IVF linked to slight increase in risk of some cancers

A large observational study from Great Britain paints a mixed picture of cancer risks associated with assisted reproduction technologies such as in vitro fertilization (IVF).

Among nearly 256,000 women who had assisted reproduction over a 2-decade period and were followed for more than 2.25 million person-years, there was no significant increase in risk of uterine cancers or invasive breast cancers.

However, these women were at slight but significantly increased risk for in situ breast cancers and invasive or borderline ovarian cancers, although the ovarian tumors may be related more to patient factors than to the assisted reproduction technology itself, reported Alastair Sutcliffe, MD, PhD, from University College London, and his colleagues.

“We were not able to distinguish between a genuine increase in risk of borderline ovarian tumors and other explanations including surveillance bias. Further investigation of this and longer follow-up is warranted to continue monitoring these important outcomes in this ever-growing population,” they wrote in BMJ.

Women who undergo IVF and related procedures are typically exposed to high levels of estradiol, luteinizing hormone, follicle-stimulating hormone, and multiple ovarian punctures, all of which are potentially carcinogenic, the authors noted.

Previous studies of cancer risk in women who undergo assisted reproduction treatment have had conflicting or inconsistent results and lacked information on potential confounders, they pointed out.

To get a better sense of the potential risks, the investigators looked at linked data from the United Kingdom’s Human Fertilization and Embryology Authority and national cancer registries. They identified a total of 255,786 women treated from 1991 through 2010. Total follow-up was for 2,257,789 person-years.

They found that, during an average 8.8 years of follow-up, women had no significant increase in risk of tumors of the uterine corpus, with 164 cancers observed vs. 146.9 expected, for a standardized incidence ratio (SIR) of 1.12 (95% confidence interval, 0.95-1.30).

Similarly, there was no significant increase in risk of either breast cancer overall (2,578 observed vs. 2,641.2 expected; SIR, 0.98; 95% CI, 0.94-1.01) or invasive breast cancer (2,272 observed vs. 2,371.4 expected; SIR, 0.96; 95% CI, 0.92-1.00).

As noted, however, there was an increased risk of in situ breast cancer with 291 vs. 253.5 cases, respectively, translating into a SIR of 1.15 (95% CI, 1.02-1.29), for an absolute excess risk (AER) of 1.7 cases per 100,000 person-years, associated with an increasing number of treatment cycles (P = .03).

Additionally, the women in the study had an increased risk of ovarian cancer with an observed incidence of 405 vs. 291.82 expected, for an SIR of 1.39 (95% CI, 1.26-1.53) and an AER of 5.0 cases per 100,000 person-years.

There was a significantly increased risk for both invasive tumors, with 264 cases vs. 188.1 expected, for an SIR of 1.40 (95% CI, 1.24-1.58) and an AER of 3.4 cases per 100,000 person-years, and borderline ovarian cancers, with 141 vs. 103.7, for an SIR of 1.36 (95% CI, 1.15-1.60) and an AER of 1.7 cases per 100,000 person-years.

Increased risks of ovarian tumors were limited to women with endometriosis, low parity, or both. This study found no increased risk of any ovarian tumor in women treated because of only male-factor or unexplained infertility.

Women who had previously given birth and did not have a diagnosis of endometriosis had no increase in risk for ovarian cancer. Instead, increased risk appeared to be limited to women with endometriosis, few or no births (low parity), or both.

The authors emphasized that ongoing monitoring of outcomes for women who have undergone assisted reproduction is essential.

The study was funded by Cancer Research UK and the National Institute for Health Research, and supported by the NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. Three authors reported personal fees or royalties from entities not involved in the study.

SOURCE: Williams CL et al. BMJ. 2018;362:k2644.

A large observational study from Great Britain paints a mixed picture of cancer risks associated with assisted reproduction technologies such as in vitro fertilization (IVF).

Among nearly 256,000 women who had assisted reproduction over a 2-decade period and were followed for more than 2.25 million person-years, there was no significant increase in risk of uterine cancers or invasive breast cancers.

However, these women were at slight but significantly increased risk for in situ breast cancers and invasive or borderline ovarian cancers, although the ovarian tumors may be related more to patient factors than to the assisted reproduction technology itself, reported Alastair Sutcliffe, MD, PhD, from University College London, and his colleagues.

“We were not able to distinguish between a genuine increase in risk of borderline ovarian tumors and other explanations including surveillance bias. Further investigation of this and longer follow-up is warranted to continue monitoring these important outcomes in this ever-growing population,” they wrote in BMJ.

Women who undergo IVF and related procedures are typically exposed to high levels of estradiol, luteinizing hormone, follicle-stimulating hormone, and multiple ovarian punctures, all of which are potentially carcinogenic, the authors noted.

Previous studies of cancer risk in women who undergo assisted reproduction treatment have had conflicting or inconsistent results and lacked information on potential confounders, they pointed out.

To get a better sense of the potential risks, the investigators looked at linked data from the United Kingdom’s Human Fertilization and Embryology Authority and national cancer registries. They identified a total of 255,786 women treated from 1991 through 2010. Total follow-up was for 2,257,789 person-years.

They found that, during an average 8.8 years of follow-up, women had no significant increase in risk of tumors of the uterine corpus, with 164 cancers observed vs. 146.9 expected, for a standardized incidence ratio (SIR) of 1.12 (95% confidence interval, 0.95-1.30).

