Altered uterine artery blood flow impedance after danazol therapy: possible mode of action in dysfunctional uterine bleeding.

OBJECTIVE: To test the hypothesis that danazol increases the impedance to uterine circulation and hence reduces the effective uterine blood flow after a predetermined period of therapy. DESIGN: Prospective, longitudinal study. SETTING: Reproductive medicine unit of a university teaching hospital. PATIENT(S): Eight premenopausal women with dysfunctional uterine bleeding. INTERVENTION(S): Six weeks of danazol therapy. MAIN OUTCOME MEASURE(S): The uterine artery blood flow impedance as indicated by the pulsatility and resistance indices; the hormonal profile (E2, FSH, and LH levels); the uterine dimensions (length, width, anteroposterior diameter, and area); and the endometrial thickness. RESULT(S): The indices of uterine artery impedance were significantly increased after danazol therapy, indicating a possible reduction in the effective uterine artery blood flow. There was no statistically significant change in the hormonal profile, uterine dimensions, or endometrial thickness. CONCLUSION(S): Danazol therapy for 6 weeks results in a significant increase in the uterine artery impedance and hence a possible reduction in the effective uterine artery blood flow. This may explain in part its efficacy in the management of dysfunctional uterine bleeding and in the preoperative preparation of women undergoing endoscopic endometrial ablation. The exact mechanism for its action in this regard remains to be determined but appears to be independent of E2 levels. This preliminary finding may help in monitoring the treatment of dysfunctional uterine bleeding, preoperative and postoperative investigation of women undergoing endoscopic endometrial ablation, and the development of alternative treatment strategies for dysfunctional uterine bleeding in the future.

Indices of differential endometrial: myometrial growth may be used to improve the reliability of detecting endometrial neoplasia in women on tamoxifen.

The aim of this study was to test the hypothesis that the use of indices of differential endometrial: myometrial growth may be a non-invasive method of improving the reliability of detecting endometrial neoplasia in women on tamoxifen. Thirty postmenopausal women were involved in this prospective study. Nineteen had been treated with tamoxifen for 2 years or more, and eleven were age- and ponderal index-matched controls who had never been exposed to tamoxifen and who were non-smokers. Transvaginal ultrasonography and color Doppler imaging were performed, to measure the length, anteroposterior diameter, uterine sagittal area, endometrial thickness and uterine blood flow (using the pulsatility index and the resistance index as measures of uterine blood flow impedance). The anteroposterior diameter: endometrial thickness ratio and product, and the saggital area: endometrial thickness ratio and product were used as indices of differential endometrial: myometrial growth. The predictive values (sensitivity, specificity, positive and negative predictive values) of each index were calculated using established criteria. For the purpose of analysis the women were allocated to three groups: controls (group 1); women on tamoxifen without endometrial neoplasia (group 2) and women on tamoxifen who developed endometrial neoplasia (group 3). The mean age was similar in the three groups as was the duration of tamoxifen treatment in groups 2 and 3. Analysis of the decision matrix based on increased endometrial thickness (> 5 mm) alone revealed good sensitivity (100%) and negative predictive value (100%) but poor specificity (46.15%) and positive predictive value (26.32%). However, when the indices of differential endometrial: myometrial growth were taken into consideration, the sensitivities and negative predictive values were similar but the specificities and positive predictive values were significantly improved, indicating an improvement in the reliability of predicting the development of endometrial neoplasia.

Intrafollicular hemodynamics before the administration of human chorionic gonadotropin in women at risk of the ovarian hyperstimulation syndrome.

OBJECTIVE: To test the hypothesis that alteration of intrafollicular hemodynamics precedes the ovarian hyperstimulation syndrome (OHSS). DESIGN: A prospective study. SETTING: The IVF unit and the Doppler imaging laboratory of King's College Hospital, London. PATIENTS: Twenty-four women undergoing IVF and considered to have an exaggerated response to ovarian stimulation and hence at risk of OHSS. INTERVENTIONS: Transvaginal Doppler imaging of the intrafollicular blood flow was performed before hCG administration to determine the indexes of intrafollicular hemodynamics. MAIN OUTCOME MEASURES: Moderate or severe OHSS. RESULTS: There was no statistically significant difference in mean age (32.63 +/- 1.77 versus 31.48 +/- 3.87), duration of infertility (6.00 +/- 2.19 versus 5.29 +/- 2.73), maximum peak systolic velocity (0.25 +/- 0.16 versus 0.26 +/- 0.21 m/s), mean of six maximal peak systolic velocity (0.15 +/- 0.04 versus 0.21 +/- 0.10), minimum pulsatility index (0.76 +/- 0.26 versus 0.59 +/- 0.23), mean of six minimal pulsatility indexes (0.89 +/- 0.30 versus 0.79 +/- 0.14), minimum resistance index (0.47 +/- 0.06 versus 0.41 +/- 0.10), and mean of six minimal resistance indexes (0.56 +/- 0.05 versus 0.53 +/- 0.06) of intrafollicular blood flow between the women who developed moderate or severe OHSS and matched controls. CONCLUSION: Measurement of intrafollicular hemodynamics before hCG administration does not predict the development of the OHSS.

