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Skin Vascular Reactivity in Women with Ovarian Hyperstimulation Syndrome
Objective: The role of different ER subtypes, ER-a and ER-b, in estrogen-dependent development, differentiation and growth of endometrium throughout the menstrual cycle and early pregnancy is still to be defined. In this study, we investigated the temporal and spatial expression of ER subtypes in human endometrium throughout the menstrual cycle. Design: The intracellular localization and intensity of ER-a and ER-b receptors were evaluated by immunohistochemistry using frozen sections. Materials and Methods: Endometrial tissue samples (n524) were obtained from cycling women undergoing hysterectomy for benign diseases. Days of the menstrual cycle phases were determined by menstrual history and endometrial histology. Samples were grouped according to menstrual cycle phases: early proliferative (days 1–5), mid-proliferative (days 6 –10), late proliferative (days 11–14), early secretory (days 15–18), mid-secretory (days 19 –23) and late secretory (days 24 –28). Immunohistochemical reactivity was evaluated in a semi-quantitative fashion using an H-score system incorporating both the intensity [0 (absent) to 4 (most intense)] and distribution of specific staining ER-a and ER-b antibodies preincubated with their corresponding antigen peptides were used as negative controls. Results: Throughout the menstrual cycle endometrial stromal and glandular cells expressed both ER subtypes in their cytoplasms and nuclei. Both ER subtypes showed stronger cytoplasmic staining in stromal and glandular cells during the early proliferative phase. As the cytoplasmic staining became less intense by late proliferative phase, there was a gradual increase in the nuclear staining for both ER subtypes. During the secretory phase, ER-a was immunolocalized mostly to the nuclei in the functional layer while its intensity declined markedly in the basal layer. On the other hand, ER-b immunoreactivity was mostly cytoplasmic in the functional layer, while it was mostly nuclear in the basal layer. Conclusion: Based on our findings, we speculate that ER-a and ER-b expression in various components of the endometrium is regulated differently. We observed an inverse correlation between the intensity of cytoplasmic and nuclear staining for both receptor subtypes irrespective of cycle stage. Better understanding of the regulation of ER subtypes may reveal their role in endometrial function.
P-153 Skin Vascular Reactivity in Women with Ovarian Hyperstimulation Syndrome. L. C. Foong, B. Bhagavath, J. Kumar. Department of Obstetrics and Gynecology, National University of Singapore, Singapore. Objectives: Although the majority of data suggest that an increase in capillary permeability is the crucial primary event in the development of severe ovarian hyperstimulation syndrome (OHSS), it has been suggested that this pathology may be secondary to peripheral arteriolar vasodilatation (Fertil. Steril. 1991;56:1077–1083). Capillaries are normally protected from the effects of arterial pressure by a pre-capillary vasoconstrictor response (Acta Physiol. Scand. 1976;97:447– 456). A failure of this protective mechanism may result in arteriolar vasodilatation and capillary damage. The objectives of this study are (1) to determine whether there are any differences in these vasoconstrictor responses between normal women and those with OHSS and (2) whether treatment of OHSS alters these responses. Design: Pregnant women who had used assisted reproductive techniques (ART) to achieve pregnancy were asked to participate in the study. Those that developed severe OHSS had skin vascular responses assessed before and after treatment for the condition. Those that did not develop OHSS were used as controls and studied twice, one week apart (control 1 and 2) under similar controlled conditions. Materials and Methods: Skin capillary blood flow over the ankle was measured under standardized conditions using a laser Doppler machine. The change in blood flow following a non-invasive vascular challenge was used as an index of the pre-capillary vasoconstrictor response and thus of vascular reactivity. The normal vasoconstrictor response to the challenge results in a reduction in blood flow, represented by a negative percentage change in blood flow. Results were analyzed using Wilcoxon or Mann Whitney U tests. Results: Thirteen women with OHSS and nine control women have been studied to date. Median (range) percentage changes in blood flow were significantly different after treatment in women with OHSS: pre-treatment: 238.4% (298.3 to 22.7), post-treatment: 264.5% (292.5 to 235.4) [p5 0.009]. In comparison, there were no differences between the two control studies: control 1: 275.1% (296.3 to 233.2), control 2: 281.3% (296.1 to 261.8). OHSS pre-treatment responses were significantly different from
FERTILITY & STERILITYt
control 2 (p50.003) but not from the control 1 group studies (p50.06). There were no differences between the OHSS post-treatment group and either of the control studies. Conclusion: Women with OHSS have an attenuation of vascular reactivity when compared to normal women. This abnormality returns to normal following treatment for the condition. Greater numbers are required to confirm and assess the significance of this finding and these studies are currently in progress.
