Serum vascular endothelial growth factor as a possible marker for early ectopic pregnancy

BACKGROUND: This study evaluated serum vascular endothelial growth factor (VEGF) concentrations in women with normal intrauterine pregnancy (IUP), arrested IUP and ectopic pregnancy (EP). METHOD: This was a prospective, case-control study evaluating serum VEGF concentrations among 45 early pregnant women who subsequently were found to have an EP, a normal IUP or an arrested IUP (15 women in each group). Patients were stratified according to serum VEGF concentrations above and below 200 pg/ml. RESULTS: There was a significant difference in VEGF concentrations among women with EP, arrested IUP and normal IUP (306.1 +/- 26.5, 169.7 +/- 16.6 and 27.0 +/- 4.4 pg/ml respectively, P < 0.001). With a cut-off concentration of 200 pg/ml, serum VEGF could distinguish normal IUP from EP with a sensitivity of 88%, a specificity of 100% and a positive predictive value of 100%. Between EP and arrested IUP, the sensitivity was 87.5%, specificity 75% and positive predictive value of 77.8%. CONCLUSIONS: VEGF is a potential marker for EP. Its concentrations in women with EP are higher than in those with normal and arrested IUP.     

Fertility outcome after ectopic pregnancy and use of an intrauterine device at the time of the index ectopic pregnancy

Fertility after ectopic pregnancy (EP) was investigated in a non-selected population taking into account intrauterine device (IUD) use at the time of the EP. Between January 1992 and June 1996, 647 women listed in the EP register of Auvergne (France) were followed up. The analysis included only the 328 women who were seeking to become pregnant: 23 women using IUD at the time of the index EP (IUD users) and 305 IUD non-users. Among IUD users, there was no recurrence of EP, and the 1 year cumulative rate was 87% [95% confidence interval (CI): 73-100%] for intrauterine pregnancies and 86% (95% CI: 72-100%) for deliveries. Among IUD non-users, the 2 year cumulative rate for recurrence of EP was 28% (95% CI: 17-39%), and the 1 year cumulative rates were 60% (95% CI: 53-66%) for intrauterine pregnancies and 44% (95% CI: 38-56%) for deliveries. The adjusted intrauterine pregnancy rate of IUD users was not significantly different from that of IUD non-users. However, IUD non-users had more miscarriages, so their delivery rate was lower.     

Vascular endothelial growth factor (VEGF) concentrations are elevated in peritoneal fluid of women with endometriosis

Active endometriosis is characterized by hypervascularizationboth within and surrounding the implant; therefore the presenceof angiogenic factors in the peritoneal environment would beof great importance. Vascular endothelial growth factor (VEGF)is a potent angiogenic factor involved in both physiologicaland pathological angiogenesis. We sought to determine if VEGFwas present in the peritoneal fluid of women with and withoutendometriosis, and to establish if differences exist betweenthese groups. VEGF was present in all patients sampled. Thefluid from patients with endometriosis contained significantlygreater amounts of VEGF than controls. Cyclic variations inVEGF concentration were seen in fluid from patients with endometriosis,the VEGF concentration in proliferative phase being significantlyhigher than in the secretory phase. The concentration of VEGFin this fluid was also significantly higher than that foundin the proliferative and secretory phases of women without endometriosis.No cyclic variations in VEGF were seen in the control group.We suggest that elevated levels of VEGF in the peritoneal fluidof patients with endometriosis may be critical in the pathogenesisof endometriosis.     

Spontaneous conception and intrauterine pregnancy in a symptomatic missed abortion of ectopic pregnancy conceived in the previous cycle

We encountered a rare case of combined intrauterine and extrauterinepregnancy that occurred following separate spontaneous ovulations.A 33 year old woman visited our hospital with the chief complaintof abdominal pain on April 16, 1993. Her last menstruation wasfrom March 23 for 6 days. However, the urinary human chorionicgonadotrophin (HCG) on April 19 was 1024 IU/L Pelvic examinationand ultrasonography indicated an extrauterine pregnancy, whichwas confirmed by laparotomy and histo-logical identificationof trophoblast cells. The urinary HCG concentration markedlydecreased after the operation. However, the HCG level increasedagain on the fifth postoperative day, and a gestational sac(11 mm) was identified in the uterine cavity on the 11th post-operativeday, indicating that this intrauterine pregnancy was establishedfollowing spontaneous ovulation which occurred before the removalof the extrauterine pregnancy. This case indicates that a combinedpregnancy can occur not only after simultaneous multiple ovulationsbut also after the separate spontaneous ovulations.     

