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Multiplexed Fluorescent Immunohistochemical Staining of Four Endometrial Immune Cell Types in Recurrent Miscarriage
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Extracellular Vesicles: An Important Biomarker in Recurrent Pregnancy Loss?

Nina Rajaratnam1, Nadja E Ditlevsen1, Jenni K Sloth2

  • 1Department of Obstetrics and Gynecology, Aalborg University Hospital, 9000 Aalborg, Denmark.

Journal of Clinical Medicine
|July 2, 2021
PubMed
Summary

In recurrent pregnancy loss (RPL), elevated CD9 extracellular vesicles (EVs) before week 6 of pregnancy may predict miscarriage. Intravenous immunoglobulin (IVIG) treatment increased EV levels in women with live births.

Keywords:
EV Arrayexosomesextracellular vesicleshabitual abortionmicrovesiclesrecurrent miscarriagerecurrent pregnancy loss

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Area of Science:

  • Reproductive biology
  • Biomarker discovery
  • Immunology

Background:

  • Recurrent pregnancy loss (RPL) affects 1-3% of couples and has multifactorial causes.
  • Extracellular vesicles (EVs) are crucial in physiological processes and reflect cellular states, with altered levels observed in pregnancy disorders.
  • RPL patients face a higher risk of pregnancy complications.

Purpose of the Study:

  • To investigate if specific EV markers in plasma can predict pregnancy loss (PL) in women with RPL.
  • To assess EV changes before and during early pregnancy.
  • To evaluate the impact of intravenous immunoglobulin (IVIG) treatment on EV levels.

Main Methods:

  • A prospective study included 31 women with RPL, divided into live birth (LB) and PL groups.
  • Five plasma samples were collected per participant: pre-pregnancy and at gestational weeks 6, 8, 10, and 16.
  • Seventeen EV markers were analyzed using EV Array, a method for capturing small EVs via antibody panels.

Main Results:

  • The PL group showed a significant increase in the EV marker CD9 from pre-pregnancy to gestational week 6 compared to the LB group.
  • Changes in the other 16 EV markers were not significant between groups.
  • One case of late PL exhibited a sharp increase in nine markers after gestational week 10.
  • IVIG treatment led to an overall increase in all 17 markers in the LB group, significant for 15 markers.

Conclusions:

  • Elevated CD9 levels in early pregnancy may serve as a potential predictor for miscarriage in women with RPL.
  • Further research with larger cohorts is needed to confirm CD9 as a predictive biomarker for RPL.
  • IVIG treatment appears to influence EV levels, warranting further investigation into its mechanisms and effects.