P-154 Low-Dose Dexamethasone: An Alternative to the Treatment of Hyperandrogenic Infertility. K. Biberog˘lu, A. Erdem, M. Erdem, O. Karabacak, R. Gursoy. Department of Obstetrics and Gynecology, University Hospital of Gazi, Ankara, Turkey. Objective: To evaluate the influence of low-dose dexamethasone treatment solely or in combination with other ovulation induction agents on pregnancy rates in hyperandrogenic infertile women; also to correlate pregnancy rates with androgen levels before and after dexamethasone suppression. Design: A retrospective chart review of all individuals from 1991 to 1998 attending for infertility treatment at a private and university setup were performed. Data of one hundred eleven ovulatory or anovulatory hyperandrogenic infertile women excluding severe male factor infertility were evaluated. Materials and Methods: Suppression of androgen levels, pregnancy rate and time to pregnancy after 0.25 mg. of oral overnight dexamethasone with or without clomiphene citrate and/or gonadotropin were evaluated. Results: The age and the duration of infertility (mean 6 SD) for only dexamethasone and dexamethasone plus clomiphene citrate and/or gonadotropin treatment groups were 27.8 6 4.0 years, 5.9 6 4.3 years and 27.7 6 3.9 years, 5.6 6 3.9 years, respectively. Serum free testosterone (FT) levels were significantly suppressed fifteen days after dexamethasone suppression, in both groups. Serum FT levels (mean 6 SD) before and after dexamethasone therapy were 4.68 6 1.31 ng./ml. and 1.62 6 1.21 ng./ml., respectively, (p,0.001). The overall pregnancy rate was 43.2% (48 of 111 women) for a mean (6SD) duration of 6.47 (65.22) months of treatment. The pregnancy rates for only dexamethasone and dexamethasone plus clomiphene citrate and/or gonadotropin treatment groups were 34.5% and 51.8%, respectively. But, there was no statistically significant difference between the two groups with respect to pregnancy rates (p.0.05). Also, the mean time to pregnancy (8.1 months for only dexamethasone group vs. 11.5 months dexamethasone plus clomiphene citrate and/or gonadotropin group) were not statistically different between the two groups (p.0.05). For the entire group, the mean FT levels before and after dexamethasone suppression and the mean duration of treatment were not significantly different between pregnant and non-pregnant subjects. Although, the presence of other relative infertility factors (endometriosis, tubal/peritoneal, etc) besides hyperandrogenism has no negative impact on pregnancy rates (47.4% vs. 34.3%, p.0.05), male subfertility has a significant negative impact on outcome; 49.4% vs. 29.4% pregnancy rates, (p50.05). The age of woman and the duration of infertility are the most powerful demographic predictors of the outcome. Higher pregnancy rates were achieved when the age was younger and the duration of infertility was shorter (p,0.01). Conclusion: Low-dose dexamethasone without additional ovulatory agents is a reasonable alternative to the treatment of hyperandrogenic infertility, with comparable results without high medical costs and additional complications of hyperstimulation, multipl pregnancy and increased abortion.
P-155 Low-Dose Gonadotropins plus Intrauterine Insemination Treatment in Patients with Clomiphene Resistant Polycystic Ovary Syndrome. R. Pabuc¸cu, N. K. Duru, E. Orhon, T. Ku¨c¸u¨k, M. C. Yenen. GATA School of Medicine, Ankara, Turkey. Objectives: Ovulation induction (OI) with gonadotropins is widely accepted as the second-line treatment in clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). Low-dose step-up regimen was suggested to have comparable pregnancy rates (PR) with minimal risk of multiple pregnancy and ovarian hyperstimulation syndrome. This study was designed to determine the effect of intrauterine insemination (IUI) added to low-dose gonadotropins in patients with CC-resistant PCOS.
