Fertility Treatment Impact on Cardiometabolic Health in Offspring Found Extremely Small

A multinational multicohort analysis of more than 35 500 offspring conceived naturally or using assisted reproductive technology (ART), found differences in cardiometabolic health outcomes between the 2 populations were small and statistically insignificant.

The study is the largest and, with more than 25 years of follow-up, the longest to date that has focused on potential variation in blood pressure, lipids, and glycemic measures between naturally- and ART-conceived children.

The study authors, led by Ahmed Elhakeem, MPH, PhD, a research fellow in epidemiology, Bristol Medical School, Population Health Science, University of Bristol, in England, write that the rapid rise in use of ART that has led to more than 8 million births worldwide has not been free of controversy. Writing in the European Heart Journal they cite a range of systematic reviews that have reported higher blood pressure, glucose, and triglycerides in ART-conceived offspring. The studies in these reviews, however, have been small, of limited duration, and subject to both selection and publication bias, according to Elhakeem and colleagues.

Further, they state, no studies have explored how associations between cardiometabolic outcomes in ART-conceived offspring change with increasing age, leaving open the question of whether associations observed in early childhood persist to adulthood.

Elhakeem et al designed their population-based pooled cohort analysis to broaden general understanding of this association and to extend surveillance up to young adulthood.

For the study, Elhakeem et al recruited cohort studies from the Assisted Reproductive Technology and Future Health (ART-Health) Cohort Collaboration, a multinational collaboration of 26 cohort studies. From ART-Health, the team identified 14 cohorts that met inclusion criteria for the analysis.

From these 14 cohorts, data were obtained on 35 938 individuals (654 conceived via ART). Mean follow-up age ranged from 13 months to 27.4 years, however participants in 11 of the 14 cohorts were younger than age 10 years.

The primary outcomes of interest for the study were differences between ART-and naturally-conceived children in systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate (HR), lipids, and markers of hyperglycemia and insulin resistance. Differences were assessed in multiple linear regression models and combined using meta-analysis. Elhakeem and team also performed a pooled trajectory analysis to evaluate change in observed associations with age.

FINDINGS

There were no statistically signficant pooled differences based on the meta-analysis for offspring conceived with ART vs natural conception for SBP (-0.53 mm Hg [95% CI, -1.59 to 0.53]), DBP (-0.24 mm Hg [-0.83 to 0.35]), or HR (0.02 beat/min [95% CI, -0.91 to 0.94]).

The researchers did, however, report just slightly significantly higher measures among offspring conceived with ART for total cholesterol (2.59% [95% CI, 0.10 to 5.07]), HDL cholesterol (4.16% [95% CI, 2.52 to 5.81]), and LDL cholesterol (4.95% [95% CI, 0.47-9.43]) compared to naturally conceived offspring. Further analysis demonstrated no statistical differences for triglycerides, glucose, insulin, and glycated hemoglobin.

The investigator’s age-change trajectory analysis for BP, heart rate, lipids, and glucose included 17 244 offspring of which 244 were conceived with ART. The age range of outcome assessment was from 2.9 to 26.5 years. This analysis demonstrated lower BP during childhood in ART-conceived offspring with subtle increases toward young adulthood. The researchers also report subtle trajectories to higher triglycerides and lower HDL-C in young adulthood in this group. Most of these observed differences, they emphasized, were not statistically significant.

“Parents conceiving or hoping to conceive through assisted reproductive technology and their offspring should be reassured that cardiometabolic health appears to be comparable in ART-conceived and naturally conceived children,” said Elhakeem in a statement from the University of Bristol. “Studies with longer follow-up would now be beneficial to examine how results might change across adulthood.”

“This important research is only possible through large scale international collaboration and longitudinal health studies, where participants contribute health data throughout their entire lives,” added senior author Deborah Lawlor, MBChB, MPH, a professor of Epidemiology at the Bristol Medical School and chair of the British Heart Foundation.

Reference: Elhakeem A, Huang J, Inskip H, et al. Long-term cardiometabolic health in people born after assisted reproductive technology: a multi-cohort analysis. Eur Heart J. Published online February 6, 2023. doi:10.1093/eurheartj/ehac726