Fertility Drugs and Cancer (Part 1)

by Kallie Fell, Executive Director on March 9, 2021

Is‌ ‌there‌ ‌a‌ ‌link‌ ‌between‌ ‌fertility‌ ‌drugs‌ ‌and‌ ‌cancer?‌ ‌This‌ ‌question‌ ‌has‌ ‌bothered‌ ‌me‌ ‌for‌ ‌a‌ ‌long‌ ‌time.‌ ‌It’s‌ ‌an‌ ‌important‌ ‌question.‌ ‌It’s‌ ‌a‌ ‌topic‌ ‌that‌ ‌we‌ ‌have‌ ‌and‌ ‌will‌ ‌continue‌ ‌to‌ ‌discuss‌ ‌on‌ ‌‌Venus‌ ‌Rising‌.‌ ‌ ‌ 

‌In‌ ‌fact,‌ ‌during‌ ‌a‌ ‌recent‌ ‌interview‌ ‌with‌ ‌Valerie‌ ‌Landis,‌ ‌I‌ ‌was‌ ‌presented‌ ‌with‌ ‌three‌ ‌different‌ ‌studies‌ ‌that‌ ‌supposedly‌ ‌conclude‌ ‌that‌ ‌no,‌ ‌there‌ ‌is‌ ‌no‌ ‌link‌ ‌between‌ ‌fertility‌ ‌drugs‌ ‌and‌ ‌cancer.‌ ‌As‌ ‌excited‌ ‌as‌ ‌Valerie‌ ‌was‌ ‌about‌ ‌“bio-hacking”‌ ‌the‌ ‌female‌ ‌body,‌ ‌I‌ ‌am‌ ‌less‌ ‌convinced‌ ‌that‌ ‌this‌ ‌is‌ ‌healthy.‌ ‌Since‌ ‌I‌ ‌couldn’t‌ ‌address‌ ‌these‌ ‌studies‌ ‌on‌ ‌the‌ ‌podcast,‌ ‌I‌ ‌decided‌ ‌to‌ ‌write‌ ‌about‌ ‌each‌ ‌study.‌ ‌Here‌ ‌is‌ ‌study‌ ‌number‌ ‌one,‌ ‌published‌ ‌in‌ ‌2016:‌‌ ‌Ovarian‌ ‌Stimulation‌ ‌for‌ ‌In‌ ‌Vitro‌ ‌Fertilization‌ ‌and‌ ‌Long-term‌ ‌Risk‌ ‌of‌ ‌Breast‌ ‌Cancer‌.‌ ‌ ‌ ‌

Briefly,‌ ‌the‌ ‌goal‌ ‌of‌ ‌this‌ ‌study‌ ‌was‌ ‌to‌ ‌assess‌ ‌the‌ ‌long-term‌ ‌risk‌ ‌of‌ ‌‌breast‌ ‌cancer‌‌ ‌after‌ ‌ovarian‌ ‌stimulation‌ ‌for‌ ‌IVF‌ ‌utilizing‌ ‌a‌ ‌cohort‌ ‌of‌ ‌women‌ ‌from‌ ‌12‌ ‌IVF‌ ‌clinics‌ ‌in‌ ‌the‌ ‌Netherlands.‌ ‌The‌ ‌study‌ ‌sample‌ ‌included‌ ‌19,158‌ ‌women‌ ‌who‌ ‌started‌ ‌IVF‌ ‌treatment‌ ‌between‌ ‌1983‌ ‌and‌ ‌1995‌ ‌(IVF‌ ‌group)‌ ‌and‌ ‌5,950‌ ‌women‌ ‌starting‌ ‌other‌ ‌fertility‌ ‌treatments‌ ‌between‌ ‌1980‌ ‌and‌ ‌1995‌ ‌(non-IVF‌ ‌group).‌ ‌ 

‌Researchers‌ ‌found‌ ‌that,‌ ‌among‌ ‌women‌ ‌undergoing‌ ‌fertility‌ ‌treatment‌ ‌in‌ ‌the‌ ‌Netherlands‌ ‌between‌ ‌1980‌ ‌and‌ ‌1995,‌ ‌IVF‌ ‌treatment‌ ‌compared‌ ‌with‌ ‌non-IVF‌ ‌treatment‌ ‌was‌ ‌not‌ ‌associated‌ ‌with‌ ‌increased‌ ‌risk‌ ‌of‌ ‌breast‌ ‌cancer‌ ‌after‌ ‌a‌ ‌21-year‌ ‌follow-up.‌ ‌Further,‌ ‌breast‌ ‌cancer‌ ‌risk‌ ‌among‌ ‌IVF-treated‌ ‌women‌ ‌was‌ ‌also‌ ‌not‌ ‌significantly‌ ‌different‌ ‌from‌ ‌that‌ ‌in‌ ‌the‌ ‌general‌ ‌population.‌ ‌This‌ ‌sounds‌ ‌like‌ ‌good‌ ‌news.‌ ‌Let’s‌ ‌investigate‌ ‌a‌ ‌bit‌ ‌more.‌ ‌ ‌

