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Concentration of soluble urokinase plasminogen activator receptor (suPAR) in the pre-ovulatory follicular fluid is associated with development of ovarian hyperstimulation syndrome during ovarian stimulation

  • Assisted Reproduction Technologies
  • Published:
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Abstract

Purpose

Investigating whether pre-ovulatory follicular fluid (FF) levels of selected proteins differ between women who do or do not develop severe ovarian hyperstimulation syndrome (OHSS) and evaluate whether they potentially could guide a “freeze-all” strategy.

Methods

FF was collected during a randomized controlled trial comparing OHSS in antagonist versus agonist protocol including 1050 women in their first assisted reproductive technology (ART) cycle during year 2009–2013. The present sub-study is a matched case-control study comparing FF levels of soluble urokinase plasminogen activator receptor (suPAR), C-reactive protein, placental growth factor, vascular endothelial growth factor, and angiopoietins 1 and 2 in OHSS cases (n = 25, severe OHSS, and ≥ 15 oocytes), high-risk controls (n = 25, no OHSS, and ≥ 15 oocytes), and low-risk controls (n = 25, no OHSS, and 5–8 oocytes).

Results

FF level of suPAR differed significantly between the three groups (p = 0.018) with mean (SD) levels of 2.3 (0.4) μg/L, 2.6 (0.8) μg/L, and 2.8 (0.6) μg/L in OHSS cases, high-risk controls, and low-risk controls, respectively. Receiver operating characteristic curve analysis demonstrated that suPAR levels could predict severe OHSS (AUC 0.678; 95% CI 0.553–0.803) with a sensitivity of 64% and a specificity of 66%. None of the other investigated proteins differed between the three groups or between OHSS cases and combined controls.

Conclusion

The pre-ovulatory FF level of suPAR was significantly lower in women develo** severe OHSS, indicating that the plasminogen activator system could be involved in the pathophysiology of OHSS. However, suPAR did not provide a satisfying predictive value for the prediction of OHSS.

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Funding

For the primary RCT, an unrestricted research grant was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD). The funders had no influence on the idea, data collection, analyses, or conclusions of the study.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, The Fertility Clinic, Copenhagen University Hospital Hvidovre, Kettegård Alle 30, 2650, Hvidovre, Denmark

    A. G. Grynnerup, M. Toftager, A. Zedeler, J.W. Bogstad, L. Prætorius, A. Pinborg & K. Løssl

  2. Laboratory of Reproductive Biology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

    M. L. Grøndahl & C. Yding Andersen

  3. The Fertility Clinic, Copenhagen University Hospital Herlev, Herlev, Denmark

    M. L. Grøndahl

  4. Clinical Research Centre, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark

    S. Sørensen

  5. The Fertility Clinic, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark

    K. Løssl

Authors
  1. A. G. Grynnerup
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  2. M. Toftager
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  3. A. Zedeler
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  4. J.W. Bogstad
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  5. L. Prætorius
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  6. M. L. Grøndahl
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  7. C. Yding Andersen
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  8. S. Sørensen
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  9. A. Pinborg
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  10. K. Løssl
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Corresponding author

Correspondence to A. G. Grynnerup.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

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Grynnerup, A.G., Toftager, M., Zedeler, A. et al. Concentration of soluble urokinase plasminogen activator receptor (suPAR) in the pre-ovulatory follicular fluid is associated with development of ovarian hyperstimulation syndrome during ovarian stimulation. J Assist Reprod Genet 35, 2187–2193 (2018). https://doi.org/10.1007/s10815-018-1314-2

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  • DOI: https://doi.org/10.1007/s10815-018-1314-2

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