A potential novel strategy, inhibition of vasopressin-induced VEGF secretion by relcovaptan, for decreasing the incidence of ovarian hyperstimulation syndrome in the hyperstimulated rat model.

OBJECTIVE: To investigate the effects of V1A receptor antagonist through inhibition of vasopressin-induced VEGF secretion in an experimental model. STUDY DESIGN: Thirty rats were randomly divided into five groups. Four groups were given 10IU pregnant mare serum gonadotropin/day (sc) at 8:00-8:30am on days 22-25 of life. They were administered 30IU hCG at 8:00-8:30am on day 26 of life. On days 26 and 27 of life at 8:00am and 4:00pm, (ip) per animal, 50µg/kg/day GnRH antagonist in the GnRH antagonist group, 0.3mg relcovaptan in the high dose relcovaptan group, and 0.15mg relcovaptan in the low dose relcovaptan group were administered. The control group was given the same dosage of 0.9% saline solution (ip) on days 22-26 day of life. The main outcomes were weight gain, ovarian weights, peritoneal fluid VEGF values, corpus luteum count, and atretic follicle count. RESULTS: Weight gain was highest in the OHSS group; it was almost twice as much in the OHSS group than it was in the control group. Ovarian weights were significantly lower in all treatment groups (p=0.03). There was no statistically significant difference in ovarian weights between the GnRH antagonist and relcovaptan groups (p=0.176). The evaluation of peritoneal fluid VEGF-A levels revealed statistically significant differences between levels in the treatment groups and in the OHSS group (p=0.005). Atretic follicle count in the OHSS group was significantly lower (p=0.048). In all treatment groups, CL counts were prominently lower than they were in the OHSS group (p=0.002). CONCLUSION: Relcovaptan may be a novel strategy for decreasing risk of OHSS by inhibition of vasopressin-induced VEGF secretion through V1A receptor antagonist.

Comparison of the clinical value of CA 19-9 versus CA 125 for the diagnosis of endometriosis.

Preoperative blood samples and intraoperative tissue specimens were obtained from 101 patients with endometriosis and 78 patients without endometriosis referred for benign gynecologic operations to investigate the clinical value of serum and tissue CA 19-9 levels in the diagnostic evaluation of endometriosis as compared to CA 125. Our prospective cohort study showed that serum CA 19-9 is a valuable marker in the diagnosis of endometriosis, and it may be used to predict the patients with severe endometriosis when used with CA 125.

Therapeutic value of trichloroacetic acid in the treatment of isolated genital warts on the external female genitalia.

OBJECTIVE: To evaluate the value of 85% trichloroacetic acid (TCA) in the treatment of human papillomavirus (HPV)-associated genital warts of the external genitalia and to detect the recurrence rate and side effects of this therapeutic regimen. STUDY DESIGN: All patients with a suspected HPV-related papillary vulvar lesion after initial examination underwent vulvoscopic evaluation with a magnification of 8-20x using acetic acid and toluidine blue. Under local anesthesia, biopsies were taken from acuminate or papillary warts for histopathologic confirmation and from suspicious areas to exclude preinvasive or invasive diseases. Following histopathologic diagnosis, patients were treated with 85% TCA. RESULTS: Overall, 51 patients with isolated vulvar and/or perianal genital warts were included. Of those patients, 11 (21.5%) had acuminate and 40 (78.5%) had papular genital warts. All the women had lesions of the labia minora. The other localizations were as follows: labia majora, 18 (35.3%); lateral vulva, 5 (9.8%); clitoris, 9 (17.6%); fourchette, 16 (31.3%); and perianal area, 7 (13.7%). All lesions were successfully treated by the end of the treatment period (median, 4; range 2-5). None of the patients had recurrence or new lesions during the 6-month follow-up period. In the second 6 months, 9 patients (17.6%) were diagnosed with recurrent lesions. Although all the patients experienced transient burning pain during therapy, none of them discontinued the therapy. Ulceration was observed in 8 patients (15.6%). Of those patients only 3 had permanent scarring (5.8%). CONCLUSION: We recommend the use of TCA in patients with external genital warts, especially for mild to moderate cases. It is associated with a high success rate and low morbidity if sufficient care is taken during application.

Effects of four different regimens of hormone replacement therapy on hemostatic parameters: a prospective randomized study.

OBJECTIVE: To compare the effects of four different regimens including oral and transdermal formulations with or without progestins on the hemostatic system in a prospective randomized fashion. METHODS: Eighty-eight women were randomized to four groups receiving continuous transdermal estradiol 50 microg/day (tE2), oral conjugated equine estrogen 0.625 mg/day (CEE 0.625 mg), oral conjugated equine estrogen 0.625 mg/day plus medroxyprogesterone acetate 2.5 mg/day (CEE 0.625 mg/MPA 2.5 mg), or oral 2 mg 17-beta estradiol combined with 1 mg norethistrone acetate (E2/norethistrone). The hysterectomized patients received only estrogen, and the remaining women received the estrogen plus progesterone combination regimens. As a marker of hemostatic system fibrinogen, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) levels were measured initially, and after 1 and 6 months of therapy. RESULTS: The treatment groups were well matched for baseline characteristics including age, height, weight, body mass index, and systolic and diastolic blood pressures. During the study period fibrinogen levels were below the baseline values in all groups. However, the decrease was only statistically significant in patients treated with oral 0.625 mg/day CEE. tPA levels were decreased significantly by tE2, CEE 0.625 mg, and CEE 0.625 mg/MPA 2.5 mg. PAI-1 levels were decreased significantly by CEE 0.625 mg, and CEE 0.625 mg/MPA 2.5 mg. When the effects of the four different regimens were compared using percentage changes from the baseline, no significant difference was found among the treatment groups. CONCLUSION: One of the treatment regimens resulted in a more coagulable state. Oral therapy with CEE decreased the levels of all parameters, and MPA did not impair this beneficial effect, except for in fibrinogen. Transdermal therapy had a minimal effect. No significant difference was noted among the four regimens.

