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

Context: Assisted reproduction technologies (ART), classic 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.