Endometrial sampling during sonohysterography (SHGes) in the management of abnormal uterine bleeding

Endometrial sampling during sonohysterography (SHGes) in the management of abnormal uterine bleeding

Materials/Methods: Lesions resected from women participating in an IRB- approved clinical trial of a new treatment for endometriosis were formalin fix...

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Materials/Methods: Lesions resected from women participating in an IRB- approved clinical trial of a new treatment for endometriosis were formalin fixed, paraffin embedded, cut and evaluated by H&E staining. We evaluated CD10 IHC in 22 women [aged 20 – 45 years (38 ⫾ 8 years: means ⫾ SD)] with 44 lesions that were negative and 32 that were positive on H&E. We included a disproportionately higher number of negative specimens to test whether CD10 might improve diagnostic sensitivity. CD10 IHC was performed on paraffin-fixed sections using a monoclonal anti-CD10 (Novacastra, clone 56C6) at 1:20 dilution, with a streptavidinbased detection system (Ventana). For each woman, an endometrial biopsy obtained at the same surgery served as a positive control. When CD10 IHC was positive, a pathologist examined the corresponding H&E staining to determine if the initial diagnosis was correct. We used Fishers exact test with Statview software to compare the number of lesions considered positive for endometriosis by each method. Two-tailed p ⬍0.05 was considered significant. Sample size was determined by study interval and sample availability, and not by power analysis. Results: The addition of CD10 IHC detected more positive endometriosis lesions than H&E staining alone (54% vs 42%, p ⬍0.0001). Of 44 specimens judged negative by H&E staining, CD10 staining was diagnostic of endometriosis in 9 and suggestive in 3 cases that could not be confirmed because of the presence of inflammation. CD10 and H&E staining were concordant in the remaining 32 negative and 32 positive specimens. CD10 was present in the stroma of all endometrial biopsies. 16 women had a pathologic diagnosis of endometriosis by H&E staining. The stage of disease by inspection at surgery was minimal (n ⫽ 10), mild (n ⫽ 4), moderate (n⫽1) and severe (n ⫽ 2) using the revised ASRM (American Society of Reproductive Medicine) classification. (One woman had two procedures.) Six women with negative H&E results had no (n ⫽ 2) or minimal (n ⫽ 4) endometriosis at surgery; two of those with minimal disease had positive CD10 IHC. Conclusions: This study shows that the adjunctive use of CD10 improves diagnostic sensitivity compared to H&E alone. However, since the positive diagnoses from H&E staining were unchanged, perhaps CD10 should be used only to verify negative results, so as to minimize additional expense. In this setting it may improve diagnostic accuracy for women with minimal endometriosis, which is essential for determining proper treatment. Supported by: Division of Intramural Research, NICHD, NIH.

IMAGING IN REPRODUCTIVE MEDICINE SPECIAL INTEREST GROUP Wednesday, October 16, 2002 2:00 P.M. O-235 The antral follicle count (AFC) correlates with metaphase II oocytes and ART cycle outcome: An update. Jeffrey D. Fisch, G. Sher. Sher Institute for Reproductive Medicine, Las Vegas, NV; Sher Institute for Reproductive Medicine, and Dept of Ob/Gyn, Univ of Nevada Sch of Medicine, Las Vegas, NV. Objective: We reported the antral follicles count (AFC) correlated with Metaphase II (MII) oocytes obtained in that cycle among an initial cohort of 80 patients. Since then, we have accumulated data on an additional 120 patients. This update correlated the AFC with MII oocytes recovered in that cycle and with the cycle outcome among a large cohort. Design: Prospective, observational study in a private practice setting. Materials/Methods: Infertile couples undergoing treatment with ART (n ⫽ 200) had a baseline ultrasound evaluation prior to ovarian stimulation to exclude cyst formation. Recombinant gonadotropins were used for ovarian stimulation after pituitary desensitization with a GnRHa in a long protocol. Ovulation was triggered with hCG when 2 follicles measured ⱖ18mm in diameter and half the remainder were ⱖ15mm. Oocytes were recovered transvaginally under ultrasound guidance 34 –35 hours later. Antral follicles visualized at baseline evaluation were counted and correlated with the MII oocytes retrieved in that cycle using a Pearson coefficient. Differences in rates were analyzed using Chi-square tests. Significance was set at p ⬍0.5. Results: The mean patient age was 32 years (range: 19 – 44). Mean cycle day 3 FSH level was 6.8mIU/ml (range: 1.7–18). The number of antral follicles seen on baseline ultrasound (mean: 15; range: 4 –35) correlated