Prediction of oocyte recovery rate by transvaginal ultrasonography and color Doppler imaging before human chorionic gonadotropin administration in in vitro fertilization cycles.

OBJECTIVE: To detect and quantify follicular vascularity before hCG administration in women undergoing IVF-ET. To correlate follicular vascularity with the oocyte recovery rate after direct follicle aspiration. DESIGN: A prospective, longitudinal study of consecutive women undergoing IVF-ET at the assisted conception unit of King's College Hospital, London and having at least 20 follicles between the two ovaries on the day of hCG administration. INTERVENTIONS: An Acuson 128XP1O computed sonography system (Acuson Ltd., Uxbridge, United Kingdom) was used to measure follicular diameters, indices of blood flow impedance (pulsatility index), peak systolic velocities (Vmax), and the proportion of follicles demonstrating pulsatile vascularity, i.e., follicular vascularity index. For the purpose of analysis, each woman was classified into one of four groups (I to IV) based on their oocyte recovery rate. RESULTS: The mean age, duration of infertility, Dmax, pulsatility index, and Vmax were similar in the four groups, but the follicular vascularity index was higher in the groups with the highest oocyte recovery rates. Furthermore, there was a positive correlation between the follicular vascularity index and the oocyte recovery rate. CONCLUSION: The follicular vascularity index correlates positively with oocyte recovery rates. Detection and quantification of follicular vascularity with color Doppler imaging can therefore be used to predict oocyte recovery rate and hence may be useful in determining the most appropriate time to administer hCG to optimize oocyte recovery rates.

Total ovarian volume before human chorionic gonadotrophin administration for ovulation induction may predict the hyperstimulation syndrome.

Total ovarian volumes were measured before the administration of HCG in 42 women undergoing treatment for infertility by in-vitro fertilization (IVF) and embryo transfer and considered to have an exaggerated response to stimulation ( > 20 follicles). Seven women who subsequently developed moderate or severe ovarian hyperstimulation syndrome (OHSS) (n = 7; group 1) were compared with 35 matched controls (five matched controls per case; n = 35; group 2) of similar age, number of follicles and duration of infertility who underwent follicular stimulation, oocyte recovery, in-vitro fertilization and embryo transfer during the same period but did not develop moderate or severe OHSS. The mean age, duration of infertility and total number of follicles were similar but the mean total ovarian volume was significantly higher in the group of women who developed moderate or severe OHSS compared with controls (271.00 +/- 87.00 versus 157.30 +/- 54.20 ml; P < 0.01). We conclude that total ovarian volume measured before HCG administration is higher in women who develop moderate or severe OHSS compared with controls and may therefore be used as an additional parameter in the preventative strategy for the ovarian hyperstimulation syndrome.

Pituitary down-regulation prior to in-vitro fertilization and embryo transfer: a comparison between a single dose of Zoladex depot and multiple daily doses of Suprefact.

In order to further evaluate the endocrinological, embryological and clinical efficacy of a single injection of the gonadotrophin-releasing hormone (GnRH) analogue Zoladex (goserelin), 142 women underwent pituitary down-regulation prior to in-vitro fertilization and embryo transfer: 71 with a single injection of Zoladex depot (group I) and 71 matched controls with multiple daily injections of Suprefact (buserelin; group II). Ovarian stimulation was performed with human menopausal gonadotrophin (HMG) and ovulation induction with human chorionic gonadotrophin (HCG). HMG and hydroxyprogesterone caproate depot were given for luteal phase support. The mean (+/- SD) age (34.01 +/- 4.42 versus 34.81 +/- 4.00 years), mean total dosage of HMG (61.25 +/- 26.87 versus 56.17 +/- 25.18 ampoules), mean daily dosage of HMG (4.74 versus 4.94 ampoules), duration of HMG stimulation (12.91 +/- 3.68 versus 11.31 +/- 3.46 days) and oestradiol concentration on the day of HCG (10,082 +/- 8007 versus 9440 +/- 7840 pmol/l) were similar in both groups but the mean total number of injections (GnRH and HMG) (13.55 +/- 3.35 versus 55.37 +/- 31.92) was significantly lower in group I. Furthermore, the proportion of women down-regulated by 2 weeks and pregnancy rate per embryo transfer were significantly higher in the Zoladex group, while miscarriage rates were similar. We conclude that a single dose of Zoladex is quicker, more convenient and should be investigated as an equally effective alternative to multiple doses of Suprefact for pituitary down-regulation prior to assisted conception. Further studies are required to test the teratogenicity and effectiveness of Zoladex.