Comparison of basal and clomiphene citrate induced FSH and inhibin B, ovarian volume and antral follicle counts as ovarian reserve tests and predictors of poor ovarian response in IVF.

PURPOSE: To compare basal and clomiphene citrate (CC) induced follicle-stimulating hormone (FSH), estradiol (E2), and inhibin B levels with ultrasound indices of ovarian reserve in infertile women and to test the prognostic value of these tests on response to ovarian stimulation in in vitro fertilization (IVF). METHODS: Fifty-six patients had basal and CC induced serum hormone levels and ultrasound measured mean ovarian volume (MOV) and mean antral follicle counts (MFC). Thirty-two patients were then appropriately selected to have a total of 41 cycles of IVF/ICSI treatment. RESULTS: Women with diminished ovarian reserve had lower MOV, MFC, day 3 and day 10 inhibin B levels (p < 0.001). Only basal and CC induced FSH and inhibin B correlated with MOV and MFC. Poor responders in IVF/ICSI had higher basal FSH (p < 0.05), lower basal and induced inhibin B levels (p < 0.05), and lower MOV and MFC (p < 0.01) than normal responders. Ovarian volume alone was better than age and basal hormones in predicting poor ovarian response, while abnormal CC test was the only independent significant factor in predicting ovarian response. However, age was the only independent predictor of pregnancy in IVF as compared to hormonal and ultrasound indices of ovarian reserve. CONCLUSION: CC test and ovarian volume are better than other hormonal and sonographic tests in predicting the response to ovarian stimulation in IVF cycles.

Single-dose methotrexate for the treatment of unruptured ectopic pregnancy.

OBJECTIVE: The objective of this study was to review our experience with single dose intramuscular methotrexate (MTX) for the treatment of ectopic pregnancy and to evaluate major confounding factors that relate to the success of therapy. PATIENTS AND METHODS: The selection criteria were patients who had a stable hemodynamic status and an ectopic gestational mass of <4 cm. on ultrasound. Patients were not excluded from MTX therapy either by a baseline serum beta-hCG titer or by the presence of fetal cardiac activity demonstrated on ultrasonography. Thirty- four of 86 patients diagnosed with ectopic pregnancy and treated with single-dose MTX between July 1999 and November 2001 were reviewed retrospectively. RESULTS: The mean pre-treatment beta-hCG level was 2,490+/-2,912 mIU/ml. Twenty-two patients (73.3%) were successfully treated with a single-dose of MTX. Eight patients (26.6%) required a second dose 1 week after the first injection and 2 patients received three doses. Thirty of the 34 patients (88%) were successfully treated with MTX. The mean pre-treatment beta-hCG level was significantly lower in patients who were successfully treated with MTX than in patients who failed MTX therapy (1,932+/-2,361 mIU/ml vs. 6,955+/-2,690 mIU/ml respectively, p<0.05). The mean pre-treatment serum beta-hCG level was higher in patients who had a second MTX injection as compared to patients who were successfully treated with a single injection of MTX (3,272+/-3,551 mIU/ml vs. 1,280+/-2,273 mIU/ml respectively, p>0.05). The mean time to resolution of beta-hCG was 26.5 days (10 to 37 days) with MTX. All 3 patients who failed medical therapy had beta-hCG level >4,000 mIU/ml and 2 of them had positive fetal cardiac activity. CONCLUSION: In conclusion, this study showed that medical treatment of ectopic pregnancy with systemic single-dose methotrexate seems to be an option for some patients with unruptured tubal pregnancy.

Age-related changes in ovarian volume, antral follicle counts and basal FSH in women with normal reproductive health.

OBJECTIVE: To investigate the relation between ultrasound-based ovarian volume and antral follicle counts and hormonal parameters of ovarian reserve in a group of women with normal reproductive health. STUDY DESIGN: Prospective study. One hundred eight women with at least one previous pregnancy reaching term were divided into three age groups (group 1 = 35-39 years, group 2 = 40-44 years, and group 3 = 45-50 years). Basal hormone measurements and transvaginal ultrasonography estimation of ovarian volume and follicle counts were performed in the early follicular phase (day 3) of the menstrual cycle. RESULTS: There were significant differences in FSH (P < .0001) and E2 (P < .002) levels when group I was compared to groups II and III. There was a significant decrease in mean follicle counts (MFC) between groups I and III (P < .05). The decrease in mean ovarian volume (MOV) with age was not statistically significant. Age strongly correlated with MFC (r = -.38, P < .001) and weakly with MOV (r = -.29, P < .05). However, basal FSH correlated positively with age (r = .50, P < .001) and negatively with MOV (r = -.590, P < .001) and MFC (r = -.658, P < .001). Basal E2 correlated with MOV (r = .50, P < .001) and MFC (r = .50, P < .001). There was also a strong positive correlation between MFC and MOV (r = .777, P < .001). CONCLUSION: There was a decrease in MOV and MFC with aging coincident with increasing basal FSH levels after age 35 in women with normal reproductive health.