Serum vascular endothelial growth factor and Doppler blood flow velocities in in vitro fertilization: relevance to ovarian hyperstimulation syndrome and polycystic ovaries

Agrawal, Rina; Conway, Gerard S.; Sladkevicius, Povilas; Tan, S.L.; Engmann, Lawrence; Payne, N. N.; Bekir, Jinan; Campbell, Stuart; Jacobs, Howard S.

doi:10.1016/s0015-0282(98)00249-0

Cited by 114 publications

(53 citation statements)

References 24 publications

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“…In a previous report, the systemic VEGFA inhibition resulted in the down-regulation of claudin 5 in the endothelium of the thecal vasculature of ovaries (Rodewald et al 2007). If the ovarian blood flow and VEGFA expression in blood circulation significantly increase in the PCO syndrome (Agrawal et al 1998a(Agrawal et al , 1998b, the enhanced permselectivity of endothelial cells would thus be mediated by the up-regulation of claudin.…”

Section: Discussionmentioning

confidence: 85%

“…In the previous studies, several growth factors were implicated in the angiogenesis and maintenance of blood flow within the living animal ovary, including basic fibroblast growth factor, transforming growth factor-b, luteinizing hormone, platelet-derived growth factor, and vascular endothelial growth factor A (VEGFA; Gospodarowicz 1974, Findlay 1986, Klagsbrun 1991, Chegini & Flanders 1992, Folkman & Shing 1992, Van Blerkom et al 1997. Some physiological evidence has demonstrated a positive correlation between VEGFA and ovarian stromal blood flow velocities in PCO syndrome women (Agrawal et al 1998a(Agrawal et al , 1998b. The increase in blood flow in both the ovarian cortex and medulla of the PCO model mice might be associated with stromal hyperplasia and excessive follicular development due to anovulation, considering the total volume expansion and cellular proliferation of the ovaries (Hughesdon 1982).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Permselectivity of blood follicle barriers in mouse ovaries of the mifepristone-induced polycystic ovary model revealed by in vivo cryotechnique

Zhou

Ohno²,

Terada³

et al. 2008

Reproduction

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Despite the potential association of polycystic ovary (PCO) syndrome with hemodynamic changes, follicular microenvironment and the involvement of blood follicle barriers (BFB), a histopathological examination has been hampered by artifacts caused by conventional preparation methods. In this study, mouse ovaries of a mifepristone-induced PCO model were morphologically and immunohistochemically examined by in vivo cryotechnique (IVCT), which prevents those technical artifacts. Ovarian specimens of PCO model mice were prepared by IVCT or the conventional perfusion fixation after s.c. injection of mifepristone. Their histology and immunolocalization of plasma proteins, including albumin (molecular mass, 69 kDa), immunoglobulin G (IgG, 150 kDa), inter-a-trypsin inhibitor (ITI, 220 kDa), fibrinogen (340 kDa), and IgM (900 kDa), were examined. In the PCO model, enlarged blood vessels with abundant blood flow were observed in addition to cystic follicles with degenerative membrana granulosa. The immunolocalization of albumin and IgM in the PCO model were similar to those in normal mice. Albumin immunolocalized in the blood vessels, interstitium or follicles, and IgM was mostly restricted within the blood vessels. In contrast, immunolocalization of IgG, ITI, and fibrinogen changed in the PCO model. Both IgG and ITI were clearly blocked by follicular basement membranes, and hardly observed in the membrana granulosa, though fibrinogen was mostly observed within blood vessels. These findings suggest that increased blood flow and enhanced selectivity of molecular permeation through the BFB are prominent features in the PCO ovaries, and changes in hemodynamic conditions and permselectivity of BFB are involved in the pathogenesis and pathophysiology of PCO syndrome. Reproduction (2008) 136 599-610

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Permselectivity of blood follicle barriers in mouse ovaries of the mifepristone-induced polycystic ovary model revealed by in vivo cryotechnique

Zhou

Ohno²,

Terada³

et al. 2008

Reproduction

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“…Those factors, and possibly others, may act in concert with estrogen to promote increase in CBF during the luteal phase. We did not measure the levels of those nonsteroidal factors in the present study; however, it is known that there is a correlation between the serum level of VEGF and relaxin and the number of oocytes/corpora lutea and steroidal hormones during natural or stimulated cycles (1,17,18).…”

