Fluid Vascular Endothelial Growth Factor Concentrations Research Articles

Effects of maternal western-style diet on amniotic fluid volume and amnion VEGF profiles in a nonhuman primate model.

During pregnancy, high fat diet (HFD) induces maternal obesity, insulin resistance, and placental inflammatory responses that compromise placental and fetal development. Whether maternal HFD would adversely affect amniotic fluid volume (AFV) has not been explored. Vascular endothelial growth factor (VEGF) is expressed in the amnion and has been proposed as a regulator of AFV. Our aim was to investigate the effects of HFD on AFV and the associated changes in VEGF and soluble VEGF receptor 1 (sFlt‐1) expression profiles in three amnion regions of a nonhuman primate model. Further, we examined the relationships between VEGF expression and HFD‐induced changes in maternal metabolic status. Japanese macaques were maintained on control or HFD and amniotic fluid index (AFI) was measured as an ultrasonic estimate of AFV. Amniotic fluid VEGF concentrations were determined by ELISA and amnion VEGF and sFlt‐1 mRNA levels by real‐time RT‐qPCR. HFD increased maternal plasma triglyceride while glucose levels were unchanged. Maternal weight gain was found in diet‐sensitive animals whereas amniotic fluid VEGF concentration was reduced in diet‐resistant animals. HFD did not alter AFI and there was no correlation between AFI and maternal weight or amniotic fluid VEGF concentrations. VEGF mRNA levels were lowest in secondary placental amnion while sFlt‐1 mRNA were lowest in the primary placental amnion. HFD did not affect amnion VEGF or sFlt‐1 mRNA expression. These findings suggest that although maternal HFD increased maternal weight in diet‐sensitive and reduced amniotic fluid VEGF concentrations in diet‐resistant phenotype, AFV as indicated by the AFI, was not significantly affected.

Correlation of vascular endothelial growth factor with magnetic resonance imaging in chronic subdural hematomas

BackgroundChronic subdural hematoma (CSDH) is an inflammatory angiogenic disease. It is believed that vascular endothelial growth factor (VEGF) plays an important role in pathological CSDH angiogenesis. MethodsIn this study, magnetic resonance imaging (MRI) results were used to assign 115 primary CSDH patients to four MRI types. The four MRI types are described as follows: type 1 (T1-weighted low, T2-weighted low), type 2 (T1-weighted high, T2-weighted low), type 3 (T1-weighted mixed, T2-weighted mixed), and type 4 (T1-weighted low/high, T2-weighted high). The four MRI types were then correlated with CSDH stage and patient hematoma fluid and serum VEGH concentrations that were measured using an enzyme-linked immunosorbent assay (ELISA). Neurological status was assessed by Markwalder scoring at admission and six-month follow-up. ResultsThe mean VEGF concentration was significantly higher in CDSH hematoma fluid samples than in patient sera (p<0.01). In unilateral CSDH hematoma fluid samples, VEGF concentration was highest in type 1 (21,613.5±1473.3pg/ml), next highest in type 2 (18,071.8±1737.1pg/ml), lower in type 3, and lowest in type 4 patients (13,153.7±3854.4pg/ml, 7265.7±726.2pg/ml, respectively). High VEGF concentrations strongly correlated with MRI type (unilateral CSDH group r=0.838, bilateral CSDH group r=0.851, p<0.01). Moreover, higher hematoma fluid VEGF concentrations correlated with markedly higher recurrence in type 1 (3/19, 15.8%) vs. type 4 unilateral CSDH patients (1/27, 3.7%). ConclusionsThe present study reports a significant correlation between CSDH hematoma fluid VEGF concentration and MRI results. Therefore, MRI results could be used to predict hematoma fluid VEGF concentrations in CSDH patients.

Pleural fluid osteopontin, vascular endothelial growth factor, and urokinase-type plasminogen activator levels as predictors of pleurodesis outcome and prognosticators in patients with malignant pleural effusion: a prospective cohort study.

