P4467PCSK9 and Lp(a) levels of children born after assisted reproduction technologies: results from a pilot study

Abstract Background Since the introduction of Assisted Reproduction Technologies (ART) in clinical practice several studies have addressed concerns regarding the long-term health of the offspring and have revealed indications of an adverse cardiovascular/cardiometabolic outcome. Proprotein convertase subtilisin/kexin type 9 (PCSK9) and lipoprotein (a) (Lp[a]) levels have been associated with cardiovascular risk. Purpose To investigate PCSK9 and Lp(a) levels of children born after ART compared with naturally conceived (NC) controls. Methods In this case-control study, 73 sex- and age-matched children (mean age 98±35 months) of ART (intracytoplasmic sperm injection [ICSI]: n=33, classic in vitro fertilization [IVF]: n=40) and 73 NC children were assessed. Blood lipid profile, including PCSK9 and Lp(a) levels, was measured. Children were grouped according to age (<8 years, 8–10 years, ≥10 years). Results In the univariate model of the overall population, circulating PCSK9 levels were related to total cholesterol (r=0.186, P=0.025), LDL-C (r=0.180, P=0.029) and SBP (r=0.199, P=0.021). Similarly, circulating Lp(a) levels were related to age (r=0.269, P=0.001), apoB (r=0.214, P=0.01), birth weight (r=−0.183, P=0.037), height (r=0.263, P=0.001), waist-to-hip ratio (r=−0.350, P<0.001), HOMA-IR (r=0.319, P<0.001), insulin (r=0.316, P<0.001), and hsCRP (ρ=0.241, P=0.018). No significant differences were observed regarding lipid biomarkers between ART and NC children. (p=0.515 for PCSK9 and p=0.277 for Lp(a) values). It is noteworthy that a significant interaction was found between age groups and conception method (P<0.001) showing that PCSK9 levels increase with age in ART children, while they decline with age in NC offspring (Figure 1). IVF children showed higher levels of adjusted mean Lp(a) than ICSI (13.5 vs. 6.8 mg/dl, P=0.010) and NC children (12.3 vs. 8.3 mg/dl, P=0.048). Mean LogPCSK9 concentrations with the st Conclusions PCSK9 and Lp(a) levels did not differ between ART and NC children. Nonetheless, PCSK9 levels increase with age in ART children indicating a gradual deterioration of lipidemic profile that could lead to increased cardiovascular risk. Moreover, our results imply that ART method may be of importance given that classic IVF is associated with higher levels of Lp(a). The impact of the method of conception on PCSK9 and Lp(a) values should be validated in larger patient series.