The Impact of Assisted Reproductive Technology on the Association between First-Trimester Pregnancy-Associated Plasma Protein A and Human Chorionic Gonadotropin and Adverse Pregnancy Outcomes

Abstract

We evaluated the impact of assisted reproductive technology (ART) on the association between first-trimester pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotropin (β-hCG) and adverse pregnancy outcomes. PAPP-A and β-hCG levels were obtained between 11 and 13 (6)/ (7) weeks' gestation and 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. Adverse outcomes included small-for-gestational-age (SGA) infants, preeclampsia, pregnancy loss, and preterm delivery (PTD). Univariate and multivariate analyses were used to estimate the association. Of 4000 women meeting the inclusion criteria, 265 (7.6%) pregnancies were conceived by ART. ART pregnancies with low PAPP-A had a higher risk of having an SGA infant (odds ratio [OR] = 4.1, 95% confidence interval [CI] 1.2, 14.0) or PTD < 32 weeks (OR = 5.3, 95% CI 1.5, 18.6) compared with non-ART pregnancies with low PAPP-A (OR = 2.8, 95% CI 1.7, 4.7; OR = 3.9, 95% CI 2.1, 7.0, respectively). High PAPP-A was associated with pregnancy loss (OR = 6.1, 95% CI 1.1, 33.7) in ART pregnancies. Low β-hCG was associated with increased risk for PTD only in ART pregnancies (OR = 8.3, 95% CI 1.9, 35.9) for PTD < 37 weeks (OR 6.1, 95% CI 1.6, 23.0) for PTD < 35 weeks and (OR = 10.8, 95% CI 2.7, 43.7) for PTD < 32 weeks. High β-hCG was associated with increased risk for SGA (OR = 1.6, 95% CI 1.0, 2.5) and PTD < 37 weeks (OR = 1.4, 95% CI 1.0, 1.9) in non-ART pregnancies. The association between PAPP-A and β-hCG with adverse pregnancy outcomes is influenced by the mode of conception.

Nuchal translucency measurement, freeβ-hCG and PAPP-A concentrations in IVF/ICSI pregnancies: systematic review and meta-analysis

“…Of those, all considered IVF, 15 considered ICSI, and five reported data concerning IVF/ICSI together . In one case, the type of ART was not specified . Anckaert et al reported data for all type of infertility but also separately for male infertility and female/unexplained infertility.…”

“…The following potential biases in the methodology of the studies included in the review were evaluated: different protocols of ART, characteristics and size of the population, ultrasound and laboratory methodology, large interval of study (from 2001 to 2016) with different correction factors and statistical approaches used for conversion of the measured raw values of free β ‐hCG and PAPP‐A to MoMs. Main characteristics of considered study are provided in Table …”

Low birth weight: is it related to assisted reproductive technology or underlying infertility?

“…Additionally, PAPP-A levels have been associated to a higher risk of small for gestational age (SGA, <10 th percentile of weight) (42, 43) and are directly correlated with insulin-like growth factor (IGF) bioavailability. The IGF system plays an important role in the communication between the embryo and the endometrium, with IGF-2 likely stimulating implantation and invasion (28).…”

Down Syndrome Screening in Pregnancies Conceived after Assisted Reproductive Technologies

“…However, Amor et al (2009) found that PAPP-A levels were reduced in ART pregnancies with or without pregnancy complications (e.g., preeclampsia or low birth weight). In other study by Zhong et al (2010), ART pregnancies with low PAPP-A level values were at higher risk for small-for-gestational-age infants or preterm delivery less than 32 weeks of gestation when compared with spontaneous pregnancies with low PAPP-A values. Recent studies have suggested that vanishing twin might have the impact on serum marker level alterations.…”