Mixed Cancer Risk for Women After IVF

More in situ breast cancer, ovarian cancers, but not others



Assisted reproduction had a mixed association with cancer risk, a study of more than 250,000 British women showed.

Women who underwent assisted reproduction procedures did not have an increased risk of invasive breast or uterine cancer as compared with the general population. However, they did have slightly higher rates of noninvasive breast and both invasive and borderline ovarian cancers.

The findings add to an inconsistent epidemiologic picture of the association between assisted reproduction and cancer, the researchers said.

"Increased risks of ovarian tumors were limited to women with endometriosis, low parity, or both," Alastair G. Sutcliffe, MD, of University College London and Great Ormond Street Institute of Child Health, and co-authors reported in The BMJ. "This study found no increased risk of any ovarian tumor in women treated because of only male-factor or unexplained infertility.

"Our results suggest that ovarian tumor risks could be due to patient characteristics, rather than assisted reproduction itself, although both surveillance bias and the effect of treatment are also possibilities. Ongoing monitoring of this population is essential."

Two studies reported at the recent European Society of Human Reproduction and Embryology meeting showed slightly increased risks of prostate and ovarian cancers in patients undergoing assisted reproduction procedures. However, investigators in both studies implicated the patients' underlying infertility, not the treatments, in the cancer associations.

Sutcliffe and co-authors also expressed doubt that infertility treatments could increase the risk of cancer, but acknowledged that the association could not be ruled out definitively by the data.

Multiple previous studies examined the relationship between assisted reproduction and cancer, yielding an extensive history of inconsistent results. Many of the studies were small and had low cancer rates. Sutcliffe and colleagues sought to overcome some of the limitations of previous studies by means of a large population-based linkage study that addressed potential confounding factors, such as parity and infertility diagnosis.

Study Details

The study included 266,000 women who underwent assisted reproduction procedures in England, Wales, and Scotland from January 1991 to December 2010, as determined by records of the Human Fertilization and Embryology Authority (HFEA). The investigators defined assisted reproduction as "treatments or procedures that include in vitro handling of both human oocytes and sperm or embryos, for the purpose of reproduction."

The researchers linked the HFEA records to the National Health Service Central Registers, which maintain records on deaths and cancer. Women who had cancer diagnoses prior to starting assisted reproduction treatment were excluded. The patients were followed to cancer diagnosis, death, immigration, or the end of the study (March 2011).

To assess cancer risk, the investigators used nationally representative data to calculate the expected number of cancers by 5-year age increments for the general population of women in England and Wales.


Data analysis included 255,786 women undergoing assisted reproduction procedures and 2,257,789 person-years of follow up. Mean follow-up was 8.8 years, and 105,436 of the patients were followed for at least 10 years.

The study population had a mean age of 34.7 at the start of treatment. Infertility involved one or more female factors in 111,658 cases, male factors in 84,871 cases, and was unexplained in 47,757 cases.

The results showed 2,578 diagnosed breast cancers as compared with an expected number of 2,641. Various subgroup analyses failed to identify an increased risk of breast cancer in any group of women undergoing assisted reproduction. The analysis did show a significant association between in situ breast cancer and increasing number of cycles of infertility treatment (SIR 1.15, 95% CI 1.02-1.29).

With respect to uterine cancer, 164 cancers were diagnosed, whereas 147 would have been expected. The difference translated into a standardized incidence ratio (SIR) of 1.12, which did not achieve statistical significance (95% CI 0.95-1.30). Subgroup analysis showed significantly higher rates of uterine cancer in women with ovulatory disorders (SIR 1.59, 95% CI 1.13-2.17), a significant trend of increasing risk with decreased parity (P<0.001), and a significant trend of decreased risk with increasing parity (SIR 0.42, 95% CI 0.14-0.99).

The records showed 405 cases of ovarian cancer, whereas 292 would have been expected, a difference that achieved statistical significance (SIR 1.39, 95% CI 1.26-1.53). The risk was elevated across most age groups, but a significant trend was observed between cancer risk and decreasing age at first treatment for infertility (P<0.001). The risk also was significantly increased in women who had any diagnosed fertility factor (SIR 1.66, 95% CI 1.46-1.88).

Separation of ovarian cancers into invasive or borderline showed an increased risk for each category (SIR 1.40, 95% CI 1.24l-1.58; SIR 1.36, 95% CI 1.15-1.60). There was also a significant association between increasing ovarian cancer risk and decreasing age at first treatment for infertility (P=0.02) and a significantly increased risk among women with any diagnosed female fertility factor (SIR 1.66, 95% CI 1.41-1.94).

Similar associations were observed for the risk of borderline ovarian cancer, including younger age at first treatment for infertility (P<0.001) and any diagnosed female fertility factor (SIR 1.66, 95% CI 1.33-2.05).

Source