Longer time‐to‐pregnancy in spontaneously conceived pregnancies is associated with lower PAPP‐A and free β‐hCG in first trimester screening for Down syndrome

Abstract

The aim of this study was to investigate whether subfertility, measured as longer time-to-pregnancy (TTP) in spontaneously conceived pregnancies, affects the first trimester levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotrophin (β-hCG) and hence the risk estimates in Down syndrome screening. The study included a cohort of 10 469 singleton pregnant women who underwent first trimester combined screening and responded to a questionnaire regarding TTP. PAPP-A and free β-hCG levels were measured between gestational week 8 + 0 and 13 + 6 and were related to TTP. The median PAPP-A and free β-hCG MoMs were significantly lower in women with a TTP ≥24 months compared with the reference group with a TTP <6 months (PAPP-A: 0.96 vs 1.06 MoM, p = 0.003; free β-hCG: 1.04 vs 1.12 MoM, p = 0.03). This led to an increased odds for trisomy 21 risk ≥1 : 300 for TTP ≥24 months compared with TTP <6 months, but when adjusting for potential confounders, the odds ratio (OR) lost significance (OR 1.4, 95% confidence interval; 0.8-2.4). Time-to-pregnancy ≥24 months in spontaneously conceived pregnancies is associated with decreased levels of PAPP-A and free β-hCG.