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Hum. Reprod. Advance Access originally published online on February 26, 2009
Human Reproduction 2009 24(6):1330-1338; doi:10.1093/humrep/dep046
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© The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Pregnancies conceived using assisted reproductive technologies (ART) have low levels of pregnancy-associated plasma protein-A (PAPP-A) leading to a high rate of false-positive results in first trimester screening for Down syndrome

D.J. Amor1,2,3,4,8, J.X. Xu1,2, J.L. Halliday1,2, I. Francis3, D.L. Healy5,6, S. Breheny5,6, H.W.G. Baker4,7 and A.M. Jaques1

1 Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia 2 Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia 3 Victorian Clinical Genetics Services, Royal Children's Hospital, Parkville, Victoria, Australia 4 Melbourne IVF, East Melbourne, Victoria, Australia 5 Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia 6 Monash IVF, Richmond, Victoria, Australia 7 Department of Obstetrics and Gynaecology, University of Melbourne, Royal Women's Hospital, Parkville, Victoria, Australia

8 Correspondence Address. Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Rd, Parkville 3052, Australia. Tel: +61-3-83-41-62-93; Fax: +61-3-83-41-63-90; Email: david.amor{at}mcri.edu.au

BACKGROUND: First trimester screening (FTS) for Down syndrome combines measurement of nuchal translucency, free beta-human chorionic gonadotrophin and pregnancy-associated plasma protein-A (PAPP-A). The aim of this study was to undertake a detailed analysis of FTS results in singleton pregnancies conceived using assisted reproductive technologies (ART) and non-ART pregnancies.

METHODS: A record linkage study compared outcomes in 1739 ART-conceived and 50 253 naturally conceived pregnancies.

RESULTS: Overall, significantly lower PAPP-A levels were detected in ART pregnancies (0.83 multiples of median, MoM) than in controls (1.00 MoM) (t-test P < 0.001). This difference remained after excluding complicated pregnancies. Analysis of factors affecting PAPP-A levels suggested fresh compared with frozen embryo transfers and use of artificial cycles compared with natural cycles for frozen transfers were associated with lower values. The adjusted odds ratio (AdjOR) for receiving a false-positive result was 1.71 (95% CI 1.44–2.04; P < 0.001) for ART pregnancies compared with non-ART pregnancies, and this leads to a higher AdjOR (1.24, 95% CI 1.03–1.49; P = 0.02) for having a chorionic villous sampling (CVS) or amniocentesis.

CONCLUSIONS: ART pregnancies have reduced FTS PAPP-A levels leading to an increased likelihood of receiving a false-positive result and having a CVS/amniocentesis. Lower PAPP-A may reflect impairment of early implantation with some forms of ART.

Key words: ART/PAPP-A/pregnancy screening/pregnancy complications/hormonal stimulation

Submitted on October 7, 2008; resubmitted on January 15, 2009; accepted on January 21, 2009.


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