ORIGINAL ARTICLE
Georg Griesinger Æ Konstantinos Dafopoulos
Askan Schultze-Mosgau Æ Wolfgang Jelkmann
Soeren von Otte Æ Dagmar Diesing Æ Klaus Diedrich
Vascular endothelial growth factor response to exogenous chorionic
gonadotropic hormone in the luteal phase of women with a history
of severe ovarian hyperstimulation syndrome
Received: 16 November 2005 / Accepted: 20 November 2005 / Published online: 12 January 2006
Ó Springer-Verlag 2006
Abstract Ovarian hyperstimulation syndrome (OHSS) is
a severe complication of ovarian stimulation. No reli-
able test exists to predict the syndrome. The objective of
the present prospective observational study was to
examine vascular endothelial growth factor (VEGF)
secretion after human chorionic gonadotropin (hCG)
administration in the luteal phase of a spontaneous cycle
of women with a history of severe OHSS. Five women
with a history of severe OHSS were administered 250 lg
recombinant hCG intravenously on day 21 of a spon-
taneous menstrual cycle. Plasma samples were collected
at regular intervals from 15 min before hCG to 6 h
thereafter and the free VEGF plasma concentrations
were determined. Plasma levels of free VEGF remained
at the lower detection limit of the assay throughout the
observational period. Women with previous severe
OHSS do not show a significant short-time response of
VEGF secretion upon hCG administration. No evidence
was found to support the notion that women inclined to
develop a severe form of the syndrome after ovarian
stimulation could possibly be identified by the VEGF
short-time secretory response to exogenous hCG in the
luteal phase of a spontaneous cycle.
Keywords Ovarian hyperstimulation syndrome Æ
Vascular endothelial growth factor Æ hCG Æ
Luteal phase Æ Prognostic test
Introduction
Severe ovarian hyperstimulation syndrome (OHSS) is a
rare and potentially life-threatening complication of
ovarian hyperstimulation for assisted reproduction [1,2].
The pathophysiology of the syndrome has not been
completely elucidated yet; however, the vascular fluid
leakage associated with OHSS is thought to result from
an increased capillary permeability of endothelial sur-
faces under the action of several vasoactive factors [3].
Vascular endothelial growth factor (VEGF) is a heparin-
binding disulfide-linked homodimeric protein that in-
duces angiogenesis and possesses a potent effect on
vascular permeability. VEGF has been proposed to be
the major capillary permeability agent in OHSS ascites
fluid [4]. The serum, peritoneal and follicular fluid con-
centrations of VEGF appear to be correlated with the
development and course of the syndrome in patients
hyperstimulated for IVF [5–8].
In the ovary, VEGF mRNA is expressed by gran-
ulosa and theca cells and expression is enhanced by
human chorionic gonadotropin (hCG) in both dose-
and time-dependent manners [5, 6, 9]. The finding of an
hCG-induced increase in VEGF secretion has also been
confirmed in vivo in women undergoing ovarian hy-
perstimulation [10–13]. Furthermore, it has been sug-
gested that hCG enhances in vitro expression of VEGF
mRNA by luteinized granulosa cells [14] to a much
greater extent in patients who develop severe OHSS as
compared with patients without symptoms of the syn-
drome after ovarian stimulation. This has also been
suggested from in vivo studies [12]. These findings are
in accordance with the clinical observation that while
no technique is 100% effective in preventing severe
hyperstimulation in women at risk, the syndrome can
be almost totally excluded by withholding the ovula-
tion-inducing trigger of hCG in these patients. Notably,
the syndrome occurs exclusively post-ovulatory and is
closely related to the lifespan of the corpus luteum.
G. Griesinger (&) Æ K. Dafopoulos Æ A. Schultze-Mosgau
S. von Otte Æ D. Diesing Æ K. Diedrich
Department of Obstetrics and Gynecology, Universitaetsklinikum
Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160,
23538 Luebeck, Luebeck
E-mail: georg.griesinger@frauenklinik.uni-luebeck.de
W. Jelkmann
Institute of Physiology, Universitaetsklinikum Schleswig-Holstein,
Campus Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Luebeck
Arch Gynecol Obstet (2006) 274: 29–33
DOI 10.1007/s00404-005-0112-0