D. Rizos

Concentrations of angiogenic factors in follicular fluid and oocyte-cumulus complex culture medium from women undergoing in vitro fertilization: association with oocyte maturity and fertilization

OBJECTIVE To determine the concentration of angiogenic factors (vascular endothelial growth factor [VEGF], basic fibroblast growth factor [bFGF], and angiogenin) in the follicular fluid (FF) and oocyte-cumulus complex culture medium (CM) of women undergoing IVF and to investigate the association of the concentrations with the maturity and fertilization of the oocyte. DESIGN Prospective study. SETTING Academic tertiary-care institution. PATIENT(S) IVF patients with unexplained or tubal factor infertility. INTERVENTION(S) Analysis of VEGF, bFGF, and angiogenin FF and CM concentrations. MAIN OUTCOME MEASURE(S) Oocyte maturity and fertilization and FF and CM angiogenic factor concentrations. RESULT(S) VEGF, bFGF, and angiogenin were determined in FF and CM. FF angiogenin concentrations were significantly higher when the oocyte was mature versus immature. CM VEGF concentrations were significantly higher when the oocyte was nonfertilized versus fertilized. Positive correlations were observed between angiogenic factors in CM. CONCLUSION(S) VEGF, bFGF, and angiogenin (determined for the first time) are secreted in the FF and CM. Elevated CM VEGF concentrations, probably implying oocyte-cumulus complex hypoxia, are negatively associated with oocyte fertilization. Elevated FF angiogenin concentrations are positively associated with oocyte maturity, possibly indicating angiogenins biological role beyond neovascularization.

Inflammatory cytokines in newborn infants

Serum levels of IL-1beta, IL-6 and TNF-alpha were measured in 48 healthy, termed neonates on the 1st (N1), 5th (N5) and 40th (N40) day after birth, compared with those in maternal serum (MS), umbilical cord (UC) and adult controls. Cytokine values in N1 and N5 were significantly elevated, than those in UC and in controls (P<0.0001). IL-1beta and IL-6 declined significantly from N1 to N40 (P<0.0001), while TNF-alpha increased significantly from N1 to N5 and declined thereafter. MS infinity IL-1beta and IL-6, but not MS infinity TNF-alpha, were significantly higher than those of controls (P<0.0001). IL-1beta values depended on the mode of delivery. In conclusion, the increased concentrations of IL-1beta, IL-6 and TNF-alpha during the perinatal period might suggest their involvement in an inflammation-like process during normal parturition, and reflect also a newborn immune response to the stress of delivery and environmental changes.

Hormonal and ultrasound characteristics of menstrual function during chronic hemodialysis and after successful renal transplantation

The cycles of 11 renal transplant recipients (RTR), at least 24 months after stabilization of graft function and four hemodialyzed (HD) patients, menstruating regularly, were evaluated by concurrent and systematic determinations throughout the cycle of LH, FSH, estradiol, progesterone, testosterone, prolactin and SHBG and in the case of RTR also by ultrasound follow‐up. Biphasic estradiol secretion, midcycle LH and FSH surge, duration of luteal phase, midluteal progesterone values and in the case of RTR, ultrasonic parameters were consistent with: (1) normal ovulatory cycles in five RTR; (2) ovulatory cycles with luteal phase deficiency in five RTR and two HD patients; (3) anovulatory cycles in one RTR and two HD patients. Thus, in HD patients only abnormal cycles of central etiology were found, while in RTR, luteal phase deficiency was a very common syndrome, in equal percentage with normal ovulatory cycles.

Determinants of serum leptin levels in healthy postmenopausal women

The aim of this study was to evaluate factors that influence leptin levels in postmenopausal women. One hundred and forty-four postmenopausal women were evaluated cross-sectionally. In every woman a complete medical history was obtained, body mass index (BMI) was recorded and morning fasting blood was obtained for the determination of serum leptin, follicle stimulating hormone (FSH), estradiol, testosterone, Δ4androstendione, dehydroepiandrosterone sulphate (DHEAS) and insulin. In univariate analysis, age, BMI and insulin were positively correlated with serum leptin, while DHEAS showed a negative association with leptin concentrations (age r=0.21, p=0.005, BMI r=0.41, p=0.0001, insulin r=0.20, p=0.008, DHEAS r=−0.28, p=0.0001). In stepwise multivariate regression analysis serum leptin could be best predicted from BMI, serum insulin and serum DHEAS [leptin= (1.41 * BMI) −(0.01 * DHEAS) + (3.26 * insulin) −26.3; model r2=0.24, p=0.001]. In conclusion, BMI and serum insulin have a positive while serum DHEAS has a negative impact on serum leptin. Neither endogenous estradiol, nor endogenous testosterone are associated with leptin levels. Further studies are needed to elucidate the role of leptin in determining body weight and composition in postmenopausal women.

