First trimester serum and ultrasound marker distribution in singleton pregnancy conceived with assisted reproductive technology

Aim of the study: to evaluate distribution of ultrasound and biochemical markers (PAPP-A and free beta-hCG) in first trimester prenatal screening in single pregnancy conceived with assisted reproductive technology, and to define association between biochemical markers level and course of pregnancy in first trimester.

Material and methods: blood sampling and nuchal translucency thickness (NT) measurement in 109 singleton pregnancies conceived by traditional in-vitro fertilization (IVF –71 cases, among them 15 cases after frozen embryo transfer (FET)) and intracytoplasmic sperm injection (ICSI –38 cases, among them 17 cases after FET). Women after spontaneous embryo reduction were excluded. Screening performed in 10–14 weeks of gestation (level of PAPP-A, β-hCG and nuchal translucency measurement). Levels of biochemical markers converted to multiples of the median (MoM). MoM < 5th percentile was defined as low PAPP-A or β-hCG and those > 90th percentile as high. Mean age of study group was 37.1 + 0.5 years. 95 women with spontaneous pregnancy were enrolled to control group.

Results: in fresh IVF/ICSI subgroup PAPP-A MoM was significantly lower compared with the matched controls (0.64 and 0.69 vs. 0.98, P<0.001). There were no differences of PAPP-A level between frozen embryo transfer subgroup and control one. Fetal nuchal translucency (NT) thickness in study group was lower than in control one (0.92 MoM vs. 1.00 MoM respectively, P<0.0001). In study group there were 3.1% children with congenital malformations and in control group –2.9%. Malformations of cardiovascular system dominated (82% cases). The false-positive rate (FPR) in ART pregnancy group compared with the matched controls (on the overall age biasis) was higher (IVF 11.3% vs. 6.0%, P<0.01).

We elicited association between biochemical markers level and course of pregnancy in the first trimester. The lowest PAPP-A accompanied with normal level of β-hCG registered in women with threatened abortion (in 76% cases), that in majority of cases associated with clinical features of threatened abortion (for example suhorionical hematoma, horion hypoplasia, presentation and abraption). Statistical analysis revealed, that low PAPP- A levels correlated with threatened abortion (r=0.77, p<0.005).

Conclusions Further randomizes studies are needed to establish standard values of biochemical markers for prenatal screening of ART pregnancies, because low PAPP-A levels (accompanied with normal β-hCG level) may be primary associated with trophoblast invasion features and “mother-placenta-fetus” system formation but not fetus chromosomal abnormality.