Kate Johnson

October 29, 2014

HONOLULU — Infertile women, whether or not they undergo treatment for in vitro fertilization (IVF), do not face an increased risk for cancer, according to three studies presented here at the American Society for Reproductive Medicine 2014 Annual Meeting.

"Overall, the studies are reassuring," said Humberto Scoccia, MD, from the University of Illinois in Chicago, who was not involved in the research.

"The number of patients in the studies was fairly large," he told Medscape Medical News. "The problem is that the follow-up is short. Most of the cancers — endometrial, breast, uterine, colorectal — occur much later in life, so it will be interesting to see what happens with more follow-up."

The OMEGA Project, a historic Dutch cohort study with prospective follow-up, studied women for a median of 17 years.

Two separate analyses of that cohort showed that the risk for colorectal and endometrial cancer was no higher in 19,158 women who had undergone at least one cycle of IVF than in 5950 women who had reported fertility problems and had not undergone IVF treatment.

In addition, a population-based cohort analysis of 53,872 women in Illinois, New York, and Texas showed no increased risk for any form of cancer after assisted reproductive technology, whether they had IVF or non-IVF treatment. However, the duration of follow-up was not much beyond three years.

In the OMEGA cohort, median age was approximately 50 years, and the first IVF treatment occurred at a median age of 33 years. Patients underwent 1 or 2 cycles of IVF (32%), 3 or 4 cycles (33%), or 5 or more cycles (23%); data were missing for 13% of the patients.

More IVF patients than non-IVF patients had never given birth (36% vs 27%).

 
Overall, the studies are reassuring.
 

The standard incidence ratio for colorectal cancer, compared with the general Dutch population, was not significantly different between the IVF and non-IVF patients (1.07 and 0.77), reported Mandy Spaan, MSc, from the Netherlands Cancer Institute in Amsterdam. The pattern was similar for colon cancer (1.05 vs 0.66) and rectal or sigmoid cancer (1.09 vs 0.96).

There was a nonsignificant increased risk for colorectal cancer in the first 4 years after IVF treatment, but this risk decreased with longer follow-up. There was no significant association between colorectal cancer risk and cause of subfertility or between risk and oral contraceptive use.

The risk for endometrial cancer was not significantly different between the general Dutch population and the infertile women in the cohort (1.22), and there was no significant difference between patients who had undergone IVF and those who had not (1.13 vs 1.41), reported Alexandra van den Belt-Dusebout, MSc, also from the Netherlands Cancer Institute.

However, the risk for endometrial cancer was higher in infertile nulliparous women in the cohort than in the general population (1.90), and was lower infertile parous women (0.76). The difference between nulliparous and parous women was statistically significant (hazard ratio, 0.37).

A previous study found a significant 2-fold increased risk for endometrial cancer in infertile women treated with follicle-stimulating hormone or human menopausal gonadotropin, but that study did not take confounders, such as total dose of fertility drugs and reason for subfertility, into account, said van den Belt-Dusebout (Am J Epidemiol. 2009;170:1408-1414).

In contrast, the risk for endometrial cancer in the OMEGA cohort was not significantly associated with cause of infertility or number of IVF cycles, she noted.

Some Question About Melanoma

In the American study, which had a much shorter follow-up, cycle-specific records for individual women in the Society for Assisted Reproductive Technology Clinic Outcome Reporting System were linked to state cancer registries.

There was no excess cancer risk in women who had undergone any assisted reproductive technology by age, parity, diagnosis, number of cycles, or cumulative dose, compared with the general population, reported Barbara Luke, ScD, epidemiologist and professor of obstetrics, gynecology, and reproductive biology at Michigan State University in East Lansing.

However, there was a trend toward an increased risk for melanoma in women who underwent assisted reproductive technology.

For melanoma overall, the incidence ratio was 1.15; this rose to 1.57 in the first two years after a live birth. Women who had become pregnant but then miscarried had an even higher incidence in the first 2 years after IVF (1.90), and 3 or more years after treatment (1.76).

"Although it is not significant, it certainly raises some suspicion, and there is a need for more numbers and longer follow-up," said Dr. Luke.

 
Although it is not significant, it certainly raises some suspicion, and there is a need for more numbers and longer follow-up.
 

"Studies like these are important because they help to build our knowledge base around the potential associations between treatment with assisted reproductive technology and risk of cancer," said Louise Stewart, PhD, a research fellow at the Centre for Population Health Research at Curtin University in Perth, Australia. Dr. Stewart has been involved in research showing an increased risk for IVF and borderline ovarian tumors (Gynecol Oncol. 2013;129:372-376) and an increased risk for melanoma with IVF (Melanoma Res. 2013;23:489-495).

"We did not find an overall association between IVF treatment and melanoma, but we did find an increased rate of melanoma in women who had IVF and gave birth," she told Medscape Medical News.

"I think it would certainly be worthwhile following the American cohort over a longer period of time," she said.

The Dutch studies were supported by the Dutch Cancer Society and a grant from the Department of Obstetrics and Gynecology of Erasmus University Medical Center. The American study was supported by the National Institutes of Health. Dr. Spaan, Dr. van den Belt-Dusebout, and Dr. Stewart have disclosed no relevant financial relationships. Dr. Luke is the epidemiologist for the Society for Assisted Reproductive Technologies.

American Society for Reproductive Medicine (ASRM) 2014 Annual Meeting: Abstracts 0-147, 0-149, and 0-153. Presented October 21, 2014.

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