MATERNAL SERUM PROTEOME PROFILE OF EARLY PLACENTATION IN IVF IS DISTINCT FROM NORMAL PLACENTATION
Mervi Haapsamo1,
Juha Rasanen2,
Melissa Standley3, Archana Thomas3,
Thomas Jacob3,
John Michaels3, Xinfang Lu3,
Jodi Lapidus3,
Michael Gravett4,
Srinivasa Nagalla3
1University of
Oulu, Obstetrics and Gynecology, Oulu, ;
2Oregon Health &
Science University, Obstetrics & Gynecology, Portland, Oregon;
3ProteoGenix,
Inc., Beaverton, Oregon;
4University of
Washington, Department of OB/GYN, Seattle, Washington
OBJECTIVE: Placentation following IVF may differ from normal placentation, and result in differences in placental proteins detected in maternal serum. Our objective was to characterize the maternal serum proteome in early pregnancy in IVF and in spontaneous pregnancies.
STUDY DESIGN: 110 women (55 IVF and 55 spontaneous pregnancies) from a prospective cohort were included. Maternal sera were collected at 11 and 19 gestational weeks. Proteome analysis was performed using fluorescence 2-D gel electrophoresis (2-DIGE), multidimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS) and label-free quantification. Pair-wise comparison was performed using χ2 goodness-of-fit tests. Statistical significance for each protein was determined after adjusting for multiple comparisons via the false-discovery rate (FDR) method. Immunoassays were used for accurate quantification and evaluated using the Receiver Operating Characteristic (ROC) curves.
RESULTS: Gestational age at delivery or perinatal outcome did not differ between the groups. 2D LC-MS/MS analysis identified 368 unique proteins. Protein expression differences were noted in extra-cellular matrix, cytoskeletal, vascular, complement and transport proteins; all are important in placentation. Pregnancy specific glycoprotein-1 (PSG1), somatomamotrophin-1, and lipopolysaccharide binding protein were significantly increased (p<0.05) at 11 weeks of gestation in IVF pregnancies. Most of these differences disappeared by 19 weeks (only PSG1 remained significantly different). Commonly measured pregnancy proteins (pregnancy associated plasma protein-1, chorionic gonadotrophin, endoglin, fibronectin) had similar trends from 11 to 19 weeks in both groups.
CONCLUSION: First trimester maternal serum proteome analyses identified distinct differences in protein detection between IVF and spontaneous pregnancies that persisted until mid-gestation. These findings may help explain adverse pregancy outcomes associated with IVF pregnancy and suggest early, selective treatments.
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