When patients ask if infertility treatments like IVF cause cancer, this is what I tell them

At almost every visit I get asked by patients if there are any long-term side effects of fertility treatment and in vitro fertilization (IVF).

While weight gain (5 pounds over the course of a year) fits in this category, usually patients are asking me about cancer. With cancer affecting nearly every family, it is clear why patients would be concerned about this. A recently updated position piece (1) by the American Society for Reproductive Medicine reviews the current literature on the association between fertility treatment and cancer, including ovarian, breast and uterine cancer.

Why an ironclad answer to does IVF cause cancer? (or fertility drugs) is elusive

A definitive answer to the questions of does IVF cause cancer? or do fertility medications? is elusive as people have different risk factors, studies have methodological limitations, and the incidence of these cancers is low. However, as fertility treatment becomes more accepted (1 million cycles of IVF worldwide) it is essential to have solid data to counsel patients.

As background, infertility, nulliparity (having no children by choice or by inability), and late menopause are all associated with increased risk of cancer – even if no fertility drugs are taken.

Certain disease states like PCOS (polycystic ovary syndrome) and endometriosis are over represented in studies on fertility drugs and are associated with increased cancer risk even if no medications are taken. Selection, detection, and recall bias also complicate the results of studies as few studies can be randomized and controlled when studying cancer incidence.

Ovarian cancer risk factors from infertility treatments

According to the Practice Committee of ASRM, the majority of studies have shown no significant increase in ovarian cancer following the use of fertility drugs when compared with infertile controls and/or the general population. Because ovarian cancer typically presents much later in life, a woman should always remind her doctor that she did fertility treatment so that proper surveillance can be performed, as new studies may shed greater clarity on the long-term risks.

Borderline ovarian cancers, a unique subset of ovarian cancer, are slow, 95% curable and are also not associated with fertility treatments in most studies. Several studies have shown a slight increase in borderline tumors, but any increase is small. And these tumors are slow-growing and have a favorable prognosis if treated.

Breast cancer risk from IVF and fertility drugs

Some breast cancers are estrogen and progesterone sensitive. Therefore, people are concerned that fertility drugs could increase the risk for these cancers. While it is true that a patient currently harboring a hormone sensitive breast cancer would experience a growth of that cancer during times of high estrogen or progesterone (IVF treatment intervals or pregnancy), studies have not shown an increased incidence of new breast cancer diagnoses.

There have been seven systematic reviews or meta-analyses that have shown no increase in breast cancer. Several studies have followed women at least 30 years after fertility treatment and have still seen no increase of incidence. However, nulliparity, infertility and late age at first childbirth are all risk factors for breast cancer. Remember, the baseline risk is that 1 in 8 women will be diagnosed with breast cancer in the United States in their lifetimes.

Endometrial cancer (uterine cancer) & fertility treatment

Unopposed estrogen is a risk factor for endometrial cancer. Fertility treatment, however, uses both estrogen and progesterone, therefore it is not considered unopposed in most cases. Obesity and hyperinsulinemia (associated with diabetes and PCOS), which are causally linked to ovulation problems, can cause unopposed estrogen, thereby making the background risk for cancer higher than in the general population. Nine studies and three reviews were used to evaluate the risk of endometrial cancer and fertility drugs and a majority showed no increased risk of cancer for any type of drug used for fertility.

Malignant melanoma, cervical, thyroid and colon cancers, and non-Hodgkin lymphoma were also not found to have sufficient data to suggest that they would be causally related to fertility treatment.

Be vigilant & reduce your cancer risks

While all of us will have to continue careful surveillance for cancer and follow cancer reduction strategies such as less alcohol, less red meat, more exercise and attention to maintaining a proper weight, it does not appear that the fertility treatments and medication increase the risk of cancer when used appropriately.

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1. Fertility drugs and cancer: a guideline
Practice Committee of the American Society of Reproductive Medicine Fertility and Sterility Vol 106, No. 7, December 2016 pg. 1617

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