Similarly, there was no significant increase in risk of either breast cancer overall (2,578 observed vs. 2,641.2 expected; SIR, 0.98; 95% CI, 0.94-1.01) or invasive breast cancer (2,272 observed vs. 2,371.4 expected; SIR, 0.96; 95% CI, 0.92-1.00).

As noted, however, there was an increased risk of in situ breast cancer with 291 vs. 253.5 cases, respectively, translating into a SIR of 1.15 (95% CI, 1.02-1.29), for an absolute excess risk (AER) of 1.7 cases per 100,000 person-years, associated with an increasing number of treatment cycles (P = .03).

Additionally, the women in the study had an increased risk of ovarian cancer with an observed incidence of 405 vs. 291.82 expected, for an SIR of 1.39 (95% CI, 1.26-1.53) and an AER of 5.0 cases per 100,000 person-years.

There was a significantly increased risk for both invasive tumors, with 264 cases vs. 188.1 expected, for an SIR of 1.40 (95% CI, 1.24-1.58) and an AER of 3.4 cases per 100,000 person-years, and borderline ovarian cancers, with 141 vs. 103.7, for an SIR of 1.36 (95% CI, 1.15-1.60) and an AER of 1.7 cases per 100,000 person-years.

Increased risks of ovarian tumors were limited to women with endometriosis, low parity, or both. This study found no increased risk of any ovarian tumor in women treated because of only male-factor or unexplained infertility.

Women who had previously given birth and did not have a diagnosis of endometriosis had no increase in risk for ovarian cancer. Instead, increased risk appeared to be limited to women with endometriosis, few or no births (low parity), or both.

The authors emphasized that ongoing monitoring of outcomes for women who have undergone assisted reproduction is essential.

The study was funded by Cancer Research UK and the National Institute for Health Research, and supported by the NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. Three authors reported personal fees or royalties from entities not involved in the study.

SOURCE: Williams CL et al. BMJ. 2018;362:k2644.

A large observational study from Great Britain paints a mixed picture of cancer risks associated with assisted reproduction technologies such as in vitro fertilization (IVF).

Among nearly 256,000 women who had assisted reproduction over a 2-decade period and were followed for more than 2.25 million person-years, there was no significant increase in risk of uterine cancers or invasive breast cancers.

However, these women were at slight but significantly increased risk for in situ breast cancers and invasive or borderline ovarian cancers, although the ovarian tumors may be related more to patient factors than to the assisted reproduction technology itself, reported Alastair Sutcliffe, MD, PhD, from University College London, and his colleagues.

“We were not able to distinguish between a genuine increase in risk of borderline ovarian tumors and other explanations including surveillance bias. Further investigation of this and longer follow-up is warranted to continue monitoring these important outcomes in this ever-growing population,” they wrote in BMJ.

Women who undergo IVF and related procedures are typically exposed to high levels of estradiol, luteinizing hormone, follicle-stimulating hormone, and multiple ovarian punctures, all of which are potentially carcinogenic, the authors noted.

Previous studies of cancer risk in women who undergo assisted reproduction treatment have had conflicting or inconsistent results and lacked information on potential confounders, they pointed out.

To get a better sense of the potential risks, the investigators looked at linked data from the United Kingdom’s Human Fertilization and Embryology Authority and national cancer registries. They identified a total of 255,786 women treated from 1991 through 2010. Total follow-up was for 2,257,789 person-years.

They found that, during an average 8.8 years of follow-up, women had no significant increase in risk of tumors of the uterine corpus, with 164 cancers observed vs. 146.9 expected, for a standardized incidence ratio (SIR) of 1.12 (95% confidence interval, 0.95-1.30).

Similarly, there was no significant increase in risk of either breast cancer overall (2,578 observed vs. 2,641.2 expected; SIR, 0.98; 95% CI, 0.94-1.01) or invasive breast cancer (2,272 observed vs. 2,371.4 expected; SIR, 0.96; 95% CI, 0.92-1.00).

As noted, however, there was an increased risk of in situ breast cancer with 291 vs. 253.5 cases, respectively, translating into a SIR of 1.15 (95% CI, 1.02-1.29), for an absolute excess risk (AER) of 1.7 cases per 100,000 person-years, associated with an increasing number of treatment cycles (P = .03).

Additionally, the women in the study had an increased risk of ovarian cancer with an observed incidence of 405 vs. 291.82 expected, for an SIR of 1.39 (95% CI, 1.26-1.53) and an AER of 5.0 cases per 100,000 person-years.

There was a significantly increased risk for both invasive tumors, with 264 cases vs. 188.1 expected, for an SIR of 1.40 (95% CI, 1.24-1.58) and an AER of 3.4 cases per 100,000 person-years, and borderline ovarian cancers, with 141 vs. 103.7, for an SIR of 1.36 (95% CI, 1.15-1.60) and an AER of 1.7 cases per 100,000 person-years.

Increased risks of ovarian tumors were limited to women with endometriosis, low parity, or both. This study found no increased risk of any ovarian tumor in women treated because of only male-factor or unexplained infertility.

Women who had previously given birth and did not have a diagnosis of endometriosis had no increase in risk for ovarian cancer. Instead, increased risk appeared to be limited to women with endometriosis, few or no births (low parity), or both.

The authors emphasized that ongoing monitoring of outcomes for women who have undergone assisted reproduction is essential.

The study was funded by Cancer Research UK and the National Institute for Health Research, and supported by the NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. Three authors reported personal fees or royalties from entities not involved in the study.

SOURCE: Williams CL et al. BMJ. 2018;362:k2644.