Proteomics of Children Born After Intracytoplasmic Sperm Injection Reveal Indices of an Adverse Cardiometabolic Profile

CONTEXT: Assisted reproduction technologies (ART), classic in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI) are increasingly used. Several studies have demonstrated an unfavorable cardiometabolic profile of the ART offspring. Proteomics is a state-of-the-art technology used for the identification of early biomarkers of disease. OBJECTIVES: To investigate the proteomic profile of children born after ICSI compared with naturally conceived (NC) controls in search of cardiometabolic risk markers. DESIGN: Cross-sectional case-control study: qualitative, comparative proteomic plasma analysis. SETTING: Pediatric Endocrinology and IVF Outpatient Clinics, University of Athens and the Biomedical Research Foundation of the Academy of Athens. PARTICIPANTS: Forty-two sex- and age-matched couples of ICSI and NC children were assessed. Ten pairs additionally matched for birth weight and twin/single pregnancies were submitted to proteomic analysis. INTERVENTION: Medical history, clinical examination, and blood biochemical, hormonal, and proteomic analyses. MAIN OUTCOME MEASURES: (1) Differences in auxological and laboratory data between groups. (2) Differences in plasma proteomic profile in 10 individual pairs and pooled samples. RESULTS: The ICSI group had shorter gestation, more cesarean sections, smaller birth weight/length, and advanced maternal age. No major differences were observed regarding biochemical markers. Proteomic analysis revealed 19 over- and three underexpressed proteins in ICSI. Most overexpressed proteins are implicated in acute-phase reaction, blood coagulation, complement pathway activation, and iron and lipid metabolism, suggesting a subclinical unfavorable cardiometabolic profile. CONCLUSIONS: This study applies proteomics in ICSI-conceived children, providing evidence for an early adverse cardiometabolic profile and supporting the necessity of their long-term monitoring.