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; M. Toftager; A Zedeler; J W Bogstad; L Prætorius; M. L. Grøndahl; C Yding Andersen; S. Sørensen; A. Pinborg; K. Løssl

doi:10.1007/s10815-018-1314-2

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, M. Toftager, A Zedeler, J W Bogstad, L Prætorius, M. L. Grøndahl, C Yding Andersen, S. Sørensen, A. Pinborg, K. Løssl

Department of Clinical Medicine

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 Bfreeze-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.

Original language	English
Journal	Journal of Assisted Reproduction and Genetics
Volume	35
Issue number	12
Pages (from-to)	2187-2193
Number of pages	7
ISSN	1058-0468
DOIs	https://doi.org/10.1007/s10815-018-1314-2
Publication status	Published - Dec 2018

Keywords

Adult
Female
Fertilization in Vitro
Follicular Fluid/enzymology
Humans
Oocytes/enzymology
Ovarian Hyperstimulation Syndrome/enzymology
Ovulation/genetics
Ovulation Induction/adverse effects
Receptors, Urokinase Plasminogen Activator/genetics
Solubility

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Grynnerup, A. G., Toftager, M., Zedeler, A., Bogstad, J. W., Prætorius, L., Grøndahl, M. L., Yding Andersen, C., Sørensen, S., Pinborg, A., & Løssl, K. (2018). 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. Journal of Assisted Reproduction and Genetics, 35(12), 2187-2193. https://doi.org/10.1007/s10815-018-1314-2

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. / Grynnerup, A. G.; Toftager, M.; Zedeler, A et al.
In: Journal of Assisted Reproduction and Genetics, Vol. 35, No. 12, 12.2018, p. 2187-2193.

Research output: Contribution to journal › Journal article › Research › peer-review

Grynnerup, AG, Toftager, M, Zedeler, A, Bogstad, JW, Prætorius, L, Grøndahl, ML, Yding Andersen, C, Sørensen, S, Pinborg, A & Løssl, K 2018, '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', Journal of Assisted Reproduction and Genetics, vol. 35, no. 12, pp. 2187-2193. https://doi.org/10.1007/s10815-018-1314-2

Grynnerup AG, Toftager M, Zedeler A, Bogstad JW, Prætorius L, Grøndahl ML 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. Journal of Assisted Reproduction and Genetics. 2018 Dec;35(12):2187-2193. doi: 10.1007/s10815-018-1314-2

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title = "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",

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 Bfreeze-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 = "Adult, Female, Fertilization in Vitro, Follicular Fluid/enzymology, Humans, Oocytes/enzymology, Ovarian Hyperstimulation Syndrome/enzymology, Ovulation/genetics, Ovulation Induction/adverse effects, Receptors, Urokinase Plasminogen Activator/genetics, Solubility",

author = "Grynnerup, {A. G.} and M. Toftager and A Zedeler and Bogstad, {J W} and L Pr{\ae}torius and Gr{\o}ndahl, {M. L.} and {Yding Andersen}, C and S. S{\o}rensen and A. Pinborg and K. L{\o}ssl",

year = "2018",

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doi = "10.1007/s10815-018-1314-2",

language = "English",

volume = "35",

pages = "2187--2193",

journal = "Journal of Assisted Reproduction and Genetics",

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TY - JOUR

T1 - 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

AU - Grynnerup, A. G.

AU - Toftager, M.

AU - Zedeler, A

AU - Bogstad, J W

AU - Prætorius, L

AU - Grøndahl, M. L.

AU - Yding Andersen, C

AU - Sørensen, S.

AU - Pinborg, A.

AU - Løssl, K.

PY - 2018/12

Y1 - 2018/12

N2 - 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 Bfreeze-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.

AB - 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 Bfreeze-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.

KW - Adult

KW - Female

KW - Fertilization in Vitro

KW - Follicular Fluid/enzymology

KW - Humans

KW - Oocytes/enzymology

KW - Ovarian Hyperstimulation Syndrome/enzymology

KW - Ovulation/genetics

KW - Ovulation Induction/adverse effects

KW - Receptors, Urokinase Plasminogen Activator/genetics

KW - Solubility

U2 - 10.1007/s10815-018-1314-2

DO - 10.1007/s10815-018-1314-2

M3 - Journal article

C2 - 30232642

SN - 1058-0468

VL - 35

SP - 2187

EP - 2193

JO - Journal of Assisted Reproduction and Genetics

JF - Journal of Assisted Reproduction and Genetics

IS - 12

ER -