Vascular endothelial growth factor (VEGF) levels as a tool to discriminate between malignant and nonmalignant ascites

Ascites formation is commonly associated with cancer, although it is also present in other diseases. The aim of this study was to evaluate the usefulness of vascular endothelial growth factor as a malignancy marker in ascites of different etiologies. The levels of VEGF in 32 malignant and in 31 non-malignant ascites were determined by enzyme immunoassay (ELISA). VEGF levels were significantly higher in malignant than in non-malignant ascites (median=1265.9 pg/ml x 114.6 pg/ml; p<0.0001). We observed 72% sensitivity and 90% specificity, using 662 pg/ml as a cut-off value. Therefore, this approach can be used as a marker for a first screening to discriminate between malignant and nonmalignant ascites.     

Levels of vascular endothelial growth factor (VEGF) in serum of patients with endometriosis

BACKGROUND: Elevated concentrations of vascular endothelial growth factor (VEGF) have been detected in the peritoneal fluid of patients with endometriosis. Furthermore, it was postulated that VEGF is involved in the development of endometriotic lesions. The present study is aimed at determining whether high levels of VEGF could also be found in the serum of patients with endometriosis. METHODS: VEGF levels were measured by enzyme-linked immunosorbent assay (ELISA) in serum from 131 subjects with surgically confirmed endometriosis and 146 controls with no clinical evidence of the disease or detectable endometriotic lesions at the time of surgical examination. Parameters such as demographics, personal habits, menstrual characteristics and clinical profile were collected from each subject included in this study. RESULTS: The mean VEGF levels were not significantly modulated in serum samples of cases compared with controls in a crude general linear model and in a model adjusted for possible confounders. VEGF serum levels did not correlate with the score, stage of endometriosis or the presence of benign gynaecological disorders. However, a correlation was found between circulating concentrations of VEGF and body mass index. CONCLUSION: Although VEGF seems to play a pivotal role locally in the implantation and development of endometriotic lesions, the disease is not associated with a significant modulation in the levels of circulating VEGF.     

Vascular endothelial growth factor (VEGF), VEGF receptors expression and microvascular density in benign and malignant thyroid diseases

Angiogenesis is critical for the growth and metastatic spread of tumours. Vascular endothelial growth factor (VEGF) is the most potent inducer of neovasculature, and its increased expression has been related to a worse clinical outcome in many diseases. The purpose of this study was to evaluate the relation between VEGF, its receptors (VEGFR-1 and VEGFR-2) and microvessel density (MVD) in thyroid diseases. Immunostaining for VEGF and VEGF receptors was performed in 66 specimens of thyroid tissue, comprising 17 multinodular goitre (MNG), 14 Graves' disease, 10 follicular adenoma, 8 Hashimoto's thyroiditis, 7 papillary carcinoma and 10 normal thyroid specimens. Thyrocyte positivity for VEGF and VEGF receptors was scored 0-3. Immunohistochemistry for CD31, and CD34 on the same sections was performed to evaluate MVD. Immunohistochemical staining of VEGF in thyrocytes was positive in 92% of all the thyroid tissues studied. Using an immunostaining intensity cut off of 2, increased thyrocyte staining was seen in follicular adenoma specimens, MNG and normal thyroids compared with Hashimoto's thyroiditis and Graves' disease (P < 0.05). Similarly, VEGF thyrocyte expression in Graves' disease was less than other pathologies (P < 0.05). VEGFR-1 expression and the average MVD score did not differ between the different thyroid pathologies. VEGF expression was lower in autoimmune pathologies compared to autonomous growth processes. Conversely, both VEGFR-1 and VEGFR-2 were widely expressed in benign and neoplastic thyroid disease, suggesting that the up-regulation of VEGF and not its receptors occurs as tissue becomes autonomous. There was no clear relationship between MVD measurement and thyroid pathology.     

Endovaginal sonography for the early diagnosis of intrauterine and ectopic pregnancies.

