Children and young adults who were conceived by in vitro fertilization (IVF) have a slightly increased risk of developing cancer, relative to those conceived naturally, researchers from Sweden reported Monday in the journal Pediatrics.

They emphasize, however, that this is probably not due to the IVF procedure itself, but rather to a variety of other factors, including the tendency for IVF babies to be born prematurely and to have respiratory problems at birth.

The researchers also stress that the individual risk of cancer for a child born via IVF is very low.

While the absolute risk cannot be exactly calculated from the available data, Dr. Bengt Kallen of the University of Lund noted in an email to Reuters Health: “The total risk for a childhood cancer may be around 2 per 1,000 children (probably a little less) and the risk after IVF is 3 per 1,000 - still a very low individual risk.”

This level of risk, Kallen said, should not affect the decision of a couple considering IVF.

In vitro fertilization, the most technologically advanced of assisted reproductive technologies, involves removing an egg cell from a woman’s body, fertilizing it in the lab, and placing it in the woman’s womb. It can cost up to $15,000 per “cycle” of medications and procedures, with successful pregnancies often requiring several cycles.

Studies of cancer in IVF children have failed to show a clear-cut increase in risk, but most studies were too small to answer the question, Kallen and colleagues note in their report.

In an earlier study of 16,280 Swedish children born after IVF during a follow-up period of 1 to 20 years, Kallen’s team noted a suggestion of a higher risk of cancer in IVF kids; 8 more children developed cancer than would be expected in the general population (29 cases vs 21 expected). The difference, however, may have been due to chance.

Their latest study expands the follow-up time of the previously studied children conceived by IVF and adds a number of other IVF children - bringing the total number of children to nearly 30,000, and the total number of cancer cases to 53 (including the 29 previously identified).

Fifty-three is 15 more than the 38 cases expected in the general population of children, the investigators note, and is probably not due to chance alone.

Infants born after IVF had a 42 percent higher likelihood of childhood cancer than those who were not.

Among the 53 cancers in IVF children, 18 were blood cancers (against 12 expected cases). Fifteen of these blood cancers were acute lymphoblastic leukemia. There were also 15 cancers of the central nervous system (against 8 expected cases); 7 of these were brain tumors. Two IVF children had eye tumors, whereas 1 would have been expected.

Of note, according Kallen and colleagues, there were 6 cases of a rare white blood cell disorder called histiocytosis (against 1 expected). Five of these were found in the earlier study.

Histiocytosis occurs when there are too many of a type of white blood cell that normally resides in the skin, where it helps fight infections and destroy certain foreign substances in the body. In histiocytosis, these cells accumulate on bones and other parts of the body, particularly the head and neck, causing a wide range of problems.

“We do not understand the apparently increased risk for histiocytosis,” Kallen told Reuters Health. “It has not been reported in other studies and may well be a random phenomenon.” That’s because all but one of the cases of the condition - which is not usually regarded as malignant - were actually from the older study.

Kallen emphasized that “infants born after IVF differ in some respects from other infants” and several factors other than IVF likely contribute to their higher risk of cancer.

For example, multiple births are common in IVF pregnancies and Kallen’s team found a “slight excess” of multiple-birth IVF children who developed cancer.

Being heavy at birth and suffering birth asphyxia have consistently been shown to increase the risk of cancer and both were risk factors for cancer in the current study.

In addition, two of the IVF children who developed cancer had Down syndrome and it is well known that children with Down syndrome are at increased risk of cancer, particularly childhood leukemia.

The researchers conclude that more studies on large populations are necessary to permit analysis of such a “rare outcome” as cancer and notably of specific types of cancer in children conceived by IVF.

SOURCE:  Pediatrics, August 2010