Abstract

BackgroundThe potential role of antinuclear antibodies (ANA) in recurrent pregnancy loss (RPL) pathogenesis is still debated, although some evidences suggest that they could affect pregnancy outcome, leading to a higher miscarriage rate in these patients. A hypothesized mechanism is through changes in uterine flow in pre-conceptional stage, by modifying endometrial receptivity in RPL. However, scant data are available, in pregnancy, about their role in RPL placental perfusion, also in relation to its potential treatments, such as low molecular weight heparin (LMWH). The aim of this study is to retrospectively further investigate the correlation between two-dimensional (2D) and three-dimensional (3D) uterine and placental flow indexes and the presence or the absence of ANA in women with unexplained RPL (uRPL), treated or not treated with LMWH.Methods2D Doppler measurement of pulsatility index (PI) of the uterine arteries and 3D ultrasonography determination of vascularization index (VI), flow index (FI) and vascularization flow index (VFI) was carried out with the aid of the virtual organ computer-aided analysis (VOCAL) technique in LMWH treated (n 24) and not treated-uRPL patients (n 20) and in the relative control group (n 27), each group divided in ANA+ and ANA- subgroups. Serum assay for the presence of ANA was performed in all women.ResultsNo differences were found in PI, VFI and VI values, by comparing the different groups. A difference in VI values was found for ANA- patients between RPL women not treated with LMWH and the treated ones (p = 0,01), which have lower VI values and similar to controls. By considering only ANA- treated and not treated RPL patients, the ROC curve shows an area of 0,80 and at the VI cut-off of 11,08 a sensitivity of 85% and a specificity of 67%.ConclusionsLMWH could exert a potential beneficial effect in restoring the physiological blood flow supply in terms of VI in uRPL ANA- status, suggesting to include ANA and VI investigations in the RPL diagnostic algorithm in a research context, since further studies are needed to clarify this challenging hypothesis in order to try to ameliorate ANA and abnormal placental vascularization negative influence on RPL pregnancy outcome .

Highlights

  • The potential role of antinuclear antibodies (ANA) in recurrent pregnancy loss (RPL) pathogenesis is still debated, some evidences suggest that they could affect pregnancy outcome, leading to a higher miscarriage rate in these patients

  • There are some experimental data that suggests the existence of a possible correlation between ANA and changes in the uterine blood flow in non pregnant women affected by RPL [10,11,12]: the uterine perfusion, regulates the endometrial receptivity and its alteration might be associated with pregnancy complication at an early stage

  • Scant data are available, in pregnancy, about the role of ANA in placental perfusion in relation to RPL and its potential medical treatments, such as low molecular weight heparin (LMWH), which is empirically used in clinical practice [1] for other potential therapeutic properties: prevention of trophoblast apoptosis, enhancement of trophoblast invasiveness, improvement of the endothelial and vascular environments, regulation of embryo implantation, immune functions, beyond its well known anticoagulant effects and inhibitory action on the complement system [13]

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Summary

Introduction

The potential role of antinuclear antibodies (ANA) in recurrent pregnancy loss (RPL) pathogenesis is still debated, some evidences suggest that they could affect pregnancy outcome, leading to a higher miscarriage rate in these patients. There are some experimental data that suggests the existence of a possible correlation between ANA and changes in the uterine blood flow in non pregnant women affected by RPL [10,11,12]: the uterine perfusion, regulates the endometrial receptivity and its alteration might be associated with pregnancy complication at an early stage. Scant data are available, in pregnancy, about the role of ANA in placental perfusion in relation to RPL and its potential medical treatments, such as low molecular weight heparin (LMWH), which is empirically used in clinical practice (even if not recommend in the European Society of Human Reproduction and Embryology -ESHRE guidelines) [1] for other potential therapeutic properties: prevention of trophoblast apoptosis, enhancement of trophoblast invasiveness, improvement of the endothelial and vascular environments, regulation of embryo implantation, immune functions, beyond its well known anticoagulant effects and inhibitory action on the complement system [13]

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