Endovaginal sonography, together with beta-HCG titre, was used to diagnose ectopic pregnancy in 58 patients. Transabdominal ultrasound failed to conclude this diagnosis. The data from endovaginal sonography revealed the presence of a gestational sac in all 15 patients with normal pregnancies at a beta-HCG level of 1042 mIU/ml. Of the 23 patients with pathological pregnancies only 61% had an intrauterine gestational sac. Only 15% of the 20 patients with ectopic pregnancies showed an increase in beta-HCG greater than 66% in 48 h, while in normal pregnancy, this increase was found in 71% of the patients. The endovaginal findings of the ectopic gestation revealed a complex adnexal mass in 55%, a cystic mass in 30% and fluid in the cul-de-sac in 20%. The diagnostic indices of adnexal and cul-de-sac sonographic findings in the ectopic group further improved specificity and positive predictive accuracy. The detection of ectopic versus intrauterine gestation showed a high sensitivity of 95%, a specificity of 100%, a positive predictability of 100% and a negative predictability of 97%. The data confirm the value and reliability of endovaginal and cul-de-sac sonography, combined with measurement of the beta-HCG level in the early diagnosis of ectopic pregnancy. This combined approach not only makes the differentiation between normal and extrauterine gestation more accurate but also helps to avoid unnecessary diagnostic laparoscopy and hospitalization.     

Maternal serum alpha-fetoprotein levels in ectopic pregnancy

Maternal serum alpha-fetoprotein (AFP) was measured at the time of presentation in 44 women with histologically proven ectopic pregnancy. Serum AFP levels were within the reference range in 32 women. Eleven women (25%) had AFP levels above the 90th centile of the normal range, including five women with a live fetus seen ultrasonically preoperatively. The two women with a ovarian pregnancy and a cornual pregnancy had levels below the median value for gestational age.     

Salpingectomy - the laparoscopic surgical choice for ectopic pregnancy

The aim of this study was to assess the fertility outcome afterectopic pregnancy (EP) treated by laparoscopic salpingectomy.Among the 375 patients who underwent this operation betweenJanuary 1983 and December 1993, there were 145 patients whodesired pregnancy and whose contralateral tube was not obstructed.The overall rate of intrauterine pregnancy (IUP) was 50.3%,with an EP rate of 15.2%, These results were analysed accordingto the patients‘ past history together with the conditionof the contralateral tube at the time of the laparoscopy. Wedefined two groups. Group 1 included patients who had no previoushistory of tubal surgery and whose contralateral tube was normal.Group 2 comprised those patients who had a previous historyof tubal surgery and/or those whose tube was pathological, butnot obstructed. Postoperative fertility of the patients in group1 was significantly higher than that of the patients in group2, with IUP rates of 75 and 36.6% respectively (P < 0.001),and a risk of EP recurrence of 9.6 and 183% respectively. Ingroup 1, the actuarial IUP rate at 24 months was significantlyhigher than that for the patients in group 2 (66.7 versus 36.9%;P < 0.001). The patient’s past history and the conditionof the contralateral tube were the two major factors relatedto fertility outcome after laparoscopic salpingectomy for EP.In patients with no past history of tubal surgery or infertilityand whose contralateral tube was normal, the fertility resultsafter laparoscopic salpingectomy appeared comparable to thoseobserved after conservative laparoscopic treatment     

Induced abortions and risk of ectopic pregnancy

The relationship between induced abortions and subsequent riskof ectopic pregnancy has been analysed using data from a case-controlstudy conducted in Milan, Italy. The cases were 158 women witha diagnosis of ectopic pregnancy confirmed by laparoscopy orlaparotomy, admitted to a network of university and generalhospitals. Two control groups were selected. The first one (obstetriccontrols) included 243 women who gave birth at term (more than37 weeks gestation) to healthy infants at the same hospitalswhere the cases had been identified. The second control group(non-obstetric controls) was a random sample of 158 women ofcomparable age interviewed in the same calendar period, admittedto hospital for a broad spectrum of acute, non-gynaecologicalor obstetric conditions. A total of 35 out of 158 cases (22%)reported one or more previous induced abortions; the correspondingfigures were 29 out of 243 (12%) obstetric controls and 29 outof 158 (18%) non-obstetric ones. The risk of ectopic pregnancywas higher in women reporting induced abortions: the estimatedmultivariate relative risks (relative risk) for any inducedabortions were 2.9 [95%, confidence interval (CI) 1.6–5.3]in comparison with obstetric controls and 2.5 (95% CI 1.2–5.0)in comparison with women admitted to hospital for other conditions.The risk increased with number of induced abortions, being,compared to women with no induced abortion, 13.1 (95% CI 3.2–54.5)and 3.8 (95% CI 1.1–12.7) in women reporting two or moreinduced abortions when the comparison groups were respectivelyobstetric and non-obstetric controls. This study shows an increasedrisk of ectopic pregnancy after induced abortion. The consistencyof the results when comparison was made with two different controlgroups, and the direct relationship between number of previousinduced abortions and risk give some support to this association.     

