Abstract

The incidence of pulmonary and venous thromboembolism is increased during the first trimester of pregnancies after assisted reproductive technology (ART) compared to spontaneous conception. We previously found that haemostatic plasma variables changed but within normal limits during controlled ovarian hyperstimulation (COH) concomitant with a major increase in plasma microvesicles (MVs) and markers indicating cell activation. We now explored the proteome of these MVs. Thirty-one women undergoing ART were blood sampled at down-regulation (DR) of oestrogen and at high level stimulation (HLS) with its 10–100-fold increased oestrogen level. Samples were analysed by liquid chromatography and tandem mass spectrometry to identify and quantify the proteome. We identified 306 proteins in the MVs and 72 had changed significantly at HLS compared to DR and more than 20% of them were associated with haemostasis. Thus, proteins related to both haemostasis and complement activation altered in plasma MVs in parallel with MV activation during COH. This needs to be further explored in the clinical context.

Highlights

  • The incidence of pulmonary and venous thromboembolism is increased during the first trimester of pregnancies after assisted reproductive technology (ART) compared to spontaneous conception

  • In 2013 we found that the incidence of venous thromboembolism (VTE) increased during the first trimester of ART pregnancies with a sevenfold increase in pulmonary embolism (PE) as compared to matched pregnant ­women[3]

  • We identified 1,199 proteins in the MV fraction of plasma during the controlled ovarian hyperstimulation (COH) phase of ART

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Summary

Introduction

The incidence of pulmonary and venous thromboembolism is increased during the first trimester of pregnancies after assisted reproductive technology (ART) compared to spontaneous conception. We previously found that haemostatic plasma variables changed but within normal limits during controlled ovarian hyperstimulation (COH) concomitant with a major increase in plasma microvesicles (MVs) and markers indicating cell activation. Proteins related to both haemostasis and complement activation altered in plasma MVs in parallel with MV activation during COH. This needs to be further explored in the clinical context. In 2013 we found that the incidence of venous thromboembolism (VTE) increased during the first trimester of ART pregnancies with a sevenfold increase in pulmonary embolism (PE) as compared to matched pregnant ­women[3]. Flow cytometric studies are restricted to capture quantitative and qualitative changes of membrane bound proteins, whilst proteomic analysis offers a possibility to capture modifications in the whole proteome of the MVs

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