IVF Not Linked to Breast Cancer Risk

Diana Phillips

August 24, 2016

Women who undergo in vitro fertilization (IVF) are not at increased risk of developing breast cancer, a Dutch study shows.

The findings are consistent with those of previous research showing no significant association between assisted reproductive technology and breast cancer, including a recent study reported by Medscape Medical News from the American Society for Reproductive Medicine 2015 Annual Meeting.

"This is good news, given that the data have been conflicting. This offers some peace of mind to providers and patients," Mia Gaudet, PhD, director, Breast and Gynecological Cancer Research, American Cancer Society, told Medscape Medical News. Dr Gaudet was not involved in the study.

For the current investigation, Alexandra W. van den Belt-Dusebout, PhD, from the Netherlands Cancer Institute, Amsterdam, the Netherlands, and colleagues reviewed data from a historical cohort (the OMEGA Study) of women treated for infertility to assess the long-term risk for breast cancer after ovarian stimulation for IVF. The sample included 19,158 women who started IVF treatment between 1983 and 1995 and 5950 women who began other fertility treatments between 1980 and 1995. The median age at follow-up for those in the IVF and non-IVF groups was 53.8 and 55.3 years, respectively, and the median follow-up was 21.1 years.

The IVF group included women who started ovarian stimulation for the procedure between 1983 and 1995 in one of 12 IVF clinics in the Netherlands. The non-IVF comparison group consisted of women who started fertility treatments other than IVF (tubal surgery, low-dose ovarian stimulation, intrauterine insemination, hormonal treatment) between 1980 and 1995 in one of four clinics, the authors report in an article published in the July 19 issue of JAMA.

The total number of invasive and in situ breast cancers observed in the study population overall was 839, including 619 in the IVF group and 220 in the non-IVF group, according to linked data from the Netherlands Cancer Registry (1989 - 2013), These numbers reflect similar cumulative incidences of 3.0% and 2.9%, respectively, the authors report (P = .85). "The risk did not differ by type of fertility drugs or subfertility diagnosis and was not increased at 20 or more years after IVF treatment," they state, noting also that the rates are similar to those observed in the general population.

Notably, women who underwent seven or more IVF cycles had a significantly decreased risk of developing breast cancer compared with those who underwent only one or two cycles (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.39 - 0.77), and women who had a poor response to their first IVF cycle were less likely to develop cancer than the overall study population (HR, 0.77 [95% CI, 0.61 - 0.96] for less than four vs four or more collected oocytes).

Women who had children had a significantly higher breast cancer risk than women who did not (HR, 1.35; 95% CI, 1.16 - 3.73). Women who were aged 35 years or older at first birth also had a significantly higher risk compared with those who were younger than 25 years at first birth (HR, 1.73 [95% CI, 1.30-2.30] for women aged 35-39 years and HR, 2.52 [95% CI, 1.71-3.73] for women aged 40 years or older).

"Since IVF comprises several phases and treatment schedules changed over time, unraveling the potentially opposite effects of several components of the IVF procedure is challenging," the authors acknowledge.

For example, there are multiple possible explanations for the fact that women treated with more IVF cycles in the current study had the lowest breast cancer risk.

"Explanations could be that women treated with more IVF cycles received more [human chorionic gonadotropin], had longer periods of down-regulation with low estradiol and progesterone levels, or because of some inherent characteristic of the women that required more IVF cycles," the authors write.

The higher breast cancer risk among parous vs nulliparous women in the current study, in contrast to data in the literature suggesting that nulliparous women are at increased risk, may be a result of the temporary increase in breast cancer risk after giving birth, the authors propose. "As this increased risk may last 20 to 30 years, many parous women in the cohort had not yet reached the ages at which parity would exert a protective effect on breast cancer risk. Furthermore, the late age at first birth in the cohort (median, 31.5 years; 75th quartile, 35.0 years) may have precluded the observation of a reduced risk associated with parity."

Because the study results are largely based on IVF treatment protocols used until 1995, during which the number of ampules of gonadotropins used peaked before declining, the findings may not be generalizable to contemporary IVF treatments, which "largely consist of protocols with antagonists and shorter periods of downregulation," the authors write. The newer protocols, they explain, may be associated with less risk reduction and the need for fewer IVF cycles because of improved success rates.

Because only 14% of the cohort had reached age 60 years, "follow-up is necessary to evaluate postmenopausal breast cancer risk after ovarian stimulation for IVF," the authors stress.

"The size of the study is one of its strengths. It adds a significant amount of evidence indicating there is no association between breast cancer and in vitro fertilization," Dr Gaudet told Medscape Medical News. "However, it’s important to note some of the limitations of the study, especially differences in IVF drugs and strategies that are used today compared with those that in the study. More research is warranted before we can say these findings are conclusive and generalizable across patients."

This study was supported by the Dutch Cancer Society, the Health Research and Development Counsel, and the Dutch Ministry of Health. Several coauthors disclosed various financial relationships with Ferring Pharmaceuticals, Merck Serono, and MSD. Dr Gaudet has disclosed no relevant financial relationships.

JAMA. 2016;316:300-312. Abstract

For more news, join us on Facebook and Twitter


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.