Section: Discussionmentioning

confidence: 95%

Cerebral blood flow is increased during controlled ovarian stimulation

Nevo¹,

Soustiel²,

Thaler³

2007

American Journal of Physiology-Heart and Circulatory Physiology

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Estrogen appears to enhance cerebral blood flow (CBF). An association between CBF and physiologically altered hormonal levels due to menstrual cycle, menopause, or exogenous manipulations such as ovariectomy or hormone replacement therapy has been demonstrated. The purpose of this study was to determine the association between ovarian stimulation and CBF in vivo by measuring blood flow in the internal carotid artery (ICA) after pituitary suppression and during controlled ovarian stimulation in women undergoing in vitro fertilization treatment cycles. ICA volume flows were measured by angle-independent dual-beam ultrasound Doppler in 12 women undergoing controlled ovarian stimulation. Measurements were performed after pituitary/ovarian suppression, in the late follicular phase, and at midluteal phase. Blood flow in the ICA increased by 22.2% and 32% in the late follicular and midluteal phases compared with the respective values obtained during ovarian suppression (P Ͻ 0.0005 and P Ͻ 0.0001, respectively). There was a significant correlation between increments in estrogen levels and increments in CBF when the late follicular phase was compared with the ovarian suppression period (r ϭ 0.8, P Ͻ 0.001). Mean blood flow velocity significantly increased (by 15.7% and 16.9%, respectively) and cerebral vascular resistance significantly decreased (by 17.6% and 26.5%) during the late follicular and midluteal phases compared with respective measures during ovarian suppression. There was a significant correlation between an increase in estrogen levels and a decrease in cerebral vascular resistance when the late follicular phase was compared with the ovarian suppression period (r ϭ Ϫ0.6, P Ͻ 0.05). These changes imply sex hormone-associated intracranial vasodilation leading to increased CBF during controlled ovarian stimulation.estrogen; progesterone; angle-independent Doppler; in vitro fertilization RECENT REPORTS HAVE SUGGESTED that the cerebral circulation may be affected by hormonal status. Increased cerebral blood flow (CBF) velocities were observed in the presence of high levels of estradiol (3,25). Progesterone was shown to increase peripheral blood flow in pigs (24) and to have neuroprotective properties in male rats (12). However, there is little information regarding the effect of estrogen and progesterone on CBF in human subjects.During controlled ovarian stimulation that is utilized for in vitro fertilization (IVF) treatment cycles, there is a significant increase in serum estradiol levels during the hyperstimulated follicular phase and the luteal phase (13). The source of estrogen during an IVF cycle is the hyperstimulated follicles in the follicular phase and the corpora lutea during the luteal phase. Progesterone levels start to increase after the induction of final oocyte maturation by human chorionic gonadotropin (hCG), and supraphysiological levels are encountered during the luteal phase (11). Progesterone is secreted during the luteal phase from multiple corpora lutea that develop after trigger of oocyte ma...

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“…9 We speculated that elevated luteinizing hormone levels may be responsible for increased stromal vascularization by different mechanisms: neoangiogenesis, catecholaminergic stimulation, and leukocyte and cytokine activation. 9 In addition, Agrawal et al 13 suggested that in polycystic ovary syndrome, a high concentration of vascular endothelial growth factor might be related to increased ovarian stromal velocities. Since then, many other studies showed that increased ovarian blood flow is a common feature of polycystic ovaries.…”

Section: Discussionmentioning

confidence: 99%

Two- and Three-Dimensional Sonographic and Color Doppler Techniques for Diagnosis of Polycystic Ovary Syndrome

Battaglia

Morotti

et al. 2012

Journal of Ultrasound in Medicine

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Objectives The purpose of this work was to study the role of 2‐dimensional (2D) and 3‐dimensional (3D) sonographic and Doppler techniques in the diagnosis of polycystic ovary syndrome. Methods A total of 112 young adult lean women with polycystic ovary syndrome and 52 healthy volunteers with regular ovulatory cycles, matched for age and body mass index, underwent a detailed history, medical examination, hormonal assay, and 2D and 3D sonographic and Doppler flow ovarian evaluation during the early follicular phase. Results The Ferriman‐Gallwey score, circulating androgen levels, ovarian volume, and mean number of small subcapsular follicles on 2D and 3D sonography were significantly higher in the patients with polycystic ovary syndrome than the controls (P < .001). A stromal score of 1 or 2 was found in all of the patients but none of the controls. The ovarian stromal/total area ratio was 0.32 or higher in 104 of 112 of the patients (93%), which was significantly higher than in the controls (P < .001). On Doppler analysis, the lowest ovarian stromal resistance levels were found in the patients. On 3D sonography, the total ovarian stromal volume, ovarian stroma/total ovarian volume ratio, and stromal mean grayness were significantly higher in the patients than the controls. With 3D power Doppler imaging, ovarian vascularization measurements were significantly lower in the controls than the patients. The ovarian stroma/total ovarian volume ratio was the most accurate predictor of both hyperandrogenemia (area under the curve, 0.915; P < .0001) and hirsutism (area under the curve, 0.891; P < .0001). Conclusions Our data strongly support the use of 3D sonography with analysis of stromal volume and vascularization in the diagnosis of polycystic ovary syndrome.

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Serum vascular endothelial growth factor and Doppler blood flow velocities in in vitro fertilization: relevance to ovarian hyperstimulation syndrome and polycystic ovaries

Cited by 114 publications

References 24 publications

Permselectivity of blood follicle barriers in mouse ovaries of the mifepristone-induced polycystic ovary model revealed by in vivo cryotechnique

Permselectivity of blood follicle barriers in mouse ovaries of the mifepristone-induced polycystic ovary model revealed by in vivo cryotechnique

Cerebral blood flow is increased during controlled ovarian stimulation

Two- and Three-Dimensional Sonographic and Color Doppler Techniques for Diagnosis of Polycystic Ovary Syndrome

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