BackgroundRapidly growing cancer cells secrete growth-promoting polypeptides and have increased proteolytic activity, contributing to tumor progression and metastasis. Their presentation in malignant pleural effusion (MPE) and their predictive value for the outcome of pleurodesis and survival were studied.MethodsBetween February 2011 and March 2012, MPE samples were prospectively collected from 61 patients. Twenty-five patients with non-malignant pleural effusion in the same period were included as controls. Pleural fluid osteopontin (OPN), vascular endothelial growth factor (VEGF), and urokinase-type plasminogen activator (uPA) concentrations were measured.ResultsPatients with MPE had higher pleural fluid OPN, VEGF, and uPA concentrations than those with non-malignant pleural effusion, but only differences in VEGF were statistically significant (p = 0.045). Patients with distant metastases had significantly elevated pleural fluid VEGF concentrations than those without (p = 0.004). Pleural fluid OPN, VEGF, and uPA concentrations were positively correlated in most patients. However, there was no significant difference in pleural fluid OPN, VEGF, and uPA concentrations between patients with successful pleurodesis and those without. There was also no significant difference in cancer-specific survival between sub-groups with higher and lower pleural fluid OPN, VEGF, or uPA concentrations. Patients with successful pleurodesis had significantly longer cancer-specific survival than those without (p = 0.015).ConclusionsPleural fluid OPN, VEGF, and uPA concentrations are elevated in MPE but are not satisfactory predictors of pleurodesis outcome or survival. Patients with higher pleural fluid VEGF concentration have higher risk of distant metastasis. Evaluating the benefits of therapy targeting the VEGF pathway in these patients warrants further studies.

Midtrimester amniotic fluid concentrations of angiogenic factors in relation to maternal, gestational and neonatal characteristics in normal pregnancies

Objective: To describe associations among maternal/gestational/neonatal characteristics and midpregnancy amniotic fluid concentrations of the main angiogenic markers vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). Methods: In a cohort of 206 normal full-term pregnancies, midpregnancy amniotic fluid VEGF and PlGF reference values were recorded. Possible associations among the above concentrations and various parameters, such as maternal age and body mass index, race, parity, smoking, gestational age, delivery mode, birth-weight and fetal gender were investigated. Results: Midpregnancy amniotic fluid concentrations of both VEGF and PlGF increased with increasing gestational age (r = 0.173, p = 0.013 and r = 0.255, p < 0.001, respectively), whereas PlGF concentrations positively correlated with birth-weight (r = 0.154, p = 0.027). The effect of the other above-mentioned parameters on VEGF and PlGF concentrations was not significant. Conclusions: In normal pregnancies, midgestation amniotic fluid VEGF and PlGF concentrations positively correlate with gestational age. Furthermore, midgestation amniotic fluid PlGF concentrations may be a predictor of neonatal birth weight.

Agonist and antagonist coast

The use of GnRH-a in ovarian stimulation permitted stronger stimulation resulting in an increased incidence of OHSS. The first Cochrane review comparing GnRH agonist and GnRH antagonist protocols for ovarian stimulation showed no significant difference in OHSS rate between the two protocols, however, a recent Cochrane review showed a highly significant decrease in the incidence in OHSS rate in the antagonist protocol. Coasting is a commonly used procedure for preventions of OHSS. The optimum time to start coasting is when the lead follicle reaches 16 mm in diameter and hCG should be given when E2 level drops below 3000 pg/ml. Coasting may act by diminishing the functioning granulosa cell cohort. Administration of daily GnRH antagonist in high risk patients for OHSS who were down-regulated by GnRH-a resulted in rapid drop of E2 and decrease in incidence of OHSS. A series of patients who developed early OHSS were treated by daily GnRH antagonist injections, all embryos were cryopreserved. No progression to severe OHSS was observed.

Vascular endothelial growth factor and its soluble receptor in benign and malignant ovarian tumors

