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Am Fam Physician. 2005;71(5):1010-1011

About 40,000 children are born each year in the United States as a result of assisted reproductive technology (ART). Several forms of ART are available, such as in vitro fertilization, transcervical embryo transfer, gamete and zygote intrafallopian transfer, oocyte donation, embryo cryopreservation, intracytoplasmic sperm injection, and extended embryo culture. Although no organized system of surveillance has tracked children who are born following ART to assess long-term health outcomes, several studies have reported on specific aspects. Schieve and colleagues reviewed the accumulated data to provide a balanced report on the likely outcomes of ART on the health of children.

Population-based studies have presented conflicting results on the rate of spontaneous abortion in ART pregnancies. Studies are limited to pregnancies that are clinically recognized, and comparison between studies is complicated by the extent of controlling for factors such as maternal age or type of ART employed. Overall, pregnancies conceived with the patient’s oocytes and freshly fertilized embryos do not have spontaneous abortion rates greater than expected for naturally conceived pregnancies. When clomiphene is used for ovarian stimulation or thawed embryos are implanted, the rate of spontaneous abortion is higher than anticipated.

Conversely, ART pregnancies commonly are multiple. More than one half of infants born after ART are multiple births; this rate is 18 times that of the U.S. population. Most multiple births are the result of multiple embryo transfer, but embryo splitting also is common, particularly in births conceived with ovulation-inducing medications.

Several studies report increased risk of low birth weight, very low birth weight, preterm delivery, and fetal growth restriction in infants conceived using ART. These risks apply to singleton as well as multiple births and are evident in all forms of ART, with an apparent “dose-related” effect increasing with the complexity of the ART techniques employed.

Infants conceived by ART also are at risk for a broad spectrum of adverse outcomes, including low Apgar scores, prolonged hospital stay and readmission, and perinatal mortality. A specific risk exists for intraventricular hemorrhage. In one study, infants conceived using ART were four times more likely to have intraventricular hemorrhage than control subjects even after matching tightly for gestational age, birth weight, and other significant variables. Data on birth defects are more difficult to interpret. At least two studies have reported a significantly increased prevalence of birth defects (around 9 percent compared with 4 percent in the control group), but interpretation of these results is difficult because of the role of the underlying infertility condition and other factors.

Specific associations have been suggested between ART and chromosomal disorders, as well as defects in the genitourinary, central nervous, cardiovascular, gastrointestinal, and musculoskeletal systems. A recent comprehensive study of more than 5,000 children reported increased risks of cerebral palsy and developmental delay. Behavioral development, scholastic achievement, and other developmental issues are confounded by selection bias and other factors in parents who conceive using ART.

Two serious concerns expressed for children born following ART are genetic imprinting disorders and cancer. Animal studies indicate that imprinting defects are increased in ART. The rare Beckwith-Wiedemann syndrome is related to expression of only one of the parental copies of a gene and may be increased in ART-conceived children. Incomplete recognition and reporting of the syndrome make estimation of this risk difficult. Although one study suggested an association between ART and retinoblastoma, two other studies have not found increases overall in childhood cancer or in any specific cancer.

The authors conclude that data from multiple sources indicate that ART is related to several adverse outcomes in the children conceived; however, more research is necessary to clarify these risks.

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Copyright © 2005 by the American Academy of Family Physicians.

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