PCSK9 and Lp(a) levels of children born after assisted reproduction technologies

J Assist Reprod Genet. 2019 Jun;36(6):1091-1099. doi: 10.1007/s10815-019-01474-1. Epub 2019 May 11.


Purpose: Proprotein convertase subtilisin/kexin type 9 (PCSK9) and lipoprotein (a) (Lp[a]) levels are associated with cardiovascular risk. To investigate PCSK9 and Lp(a) levels of children born after assisted reproduction technologies (ART) compared with naturally conceived (NC) controls.

Methods: In this exposure-matched cohort study, 73 racial-, 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 overall population, PCSK9 levels were related to total cholesterol, low-density lipoprotein, and systolic blood pressure, while Lp(a) levels were related to age, apolipoprotein-B, birth weight, height, waist-to-hip ratio, insulin resistance, insulin, and high-sensitivity C-reactive protein. No significant differences were observed regarding lipid biomarkers between ART and NC children. However, 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. 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).

Conclusions: We show that 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 indicate that ART method may be of importance given that classic IVF is associated with higher levels of Lp(a).

Keywords: Age; Assisted reproduction technologies; Cardiovascular risk; In vitro fertilization; Lipoprotein (a); PCSK9.

MeSH terms

  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / pathology
  • Child
  • Child, Preschool
  • Female
  • Fertilization in Vitro / adverse effects
  • Humans
  • Insulin Resistance / genetics
  • Lipoprotein(a) / blood*
  • Male
  • Proprotein Convertase 9 / blood*
  • Reproductive Techniques, Assisted / adverse effects*
  • Risk Factors
  • Sperm Injections, Intracytoplasmic / adverse effects


  • Biomarkers
  • Lipoprotein(a)
  • C-Reactive Protein
  • PCSK9 protein, human
  • Proprotein Convertase 9