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CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2019; 79(01): 86-93
DOI: 10.1055/a-0764-4765
GebFra Science
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Follicular Fluid Levels of Adrenomedullin 2, Vascular Endothelial Growth Factor and its Soluble Receptors Are Associated with Ovarian Response During ART Cycles

Follikelflüssigkeitsspiegel von Adrenomedullin 2, vaskulärem endothelialen Wachstumsfaktor und dessen lösliche Rezeptoren beeinflussen ovarielle Reaktion während ART-Zyklen
Ali Ranjbaran   *
1   Womenʼs Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
,
Hamid Reza Nejabati   *
1   Womenʼs Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2   Department of Biochemistry and Clinical Laboratories, Faculty of Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
,
Tohid Ghasemnejad
1   Womenʼs Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
,
Zeinab Latifi
1   Womenʼs Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2   Department of Biochemistry and Clinical Laboratories, Faculty of Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
,
Kobra Hamdi
1   Womenʼs Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
,
Hamed Hajipour
3   Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
,
Nathalie Raffel
4   Department of Obstetrics and Gynecology, Erlangen University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
,
Zahra Bahrami-asl
3   Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
,
Parvin Hakimi
1   Womenʼs Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
,
Aynaz Mihanfar
1   Womenʼs Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
,
Mohammad Nouri
3   Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
,
Amir Fattahi
3   Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
4   Department of Obstetrics and Gynecology, Erlangen University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
› Author Affiliations
Further Information

Publication History

received 13 July 2018
revised 08 October 2018

accepted 18 October 2018

Publication Date:
17 January 2019 (online)

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Abstract

Introduction Adrenomedullin 2 (ADM2) and vascular endothelial growth factor (VEGF) affect ovarian function, especially angiogenesis and follicular development. The actions of VEGF can be antagonized by its soluble receptors, soluble Fms-like tyrosine kinase-1 (sFlt-1) and soluble VEGF receptor 2 (sVEGFR-2), as they decrease its free form. In the present study, we evaluated the relationship between follicular fluid (FF) levels of AMD2, VEGF and its soluble receptors, and ICSI outcomes.

Materials and Methods ICSI cycle outcomes were evaluated and FF levels of VEGF, sFlt-1, sVEGFR-2 and ADM2 were determined using ELISA kits.

Results FF levels of ADM2, VEGF, and sVEGFR-2 were significantly higher in non-responders compared to other ovarian response groups (p < 0.05). There were significant correlations between ADM2, VEGF and sVEGFR-2 levels as well as VEGF/sFlt-1 and VEGF/sVEGFR-2 ratios (r = 0.586, 0.482, 0.260, and − 0.366, respectively). Based on the ROC curve, the cutoff value for ADM2 as a non-responder predictor was 348.55 (pg/ml) with a sensitivity of 67.7% and a specificity of 94.6%.

Conclusions For the first time we measured FF ADM2 levels to determine the relationship to VEGF and its soluble receptors. We suggest that ADM2 could be a potential predictive marker for non-responders. Although the exact function of ADM2 in ovarian angiogenesis is not yet understood, our study may shed light on the possible role of ADM2 in folliculogenesis and ovulation.

Zusammenfassung

Einleitung Adrenomedullin 2 (ADM2) und der vaskuläre endotheliale Wachstumsfaktor (VEGF) wirken sich auf die ovarielle Funktion aus, insbesondere auf Angiogenese und Follikelentwicklung. Die Wirkung von VEGF kann durch seine löslichen Rezeptoren (den löslichen Fms-ähnlichen Tyrosinkinase-1 [sFlt-1] und den löslichen VEGF-Rezeptor 2 [sVEGFR-2]) antagonisiert werden, da diese Rezeptoren die freie Form von VEGF reduzieren. In dieser Studie haben wir den Zusammenhang zwischen den Follikelflüssigkeitsspiegeln von AMD2, VEGF und dessen löslichen Rezeptoren und dem Outcome nach ICSI untersucht.

Material und Methoden Das Outcome nach ICSI-Zyklen wurde evaluiert und die Follikelflüssigkeitsspiegel von VEGF, sFlt-1, sVEGFR-2 und ADM2 wurden mithilfe von ELISA Kits bestimmt.

Ergebnisse Die ADM2-, VEGF- und sVEGFR-2-Spiegel in der FF waren signifikant höher in der Gruppe von Frauen ohne ovarielle Reaktion verglichen mit anderen Gruppen mit ovarieller Reaktion (p < 0,05). Signifikante Korrelationen wurden zwischen den ADM2-, VEGF- und sVEGFR-2-Spiegeln sowie den VEGF/sFlt-1- und VEGF/sVEGFR-2-Quotienten festgestellt (r = 0,586, 0,482, 0,260 bzw. − 0,366). Gemäß der ROC-Kurve betrug der Cut-off-Wert für ADM2 als Prädiktor für keine ovarielle Reaktion 348,55 (pg/ml) mit einer Sensitivität von 67,7% und einer Spezifität von 94,6%.

Schlussfolgerungen Wir haben zum ersten Mal die Follikelflüssigkeitsspiegel von ADM2 gemessen und diese Werte mit den Werten von VEGF sowie dessen lösliche Rezeptoren in Beziehung gesetzt. Wir weisen darauf hin, dass ADM2 potenziell ein prädiktiver Marker für das Fehlen einer ovariellen Reaktion sein könnte. Obwohl die genaue Funktion von ADM2 bei der ovariellen Angiogenese noch nicht vollständig geklärt ist, konnte unsere Studie etwas Licht auf auf die möglichen Rollen von ADM2 bei der Follikulogenese und der Ovulation werfen.

Key words

adrenomedullin 2 - vascular endothelial growth factor - sFlt-1 - follicular fluid - ICSI

Schlüsselwörter

Adrenomedullin 2 - vaskulärer endothelialer Wachstumsfaktor - sFlt-1 - Follikelflüssigkeit - ICSI

* These authors contributed equally and are considered co-first authors.


 

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