Major Finding: The risk of stillbirth among children conceived by assisted reproductive technology is slightly, but significantly higher than that seen among naturally conceived children, accounting for 8 more stillbirths per 1,000 ART pregnancies.
Data Source: A Nordic population registry study of 60,650 ART pregnancies compared with a control group of 360,022 naturally conceived pregnancies.
Disclosures: The study was sponsored by the European IVF Monitoring Group, a working group of the European Society of Human Reproduction and Embryology. Dr. Henningsen said she had no relevant financial disclosures.
While the risk of stillbirth among singleton pregnancies conceived by assisted reproductive technology is marginally higher than is the risk in naturally conceived children, the difference is not large enough to warrant any changes in pregnancy management.
“Although the difference in risk is significant between the two groups, the overall risk is still very low,” Dr. Anna-Karina Henningsen said. “This means that the individual woman need not be concerned about the risk of stillbirth during pregnancy.”
The findings also contribute some data to the argument of whether to induce assisted reproductive technology (ART) pregnancies at term, rather than letting the pregnancy exceed 40 weeks, Dr. Henningsen said during a press briefing.
“In Nordic countries, mothers [can carry up to] 2 weeks past term before they are induced. Obstetricians have debated whether an ART pregnancy should be managed as high risk, with earlier induction. This study tells us that no cases of stillbirth in ART pregnancies can be avoided by inducing birth earlier,” she said.
Dr. Henningsen of the Rigshospitalet, Copenhagen, presented the results of the largest-ever Nordic investigation into this issue. The prospective database study comprised 60,650 singleton pregnancies conceived by ART, comparing them with a control group of 360,022 naturally conceived pregnancies. Information was drawn from population registries in Sweden, Finland, Norway, and Denmark, including ART registries, birth and death registries, and hospital registries. The analysis included singleton pregnancies conceived by in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and frozen embryo transfer.
When defining stillbirth as the birth of a dead infant after 22 weeks' gestation, the study found an overall rate of 0.4% in both groups. However, Dr. Henningsen said, after matching the two groups for maternal parity and the infants' birth year, and controlling for maternal age and the infant's gender, the overall risk was marginally higher (hazard ratio 1.1) in the ART group. This translated into an absolute rate of 8 additional stillbirths per 1,000 among ART pregnancies, compared with the control group.
The researchers also analyzed the stillbirth risk by gestational age. While there was no difference after 40 weeks' gestation, they found a 20% increased risk of stillbirth before 40 weeks among the ART group, compared with the control group. “We believe the difference in risk of stillbirth between ART and naturally conceived children seems to occur before 37 weeks' gestation,” she said. “It is likely that some of this difference in risk is related to factors affecting the subfertile mother or father.” For naturally conceived children, she said, stillbirth is more likely to be related to congenital malformations in the fetus.
In a further analysis of both stillbirth and death within the first year of life, Dr. Henningsen found that children born of ART were 40% more likely to die than were naturally conceived children. After adjusting for confounders, the rate still remained higher at 20%. However, she noted, “This can probably be explained by the higher risk of preterm birth among ART children.”