BOSTON – Assisted reproductive technologies are associated with a small but significant risk for congenital malformations in some organ systems, reported investigators from a consortium of Nordic countries at the conjoint meeting of the International Federation of Fertility Societies and the American Society for Reproductive Medicine.
Singleton children born to parents who used assisted reproductive technology (ART) were significantly more likely than were children born through spontaneous pregnancies to have malformations of the heart, gastrointestinal tract, or urinary tract, reported Dr. Anna-Karina Aaris Henningsen of the Fertility Clinic at the Rigshospitalet in Copenhagen.
Dr. Anna-Karina Aaris Henningsen
Combined data from the extensive medical registries in Denmark, Sweden, Norway, and Finland showed that, compared with controls, singletons born with the help of ART had a 20% increase in risk for any heart malformation, 56% increase in risk for gastrointestinal anomalies, and 49% increase in risk for urinary tract malformations.
In contrast, congenital malformations of the nervous system, abdominal wall, genitals, orofacial region, limbs, or chromosomes were not more common in ART-conceived children than in spontaneously conceived controls, the investigators found.
"It’s still a very small increased risk, and there are many things we can’t answer yet, things we need to look into," Dr. Henningsen said, speaking on behalf of colleagues in the CoNARTas Study Group.
For example, it’s unclear whether the differences might be a causal effect of ART or related to underlying fertility problems of the couples using ART. In addition, there may be differences in rates of malformations between in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) techniques, or between fresh- and frozen-embryo transfer methods, she said.
In the matched cohort study, the authors also found that ART was associated with a small but significant risk for placental abruption in both singleton and twin pregnancies, compared with unassisted pregnancies, findings that were consistent across the Nordic countries.
The authors looked at population-based data on 58,714 singletons and 27,919 twins born after the introduction of IVF, ICSI, and frozen-embryo transfer in each of the participating countries. Data on ART came from national ART registers. Singletons born from ART pregnancies were matched on the mother’s parity and year of birth with a fourfold larger control group of spontaneously conceived singletons. All spontaneously conceived twins born during the study period also were counted as controls.
They used the European surveillance of congenital anomalies (EUROCAT) system to classify malformations and group them according to organ system.
In analyses looking at all children born after ART – both twins and singletons – the odds ratio for congenital heart malformations (such as common arterial truncus, transposition of great vessels, presence of a single ventricle, atrioventricular septal defect, etc.) was 1.12, with a confidence interval indicating significance. No other organ system anomalies, however, were associated with ART in the overall population.
In a multivariate analysis controlling for mother’s parity, year of birth, maternal age, child’s sex and country, the authors found that ART in singletons was associated with an odds ratio of 1.20 for congenital heart malformations, 1.56 for gastrointestinal malformations (esophageal atresia, duodenal atresia or stenosis, etc.), and 1.49 for urogenital malformations (such as bilateral renal agenesis, renal dysplasia, or congenital hydronephrosis).
In the question-and-answer portion following Dr. Henningsen’s presentation, an audience member asked whether ascertainment bias might account for the differences seen, because ART-born children may be scrutinized more closely than are spontaneously-born children for congenital malformations.
"If the child has a major malformation, it will be registered, regardless if it’s an ART child or a spontaneously conceived child," she replied.
The study was supported by the European Society of Human Reproduction and Embryology (ESHRE), the University of Copenhagen, the Danish Agency for Science, Technology and Innovation, and the Nordic Federation of Obstetrics and Gynecology (NFOG). Dr. Henningsen reported having no conflict of interest disclosures.