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Abstracts

strongly with the number of MII oocytes recovered in that cycle (mean: 14; range: 2– 47)(r ⫽ 0.80; p ⬍0.001), while other predictors of response to stimulation, (such as follicles number ⱖ15mm in diameter or peak Estradiol level), were less predictive of response. Overall pregnancy and implantation rates were 41% and 24%, respectively. Patients with an AFC ⱖ20 had significantly higher pregnancy and implantation rates (67% and 32%) than patients with an AFC ⬍10 (24% and 18%) or AFC⫽10 –19 (36 and 22%). Conclusions: Assessment of antral follicle number on baseline ultrasound prior to ovarian stimulation for ART is easy to perform and correlates well with the number of mature oocytes that will be recovered in that cycle. The AFC may be a better predictor of ovarian response than traditional indicators of ovarian reserve, and could be used alone or in conjunction with these parameters to titrate medication dosages, and determine the optimal number of embryos to transfer. Many factors influence pregnancy beyond the number of mature oocytes. However, routinely canceling “poor responders” cannot be recommended, since 24% of patients with an AFC ⬍10 developed an ongoing gestation. Supported by: None.

Wednesday, October 16, 2002 2:15 P.M. O-236 Transcervical tubal catheterization (TTC) is the treatment of choice for infertile women with proximal tubal obstruction: An experience with 1010 fallopian tubes. Ilan Tur-Kaspa, Oana Moscovici, Simon Meltzer, Ronit Peled, Jacob Rabinson, Shmuel Segal. IVF Unit, Dept of Ob/Gyn, Barzilai Medical Ctr, Ben-Gurion Univ, Ashkelon, Israel; Dept of Radiology, Barzilai Medical Ctr, Ben-Gurion Univ, Ashkelon, Israel; Epidemiology Research Institute, Barzilai Medical Ctr, Ben-Gurion Univ, Ashkelon, Israel; Dept of Ob/Gyn, Barzilai Medical Ctr, Ben-Gurion Univ, Ashkelon, Israel. Objective: To prospectively evaluate the impact of transcervical tubal catheterization (TTC) procedures, as new medical technology, on patient counseling and management, in a large cohort of infertile women with proximal tubal obstruction (PTO). Design: Prospective observational study. Materials/Methods: 625 infertile women with bilateral (61.6%) or unilateral (38.4%) PTO underwent TTC. Patients with 3.7 (1–22) years of primary (23%) or secondary (77%) infertility were referred from all over the country (the author, from the Barzilai Medical Center, performed the TTC procedures at the Barzilai, Sheba, and Assuta Medical Centers, Israel). TTC is an ambulatory procedure performed under fluoroscopic observation. A coaxial catheters system (Cook Ob/Gyn) was used to perform an hysterosalpingogram and selective salpingography, before and after tubal catheterization with a soft tip guide-wire. Results: In 86% of the patients, at least one obstructed fallopian tube was successfully recanalized by TTC. Out of 1010 proximally obstructed fallopian tubes, 82% were successfully recanalized. Five cases (0.8%) were treated later for suspected PID, while one of them conceived spontaneously the following month. Because of the TTC results, 86% of patients was recommended to try to conceive naturally. 330 consecutive patients were followed after the procedure, by a telephone questioner, for a follow-up of 1719 women’s months. They obtained a 41% of intrauterine pregnancy rate (with only 1.4% of ectopic pregnancy rate). The cumulative pregnancy rates were 71% for women aged 20 –29 years, 52% for age 30 –39, and 18.5% for women aged ⱖ40 (p ⫽ 0.03; p ⫽ 0.0002 for trend). Conclusions: TTC has a major impact on the management and counseling of infertile women with PTO. After TTC, 86% of patients are recommended to try to conceive naturally, instead of being referred for laparoscopy or ART. TTC is a safe and cost effective procedure. TTC should be recommended as first choice for further diagnosis and treatment to all infertile women with bilateral or unilateral PTO. Supported by: No support.