Declining incidence of ectopic pregnancy in a UK city health district between 1990 and 1999

BACKGROUND: On the basis of clinical impression that the number of cases of ectopic pregnancy seen in the City and Hackney Health District, London, was changing, a retrospective study of the years between 1990 and 1999 was carried out. METHODS: From the histopathology databases, cases of ectopic pregnancy and early pregnancy failure were identified. The number of deliveries at The Homerton Hospital was obtained from the Labour Ward register; the number of terminations of pregnancy and the number of fertile women was obtained from the Office for National Statistics, UK. RESULTS: There were 73 cases of ectopic pregnancy in 1990 rising to 96 in 1991 and then a fall to 52 cases in 1999. In terms of ectopic pregnancy per 100 deliveries, per all known pregnancies and per 1000 fertile women per year, there was a peak in 1991 and a fall to 1999. With regard to relative incidence per deliveries and per all known pregnancies, these falls were significant (P < 0.05). In 1991, there were 2.4 ectopic pregnancies per 100 deliveries, falling to 1.6 in 1999, a 33% fall. The reasons for this large decline are uncertain. CONCLUSIONS: There has been no change in patient population, diagnostic aids used or management protocols for patients with ectopic pregnancies.     

Vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor (PDGF) play a central role in the pathogenesis of digital clubbing

Digital clubbing is associated with many unrelated serious diseases but its pathogenesis remains a clinical enigma. It has been hypothesized that platelet clusters impacting in the distal vasculature mediate the morphological changes of clubbing. Since the multifunctional cytokines vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) are released on platelet aggregation and are hypoxically regulated, the present study has examined their role in clubbing using immunohistochemistry. Basic fibroblast growth factor (bFGF), transforming growth factor-beta 1 (TGF-beta1), microvessel density, carbonic anhydrase IX (CAIX), hypoxia inducible factor (HIF)-1alpha, and HIF-2alpha were also measured. There was a significant increase in VEGF (p = 0.01), pKDR (p = 0.03), PDGF (p = 0.017), and HIF-1alpha and HIF-2alpha (p = 0.004 and p = 0.004, respectively) expression together with a significant increase in microvessel density (p = 0.03) in the stroma in clubbed digits compared with controls. There was no difference in CAIX (p = 0.25), TGF-beta1 (p = 0.66) or bFGF (p = 0.18) between affected and control groups. These findings suggest that VEGF and PDGF are released after platelet impaction and that their expression is hypoxically enhanced in the stroma after capillary occlusion. VEGF may synergize with PDGF in inducing the stromal and vascular changes present in digital clubbing.     

Vascular endothelial growth factor (VEGF) in endometriosis

Angiogenesis is likely to be involved in the pathogenesis of endometriosis. According to the transplantation theory, when the exfoliated endometrium is attached to the peritoneal layer, the establishment of a new blood supply is essential for the survival of the endometrial implant and development of endometriosis. From the known angiogenic factors, vascular endothelial growth factor (VEGF) has emerged as a pivotally important regulator of normal angiogenesis and pathological neovascularization. The VEGF protein was evaluated immunohistochemically in the eutopic endometrium of 10 women without endometriosis (group I) at laparoscopy and the eutopic endometrium and peritoneal endometriotic lesions of 43 women with endometriosis (group II). VEGF histological scores were 9.7 +/- 4.3 and 4.0 +/- 2.6 respectively in the epithelium and stroma of the eutopic endometrium of group I women, and 10.3 +/- 2.3 and 3.6 +/- 2.3 respectively in women of group II. In red lesions, the VEGF scores were 11.1 +/- 3.0 in the epithelium and 5.1 +/- 3.0 in the stroma, and in black lesions were 8.6 +/- 2.7 and 1.6 +/- 1.6, respectively. Significantly lower values were observed in black lesions as compared with eutopic endometrium and red lesions, the values of which were similar. Scores were also evaluated according to the phase of the cycle. In eutopic as well as ectopic endometrium, no significant cyclic variations were observed throughout the cycle. However, VEGF content was found to be higher in the eutopic glandular epithelium of women with endometriosis during the late secretory phase, possibly suggesting a more likely tendency to implant. In contrast, significantly higher VEGF content was noted in red lesions as compared with black lesions. During all phases of the cycle, the VEGF content in stromal cells of red lesions was higher than in black lesions. Similarities in VEGF content were observed in the glandular epithelium of the eutopic endometrium of women with endometriosis and red lesions, suggesting that endometriosis probably arises from the peritoneal seeding of viable endometrial cells during retrograde menstruation and that red lesions can be considered as the first stage of implantation. After the attachment phase, the high VEGF levels could provoke an increase in the subperitoneal vascular network and facilitate implantation and viability in the retroperitoneal space. Lower VEGF levels in black lesions explain the decrease in both stromal vascularization, followed by fibrosis and inactivation of the implant.      