Pregnancy rates in gonadotrophin stimulated cycles with timed intercourse or intrauterine insemination for the treatment of male subfertility

OBJECTIVE To compare the pregnancy rates achieved by intrauterine insemination or timed intercourse in gonadotrophin stimulated cycles in couples whose only detectable abnormality was poor sperm quality. DESIGN Sixty-two couples with primary or secondary infertility due to male factor entered the study. The 62 couples were randomly equally divided into two groups. Each group began one of the two treatment modalities (controlled ovarian hyperstimulation in conjunction with timed intercourse or intrauterine insemination) for three consecutive cycles and then switched to the alternative treatment after one rest cycle, if pregnancy was not achieved. RESULTS Five pregnancies (3.9%) were achieved after 128 cycles with timed intercourse and 15 pregnancies (11.5%) after 130 cycles with intrauterine insemination. The difference was found to be statistically significant (P < 0.05). CONCLUSION We suggest that intrauterine insemination during hMG stimulated cycles improves the pregnancy rates of couples whose only detectable abnormality is poor sperm quality.

Menopausal symptoms are associated with subclinical atherosclerosis in healthy recently postmenopausal women

ABSTRACT Objectives To determine whether menopausal symptoms are associated with changes in arterial structure and function in healthy, recently postmenopausal women. Methods One hundred and ten postmenopausal women aged 45–55 years were included in the present cross-sectional study. Menopausal symptoms were recorded by the Greene Climacteric Scale. Anthropometric measures, blood pressure, serum lipids, glucose, insulin, sex and thyroid hormones were determined in each individual. Arterial structure, function and stiffness were assessed by intima–media thickness (IMT), flow-mediated dilation and pulse-wave velocity, respectively. Results Women with moderate to severe hot flushes had increased IMT compared to women with no or mild hot flushes (IMT in women with no hot flushes 0.61±0.08 mm, IMT in women with mild hot flushes 0.62±0.11 mm, IMT in women with moderate to severe hot flushes 0.67±0.11 mm; p = 0.034). This difference was independent of cardiovascular risk factors like age, menopausal age, smoking, blood pressure, adiposity, lipid levels, insulin resistance or hormone levels. No association was detected between psychological or psychosomatic symptoms and arterial indices. Furthermore, menopausal symptoms were not associated with serum sex steroids or thyroid hormone levels. Conclusions Carotid IMT, a surrogate marker of subclinical atherosclerosis and cardiovascular risk, was found to be increased in women with vasomotor symptoms as compared to asymptomatic women. This association was independent of cardiovascular risk factors or endogenous hormone levels. It remains to be elucidated whether the presence of menopausal symptoms is an additional cardiovascular risk factor requiring preventive intervention.

Changes of angiogenin serum concentrations in the perinatal period

The polypeptide angiogenin, a normal constituent of human plasma, might be involved in endothelium homeostasis, angiogenesis, and neovascularization accompanying various diseases. This study aimed at determining angiogenin serum concentrations in the perinatal period of healthy newborns and at forming a baseline for this protein, which in the future may serve as a diagnostic index in developmental errors of the placenta and/or newborn. One milliliter of blood was drawn on d 1 and 4 of life from 30 healthy full-term neonates, and angiogenin serum concentrations were measured by an enzyme immunoassay using a commercially available kit. In 10 cases angiogenin serum concentrations were also measured in the maternal serum before delivery and in the umbilical vein serum. Angiogenin serum concentrations (μg/L) were significantly higher in maternal serum (225.7 ± 49.6) compared with umbilical vein serum (119.0 ± 34.2) (p < 0.0002), as well as that compared with day 1 (166.4 ± 44.9) (p < 0.01) but not to d 4 neonatal serum (240.8 ± 52.6). Angiogenin serum concentrations showed a statistically significant increase from d 1 to 4(p < 10-7), as well as from umbilical cord serum to d 1 neonatal serum (p < 0.0002). A statistically significant correlation existed between values in umbilical cord serum and d 1 neonatal serum (r = 0.84, n = 10, p < 0.002) and between those in d 1 and 4 neonatal serum (r = 0.37, n = 30, p < 0.04). Sex, birth weight, or mode of delivery did not influence angiogenin serum concentrations. We conclude that a rapid increase of angiogenin serum concentrations to maternal levels takes place during the first four postnatal days in healthy full-term neonates.

