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Purpose <p>We sought to investigate whether positive-pregnancy outcome is associated with modulation of fibrin clot properties and thrombin generation with regard to neuropeptide levels.</p> Methods <p>In this prospective study, we enrolled 56 infertile women aged 32 ± 5 years, BMI 24.5 ± 5&#xa0;kg/m<sup>2</sup>, treated with letrozole in the Department of Gynecological Endocrinology of a University Hospital. We measured plasma fibrin clot permeability (Ks), efficiency of fibrinolysis (clot lysis time, CLT) along with endogenous thrombin potential and serum levels of phoenixin (PNX-14), nesfatin-1 (NES-1), and dopamine (DA) together with decreased oxytocin (OT) before and after ovarian stimulation (OS) with letrozole.</p> Results <p>At baseline, women who achieved pregnancy (<i>n</i> = 23, 41.1.1%) compared to non-pregnant women showed higher Ks (+ 21.4%, <i>p</i> = 0.002) with no differences in peak thrombin, ETP, or CLT (all <i>p</i> &gt; 0.05). In all women, OS led to shortened lag time (-6.9%) in conjunction with increased peak thrombin (+ 17.9%), with no changes in ETP and slightly lower K<sub>S</sub> (-7.7%). After OS, in all women, both ETP and peak were positively correlated with PNX-14 (<i>r</i> = 0.54, <i>p</i> &lt; 0.001 and <i>r</i> = 0.40, <i>p</i> = 0.002, respectively). Moreover, CLT was associated with PNX-14 (<i>r</i> = 0.44, <i>p</i> &lt; 0.001) and K<sub>S</sub> (<i>r</i>=-0.38, <i>p</i> = 0.004). After OS, the pregnant women showed higher ETP (+ 11.4%) along with reduced Ks (-18.1%) and prolonged CLT (+ 8.3; all <i>p</i> &lt; 0.05). Fibrin clot permeability and lysis as well as enhanced thrombin generation parameters were positively associated with PNX-14 levels.</p> Conclusion <p>Enhanced thrombin generation associated with higher PNX-14 is observed in infertile women with positive pregnancy outcomes after OS with letrozole.</p> Clinical trial registration number <p>NCT04166825.</p>

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Prothrombotic fibrin clot phenotype in pregnant women after ovarian stimulation: associations with neuropeptides

  • 期刊论文

  • 发表日期：

    2026年3月26日

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  • Magdalena Piróg,
  • Robert Jach,
  • Michał Ząbczyk,
  • Joanna Natorska

摘要

Purpose

We sought to investigate whether positive-pregnancy outcome is associated with modulation of fibrin clot properties and thrombin generation with regard to neuropeptide levels.

Methods

In this prospective study, we enrolled 56 infertile women aged 32 ± 5 years, BMI 24.5 ± 5 kg/m2, treated with letrozole in the Department of Gynecological Endocrinology of a University Hospital. We measured plasma fibrin clot permeability (Ks), efficiency of fibrinolysis (clot lysis time, CLT) along with endogenous thrombin potential and serum levels of phoenixin (PNX-14), nesfatin-1 (NES-1), and dopamine (DA) together with decreased oxytocin (OT) before and after ovarian stimulation (OS) with letrozole.

Results

At baseline, women who achieved pregnancy (n = 23, 41.1.1%) compared to non-pregnant women showed higher Ks (+ 21.4%, p = 0.002) with no differences in peak thrombin, ETP, or CLT (all p > 0.05). In all women, OS led to shortened lag time (-6.9%) in conjunction with increased peak thrombin (+ 17.9%), with no changes in ETP and slightly lower KS (-7.7%). After OS, in all women, both ETP and peak were positively correlated with PNX-14 (r = 0.54, p < 0.001 and r = 0.40, p = 0.002, respectively). Moreover, CLT was associated with PNX-14 (r = 0.44, p < 0.001) and KS (r=-0.38, p = 0.004). After OS, the pregnant women showed higher ETP (+ 11.4%) along with reduced Ks (-18.1%) and prolonged CLT (+ 8.3; all p < 0.05). Fibrin clot permeability and lysis as well as enhanced thrombin generation parameters were positively associated with PNX-14 levels.

Conclusion

Enhanced thrombin generation associated with higher PNX-14 is observed in infertile women with positive pregnancy outcomes after OS with letrozole.

Clinical trial registration number

NCT04166825.