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One type of fertility treatment was linked with a small but statistically significant increased risk of childhood cancers, according to a Danish study.

Children born from a frozen embryo transfer procedure had more than doubled risk for any type of childhood cancer, relative to those conceived normally (hazard ratio 2.43, 95% CI 1.44-4.11), reported Marie Hargreave, PhD, of the Danish Cancer Society Research Center in Copenhagen, and colleagues.

This risk of cancer for children was mainly driven by an increase in two specific types of cancer -- sympathetic nervous system tumors and leukemia, they wrote in :

• Sympathetic nervous system tumors: HR 7.82 (95% CI 2.47-24.70)
• Leukemia: HR 2.87 (95% CI 1.19-6.93)

Other types of cancers assessed, including lymphoma and central nervous system neoplasms, weren't more common in frozen embryo transfer, however.

A notable study limitation was the small number of childhood cancer cases in the sample, "which limits the statistical precision of these estimates and the results should therefore be interpreted with caution," the authors stated. "The data for specific types of cancer in particular are fragile."

Maternal infertility as a whole was not tied to an increased risk for childhood cancers among offspring. During the average 11.3 year follow-up period, the incidence rate of childhood cancer among children born to fertile women was 17.5 cases per 100,000 versus 17.6 per 100,000 in women with infertility -- just a 0.1 (95% CI -2.0 to 2.2 per 100,000) difference in incidence rate.

Interestingly, there weren't any significant links between other types of assisted productive technology with childhood cancer. These included in vitro fertilization (HR 0.96, 95% CI 0.70-1.32) and intracytoplasmic sperm injection (HR 1.33, 95% CI 0.94-1.89). Only frozen embryo transfer held this relationship.

Similarly, there were also no significant associations seen between other types of infertility treatments, including the use of fertility drugs with childhood cancer. These included several hormones and fertility drugs compared with children born to fertile women:

• Clomiphene: HR 0.95 (95% CI 0.74-1.22)
• Gonadotropins (menopausal gonadotropins and follicle-stimulating hormone): HR 1.06 (95% CI 0.88-1.29)
• Gonadotropin-releasing hormone analogs: HR 1.12 (95% CI 0.90-1.40)
• Human chorionic gonadotropin: HR 1.02 (95% CI 0.86-1.23)
• Progesterone: HR 1.08 (95% CI 0.87-1.34)
• Estrogen: HR 0.91 (95% CI 0.60-1.38)

The retrospective cohort study included data from individuals appearing in the Danish Infertility Cohort paired with over 1 million children born in Denmark. This included 2,217 children diagnosed with cancer from 1996 through 2015.

Associated effects of frozen embryo transfer weren't limited to childhood cancer, either. Children born from this method also tended to hold a higher risk for being large for gestational age, as well as have a higher average birth weight compared with children born from a fresh embryo transfer.

"This suggests that techniques involving cryopreservation induce changes in the developing embryo, potentially affecting intrauterine growth," Hargreave's group wrote. "Excessive fetal growth has been linked to increased childhood cancer risk, and epigenetic alterations have been proposed as a possible explanation."

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