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Infertility in Women and Low Absolute Risk of Cancer

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Key Points

  • After taking into account factors that could affect the results such as smoking, obesity, age, education, and reproductive age, the team found that infertile women had an overall 18% higher risk of developing cancer compared to the control group, with absolute risks of 2% compared to 1.7%.
  • Among the infertile women, 22,024 (34%) had at least 1 baby during the period studied, and 626,532 (20%) of women in the control group gave birth. The absolute risk of cancer was 1 in 56 infertile women and 1 in 86 women in the control group.
  • When the researchers excluded women who had polycystic ovary syndrome or endometriosis—both of which have been linked to an increased risk of uterine and ovarian cancers, respectively—the absolute risk of cancer was 1 in 55 among the infertile women and 1 in 88 among the control group.

A study of over 64,000 women of childbearing age in the United States has found that infertility is associated with a higher risk of developing cancer compared to a group of over 3 million women without fertility problems—although the absolute risk is very low, at just 2%. These findings were published by Murugappan et al in Human Reproduction.

Gayathree Murugappan, MD, a fellow in reproductive endocrinology and infertility at Stanford University School of Medicine who led the study, said, “We do not know the causes of the increase in cancer that we found in this study—whether it might be the infertility itself, the causes of the infertility, or the infertility treatment. We can only show there is an association between them. In the future, we hope that we will be able to understand why infertile women are at higher risk of cancer; for example, by identifying a common, underlying mechanism that can cause cancer and infertility.”

Study Methods

Dr. Murugappan and her colleagues analyzed data from 64,345 women who had been identified as being infertile by diagnosis, testing, or treatment in the Clinformatics Data Mart database between 2003 and 2016. The database contained a geographically diverse group of patients across all 50 states, although the majority of them were Caucasian.

The investigators compared them with 3,128,345 women who were not infertile and who were seeking routine gynecologic care. The women were in their 30s, and the researchers followed their progress for an average of nearly 4 years.

Findings

During the follow-up period, there were 1,310 cancers diagnosed among the infertile women and 53,116 among the control group of women who were not infertile. Breast cancer was the most common cancer in both groups. After taking into account factors that could affect the results such as smoking, obesity, age, education, and reproductive age, the team found that infertile women had an overall 18% higher risk of developing cancer compared to the control group, with absolute risks of 2% compared to 1.7%.

Senior author of the paper Michael Eisenberg, MD, Associate Professor in the Stanford University School of Medicine, said, “The low overall incidence of cancer among these women means that 1 in 49 infertile women would develop cancer during the follow-up period, compared to 1 in 59 women in the women who were not infertile.” 

The researchers found that giving birth conferred some protection on women in both groups. Among the infertile women, 22,024 (34%) had at least 1 baby during the period studied, and 626,532 (20%) of women in the control group gave birth. The absolute risk of cancer was 1 in 56 infertile women and 1 in 86 women in the control group. 

When the researchers excluded women who had polycystic ovary syndrome or endometriosis—both of which have been linked to an increased risk of uterine and ovarian cancers, respectively—the absolute risk of cancer was 1 in 55 among the infertile women and 1 in 88 among the control group.

Looking at the risk of particular cancers, they found a slightly higher risk of hormone-driven cancers of the ovary and uterus among the infertile women, although the risk of breast cancer was similar between the two groups. They also found a slightly higher risk of cancers that were not driven by hormones among the infertile women, including lung, thyroid, liver, and gallbladder cancers, as well as leukemia. “While several of these associations were significant, it is important to note that the absolute increases in risk were modest,” said Dr. Murugappan.

As the majority of cancers are diagnosed in older people, one of the limitations of the study is the age of the women, and also the short follow-up period. Other limitations include that women may have sought fertility treatment outside the insurance system; some women might be infertile without knowing because they might have been using contraception, for instance; and the cause of infertility and the treatment given was not available from the insurance claims data.

Dr. Eisenberg concluded, “Although the absolute increase in cancer risk among infertile women was small, this increase was seen in only a short period of 4 years of follow-up. We need to carry out further research with longer follow-up to determine what factors may be influencing the long-term risk of cancer for infertile women.”

Disclosure: The study authors' full disclosures can be found at academic.oup.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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