Wednesday, October 16, 2002 2:30 P.M. O-237 Endometrial sampling during sonohysterography (SHGes) in the management of abnormal uterine bleeding. Francesco Paolo Giuseppe Le-

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one, Chiara Lanzani, Enrico Ferrazzi. Dept Obstet & Gyn, DSC L Sacco, Univ of Milan, Milan, Italy. Objective: To assess the diagnostic accuracy of sonohysterography (SHG) and endometrial sampling during SHG (SHGes) compared to traditional hysteroscopy and biopsy. Design: Prospective pilot study. Materials/Methods: One hundred fifteen consecutive patients referred for abnormal uterine bleeding with inhomogeneous thickened endometrium at transvaginal sonography (TVS), and absence of focal endometrial lesions at SHG, were recruited for this study. SHG was performed with a 4.7 mm intrauterine catheter. In all patients an endometrial biopsy was performed by a 20ml syringe vacuum aspiration at the end of SHG (SHGes). Procedurerelated pain was assessed by a visual analogue scale. In all patients hysteroscopy (HYS) and hysteroscopic guided biopsy was performed. Results: Median age was 48 years (interquartile range 38 –54). At SHG and SHGes, no/mild, moderate, and severe pain was reported by 65%, 28% and 7% of patients, respectively. Endometrial sampling was inadequate in 11% of cases. Diagnostic accuracy of sonohysterography with endometrial sampling compared to the results of hysteroscopic guided biopsy is shown in table. Diagnostic accuracy of sonohysterography with endometrial sampling. Positive Negative Sensitivity Specificity predictive predictive (%) (%) value (%) value (%) Simple hyperplasia (# 77) Carcinoma (# 16)

97 94

91 99

92 94

97 99

Conclusions: Sonohysterography with endometrial sampling was a well tolerated, cost-effective and accurate procedure to investigate patients with sonographic inhomogeneous thickened endometrium, as adequate as hysteroscopy with endometrial biopsy. Supported by: None.

Wednesday, October 16, 2002 2:45 P.M. O-238 Are increased estradiol levels the only responsible factor of increased uterine perfusion in patients submitted to controlled ovarian hyperstimulation? The possible role of androgens. Silvia Ajossa, Stefano Guerriero, Anna Maria Paoletti, Roberta Bargellini, Marisa Orru, Gian Benedetto Melis. Dept Obstetrics and Gynecology-Univ of Cagliari, Cagliari, Italy. Objective: Controversial studies are present in the literature about the role of estradiol on uterine perfusion during controlled ovarian hyperstimulation (COH). As a matter of fact, while several authors found that during COH associated to IVF-ET the uterine perfusion was positively affected by estradiol (E2) secretion, other authors failed to find inverse correlation between uterine artery pulsatility index (PI)’s values and E2. The aim of this study was to explain these different results evaluating the changes in estradiol and androgen levels during COH and the possible correlation between uterine perfusion and hormonal pattern. Design: prospective study. Materials/Methods: Two groups of patients were considered: group 1 (n ⫽ 25), women that have to be submitted to COH associated with timed vaginal intercourse (TVI) in which we obtained “low-medium” COH (COH was induced by administration of rFSH with a starting dose of 300 UI. Profase was administered when E2 ranged from 500 to 1000 pg/ml and there were at least 2 follicles with a mean diameter ⬎14 mm); group 2 (n ⫽ 25), women that have to be submitted to COH associated with IFV-ET in which we obtained “high” ovarian COH (GnRH analogue was administered at 1st-3rd day of the cycle and rFSH when complete inhibition was obtained with a starting dose of 450 UI. Profase was administered when E2 ranged from 1000 to 2500 pg/ml and there were at least 4 follicles with a mean diameter ⬎17 mm). Transvaginal ultrasound, color Doppler evaluation of uterine artery and blood sample for E2, progesterone (P), total testosterone (tT), free Testosterone (fT), Androstenedione (A), 17alfa-hydroxyprogest-

