared with women who weren’t treated with the medicines, there were notable limitations to the study.

The studies included in the meta-analysis were observational, non-randomized studies.

Observational studies look at a risk factor, in this case, exposure to ovary stimulating medicines, without changing who or who isn’t exposed to it. This means that women who were or were not treated with the ovary stimulating medicines could have had specific characteristics that might have affected the results.

“Non-randomized” means the women in the studies were not randomly assigned to be treated with ovary stimulating medicines. The women chose whether or not they were going to have fertility treatment. This also could have affected the results.

“Although this study provided reassuring evidence,” the researchers wrote, “it highlights the need for further register-based studies with the potential to span longer follow-up periods, the provision of a detailed infertility treatment history, and adjustment for confounding factors so as to avoid the additive effect of infertility.”

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What this means for you

If you are considering fertility treatments or are currently undergoing them, this study offers some encouraging news that these treatments do not appear to increase breast cancer risk. Still, it is important to know that the quality of the data analyzed was not the best, which might affect the results.

Stayed tuned to Breastcancer.org Research News for the latest information on fertility treatments and breast cancer risk.

For more information on infertility issues, visit RESOLVE: The National Infertility Association, an organization devoted to providing education and support to people with fertility problems. RESOLVE is headquartered in McLean, Va., and has chapters across the country.

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Written by: Jamie DePolo, senior editor


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