An imbalance between pro-angiogenic and anti-angiogenic factors is hypothesized in the pathogenesis of ovarian cystic disease. The aim of the following study was to explore the possible role of free vascular endothelial growth factor receptor 1 (sVEGFR-1), a soluble regulator of vascular endothelial growth factor (VEGF) action, in ovarian cystoadenoma, endometriomata and cystoadenocarcinoma. Forty-eight women, of whom fourteen had ovarian serous cysts, twenty-eight had stage III–IV ovarian endometriomata, and six had stage IIIB–IIIC ovarian carcinoma, were included. Sampling of serum, peritoneal and ovarian cystic fluids and of tumor tissue was performed before, during and following surgery, respectively. Levels of VEGF and sVEGFR-1 were measured in serum, peritoneal and cystic fluid. VEGF and sVEGFR-1 expression was evaluated in tumor tissue. There were no differences in serum VEGF and sVEGFR-1 levels nor in VEGF/VEGFR-1 ratio between study groups. Peritoneal fluid VEGF levels were higher in cystoadenocarcinoma patients than in endometriosis and in cystoadenoma patients, while sVEGFR-1 peritoneal fluid concentrations were significantly higher only in endometriosis-affected women. VEGF/VEGFR-1 ratio was highest in the peritoneal fluid of cancer patients with respect to the other two groups of women. Cystic fluid VEGF and VEGFR-1 concentrations were higher in endometriomata and in cystoadenocarcinomas than in cystadenomas but the VEGF/VEGFR-1 ratio was highest in cancer patients. Western blot evidenced a marked expression of VEGF and soluble VEGFR-1 in endometriosis tissue with respect to benign cyst tissue but a lower expression of both molecules, contrary to that expected, in cancer tissue. In conclusion, all in all, our data indicate that an excess of local VEGF with respect to its soluble receptor VEGFR-1 may be a key factor in the onset and maintenance of pathological neo-angiogenesis in ovarian cyst formation.

Follicular blood flow is a better predictor of the outcome of in vitro fertilization–embryo transfer than follicular fluid vascular endothelial growth factor and nitric oxide concentrations

To investigate the relationship between follicular blood flow and the follicular fluid vascular endothelial growth factor (VEGF) and nitric oxide (NO) concentrations and to determine which factor might be a better predictor of the outcome of IVF-ET. Prospective study. Academic research laboratory. Forty-seven cycles of IVF (tubal factor, 25 cycles; male factor, 22 cycles) at the infertility clinic of Pusan National University Hospital from February 2002 to June 2002. Follicular blood flow was estimated on the day of hCG administration. Each follicular fluid sample was collected at oocyte retrieval, and follicular fluid VEGF and NO concentrations were assessed. Follicular blood flow and follicular fluid VEGF and NO concentrations according to the age of patients, the cause of infertility, and pregnancy rate. Of 47 cycles, 18 (38.3%) cycles resulted in a pregnancy. Follicular blood flow was significantly higher in the pregnant group compared with the nonpregnant group, but there was no statistically significant difference in age and infertility cause. Follicular fluid concentrations of VEGF and NO did not show statistically significant differences in age, infertility cause, or pregnancy outcome. As the follicle size increases, the follicular blood flow and follicular fluid VEGF concentrations increased significantly but the follicular fluid NO concentrations decreased. There was no correlation between VEGF and NO concentrations in the follicular fluid by linear regression analysis. Our study showed that follicular blood flow was positively associated with the outcome of pregnancy. This is the first study to investigate the direct association of the follicular blood flow with pregnancy outcome after IVF-ET. These results suggest that follicular blood flow might be a more effective prognostic marker of the pregnancy outcome of IVF than follicular fluid VEGF or NO concentrations.

Quality of oocytes and embryos in patients with polycystic ovaries

Oocytes retrieved from gonadotrophin-stimulated cycles in polycystic ovarian syndrome (PCOS) patients are of different quality and different developmental potential. We hypothesized that oocyte quality and fertilization potential might be related to the follicular fluid active renin and vascular endothelial growth factor (VEGF) concentrations. In this prospective study 20 patients with PCOS undergoing in vitro fertilization (IVF) (conventional IVF or intracytoplasmic sperm injection—ICSI) were included. Each follicular aspirate was analysed for active renin and VEGF. Oocytes and embryos were checked for quality. In empty follicular aspirates active renin concentrations were higher (mean difference: 0.05 pg/ml; range: 0.01 to 0.09 pg/ml; P=0.01) and VEGF concentrations were lower (mean difference: 169 pg/ml; range: 330 to −8 pg/ml; P=0.034) than in the aspirates containing normal appearing MII oocytes. Follicular fluid VEGF concentrations were lower in immature than in normal appearing MII oocytes (mean difference: −548 pg/ml; range: −1064 to −32 pg/ml; P=0.034). VEGF concentrations were higher in aspirates containing normal appearing MII oocytes that fertilized compared to those MII oocytes that did not (2238±691 vs. 1877±902 pg/ml; P=0.045). Differentiation of normal appearing MII oocytes that fertilize from those that do not might be the consequence of better expression and action of RAS substances and VEGF.