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erone (17-OHP) and deydroepiandrosterone-sulfate (DHEAS) were obtained before treatment, after GnRH-analogue inhibition, and every other day during rFSH treatment. Results: Different levels of E2 were present in the two groups the day of hCG administration (1557.8⫹/⫺861.5 vs 611.1⫹/⫺595.2). In patients submitted to low-medium COH, plasma levels of fT,and E2, E2/fT ratio,and E2/tT ratio increased significantly during induction of COH while uterine artery PI’s values did not change significantly (2.37⫹/⫺0.7 vs 2.54⫹/ ⫺0.2). E2/tT and E2/fT ratios remained ⬍1 during treatment. No correlation was found between PI’value of uterine artery and any of the hormonal parameters considered. In patients submitted to high COH, plasma levels of tT,and E2, E2/fT ratio, and E2/tT ratio increased significantly during induction of COH while uterine artery PI’s values decreased significantly. E2/tT and E2/fT ratios became ⬎1 during treatment. Correlation was found between PI of uterine artery and E2 plasma levels (r ⫽ 0.27, p ⬍0.03), PI of uterine artery and E2/tT (r ⫽ 0.26, p ⬍0.05)and PI of uterine artery and E2/fT ratio (r ⫽ 0.31, p ⬍0.03). Conclusions: This study showed that during induction of COH the positive effect of E2 on uterine perfusion is initially counteracted by the negative effect of increased plasma levels of free and total testosterone. Only when the E2/tT and E2/fT ratios become ⬎1, uterine artery’s PI value decreases significantly and is strigthly correlated to E2 levels. Thus, this study seems to demonstrate the positive role of COH on uterine perfusion only when high levels of E2 are present. Supported by: None.

Wednesday, October 16, 2002 3:00 P.M. O-239 Implantation site assessment analyzed using 3-dimensional transvaginal ultrasonography: The embryo does not travel far. Lawrence Grunfeld, Benjamin Sandler, Tanmoy Mukherjee, Alan Barry Copperman. Reproductive Medicine Assoc of New York, New York, NY. Objective: To investigate the relationship between site of ovulation and laterality of implantation site using 3-Dimensional ultrasonography in singleton pregnancies. To utilize this information to further understand the mechanics of embryo entry and implantation site in the uterine cavity. Design: 3-Dimensional transvaginal ultrasonography (US) was performed at 5 weeks gestation in pregnancies occurring in women with a single corpus luteum. Materials/Methods: Ultrasound monitoring was performed on 16 women with spontaneous mono-ovulatory cycles or mono-ovulatory cycles resulting from administration of clomiphene citrate. The side of the ovary with a corpus luteum of pregnancy was documented. Subsequently, a 3-Dimensional study was performed with the Kretz Voluson 530D using a mechanized transvaginal probe. Surface rendering and power Doppler imaging were performed. All orthogonal plane images of implantation sites were reviewed by the same gynecologic sonologist, and assigned to one of four patterns: right, left, center, lower segment. Results: When ovulation occurred in the right ovary, 5 of 6 gestational sacs were located on the right wall; 1 of 6 was in the direct center. The 10 left sided ovulations resulted in 8 gestational sacs located in the left wall, 1 on the right side and 1 in the lower segment (in a pregnancy that subsequently miscarried). Of the 13 sacs with documented laterality of implantation, 12 occurred on the side of the uterus ipsilateral to the side of ovulation (X2 ⬍.05). Conclusions: Utilization of 3-Dimensional transvaginal sonography provides information about site of implantation. Implantation most often occurs on the uterine surface ipsilateral to the ovulating ovary. Site of implantation may be critical in select patients especially those who do not have perfectly normal uteri. In the majority of patients, the embryo does not appear to travel far from its entry point into the uterus. Supported by: Self-funded.

Wednesday, October 16, 2002 3:45 P.M. O-240 A prospective study to evaluate the efficacy of Three- and Two-Dimensional sonohysterography in women with intrauterine lesion. Camille

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