Gregory F. Rosen

Role of vascular endothelial cell growth factor in Ovarian Hyperstimulation Syndrome.

Controlled ovarian hyperstimulation with gonadotropins is followed by Ovarian Hyperstimulation Syndrome (OHSS) in some women. An unidentified capillary permeability factor from the ovary has been implicated, and vascular endothelial cell growth/permeability factor (VEGF) is a candidate protein. Follicular fluids (FF) from 80 women who received hormonal induction for infertility were studied. FFs were grouped according to oocyte production, from group I (0-7 oocytes) through group IV (23-31 oocytes). Group IV was comprised of four women with the most severe symptoms of OHSS. Endothelial cell (EC) permeability induced by the individual FF was highly correlated to oocytes produced (r2 = 0.73, P < 0.001). Group IV FF stimulated a 63+/-4% greater permeability than FF from group I patients (P < 0. 01), reversed 98% by anti-VEGF antibody. Group IV fluids contained the VEGF165 isoform and significantly greater concentrations of VEGF as compared with group I (1,105+/-87 pg/ml vs. 353+/-28 pg/ml, P < 0. 05). Significant cytoskeletal rearrangement of F-actin into stress fibers and a destruction of ZO-1 tight junction protein alignment was caused by group IV FF, mediated in part by nitric oxide. These mechanisms, which lead to increased EC permeability, were reversed by the VEGF antibody. Our results indicate that VEGF is the FF factor responsible for increased vascular permeability, thereby contributing to the pathogenesis of OHSS.

Severe ovarian hyperstimulation in a spontaneous singleton pregnancy

Ovarian hyperstimulation syndrome in a spontaneous ovulatory cycle is exceedingly rare. We report a case of severe ovarian hyperstimulation associated with a spontaneous, otherwise normal singleton pregnancy.

Ovulation induction in women with premature ovarian failure : a prospective, crossover study

A prospective crossover study comparing ovulation induction techniques in eight women with premature ovarian failure is presented. These patients were treated with FSH rebound techniques using the GnRH-a, LA, alone in one treatment cycle and the same plus menopausal gonadotropins in the other treatment cycle. Two women ovulated in each group. We conclude that ovulation does occur in women with premature ovarian failure, but that luteal P may be inadequately secreted.

Influence of Estrogen on Prostacyclin and Thromboxane Balance in Postmenopausal Women

Abstract Although the cardioprotective effect of estrogen is well recognized, the mechanism by which this effect occurs is not well understood. One possible mechanism may involve an alteration in the local vascular equilibrium between prostacyclin (PGI2) and thromboxane A2 (TxA2), favoring PGI2. To test this hypothesis, we studied the estrogenic effect on urinary PGI2/TxB2 balance, both acutely and long term, in postmenopausal women. Seven subjects received estradiol (E2) during one visit and only the vehicle during another visit (control). Both were administered intravenously for 8 h. Serum E2 levels of 200 pg/ml were attained after E2 treatment. An additional eight subjects were treated subcutaneously with two 25-mg E2 pellets for 24 weeks; the serum E2 levels averaged between 80 and 120 pg/ml. Also, 12 premenopausal women were used for comparison of baseline prostanoid values with those of postmenopausal women. A highly specific and sensitive high-performance liquid chromatography/radioimmunoassay (HPLC-RIA) was used to quantitate PGI2 and TxA2 by measuring their stable metabolites, 6-keto-prostaglandin F1 (6-keto-PGF1 and thromboxane B2 (TxB2), respectively, in urine. The 6-keto-PGF1 and TxB2 levels in postmenopausal women were 35.6 ± 6.5 and 20.5 ± 3.8 ng/g of creatinine compared with 32.2 ± 5.3 and 16.7 ± 3.9 ng/g in premenopausal women, respectively. After E2 infusion, there was a significant increase (41%) in mean 6-keto-PGF1 levels, a 35% drop in mean TxB2 levels, and a significantly greater (65%) 6-keto-PGF1/TxB2 ratio, compared to the controls. After long-term E2 treatment, there was a progressive decrease in mean TxB2 levels and a transient increase in 6-keto-PGF1 levels. The results of our study suggest that the anticipated effects of E2 treatment on PGI2 and TxA2 metabolism in postmenopausal women do occur.

Secretory dynamics of bioactive and immunoreactive prolactin in polycystic ovary syndrome

To further investigate prolactin (PRL) secretion in polycystic ovary syndrome (PCO), the authors evaluated immunoreactive (immuno) and bioactive (bio) PRL levels in the basal state and in response to provocative testing with intravenous dopamine (DA), metoclopramide (MCP), and gonadotropin-releasing hormone (GnRH), before and after disulfiram. Basal measurements of immuno-PRL, bio-PRL, and the ratio of bio/immuno-PRL were similar in PCO and controls. The immuno-PRL decrement after DA was greater than that of bio-PRL in both groups (P less than 0.05). After MCP, immuno-PRL increased more than bio-PRL in PCO (P less than 0.01), and this immuno-PRL increment was greater than that of controls (P less than 0.05). Bio-PRL and immuno-PRL increased after GnRH in PCO, but not controls, and these responses were inhibited by disulfiram. These data confirm PRL hypersecretion in some women with PCO, which is better expressed by immunoreactivity than bioactivity. Given the assay systems and patients studied, bioactivity

The endocrinologic evaluation of a 45,X true hermaphrodite

A 13-year-old 45,X girl presented with spontaneous menses and the acute onset of progressive hirsutism. Complete endocrinologic evaluation of hirsutism was unremarkable. An exploratory laparotomy revealed a gonad containing ovarian and testicular tissue. Chromosome analysis from four different tissues confirmed the karyotype to be 45,X. She was H-Y antigen positive.

Predicting Pregnancy Outcome by the Observation of a Gestational Sac or of Early Fetal Cardiac Motion with Transvaginal Ultrasonography

Transvaginal ultrasound (US) allows for observation of the gestational sac and cardiac motion as early as 3 and 4 weeks after ovulation, respectively. The purpose of this study was to determine how well the first observation of cardiac motion, using weekly transvaginal US examinations, predicted pregnancy outcome. Three hundred sixteen pregnancies wherein the date of ovulation was known and a single gestational sac was visualized at 3 weeks after ovulation were studied. Cardiac motion was first detected at 4 weeks after ovulation in 226 (71.5%), and at 5 weeks in 67 (21.2%). In 23 patients, cardiac motion was never observed. In those patients with cardiac motion visible at 4 weeks after ovulation, 94.2% have subsequently delivered viable infants. This contrasts with only 70.1% for those patients who first had observable cardiac motion 1 week later (P = 6.7 X 10(-6]. This study demonstrates that the solo finding of a gestational sac is a poor predictor of pregnancy outcome (82.3% accurate) and that the earlier that cardiac motion is initially observed, the better the pregnancy prognosis.