Synovial concentrations of the angiogenic peptides bFGF and VEGF do not discriminate rheumatoid arthritis from other forms of inflammatory arthritis

Objectives: To investigate whether concentrations of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in aspirated synovial fluid can be used to distinguish rheumatoid arthritis from other forms of inflammatory arthritis. Methods: bFGF and VEGF concentrations were measured in aspirated synovial fluid and serum samples from 66 patients with active arthritis (clinical diagnoses: rheumatoid arthritis (35 patients), psoriatic arthritis (9), reactive arthritis (11) and arthritis UNS (11)) utilizing commercial ELISA kits. Results: In comparison with controls, elevated concentrations of VEGF were found in synovial fluid compared with in serum in all forms of arthritis. There were no significant differences in synovial fluid bFGF or VEGF concentrations between rheumatoid arthritis and the other forms of inflammatory arthritis. Conclusion: Both serum bFGF and VEGF concentrations were increased in patients with rheumatoid arthritis. Patients treated with steroids had lower synovial fluid bFGF concentrations. Synovial fluid levels of bFGF and VEGF were elevated but could not be used to distinguish rheumatoid arthritis from other forms of inflammatory arthritis.

The effects of 'coasting' on follicular fluid concentrations of vascular endothelial growth factor in women at risk of developing ovarian hyperstimulation syndrome

The aim of this study was to assess the effect of withholding gonadotrophins (coasting) during controlled ovarian stimulation (COS) on individual follicle concentrations of follicular fluid vascular endothelial growth factor (VEGF) in women at high risk of developing ovarian hyperstimulation syndrome (OHSS). Twenty-two women who had been coasted and 26 optimally responding women (control group) undergoing COS for IVF were studied. At the time of oocyte retrieval, the follicular fluid from four to six individual follicles of different sizes was collected for VEGF analysis. A total of 118 follicles was analysed in the coasted group and 137 in the control group. A negative correlation was observed between the follicle size and VEGF concentration (r = -0.18, P = 0.03) in the control group, which was not seen in the coasted group. Similarly, the correlation between oestradiol (E(2)) and VEGF (r = 0.4, P < 0.0001) observed in the control group was not apparent in the coasted group. Significantly lower concentrations of VEGF were seen in the follicular fluid of the coasted patients. It is clear that there are differences in follicular fluid VEGF concentrations between the two groups. It is possible that coasting alters the capacity of the granulosa cells to produce VEGF and/or their response to hCG and in this way acts to reduce the severity and incidence of severe OHSS.

Vascular endothelial growth factor in adnexal masses

Objectives: To determine cyst fluid and serum vascular endothelial growth factor (VEGF) concentrations in patients with ovarian masses and to investigate the efficiency of this modulator in the clinical management of cystic pelvic masses. Methods: Needle puncture for cyst fluid aspiration were performed on 88 cystic ovarian masses intraoperatively. Forty-five patients with benign and 43 patients with malignant ovarian pathology were analyzed for cyst fluid and serum VEGF concentrations. Both cystic fluid and serum VEGF concentration were determined by enzyme-linked immunosorbent assay (ELISA). Results: Cyst fluid VEGF levels of malignant cysts (40.65±17.69 ng/ml) were significantly higher than those of benign cysts (12.53±6.13 ng/ml; P<0.001). Similarly, higher serum VEGF concentrations were found in patients with malignant disease (0.72±0.17 ng/ml) compared with benign cysts (0.33±0.11 ng/ml; P<0.001). A statistically significant correlation was observed between cyst fluid and serum VEGF levels in both malignant and benign cysts. For serum VEGF, at a cut-off value of 0.41 ng/ml; sensitivity, specificity, PPV, and NPV were 95%, 78%, 80% and 95%, respectively. No significant correlation between cyst fluid VEGF concentration and tumor stage or grade could be found. Conclusions: Significantly higher concentrations of VEGF are present in cyst fluid and serum of patients with malignant ovarian cysts compared with benign ovarian ones. There is no relation between VEGF and tumor stage or grade.

