Do Fertility Drugs Increase Your Risk of Getting Cancer?

The Cancer Risk of Fertility Drugs vs. the Risks Infertility Itself Brings

Doctor talking with a woman about the possible risk of cancer after fertility drugs and infertility
While fertility drugs don't seem to increase your risk of cancer, infertility itself does. It's important for your doctor to follow-up after treatment.. JGI/Tom Grill / Getty Images

Do fertility drugs cause cancer? What about IVF treatment? It is true that a few studies seemed to find a connection between fertility drug use and an increased risk of breast or uterine cancer, specifically with the drug Clomid

All medications, including fertility drugs, come with risks.

But should you be concerned about an increased cancer risk? Let's take a look.

Fertility Drugs May Increase... or Decrease Your Cancer Risk?

In 2005, a widely publicized study reported that Clomid use might increase the risk of uterine cancer.

However, since that time, more studies have been done, and most have found no significant increase in cancer risk after Clomid use.

In fact, ironically, one study showed that women treated with fertility drugs seemed to show a decreased risk of developing uterine cancer when compared to infertile women who did not seek treatment.

Another study found a decreased risk of developing breast cancer after Clomid.

Why the discrepancies?

The problem with many of these studies is they don't take into account other potential risk factors for uterine cancer.

Namely, if a woman never experiences pregnancy, her risk of cancer increases.

Also, obesity is not only a risk factor for infertility, but it is also a risk factor for cancer.

It may not have been the fertility drugs at all. Instead, the increased incidence may be attributed to the reason behind infertility itself, or any number of other factors not taken into account in this study.

Many studies have found a possible connection between certain causes of infertility and an increased risk of cancer.

Another common problem with these studies are the sample sizes were too small.

Clomid and Other Ovarian Stimulation Drugs and Ovarian Cancer Risk

The strongest evidence that Clomid and other ovarian stimulating drugs do not increase the risk of ovarian cancer comes from a Cochrane Review, published in 2013.

The review included studies from 1990 through February 2013. The studies compiled together included 182,972 women.

Seven of the studies found no evidence of increased ovarian cancer in women who use any fertility drug (including Clomid)  when comparing their risk to other women with fertility problems who did not use fertility drugs.

According to the review, studies that did find increased cancer risk were not reliable, because they failed to take into consideration the risk of infertility itself or the sample size was too small to draw conclusions.

Borderline Ovarian Tumors and IVF?

The Cochrane review did find a possible increased risk of borderline ovarian tumors in women who went through IVF treatment.

This risk was not present after Clomid or Clomid with gonadotropins treatment alone.

The treatment of borderline ovarian tumors isn’t as intense and involved as with typical ovarian tumors, and the prognosis for women with a borderline tumor is very good.

A 2015 study tried to further investigate the possible risk of borderline ovarian tumors and fertility treatment.

What they found was that there was no strong link between borderline ovarian tumors and fertility drug use.

However, there may be a possible connection between borderline ovarian tumors and progesterone supplementation.

Researchers found that the risk of borderline ovarian tumors was higher for women who used progesterone compared to those who never did, and higher in women who had four or more cycles of progesterone supplementation.

That said, the number of women in the study with borderline tumors was small.

Follow-up studies with larger groups of women are needed.

Long-term Risk of Breast Cancer After IVF

Could IVF treatment increase your risk of breast cancer? The current research says not likely.

The largest study to date included 25,108 women, with an average follow-up of 21 years after treatment. These were women from the Netherlands, who received IVF treatment between 1980 and 1995.

There was no increased risk of breast cancer in women who received IVF compared to those who received other fertility treatments (but not IVF.)

Interestingly, researchers found the risk of breast cancer was lower for women who had 7 or more IVF cycles compared to women who had 1 or 2 cycles. It’s unclear why this is.

IVF and Ovarian Cancer

At the 2015 American Society for Reproductive Medicine (ASRM) conference, Dr. Alastair Sutcliffe of Institute of Child Health at University College London presented a study looking at the cancer risk in women who had gone through IVF treatment.

This study included over 250,000 British women and spanned treatment cycles between 1991 and 2010. 

The good news was that they found no increased risk of breast or uterine cancer in the former IVF patients. 

The bad news is that found an increased risk of ovarian cancer.

While women who had never gone through IVF had an 11 in 10,000 chance of developing ovarian cancer, the IVF patients had 15 in 10,000 odds.

The risk is small but important to recognize.

Like in the studies mentioned above, the consensus is that the increased risk isn't caused by IVF treatment itself but the fact that the women needed treatment. 

Infertility and the need for IVF are suspected as the risk. Not the fertility drugs used during treatment.

With that said, the study also found that the cancer risk was higher in the first three years after treatment.