When‌ ‌reading‌ ‌a‌ ‌peer-reviewed‌ ‌journal‌ ‌article,‌ ‌it’s‌ ‌important‌ ‌to‌ ‌look‌ ‌at‌ ‌the‌ ‌strengths‌ ‌and‌ ‌limitations‌ ‌of‌ ‌a‌ ‌study.‌ ‌All‌ ‌studies‌ ‌have‌ ‌strengths‌ ‌and‌ ‌limitations.‌ ‌Below‌ ‌are‌ ‌the‌ ‌admitted‌ ‌strengths‌ ‌and‌ ‌limitations‌ ‌by‌ ‌the‌ ‌research‌ ‌team:‌ ‌ ‌ 

‌Strengths‌ ‌of‌ ‌this‌ ‌study:‌ 

  • Large sample or cohort size (25,108 women)
  • Long and complete follow-up (median of 21 years). We would argue that although 21 years is a long time, it is not quite long enough since the median age for breast cancer diagnosis in the United States is 62. That means about half of women with breast cancer in the U.S> are diagnosed before age 62 and about half are diagnosed after age 62. 
  • Low likelihood of selection bias (96% of the cohort was linked with the population-based Netherlands Cancer Registry)

Limitations:

  • Missing data: potential confounding factors (that is, something other than what is being studied such as a subfertility diagnosis) were missing in data analysis. There was more missing data in the non-IVF group (33%) than in the IVF group (16%). 
  • Age at menopause and menopausal status at the end of follow-up were unknown for most women. Few women were postmenopausal at the completion of the study questionnaire. If IVF-treated women reach earlier menopause than women in the general population, breast cancer risk after IVF may have been underestimated. 
  • Breast cancer diagnosis for women taking fertility drugs between 1980 and 1988 could have been missed since the Netherlands Cancer Registry did not fully cover the Netherlands until 1989. 
  • Results are based on IVF treatment protocols used until 1995, it is uncertain how study results generalize to more contemporary IVF treatment since IVF treatments have changed over time. 
  • Only 14% of the cohort had reached age 60 years, as I mentioned previously, the median age for cancer diagnosis is 62 in the United Stated.  Follow-up is absolutely necessary to evaluate postmenopausal breast cancer risk after ovarian stimulation for IVF.

I started out by asking ‘is, is there a link between fertility drugs and cancer?’  This study only evaluated the long-term risk to breast cancer and only from 1980 to 1995. While this study appears optimistic, it’s important to evaluate and assess more than one study. 

A quick google search confirms that there is more to the story. Several peer-reviewed journals (listed below) have proven that some women may still be at an increased risk for breast cancer following fertility treatment, specifically those individuals who initiate such treatment at a young age1,2,3. Woah, woah, woah! This raises a big red flag in my mind. What is one population of young women that might subject themselves to fertility drugs at a young age? If you are thinking about young women on college campuses that are targeted by advertisements to ‘donate’ their eggs, your right! The article I am evaluating here by van den Belt-Dusebout, et al., doesn’t seem to include these women. 

In a different article, co-authored by our own founder and president Jennifer Lahl, published in 2017, authors describe five individual cases of egg donors who developed breast cancer despite negative genetic testing results; four of those women were under 30 years old. Authors argue that the creation of egg donor registries will help facilitate the needed long-term studies on egg donors. 

My conclusion: I’d like to be optimistic, but I am not yet convinced. Without further studies and a donor registry we cannot fully ascertain the long-term risk of fertility drugs. It is not enough to extrapolate data from the increasingly large number of studies of long-term risks looking only at infertile women who undergo ovarian stimulation in order to produce eggs for their personal IVF cycles. The problem with equating these two groups is that they differ in several ways; for example, at the time of their egg retrieval, infertile women are generally older than egg donors. If the fertility industry has nothing to hide, why do they still fail to set up registries to track egg-donors or young women subjecting themselves to fertility drugs? 

Stay tuned for parts 2 and 3 as well as upcoming Venus Rising episodes! 

Cited Studies: 

  1. Sergentanis TN, Diamantaras AA, Perlepe C, et al. IVF and breast cancer: a systematic review and meta-analysis. Hum Reprod Update. 2014;20:106–123. Meta-analysis that included 8 cohort studies, with a total cohort size of 1,554,332 women, showing no increased risk of breast cancer with IVF treatment, but recommending longer follow up periods, comparisons with infertile women, and adjustment for various confounders before conclusive statements can be made.
  1. Stewart LM, Holman CD, Hart R, et al. In vitro fertilization and breast cancer: is there cause for concern? Fertil Steril. 2012;98:334–340.
  1. Lerner-Geva L, Rabinovici J, Olmer L, et al. Are infertility treatments a potential risk factor for cancer development? Perspective of 30 years of follow-up. Gynecol Endocrinol. 2012;28:809–814. 

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