Vascular endothelial growth factor and endometriotic angiogenesis

Peritoneal endometriosis is a significant debilitating gynaecological problem of widespread prevalence. It is now generally accepted that the pathogenesis of peritoneal endometriosis involves the implantation of exfoliated endometrium. Essential for its survival is the generation and maintenance of an extensive blood supply both within and surrounding the ectopic tissue. The vascular endothelial growth factor (VEGF) family of angiogenic molecules is involved in both physiological angiogenesis, and a number of pathological conditions that are characterized by excessive angiogenesis. Increasing evidence suggests that the VEGF family may also be involved with both the aetiology and maintenance of peritoneal endometriosis. Sources of this factor include the eutopic endometrium, ectopic endometriotic tissue and peritoneal fluid macrophages. Important to its aetiology is the correct peritoneal environment in which the exfoliated endometrium is seeded and implants. Established ectopic tissue is then dependent on the peritoneal environment for its survival, an environment that supports angiogenesis. Our increasing knowledge of the involvement of the VEGF family in endometriotic angiogenesis raises the possibility of novel approaches to its medical management, with particular focus on the anti-angiogenic control of the action of VEGF.     

Evaluation of ectopic pregnancy by magnetic resonance imaging.

Patients (n = 37) suspected of ectopic pregnancy were prospectively evaluated with magnetic resonance (MR) imaging to assess the capability of MR imaging in the diagnosis of ectopic pregnancy. Five levels of confidence were defined: diagnostic, suspicious, equivocal, questionable, and negative. Tubal wall enhancement and presence of tubal haematoma or gestational sac-like structure were considered diagnostic findings. There were 21 diagnostic, two suspicious, eight equivocal, and six negative findings. MR findings were compared with the surgical findings in 18 patients. Surgical confirmation was obtained in 12 diagnostic, two suspicious, and four equivocal studies. Using the MR diagnostic criteria for tubal pregnancy, MR had 12 true positive, three true negative, three false negative, and no false positive results for the diagnosis of tubal pregnancy. Retrospective analysis of the signal intensity of haematoma and ascites was performed for these 18 surgically confirmed cases. The predominant signal intensity of tubal haematoma was an intermediate signal on T1-weighted image (WI) and a low signal on T2WI. Ascites showed signal intensity higher than that of urine on T1WI in 100% of 13 cases. In conclusion, MR imaging with use of intravenous contrast material allows a specific diagnosis of tubal pregnancy, recognizing tubal wall enhancement and fresh tubal haematoma.     

Pregnancy: Determinants of reproductive prognosis after ectopic pregnancy

The reproductive prognosis of 115 women desiring pregnancy whounderwent surgery for ectopic pregnancy between 1985 and 1990at the Clinica Luigi Mangiagalli, was analysed after a medianfollow-up period of 26 months (range 2–83). Probabilityof reproductive events was assessed by a product-limit model.Women who underwent surgery for ectopic pregnancy had a 54%probability of becoming pregnant (cumulative pregnancy rate,CPR) and a 36% probability of giving birth to a child (cumulativelivebirth rate, CLB) during the 3 years after surgery. Thesepercentages dropped with history of previous ectopic pregnancy(respectively 33%, P = 0.07, and 7%, P < 0.05). Increasingage at surgery and presence of adhesions in the contra-lateraltube seemed to be associated with poor reproductive prognosis(CPR = 40% and CLB = 12% for women aged 35 years and CPR = 37%and CLB = 20% in women with adhesions in the contra-lateraltube), but these findings were not statistically significant.No association emerged between fertility and parity or typeof surgery. The recurrence rate of ectopic pregnancy was 20%.No significant association emerged between recurrence of ectopicpregnancy and age, history of previous pregnancy, history ofprevious ectopic pregnancy, non-intact contra-lateral tube andsalpingotomy.     

