22q11.2 Deletion Syndrome in Offspring Conceived via Assisted Reproductive Technology Versus Spontaneously

TL;DR

This study compares the occurrence and outcomes of 22q11.2 deletion syndrome in children conceived through assisted reproductive technology versus natural conception.

Contribution

The study provides evidence that assisted reproductive technology does not increase the risk of 22q11.2 deletions or affect perinatal outcomes.

Findings

The prevalence of ART conceptions in 22q11.2DS patients was not significantly different from the general population.

Neonates conceived via ART were more likely to be admitted to the ICU, but other perinatal outcomes were similar.

There is no significant relationship between ART and meiotic non-allelic homologous recombination leading to 22q11.2 deletions.

Abstract

Background/Objectives: The majority of chromosome 22q11.2 deletions are de novo, resulting from meiotic non-allelic homologous recombination (NAHR). While 22q11.2 deletion syndrome (22q11.2DS)-associated phenotypes are well characterized, risk factors leading to NAHR are poorly understood, including the possible relationship with assisted reproductive technology (ART). Here we examined the prevalence of ART conceptions and medical comorbidities in patients with 22q11.2DS vs. spontaneously conceived (SC) patients with 22q11.2DS. Methods: Retrospective analysis, under IRB approval, of medical records on 1184 patients with laboratory-confirmed de novo chromosome 22q11.2 deletions was performed. ART conceptions included IVF with and without ICSI. Deletion size and obstetric, family, and medical histories were examined. Results: We identified 30 pregnancies conceived using ART (2.57%) compared with the U.S. general population rate of 2.3% (p-value = 0.6603). ART and SC sub-cohorts demonstrated no significant differences in deletion size or perinatal outcomes, including preterm birth, multiples, polyhydramnios, or congenital heart disease. Controlling for these factors, neonates conceived via ART were more likely to be admitted to the ICU (aOR = 6.3). Conclusions: Pregnancies conceived via ART, and later found to have 22q11.2DS, demonstrated no significant differences in prevalence or perinatal outcomes compared with the U.S. general population. Moreover, NAHR is unrelated to ART in this population. Likewise, associated phenotypic features are unrelated. These data will be reassuring to those families where ART was employed to conceive children who were later found to have 22q11.2DS.

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