Concentration of vascular endothelial growth factor released by cultured human luteinized granulosa cells is higher in women with polycystic ovaries than in women with normal ovaries

Objective To test the hypothesis that increased serum levels of vascular endothelial growth factor (VEGF) in women with polycystic ovaries or the polycystic ovary syndrome (PCOS) result from excess release by ovarian granulosa cells. Design Prospective study. Setting Academic research setting. Patient(s) Twenty women undergoing IVF treatment, of whom 10 had normal ovaries and 10 had polycystic ovaries. Intervention(s) Human granulosa lutein cells were isolated from follicular fluid obtained on the day of oocyte retrieval. Release of VEGF was assessed after co-incubation of granulosa lutein cells with gonadotropins and insulin. Serum and follicular fluid concentrations of VEGF were measured. Main outcome measure(s) Release of VEGF from granulosa lutein cells and serum levels of VEGF. Result(s) Incubation with human hCG, and luteinizing hormone increased release of VEGF into the culture medium. Insulin alone did not increase release of VEGF, but addition of insulin increased hCG-stimulated release of VEGF. Serum and follicular fluid VEGF concentrations and the amount VEGF released from granulosa lutein cells obtained from women with polycystic ovaries or PCOS and those who developed the ovarian hyperstimulation syndrome were greater than those from granulosa lutein cells obtained from women with normal ovaries and those who did not develop the ovarian hyperstimulation syndrome. Conclusion(s) The amount of VEGF released by granulosa lutein cells is gonadotropin dependent and is augmented by insulin. The increased circulating concentrations of VEGF in women with PCOS may not only be due to an increased number of actively secreting granulosa lutein cells but also due to increased secretory capacity of each granulosa cell.

Relationship of ovarian stimulation response with vascular endothelial growth factor and degree of granulosa cell apoptosis.

The aim of this study was to evaluate the concentration of vascular endothelial growth factor (VEGF) in follicular fluid and in granulosa cell cultures in relation to the degree of apoptosis in granulosa cells from patients with different types of ovarian response to controlled ovarian hyperstimulation. We studied 30 women who underwent controlled ovarian hyperstimulation and oocyte retrieval. Group A comprised patients with 1-4 follicles (n = 10), group B patients with 5-14 follicles (n = 10) and group C patients with >15 follicles (n = 10). Mean (+/-SD) VEGF concentrations in follicular fluid were 1232 +/- 209, 813 +/- 198 and 396 +/- 103 pg/ml for groups A, B and C respectively (P > 0.01). Concentrations of VEGF in granulosa cell supernatant were 684 +/- 316, 1101 +/- 295 and 1596 +/- 227 pg/ml respectively (P < 0.05). Percentages of apoptotic cells in granulosa cells culture was 55.02 +/- 7.5, 23.98 +/- 4.4 and 14.2 +/- 2.3% respectively (A versus B, P < 0.01, A versus C, P < 0.006, B versus C, NS). Our findings showed that in patients with decreased ovarian response to controlled ovarian hyperstimulation, follicular fluid VEGF concentration is elevated, the concentration from granulosa cells culture supernatant is decreased and the percentage of apoptotic granulosa cells is increased, while opposite findings occurred in patients with normal or hyper-responses.

Vascular endothelial growth factor (VEGF) and angiopoietin regulation by gonadotrophin and steroids in macaque granulosa cells during the peri-ovulatory interval.

The role of endothelial cell-specific growth factors in the vascularization of the primate peri-ovulatory follicle was examined. Experiments were designed firstly to detect expression of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) in granulosa cells and secondly, to determine whether gonadotrophins and/or steroids regulate their expression during the peri-ovulatory interval. Granulosa cells and follicular fluid were collected from rhesus macaques undergoing ovarian stimulation before (0 h), 12, or 36 h after a bolus of ovulatory human chorionic gonadotrophin (HCG), with or without steroid ablation and progestin replacement. VEGF, Ang-1 and Ang-2 mRNA were all detected prior to the ovulatory stimulus. Whereas follicular fluid VEGF concentrations increased 6-fold (P < 0.05) between 0 and 12 h, VEGF mRNA values were unchanged and were unaffected by steroid ablation. Ang-1 mRNA decreased from 0 to 12 h (P < 0.05), followed by a 30-fold increase (P < 0.05) at 36 h, while Ang-2 mRNA values were unchanged between 0, 12 and 36 h. Steroid ablation decreased (P < 0.05) Ang-1 mRNA at 36 h, and Ang-2 mRNA at 12 h, while only Ang-1 was restored by progestin replacement. These data suggest a dynamic expression of vascular-specific growth factors in a gonadotrophin-dependent, steroid-independent (VEGF) or steroid-dependent (Ang-1) manner in granulosa cells of peri-ovulatory follicles of primates.