Left ectopic pregnancy following gamete intra-fallopian transfer into the right fallopian tube: a report on two cases

Two cases are reported in which GIFT was performed into the right Fallopian tube, both resulting in ectopic pregnancy in the left Fallopian tube. The possible aetiological factors for the occurrence of contralateral ectopic pregnancy are discussed.     

Vascular endothelial growth factor (VEGF) is expressed by neoplastic Hodgkin-Reed-Sternberg cells in Hodgkin's disease

Vascular endothelial growth factor (VEGF) is involved in tumour angiogenesis, an important process for the growth and metastatic potential of solid tumours. Numerous studies have demonstrated up-regulation of VEGF at both mRNA and protein level in various tumours and a correlation with advanced stage and prognosis has been demonstrated in some cases. Limited information exists about its role in lymphoid malignancies and in particular, Hodgkin's disease. The present study examined the immunohistochemical expression of VEGF using the monoclonal antibody VG1 in a series of 61 cases of Hodgkin's disease, including both classical Hodgkin's disease and the nodular lymphocyte predominance variant, and correlated these results with microvessel density, using an anti-CD31 monoclonal antibody. In 41 cases (70.6%) of classical Hodgkin's disease and one of the three cases of nodular lymphocyte predominance Hodgkin's disease, the neoplastic Reed-Sternberg and Hodgkin cells expressed VEGF. The staining observed was cytoplasmic, either diffuse or with a focal paranuclear distribution. Macrophages were always positive, while reactive lymphocytes showed occasional positivity. A variable amount of strong extracellular staining was also observed in the tissue stroma and intravascular plasma staining was prominent. There was no statistically significant relationship between VEGF expression and the subtype of Hodgkin's disease or microvessel density. In vitro studies using the Reed-Sternberg cell lines L428 and KM-H2 were also performed in both normoxia and hypoxia and VEGF protein production was assessed by flow cytometry (FACS), immunoassay of cell culture supernatant, and RT-PCR. Analysis by FACS demonstrated a subset of cells in both cell lines reacting with VG1 and analysis of secreted VEGF (pg/ml per 1x10(6) cells) in cell culture supernatant confirmed the normoxic production in both cell lines and significant hypoxic induction (p<0.005). Additionally, both cell lines expressed VEGF mRNA, as demonstrated using the RT-PCR method. In conclusion, neoplastic cells express VEGF in Hodgkin's disease, as is the case in solid tumours, and this expression may be induced by hypoxia. The presence of VEGF in reactive macrophages and in the extracellular matrix might facilitate tumour progression.     

Relationship between maternal serum vascular endothelial growth factor concentration in early pregnancy and fetal and placental growth.

Vascular endothelial growth factor (VEGF) has important effects on endothelial cells increasing cell proliferation, permeability and nitric oxide production; concentrations of VEGF in the maternal serum increase during the first 10 weeks of pregnancy. In this study, the relationship of maternal serum VEGF with maternal health during pregnancy and with fetal and placental size at mid-pregnancy and at term was investigated. Serum was obtained from 539 Caucasian women with singleton pregnancies between 8 and 20 weeks of pregnancy (mean 14 weeks). Total serum VEGF concentrations were measured by direct competitive radioimmunoassay. Fetal size and placental volume were measured by ultrasound between 16 and 20 weeks gestation. Birthweight, placental weight and anthropometric measurements of the baby were obtained after delivery. Serum VEGF concentrations were found to be higher in women with a lower weight before pregnancy (P = 0.01) and in those carrying a female fetus (P = 0.002). VEGF concentrations were positively correlated with placental volume (r = 0.17, P = 0.0001) but not with fetal size between 16 and 20 weeks gestation. Serum VEGF concentrations were positively correlated with both birthweight (r = 0.10, P = 0.02) and placental weight at delivery (r = 0.13, P = 0.003). The data presented support the view that VEGF may be one of the factors involved in mediating the maternal cardiovascular adaptation to pregnancy.