So, it's not possible to completely rule out that the fertility drugs played a role in the cancer risk. Close monitoring in the years after IVF treatment may be smart.

No Increased Risk of Cancer

A meta-analysis is a research study that gathers information from several studies and evaluates them together. The University of Ottawa conducted a meta-analysis to look into whether fertility drug use increased the risk of cancer when compared to infertile women who were not treated.

The analysis included the data collected by ten different research studies, with information on women taking fertility drugs like Clomid, gonadotropins, human chorionic gonadotropin (hCG), and gonadotropin-releasing hormone agonists (GnRH).

The researchers found that when comparing infertile women treated with fertility drugs, against infertile women who were not treated, those treated with fertility drugs were not at an increased risk of developing uterine cancer.

Most interestingly, they did find that women who were treated seemed to have a lower incidence of ovarian cancer when compared to infertile women who were not treated.

In another study, this one conducted by the Danish Cancer Society, researchers did a cohort study of 54,362 women with infertility. (A cohort study is when they look at a large group of people with similar circumstances, typically over an extended period.)

In this study, the researchers found no significant increase in risk for breast cancer after fertility drug use, specifically gonadotrophins, Clomid, hCG, or GnRH.

Other studies have found similar results.

Where It Stands

The consensus is that fertility drugs do not increase your risk of developing breast or uterine cancer.

Also, some studies have looked at fertility drug use and other kinds of cancers (thyroid and skin cancers, for example), and they have also found no significant increase in risk.

However, because infertility itself is a risk factor for cancer, follow-up after diagnosis is recommended.

Women with primary infertility, who never become pregnant and give birth, as well as women diagnosed with endometriosis, may particularly have an increased risk of developing cancer. 

PCOS, a common cause of infertility, is also known to come with an increased risk of developing endometrial cancer.

Also, it's important to keep in mind that the technology of fertility treatment is changing. Lower doses of drugs are now being used than in the early days of treatment, and many of the studies on cancer and fertility treatment include women treated in the 1980s, more aggressively than they might be today.

Studies on cancer and fertility treatment also require long-term follow-up. It may be decades before we can really say what impact fertility treatment at age 35 will have on a woman who is 65 or 70 years old.

While more research must be done, for now, fertility drugs are (mostly) off the hook.

Sources:

Althuis MD, Moghissi KS, Westhoff CL, Scoccia B, Lamb EJ, Lubin JH, Brinton LA. Uterine cancer after use of clomiphene citrate to induce ovulation. American Journal of Epidemiology. 2005 Apr 1; 161(7):607-15.

Althuis MD, Scoccia B, Lamb EJ, Moghissi KS, Westhoff CL, Mabie JE, Brinton LA. Melanoma, thyroid, cervical, and colon cancer risk after use of fertility drugs. American Journal of Obstetrics and Gynecology. 2005 Sep; 193(3 Pt 1):668-74.

Bjørnholt SM1, Kjaer SK2, Nielsen TS1, Jensen A3. “Risk for borderline ovarian tumours after exposure to fertility drugs: results of a population-based cohort study.” Hum Reprod. 2015 Jan;30(1):222-31. doi: 10.1093/humrep/deu297. Epub 2014 Nov 5.

Jensen A, Sharif H, Svare EI, Frederiksen K, Kjaer SK. Risk of breast cancer after exposure to fertility drugs: results from a large Danish cohort study. Cancer Epidemiol Biomarkers Prev. 2007 Jul; 16(7):1400-7. Epub 2007 Jun 21.

Kashyap S, Moher D, Fung MF, Rosenwaks Z. Assisted reproductive technology and the incidence of ovarian cancer: a meta-analysis. Obstetrics and Gynecology. 2004 Apr; 103(4):785-94.

Knapton, Sarah. "IVF women third more likely to develop ovarian cancer.” The Telegraph.

Rizzuto I1, Behrens RF, Smith LA. “Risk of Ovarian Cancer in Women Treated with Ovarian Stimulating Drugs for Infertility.” Cochrane Database Syst Rev. 2013 Aug 13;(8):CD008215. doi: 10.1002/14651858.CD008215.pub2.

van den Belt-Dusebout AW1, Spaan M1, Lambalk CB2, Kortman M3, Laven JS4, van Santbrink EJ5, van der Westerlaken LA6,Cohlen BJ7, Braat DD8, Smeenk JM9, Land JA10, Goddijn M11, van Golde RJ12, van Rumste MM13, Schats R2, Józwiak K1,Hauptmann M1, Rookus MA1, Burger CW4, van Leeuwen FE1. “Ovarian Stimulation for In Vitro Fertilization and Long-term Risk of Breast Cancer.” JAMA. 2016 Jul 19;316(3):300-12. doi: 10.1001/jama.2016.9389.

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