Fetal neurosonography and infant neurobehavior in assisted reproductive technologies following fresh and frozen embryo transfer

Ultrasound Obstet Gynecol. 2022 Apr 25. doi: 10.1002/uog.24920. Online ahead of print.

Abstract

Objective: To explore and compare fetal cortical brain development and infant neurobehaviour in spontaneously conceived (SC) and assisted reproductive technologies (ART) offspring.

Methods: A prospective cohort study of 210 singleton pregnancies including 70 SC pregnancies, 70 conceived by in vitro fertilization (IVF) following frozen embryo transfer (ET), and 70 IVF after fresh ET. Fetal neurosonography was performed at 32±2 weeks to assess cortical development. Sulci depths were measured off-line and normalized by biparietal diameter. Additionally, Ages & Stages Questionnaires (ASQ) were obtained postnatally, at 12±1 months of corrected age. Comparisons were adjusted by maternal age, ethnicity, nulliparity, fetal sex, weight centile and gestational age at scan for neurosonography, and by maternal age, ethnicity, nulliparity, educational level, employment status, new-born's gestational age at birth, breastfeeding, infant's sex and age at the ASQ evaluation.

Results: In comparison to the SC, the fetuses conceived by ART showed statistically significant differences in cortical development, with reduced parieto-occipital (fresh ET mean[SD] 12.5mm[2.5] vs. frozen ET 13.4[2.6] vs. SC 13.4[2.6], p<0.001), cingulate (fresh ET 5.8[1.8] vs. frozen ET 6.0[2.1] vs. SC 6.4[1.9], p<0.001), and calcarine (fresh ET 13.3[3.9] vs. frozen ET 14.1[2.8] vs. SC 16.1[2.7], p=<0.001) sulci depth, together with lower Sylvian fissure grading score. Changes in cortical development were more pronounced in the fresh ET group as compared to the frozen ET. Additionally, ART infants showed lower ASQ scores, especially in the fresh ET group (global ASQ z-scores: fresh ET mean[SD] -0.3[0.4] vs. frozen ET -0.2[0.4] vs. SC 0[0.4], p<0.001).

Conclusions: Fetuses conceived by ART show a distinctive pattern of cortical development and suboptimal infant neurodevelopment, with more pronounced changes in fresh ET. These findings support the existence of in utero brain reorganization associated to ART and warrant follow-up studies to assess their long-term persistence. This article is protected by copyright. All rights reserved.

Keywords: ART; IVF; cortical folding; fetal brain; mode of conception; neurodevelopment; neurosonography; prenatal imaging.