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. 2018 Dec;35(12):2187-2193.
doi: 10.1007/s10815-018-1314-2. Epub 2018 Sep 19.

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

A G Grynnerup  1 , M Toftager  2 , A Zedeler  2 , J W Bogstad  2 , L Prætorius  2 , M L Grøndahl  3   4 , C Yding Andersen  3 , S Sørensen  5 , A Pinborg  2 , K Løssl  2   6
Affiliations

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

A G Grynnerup et al. J Assist Reprod Genet. 2018 Dec.

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 developing 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.

Keywords: Angiopoietin 1; Angiopoietin 2; CRP; Follicular fluid; Ovarian hyperstimulation syndrome (OHSS); VEGF; suPAR.

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Conflict of interest statement

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

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.

Figures

Fig. 1
Fig. 1
Follicular fluid suPAR levels in OHSS cases (n = 25) compared with combined controls (n = 50), presented as median, interquartile range, and minimum and maximum value
Fig. 2
Fig. 2
Receiver operator characteristics (ROC) curve for FF suPAR levels predicting severe OHSS
See this image and copyright information in PMC

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