Children born as a result of assisted reproductive technology (ART) represent 3.3% of Australian births. The shift toward single-embryo transfer has led to major improvements in perinatal outcomes after ART. In a previous study, the authors found a 2-fold increased risk of a major birth defect in children born after ART. The aim of this retrospective cohort study was to estimate the prevalence of birth defects overall and for a range of different ART techniques. The study also determined whether birth defect prevalence changed over time in ART pregnancies by comparing data from the earlier study (1994–1998) with the data in this study (1998–2002).
Data included all births in Western Australia from 1994 to 2002, birth defects diagnosed up to age 6 years, and information on all pregnancy terminations because of a fetal anomaly. Data on all ART procedures performed can be linked to demographic and clinical information about all births from 20 weeks of gestation, including stillbirths. Thus, data were available for all ART and all non-ART births in Western Australia from 1994 to 2002 and were analyzed using SPSS statistical software 19.0, with singleton and twin births analyzed separately.
The study included 2911 ART births and terminations of pregnancy for fetal anomaly: 1972 singletons (1328 in vitro fertilization [IVF], 633 intracytoplasmic sperm injection, and 11 partial zona dissection or subzonal insemination births) and 939 twins (643 IVF, 292 intracytoplasmic sperm injection, and 4 partial zona dissection–subzonal insemination). A total of 210,977 non-ART births and terminations occurred, 205,641 singletons and 5356 twins, including 1619 twins of unlike sex.
Mothers undergoing ART were older, less likely to have had a previous child, and less likely to smoke than non-ART mothers. Assisted reproductive technology neonates were more likely to be delivered by cesarean, to have low birth weight, and to be born preterm. A major birth defect was diagnosed by age 6 years in 172 ART singletons (8.7%) and in 11,078 singletons (5.4%) in the non-ART group. Assisted reproductive technology singletons were 1.68 times more likely than non-ART singletons to have a major birth defect diagnosed by age 6 years. The odds ratio decreased to 1.53 when adjusted for maternal age and year of birth. In the 1994–1998 time period, 10.9% and 5.6% of ART and non-ART singletons, respectively, had a major birth defect diagnosed by age 6 years. In the later time period, the prevalence of birth defects in ART singletons decreased to 7.5%, whereas the prevalence in non-ART singletons decreased only from 5.6% to 5.2%. The odds of an ART singleton having a major birth defect diagnosed by age 6 years was 1.32 in the later time period compared with 1.87 in the earlier period. The prevalence of birth defects in ART twins was 7.1% compared with 8.7% for ART singletons. The reverse was true for non-ART twins. If the whole study period is considered, ART twins were no more likely to have a major defect diagnosed than non-ART twins of unlike sex (odds ratio, 1.08; 95% CI 0.77–1.51) after adjustment for maternal age and year of birth. Few differences were seen in overall birth defect risk when intracytoplasmic sperm injection and IVF singletons or twins were compared. Fresh embryo transfer appeared to slightly increase the risk of birth defects in ART singletons compared with frozen–thawed embryo transfer, but this difference was not apparent in twins. Neonates born after fresh IVF had a greater prevalence of birth defects than those born after frozen–thawed IVF for both singletons (9.7% vs 7.3%) and twins (7.9% vs 6.9%). For intracytoplasmic sperm injection, rates of birth defects between fresh and frozen–thawed embryo transfer were 8.7% and 9.0% for singletons, respectively, and 6.1% and 6.2% for twins, respectively. The prevalence of major birth defects in ART singletons and twins according to numbers of embryos transferred suggested a pattern of increasing risks of birth defects with increasing numbers of embryos transferred. This trend was no longer apparent over time. Assisted reproductive technology twins were 2.36 times more likely to have multiple major defects diagnosed compared with non-ART twins of unlike sex. The rate of pregnancy termination for fetal anomaly was 5.8/1000 births for non-ART singletons compared with 9.7/1000 births for ART singletons. Rates for twin pregnancies were 5.8/1000 and 2.1/1000 for non-ART and ART twins, respectively. Rates of major birth defects diagnosed antenatally in singletons and twins were about 19% for ART and non-ART singletons and for ART and non-ART twins.
Singleton ART children were ~50% more likely to have a major birth defect diagnosed by age 6 years compared with non-ART children. However, ART twins were not at increased risk for birth defects compared with non-ART twins of unlike sex when terminations of pregnancy for fetal anomaly were included as well as birth defects in live and stillbirths. The use of “healthier” embryos due to improved culture media and conditions and changes in clinical practice may be responsible for the decrease in birth defects in children born as a result of ART.
Division of Population Sciences and the Department of Biostatistics and Bioinformatics, Telethon Institute for Child Health Research and the Centre for Child Health Research, University of Western Australia, Perth; and Concept Fertility Centre and the Western Australian Register of Developmental Anomalies, King Edward Memorial Hospital, Subiaco, Western Australia, Australia; and National Perinatal Epidemiology Unit, University of Oxford, Oxford, United Kingdom.