Kids conceived using assisted reproductive technology (ART) had slightly higher risks of congenital anomalies, particularly genitourinary abnormalities, according to an Australian population-based cohort study.
In the cohort of over 850,000 infants, singleton infants conceived via ART had an increased risk for major genitourinary abnormalities compared with naturally conceived singleton infants with parents with no fertility issues (adjusted risk difference [aRD] 19.0 cases per 10,000 births), reported Georgina M. Chambers, PhD, of the University of New South Wales in Sydney, and colleagues.
This risk remained when the ART-conceived infants were compared with naturally conceived singleton infants with parents who had experienced infertility (aRD 22 cases per 10,000 births), indicating that ART remained an independent risk, they noted in the Annals of Internal Medicine.
Furthermore, after accounting for parental infertility, intracytoplasmic sperm injection (ICSI) in parents without male infertility was associated with an increased risk for major genitourinary abnormalities (aRD 47.8 cases per 10,000 singleton births), and there was some suggestion of increased risk for congenital anomalies after fresh embryo transfer, but estimates were inconsistent.
“The findings of the current study should inform counseling of patients undergoing ART,” Chambers and team concluded. “The main message is that although the risk for some CAs [congenital anomalies] is elevated, the absolute increase in the relative risks seems to be small.”
“However, we caution against overuse of ICSI without clear medical indications given its independent association with certain types of CAs,” they added.
Millions of children are conceived using in vitro fertilization (IVF) and other ART methods, such as ICSI and ovulation induction and intrauterine insemination (OI/IUI), each year. Previous studies have shown that these children are at increased risk for congenital defects. Whether these congenital anomalies are associated with fertility problems in parents or ART treatments has been an ongoing question.
“We designed the study to attempt to disentangle the effect of underlying infertility of the parents from fertility treatment itself,” Chambers told MedPage Today.
“The fact that the risk of any major birth defects decreased when we adjusted for parental infertility supports the idea that a major part of this small increase in the incidence of birth defects after ART is likely explained by parents infertility,” she said. “Our study confirmed that multiple births have a higher risk of birth defects compared to singletons” — 679.8 to 840.0 per 10,000 births for plural infants versus 455.8 to 540.4 per 10,000 births for singletons.
This propensity score-weighted population-based cohort study included 851,984 infants, of whom 97.2% were singletons and 2.8% were plural infants born from 2009 through 2017 in New South Wales.
Of the singleton infants, 3.8% were ART-conceived, 1.6% were OI/IUI-conceived, 4.4% were naturally conceived from parents with a history of infertility, and 90.2% were naturally conceived from fertile mothers. Among the ART-conceived infants, 53.7% were conceived using ICSI, and 43.3% were conceived from cryopreserved embryos. Of the plural infants, 14.4% were ART-conceived, 5.9% were OI/IUI-conceived, and the rest were naturally conceived.
The overall incidence of congenital anomalies was 459 per 10,000 singleton births and 757 per 10,000 plural births.
Among singleton infants, the overall crude prevalence of any major congenital anomaly was highest in ART-conceived infants (514.8 per 10,000 births) and OI/IUI-conceived infants (502.4 per 10,000 births).
The highest crude prevalence of any major congenital anomaly in plural births was seen in the ART-IVF group (840.0 per 10,000 births), the OI/IUI-conceived group (829.8 per 10,000 births), and the group conceived from cryopreserved embryos (825.7 per 10,000 births).
The cohort only included children born at or after 20 weeks’ gestation, and the authors did not measure the overall risk for congenital anomalies, which would include spontaneous early pregnancy loss, “and does not account for potentially different prenatal screening practices for CAs between those who conceived naturally and those who used fertility treatment,” Chambers and team noted.
In addition, the observational nature of the study inherently means it cannot determine causality. They also pointed out that administrative health data hindered their ability to examine other risk factors, like family history of congenital anomalies and exposure to environmental factors.
The study was funded by the Australian National Health and Medical Research Council.
Chambers reported a relationship with the Fertility Society of Australia and New Zealand.
Co-authors reported relationships with industry, including Merck, Cadila Pharma, Merck Sharpe & Dohme, and Ferring.
Annals of Internal Medicine
Source Reference: Venetis C, et al “Risk for congenital anomalies in children conceived with medically assisted fertility treatment: a population-based cohort study” Ann Intern Med 2023; DOI: 10.7326/M23-0872.