Fertility Drugs and Cancer (Part 2)

by Kallie Fell, Executive Director on March 15, 2021

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Welcome to part two of my investigation concerning fertility drugs and cancer risk. In this article, I am going to examine a publication from 2017 titled “Use of fertility medications and cancer risk: A review and update”. 

This publication, unlike the first, was a review of recent literature or research already in existence. It didn’t perform any additional study on women that were exposed to fertility drugs; women who might be completing IVF cycles, women donating their eggs, or surrogate mothers. These types of publications can be helpful because they help summarize the work that other scientists are doing; this way readers only have one article to read rather than several. But, they can inspire false confidence if not explored more thoroughly. 

The publication is fairly short and is organized by cancer types: ovarian cancer, endometrial cancer, cervical cancer, breast cancer, thyroid cancer, colorectal cancer, and melanoma. Authors selected recent literature in each category to assess an association between fertility medication and cancer risk in women undergoing IVF for their own infertility. There are two very important observations to make about this review. First, authors do not reveal how or why certain literature was included or excluded in their review. Secondly, like the first study, authors only reviewed literature pertaining to treatment for a woman’s own infertility. That is, it did not look at studies evaluating healthy women that would be subjected to fertility drugs for other reasons, such as egg donation or egg freezing. Why is this? 

Let’s take a closer look at each of the cancer types listed in the publication and the points made in each category:   

Ovarian Cancer

  • A rare, but fatal form of cancer, ovarian cancer makes up 3% of all annual cancer diagnoses in women.
  • Authors admit that studies examining the relationship between fertility medication use and invasive ovarian cancer risk show mixed results; although there were more studies that showed no link or association versus those that did. 
  • Unlike invasive ovarian cancer, studies have found a more consistent association between borderline ovarian tumors and use of fertility medication. Borderline ovarian tumors, also called tumors of low malignant potential, are different to ovarian cancer because they don’t grow into the supportive tissue of the ovary. They tend to grow slowly and in a more controlled way than cancer cells. Even still, this finding should not be ignored.  

Endometrial Cancer

  • This is the most common cancer of the female reproductive tract and the fourth most common cancer diagnosed in women. The American Cancer Society estimates for cancer of the uterus in the United States for 2021 about 66,570 new cases of cancer of the body of the uterus (uterine body or corpus) will be diagnosed and about 12,940 women will die from cancers of the uterine body.

Some studies showed1,2 an increased risk in endometrial cancer after fertility treatment and some didn’t.

  • Recent studies examining the relationship between endometrial cancer and use of fertility medications are limited by small numbers of participants, short follow-up time and several confounding factors, such as ovulatory dysfunction and PCOS.

Cervical Cancer

  • Recent studies have found no link to cervical cancer and fertility patients. Further, some studies even showed a decreased incidence of cervical cancer in IVF patients.

Breast Cancer

  • Breast cancer is the most common cancer in women worldwide, representing about 25 percent of all cancers in women. 
  • Fertility treatments can temporarily cause and increase in circulating sex hormones levels which could then increase breast cancer risk. Studies to date, however, have not shown a consistent relationship between breast cancer risk and fertility treatment. Again, these studies are not looking at fertility drug use in healthy, fertile, young women (the women who would be donating eggs and who are often subjected to higher amounts of these drugs). Here the authors admit, “treatment, specifically those individuals who initiate such treatment at a young age.” 
  • As we pointed out in part one, authors admit that studies examining the relatedness of fertility drugs and breast cancer often suffer from short-term follow-up and other confounding variables.  Long-term follow up is very important to track women because as women age,  cancer risks increase. Stated another way, cancer often presents itself when a woman ages.
  • Results again are mixed, some studies show an increased risk and others don’t.

Thyroid Cancer

  • Thyroid cancer is more common in women than men; it is 2.9-times more common in women than men.
  • A rising incidence of thyroid cancer in the United States has caused physicians and scientists to evaluate the relationship between it and fertility drugs. 
  • Authors state that most studies show no elevated risk for thyroid cancer in women undergoing IVF for infertility, especially when evaluating gonadotropin, a hormone used to stimulate the activity of the ovaries. 
  • However, a Danish cohort of 54,362 women with infertility did show a significant association between fertility medication use and thyroid cancer. In this study clomiphene citrate (also known by its brand name, CLOMID®) use increased the risk of thyroid cancer. 

Colorectal Cancer

  • There are limited studies evaluating the risk of colorectal cancer for fertility patients. 
  • The authors of this current study evaluated three studies. 
    • Two studies concluded that fertility drugs did not significantly increase the risk of colorectal cancer.
    • Interestingly, in the third study, the women undergoing IVF for infertility did not have an increased colon cancer risk compared to the general population, but did have an increased risk compared to women receiving other subfertility treatments other than IVF, such and intrauterine insemination. 

Melanoma 

  • Most studies have not shown an increased risk of this disease after fertility treatment. 
  • One retrospective cohort study from Australia found that women giving birth following IVF had an increased rate of invasive melanoma versus women who failed to conceive after IVF. 
  • In another study, fertility treatment was not associated with malignant melanoma, except for an increased risk following use of gonadotrophins or gonadotropin-releasing hormone in women that went on to birth children. The use of clomiphene citrate has been associated with increased risk of melanoma in some studies but not all. 

The summary presented by the authors of the article in review is brief, “the collective data regarding the risk of developing cancer from use of fertility medications are reassuring, although several methodological issues in these studies limit definitive conclusions.” When I read this article and when I read the list I created for you, I find limitations and a mixed bag of results. I like my salad mixed, but not my results, especially when I am determining cancer risks. I am still in doubt that we really know whether or not there is a link between fertility drugs and cancer risks.  So far, it’s not a chance I would take.  

  1. Reigstad, M, Storeng, R, Myklebust, TÅ, Oldereid, NB, Omland, AK, Robsahm, TE, Brinton, LA, Vangen, S, Furu, K, Larsen, IK. Cancer Risk in Women Treated with Fertility Drugs According to Parity Status-A Registry-based Cohort Study. Cancer Epidemiol Biomarkers Prev. 2017 Jun;26(6):953-962. doi: 10.1158/1055-9965.EPI-16-0809. Epub 2017 Jan 20. PMID: 28108444; PMCID: PMC5457348.
  2. Kessous, R, Davidson, E, Meirovitz, M. et al. The risk of female malignancies after fertility treatments: a cohort study with 25-year follow-up. J Cancer Res Clin Oncol 142, 287–293 (2016). https://doi.org/10.1007/s00432-015-2035-x

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