Vascular endothelial growth factor is bound in amniotic fluid and maternal serum.

To study vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) concentrations and their possible binders, serum from 22 non-pregnant and 55 pregnant women (15 at weeks 10-13; 40 at term), umbilical vein (n = 24) and artery (n = 13) and amniotic fluid (a pool of 50 at weeks 15-17; 11 at term) were assessed for VEGF and PlGF by an enzyme-linked immunosorbent assay. In amniotic fluid and maternal serum VEGF concentrations were <16 ng/ml and added VEGF was not recovered. VEGF was detected in serum from mothers post-partum (137 +/- 142 ng/l, mean +/- SD), umbilical artery (421 +/- 288 ng/l) and vein (502 +/- 339 ng/l) and non-pregnant controls (182 +/- 147 ng/l), and added VEGF was fully recovered. PlGF was detected in pregnancy serum (52 +/- 23 ng/l early pregnancy; 439 +/- 217 ng/l term pregnancy) and in amniotic fluid (early pregnancy 56 ng/l; term pregnancy 30 +/- 18 ng/l). PlGF was fully recovered in all samples. Gel filtration and isoelectric focusing revealed that in maternal serum and amniotic fluid [125I]VEGF was bound to a protein with an Mr of 400-700 kDa and an isoelectric point of approximately 8. This protein was not identical with alpha-2-macroglobulin (by an immunofluorometric assay), pregnancy zone protein or pregnancy associated plasma protein-A (by immunodiffusion). In conclusion, VEGF-binding activity is present in amniotic fluid and maternal blood. It disappears after delivery and is not detectable in fetal or non-pregnant serum.

Serum Vascular Endothelial Growth Factor and Doppler Blood Flow Velocities in In Vitro Fertilization

Agrawal, Rina; Conway, Gerard; Sladkevicius, Povilas; Tan, Seang Ling; Engmann, Lawrence; Payne, Nadia; Bekir, Jinan; Campbell, Stuart; Jacobs, Howard Author Information

The pathogenesis of ovarian hyperstimulation syndrome: in vivo studies investigating the role of interleukin-1β, interleukin-6, and vascular endothelial growth factor

Objective: To evaluate systemic and ovarian changes in levels of interleukin (IL)-1β, IL-6, and vascular endothelial growth factor (VEGF) in response to hCG administration to determine which may be the potential initiator of vascular effects and to identify the main source of the substance; to evaluate serum and follicular fluid levels of these cytokines as markers of ovarian hyperstimulation syndrome (OHSS), and to compare levels of these cytokines under basal conditions in women with normal ovulation and those with polycystic ovary syndrome (PCOS). Design: Prospective controlled study. Setting: In vitro fertilization program at the Instituto Valenciano de Infertilidad, Valencia, Spain. Patient(s): Women undergoing IVF, in whom the first two study objectives were analyzed, and women with normal ovulation and patients with PCOS undergoing retrieval of immature oocytes in natural cycles or cycles stimulated for IUI but cancelled during induction of ovulation, in whom the third study objective was analyzed. Intervention(s): Serum was collected before and after hCG administration, and follicular fluid was collected at ovum pick-up. Main Outcome Measure(s): Serum and follicular fluid levels of IL-1β, IL-6, and VEGF. Result(s): There was a significant increase in serum VEGF levels after hCG administration in patients who were at risk for OHSS compared with those who were not at risk for OHSS. Significantly lower VEGF levels were found in the follicular fluid of patients who were at risk; this decrease was the only useful marker to discriminate between the two groups. Moreover, both groups had similar cytokine production under basal conditions. An increase in serum E 2 occurred coincident with a decrease in IL-1β, IL-6, and VEGF in patients with PCOS. Conclusion(s): Vascular endothelial growth factor seems to be the mediator of hCG on the vascular tree. There was an early systemic increase in VEGF that may have significance in the development of OHSS. A decrease in the follicular fluid VEGF concentration is a valid marker to identify women in whom OHSS will develop. The pattern of cytokine release in patients with PCOS under basal conditions was not different from that in women with normal ovulation.

