Fact or Fiction: Does IVF Increase the Risk of Cancer?

By Halle Tecco, MBA, MPH

As assisted reproductive technologies (ART) like in vitro fertilization (IVF) become increasingly popular, questions around the long-term safety of these interventions take on a sharp urgency. 

One concern that often surfaces is the possibility of an increased risk of cancer linked to fertility treatments. The logic is ostensibly simple but deeply unsettling: fertility treatments often involve hormonal manipulation, and some cancers, like breast cancer, are often hormonally sensitive. [1] Ergo, could fertility treatments be a trigger?

In this article, we attempt to address this rumor by looking at the existing research on the topic.

The Anxiety Overlay

Before diving into the scientific meat of the subject, it's important to appreciate the backdrop of anxiety that accompanies any discussion of fertility treatments. For couples or individuals facing infertility, every decision comes freighted with potential ramifications. Not only are you navigating the immediate complexities of treatments and the financial burdens involved, but you may also be grappling with potential downstream effects on your health. I know this because I’ve been there.

The worry is not baseless. It is well-documented that certain forms of cancer, particularly breast cancer, are influenced by hormonal factors. [1] Studies have also shown that a woman’s risk of breast cancer is related to the estrogen and progesterone made by her ovaries. [1] Research has also found that menopausal hormone therapy with estrogen alone increases the risk of endometrial cancer. [1]

Given that fertility treatments such as IVF or medications like clomiphene citrate are aimed at manipulating hormones to induce ovulation, it’s a logical leap to wonder if they might inadvertently increase the risk of cancer.

What Does the Research Say?

For years, this question remained largely unanswered. While some earlier studies suggested a possible link between fertility treatments and cancer risk, they often suffered from limitations like small sample sizes and inadequate controls for confounding factors. [2]

One 2022 meta-analysis, however, mitigates many of these issues by pooling data from multiple studies, significantly enlarging the sample size and hence, the reliability of the findings. [3] This specific study looked at 25 studies, including 617,479 participants.

The results were unambiguous: fertility treatments, including commonly used medications like clomiphene, human chorionic gonadotropin, gonadotropin analogs, and progesterone, were not associated with a significant increase in breast cancer risk. [3] Furthermore, even among women who had undergone six or more IVF cycles, the risk did not escalate. [3]

It's important to underline that the findings remained consistent even after a decade of follow-up. This long-term data is particularly reassuring, given that cancer is often a disease of latency, manifesting years if not decades after exposure to a potential risk factor. [3]

Understanding the Odds

The term 'odds ratio' is worth explaining, as it can help us interpret the results of the study. An odds ratio of 1 would signify no difference in risk between the treatment group and the general population. [4] An odds ratio below 1 would imply a protective effect (meaning a decreased risk), whereas above 1 would suggest an increased risk. [4] The odds ratio calculated in this meta-analysis was 0.97 with a 95% confidence interval of 0.90 to 1.04, straddling the line of no effect. [3] This means that the likelihood of developing breast cancer was virtually the same for 617,479 women who underwent fertility treatment as it was for those who did not. [3-4] 

While these findings are undoubtedly reassuring, let’s remember that science is an ever-evolving field, meaning new studies can conflict with past ones. Future research should consider the impact of newer fertility treatment protocols and the cumulative effect of multiple treatment cycles over a woman’s lifespan. 

American Society for Reproductive Medicine (ASRM) Weighs In

In the realm of reproductive medicine, few voices carry as much authority as the American Society for Reproductive Medicine (ASRM). Their guidelines serve as foundational texts for clinicians and patients alike, navigating the complexities of reproductive health. According to a 2016 guideline from the ASRM, the concerns around fertility treatments and cancer risk may be more spectral than real. [5] 

In 2016 guidelines, ASRM declared: “People can be reasonably reassured that there has been no meaningful increased risk of invasive ovarian cancer found following the use of fertility drugs in women experiencing infertility, nor is the risk different from one drug to another.” [5] 

Further, ASRM adds another layer of reassurance by saying, "There is fair evidence that fertility drugs are not associated with an increased risk of breast cancer or uterine cancer." This statement aligns with the meta-analysis' findings, fortifying the conclusion that breast cancer risk remains largely unaltered by fertility treatments. [3,5] 

Weighing the Risk

The potential risk of other cancers related to fertility treatments can't be definitively ruled in or out based on the current state of scientific knowledge. The backdrop to all of this is that infertility itself could be associated with an elevated risk for certain types of cancers. The question, then, is not merely whether fertility treatments elevate cancer risk, but whether they elevate it above the baseline risk associated with infertility itself.

The backdrop to all of this is that infertility itself could be associated with an elevated risk for certain types of cancers.

As we add more dimensions to the inquiry into the relationship between fertility treatments and cancer risk, the answers become less black-and-white. Individual choices around fertility treatments will need to weigh the nuanced risk of the unknown. And any risk assessment should be conducted with your healthcare provider, and tailored to your individual medical history.

This is an area ripe for further research. As we refine our understanding, we should aim not just for clearer answers, but for more sophisticated questions that account for the multidimensional interplay of risk factors.

Summing It Up

The prevailing evidence suggests that IVF does not increase the risk of ovarian, breast, or uterine cancer. [1-5] For those wading through the complex emotional, financial, and medical calculus of assisted reproduction, this is a significant piece of good news. 

But as always, medical decisions should be individualized, taking into consideration a host of factors including genetic predispositions, lifestyle variables, and existing medical conditions. 

What research does offer, however, is a data-driven respite from one specific fear, allowing people to make more informed choices as they navigate fertility treatments. By delving into the data, we can separate the rational from the emotional, the factual from the speculative. Science, in this case, offers not just answers, but also solace.

Wishing you all the best on this journey!

References:

1. National Cancer Institute. Cancer Causes and Prevention. Published April 2015. Accessed September 2023. URL
2. Kroener L, Dumesic D, Al-Safi Z. Use of fertility medications and cancer risk: a review and update. Curr Opin Obstet Gynecol. 2017;29(4):195-201. doi:10.1097/GCO.0000000000000370 URL
3. Cullinane C, Gillan H, Geraghty J, et al. Fertility treatment and breast-cancer incidence: meta-analysis. BJS Open. 2022;6(1):zrab149. doi:10.1093/bjsopen/zrab149 URL
4. Szumilas M. Explaining odds ratios [published correction appears in J Can Acad Child Adolesc Psychiatry. 2015 Winter;24(1):58]. J Can Acad Child Adolesc Psychiatry. 2010;19(3):227-229.
5. Can Fertility Drugs or IVF Increase My Risk for Cancer?. Cancer.net. Published November 2022. Accessed September 2023. URL