Low first-trimester PAPP-A in IVF (fresh and frozen-thawed) pregnancies, likely due to a biological cause

Lauren P Hunt; A M McInerney-Leo; S Sinnott; B Sutton; R Cincotta; G Duncombe; J Chua; M Peterson

doi:10.1007/s10815-017-0996-1

Low first-trimester PAPP-A in IVF (fresh and frozen-thawed) pregnancies, likely due to a biological cause

J Assist Reprod Genet. 2017 Oct;34(10):1367-1375. doi: 10.1007/s10815-017-0996-1. Epub 2017 Jul 17.

Authors

Lauren P Hunt^{1

2

3}, A M McInerney-Leo^{4

5}, S Sinnott⁶, B Sutton⁶, R Cincotta^{7

8}, G Duncombe^{7

8

9}, J Chua⁷, M Peterson^{10

6}

Affiliations

¹ Genetic Health Queensland, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, QLD, 4029, Australia. Lauren.Hunt@uq.edu.au.
² School of Natural Sciences, Griffith University, 170 Kessels Road, Nathan, QLD, 4111, Australia. Lauren.Hunt@uq.edu.au.
³ Department of Nursing and Midwifery, University of Queensland, St Lucia, QLD, 4072, Australia. Lauren.Hunt@uq.edu.au.
⁴ University of Queensland Diamantina Institute, University of Queensland, Level 7, 37 Kent Street, Translational Research Institute, Woolloongabba, QLD, 4102, Australia.
⁵ Institute of Health and Biomedical Innovation, Queensland University of Technology, GPO Box 2434, Brisbane, QLD, 4001, Australia.
⁶ Specialised Obstetric & Gynaecological Imaging (so+gi), 4A/15 Tribune Street, South Bank, QLD, 4101, Australia.
⁷ Queensland Ultrasound for Women, 1/55 Little Edward Street, Spring Hill, QLD, 4000, Australia.
⁸ Department of Obstetrics and Gynaecology, University of Queensland, St Lucia, QLD, 4072, Australia.
⁹ Centre for Clinical Research, University of Queensland, Royal Brisbane and Women's Hospital, Butterfield Street, Herston, QLD, 4029, Australia.
¹⁰ School of Natural Sciences, Griffith University, 170 Kessels Road, Nathan, QLD, 4111, Australia.

Abstract

Purpose: The purpose of this study is to confirm a difference in the first-trimester screen maternal biochemistry and false-positive rates (FPR) between pregnancies conceived spontaneously and those conceived via assisted reproductive technologies (ART).

Methods: Retrospective analysis of the complete population of women (17,889 pregnancies) who had undergone first-trimester screening between January 2004 and September 2009 at three private ultrasound clinics in Queensland, Australia was used in the study. The age, gestation, method of conception, ultrasound markers, biochemistry markers (PAPP-A, fβ-hCG), and type of biochemical analyzer platform (Brahms Kryptor, Immulite 2000) data was collated. Univariate analysis of variance (ANOVA), Spearman's rank nonparametric correlation analysis, and Binary Logistic Regression analysis were used to analyze data. Spontaneous pregnancies were used as controls. Results were considered significant when the p value was less than 0.05.

Results: After exclusions, 16,363 singleton pregnancies, including 1543 conceived via ART, were analyzed. Results from the two biochemistry platforms, Brahms Kryptor and Immulite 2000 were significantly different (p < 0.001); thus, the data was divided for analysis purposes. PAPP-A was universally significantly lower in IVF pregnancies compared to spontaneously conceived pregnancies (p < 0.001). Using the Brahms Kryptor platform, ICSI was associated with significantly decreased PAPP-A (p < 0.046), and a significantly increased FPR (p = 0.012).

Conclusions: Consistent with previous studies IVF pregnancies had significantly lower PAPP-A levels supporting the need to appropriately adjust the combined first-trimester screening (cFTS) risk algorithm for IVF conceptions. The Brahms Kryptor and Immulite 2000 platforms are significantly different; however, the universally lower PAPP-A findings support the hypothesis that the lower PAPP-A is due to a biological cause.

Keywords: Combined first-trimester screening; First-trimester maternal serum biochemistry; IVF; PAPP-A.

MeSH terms

Adolescent
Adult
Biomarkers
Chorionic Gonadotropin / blood
Cohort Studies
False Positive Reactions
Female
Fertilization in Vitro
Humans
Middle Aged
Pregnancy
Pregnancy Tests / methods*
Pregnancy Trimester, First
Pregnancy-Associated Plasma Protein-A / analysis*
Regression Analysis
Reproductive Techniques, Assisted*
Sperm Injections, Intracytoplasmic

Substances

Biomarkers
Chorionic Gonadotropin
Pregnancy-Associated Plasma Protein-A
PAPPA protein, human