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

Objective: To relate changes in serum and follicular fluid vascular endothelial growth factor (VEGF) concentrations to Doppler blood flow velocities within ovarian and uterine blood vessels during IVF cycles and to assess their relation to ovarian hyperstimulation syndrome (OHSS) and polycystic ovaries (PCO)/polycystic ovary syndrome (PCOS). Design: Prospective descriptive study. Setting: The London Women’s Clinic. Patient(s): One hundred seven patients receiving a “long” stimulation protocol of IVF. Intervention(s): Doppler blood flows were recorded in ovarian stromal and uterine arteries; serum VEGF was measured in the early follicular phase, after pituitary desensitization, on the day of hCG administration, on the day of oocyte retrieval, and on the day of ET. Main Outcome Measure(s): Serum and follicular fluid VEGF concentrations and Doppler blood flow measurements. Result(s): Serum VEGF concentrations rose after hCG administration. The rise was higher in women in whom OHSS developed. Women with PCO/PCOS had higher serum VEGF concentrations throughout the IVF cycle irrespective of whether OHSS developed. Follicular fluid VEGF concentrations were higher in women in whom OHSS developed and in women with PCO/PCOS. Doppler blood flow velocities in the ovarian blood vessels were higher in women in whom OHSS developed. Within ovarian and uterine blood vessels, blood flow velocities were higher in the early follicular phase and on the day of hCG administration in women with PCO/PCOS. A positive correlation was observed between the serum VEGF and E 2 concentrations on the days of hCG administration and oocyte retrieval and between the serum VEGF concentration and Doppler blood flow velocities throughout the IVF cycle. Conclusion(s): Our results support the role of VEGF as a mediator of OHSS and establish a possible link between VEGF, OHSS, and PCO.

Human follicle fluid vascular endothelial growth factor concentrations are correlated with luteinization in spontaneously developing follicles.

Vascular endothelial growth factor (VEGF) is a cytokine that induces angiogenesis. Angiogenesis is a prominent histologic component of the luteinization process. Luteinization is also characterized by granulosa cell progesterone secretion in response to the luteinizing hormone (LH) surge. Local VEGF production in human pre-ovulatory follicles, induced by LH, was postulated to be a luteinization mediator in women. To investigate this hypothesis, serum and fluid from the dominant follicle of 31 healthy regularly cycling multiparous women undergoing laparoscopic sterilization were obtained. VEGF was measured by enzyme-linked immunosorbent assay, and LH and progesterone were measured by radioimmunoassay. Follicle aspiration was performed at a median of 13 days from the last menstrual period (range 11-17 days). The median pre-ovulatory follicle diameter was 16 mm (range 11-23 mm). Follicle fluid VEGF concentrations (mean 6900 pg/ml, range 1200-17 100 pg/ml) were correlated positively with follicle fluid progesterone concentrations (mean 10 176 nmol/l, range 636-66780 nmol/l, r=0.62, P=0.002). This correlation was even tighter (r=0.87, P < 0.0001) when only samples from the 22 women in the earliest stages of follicle luteinization were considered. In these women serum LH concentrations were also correlated with follicle fluid VEGF concentrations (r=0.51, P=0.02). Our findings demonstrate the close dynamic relationship between VEGF production and early luteinization in human follicles during normal non-stimulated cycles.

Correlation between the amount of follicle-stimulating hormone administered and plasma and follicular fluid vascular endothelial growth factor concentrations in women undergoing in vitro fertilization

Vascular endothelial growth factor (VEGF) is a powerful mediator for vessel permeability and it is strongly implicated in angiogenesis, stimulating endothelial cell proliferation as well as capillary permeability. We studied 30 women undergoing in vitro fertilization (IVF) programs and evaluated, on the day of oocyte retrieval, VEGF levels in plasma and follicular fluid and related such concentrations to the amount of follicle-stimulating hormone (FSH) administered. Furthermore, the correlation between the number of oocytes retrieved and the VEGF concentrations both in plasma and in follicular fluid were also investigated.Results indicate that follicular fluid VEGF concentrations and the amount of pure FSH administered were directly proportional (p < 0.05). On the day of oocyte retrieval, the VEGF plasma concentrations and the number of oocytes collected were directly proportional (p < 0.05). VEGF plasma levels increased after human chorionic gonadotropin (hCG) administration (30.37± 18.60 pg/ml up to 52.62 ± 43.63 pg/ml).In conclusion, this study demonstrates that the doses of pure FSH administered to women undergoing IVF cycles have a crucial role in hCG-dependent VEGF production.