A comparison between loop diathermy conization and cold-knife conization for management of cervical dysplasia associated with unsatisfactory colposcopy.

Eighty-six women with cervical dysplasia and unsatisfactory colposcopy were managed with excisional conization--43 with outpatient loop diathermy conization under local anesthesia and 43 matched controls with cold-knife conization as inpatients under general anesthesia. Both groups were similar in terms of age, parity, and severity of dyskaryosis on initial cytology, treatment success rates, and completeness of excision. However, loop diathermy conization was significantly quicker (2.8 +/- 2.9 min vs 14 +/- 18.6 min) and associated with less intraoperative blood loss (3.3 +/- 2.8 ml vs 79.1 +/- 74.6 ml) (P < 0.01) than cold-knife conization. Furthermore, the proportion of women with at least one complication was significantly less following loop (4.7%) than cold-knife conization (20.9%) (P < 0.05). We conclude that outpatient loop diathermy conization performed under local anesthesia is quicker and causes less intraoperative blood loss and immediate postoperative complications than cold-knife conization for management of cervical dysplasia associated with unsatisfactory colposcopy.

Outpatient excisional management of cervical intraepithelial neoplasia. A prospective, randomized comparison between loop diathermy excision and laser excisional conization.

OBJECTIVE: The purpose of our study was to compare loop diathermy excision and laser excisional conization with respect to treatment time, reliability, effectiveness, and safety. STUDY DESIGN: Three hundred women with cervical intraepithelial neoplasia attending our colposcopy clinic were randomized to treatment with either loop diathermy excision (group 1, n = 150) or carbon dioxide laser excisional conization (group 2, n = 150), both performed with local anesthesia on an outpatient basis. Student's t or Mann-Whitney test were used to compare continuous data; the chi 2 test was used for categoric data. RESULTS: The mean age, parity, histologic features, depth of excision, and occurrence of residual or recurrent disease were similar; however, the mean time required to complete treatment and hemostasis (2.5 +/- 3.6 vs 24.2 +/- 11.8 min), patient discomfort, blood loss (2.77 +/- 3.76 vs 27.15 +/- 17.51 ml; p < 0.001), and considerable thermal artifact affecting histologic interpretation of excision margins (5 cases vs 25 cases; p < 0.01) were significantly less in group 1 than in group 2. CONCLUSION: In our experience outpatient loop diathermy excision is an equally effective, quicker, safer, and more reliable excisional technique than laser excisional conization.

Outcome of cryopreservation and subsequent programmed replacement of frozen-thawed embryos in an in vitro fertilisation programme: preliminary report and proposals for improvement.

In order to prevent wastage of good quality embryos and limit the number transferred in fresh in vitro fertilisation (IVF) cycles, 577 supernumerary embryos were cryopreserved for a mean duration of 6.23 +/- 4.7 months (range 1-24). Four hundred and twenty-two have been thawed so far of which 81 (19.19%) were totally lysed, 317 (75.12%) survived with at least 50% of their blastomeres intact and 180 (42.65%) cleaved. Two hundred and sixteen frozen-thawed embryos have been transferred in 62 stimulated and 11 natural cycles involving 61 patients. The mean number of embryos transferred per cycle was 2.96 +/- 0.86. Twenty-one pregnancies resulted from the 62 stimulated cycles (33.87%). No pregnancy occurred in the 11 natural cycles. Overall pregnancy rate was therefore 28.77%. Eleven singletons (eight male; three female) and one set of twins (one male one female) have so far been delivered in good condition:- six (54.5%) by caesarean section, five (45.5%) vaginally, including one by Neville Barnes forceps, one ventouse and the rest were spontaneous. Presentation was cephalic in 10 (91%) and breech in one case (9%). All were delivered at term except one premature (9%). Mean birth weight was 3.23 +/- 0.32 kg for singletons and 2.7 kg for the twins. Despite the diversity of racial, cultural and religious differences in our multinational patient population, we found embryo cryopreservation following IVF generally acceptable and our preliminary results are quite encouraging. Strategies for improving the outcome of future cycles are proposed.