Expression of CEA, CA-125 and SCC antigen by biological fluids associated with pregnancy

Carcinoembryonic antigen (CEA), cancer antigen 125 (CA-125) and squamous cell carcinoma (SCC) antigen were measured in 56 full-termed pregnancies by enzyme-immunoassays (EIA-MEIA). The measurements were done in maternal serum (MS), umbilical cord blood (UCB) and amniotic fluid (AF) samples, during delivery. Very high antigen levels were found in AF samples (median: CEA = 124 ng/ml; CA-125 = 710 U/ml; SCC = 710 ng/ml) compared to UCB and MS. CEA and SCC showed significantly lower values in MS (0.6 and 1.7 ng/ml, respectively) than in UCB (1.6 ng/ml, P = 7.7 x 10(-9); 3.55 ng/ml, P = 6.5 x 10(-6), respectively), while CA-125 had significantly higher values in MS (6 U/ml) than in UCB (0.0 U/ml, P = 17 x 10(-6); Wilcoxon paired test). All CEA values in MS were below cut-off (less than or equal to 5 ng/ml), while 10% of CA-125 and 30% of SCC values were above cut-off (less than or equal to 35 U/ml and less than or equal to 2.5 ng/ml, respectively). Amniotic fluid CEA with meconium had higher values (P = 0.0002), while the highest CA-125 values in AF samples were found in primiparae (P = 0.02). Moreover SCC in AF samples from vaginal delivered pregnancies showed significantly higher values, compared to those from cesarean section (P = 4.2 x 10(-7); Mann-Whitney U-test). Thus, our findings suggest that pregnancy has an influence on maternal serum SCC and CA-125 values, while CEA is independent of gestation and seems to conserve its diagnostic value during pregnancy as well.

Soluble form of ICAM-1, VCAM-1, E- and L-selectin in human milk

In breast milk and paired serum from 70 lactating women and 40 of their term, infection-free neonates, on the 2nd and 5th day postpartum slCAM-1, sVCAM-1, sE- and sL-selectin were measured by ELISA and compared with those in 26 healthy adults (controls). Seven infant formulas and fresh milk from five cows were also analyzed. Human colostrum values of slCAM-1, sVCAM-1 (similar to those in maternal and control serum), sE-selectin and sL-selectin (-10 and -100 times lower than in maternal and control serum) were significantly higher than those in milk, while they varied widely. None of the adhesion molecules was detected in fresh cows milk or infant formulas. Exclusively breast-fed infants showed significantly higher values of slCAM-1 and sL-selectin on the 2nd day of life than those supplemented also with formula. Only slCAM-1 values correlated positively between colostrum and time-matched maternal serum. These findings show in human milk important amounts of slCAM-1 and sVCAM-1 but minimal amounts of sE- and sL-selectin, which could affect the immune system of the neonate.

Transvaginal sonographic monitoring of the uterine effects of raloxifene and a continuous combined replacement therapy in postmenopausal women

OBJECTIVE To study the effect of 17beta-estradiol+norethisterone acetate and raloxifene on the endometrium and uterine volume in postmenopausal women. METHODS Patients were randomly assigned to 17beta-estradiol 2 mg+norethisterone acetate 1mg (E2+NETA) daily (n=90) or raloxifene HCl 60 mg (Evista) daily (n=43). Transvaginal sonography was done at baseline and at 6, 12 and 18 months, and at 6 and 12 months in-patients treated with E2+NETA and EVISTA respectively. Patients were asked to record bleeding-spotting episodes. Whenever required patients were referred for hysteroscopy+/-biopsy of the endometrium. RESULTS Patients under E2+NETA had a higher bleeding-spotting incidence (48.6%) compared with EVISTA (7.7%). Endometrial thickness increased significantly under E2+NETA as compared with baseline; however, at end point thickness reverted to baseline values. Evista had a non-stimulatory effect on the endometrium. Changes in uterine volume were not statistically significant. CONCLUSIONS Both treatment regimens provided comparable uterine safety. However, raloxifene exhibited a more favorable safety profile on the uterus as expressed in the bleeding-spotting incidence and the effect on endometrial thickness and uterine volume. Transvaginal sonography appears to be a dependable method for monitoring the effect of treatment on the uterus.