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P-153 Skin Vascular Reactivity in Women with Ovarian Hyperstimulation Syndrome. L. C. Foong, B. Bhagavath, J. Kumar. Department of Obstetrics and Gynecology, National University of Singapore, Singapore. Objectives: Although the majority of data suggest that an increase in capillary permeability is the crucial primary event in the development of severe ovarian hyperstimulation syndrome (OHSS), it has been suggested that this pathology may be secondary to peripheral arteriolar vasodilatation (Fertil. Steril. 1991;56:1077–1083). Capillaries are normally protected from the effects of arterial pressure by a pre-capillary vasoconstrictor response (Acta Physiol. Scand. 1976;97:447– 456). A failure of this protective mechanism may result in arteriolar vasodilatation and capillary damage. The objectives of this study are (1) to determine whether there are any differences in these vasoconstrictor responses between normal women and those with OHSS and (2) whether treatment of OHSS alters these responses. Design: Pregnant women who had used assisted reproductive techniques (ART) to achieve pregnancy were asked to participate in the study. Those that developed severe OHSS had skin vascular responses assessed before and after treatment for the condition. Those that did not develop OHSS were used as controls and studied twice, one week apart (control 1 and 2) under similar controlled conditions. Materials and Methods: Skin capillary blood flow over the ankle was measured under standardized conditions using a laser Doppler machine. The change in blood flow following a non-invasive vascular challenge was used as an index of the pre-capillary vasoconstrictor response and thus of vascular reactivity. The normal vasoconstrictor response to the challenge results in a reduction in blood flow, represented by a negative percentage change in blood flow. Results were analyzed using Wilcoxon or Mann Whitney U tests. Results: Thirteen women with OHSS and nine control women have been studied to date. Median (range) percentage changes in blood flow were significantly different after treatment in women with OHSS: pre-treatment: 238.4% (298.3 to 22.7), post-treatment: 264.5% (292.5 to 235.4) [p5 0.009]. In comparison, there were no differences between the two control studies: control 1: 275.1% (296.3 to 233.2), control 2: 281.3% (296.1 to 261.8). OHSS pre-treatment responses were significantly different from
FERTILITY & STERILITYt
control 2 (p50.003) but not from the control 1 group studies (p50.06). There were no differences between the OHSS post-treatment group and either of the control studies. Conclusion: Women with OHSS have an attenuation of vascular reactivity when compared to normal women. This abnormality returns to normal following treatment for the condition. Greater numbers are required to confirm and assess the significance of this finding and these studies are currently in progress.
P-154 Low-Dose Dexamethasone: An Alternative to the Treatment of Hyperandrogenic Infertility. K. Biberog˘lu, A. Erdem, M. Erdem, O. Karabacak, R. Gursoy. Department of Obstetrics and Gynecology, University Hospital of Gazi, Ankara, Turkey. Objective: To evaluate the influence of low-dose dexamethasone treatment solely or in combination with other ovulation induction agents on pregnancy rates in hyperandrogenic infertile women; also to correlate pregnancy rates with androgen levels before and after dexamethasone suppression. Design: A retrospective chart review of all individuals from 1991 to 1998 attending for infertility treatment at a private and university setup were performed. Data of one hundred eleven ovulatory or anovulatory hyperandrogenic infertile women excluding severe male factor infertility were evaluated. Materials and Methods: Suppression of androgen levels, pregnancy rate and time to pregnancy after 0.25 mg. of oral overnight dexamethasone with or without clomiphene citrate and/or gonadotropin were evaluated. Results: The age and the duration of infertility (mean 6 SD) for only dexamethasone and dexamethasone plus clomiphene citrate and/or gonadotropin treatment groups were 27.8 6 4.0 years, 5.9 6 4.3 years and 27.7 6 3.9 years, 5.6 6 3.9 years, respectively. Serum free testosterone (FT) levels were significantly suppressed fifteen days after dexamethasone suppression, in both groups. Serum FT levels (mean 6 SD) before and after dexamethasone therapy were 4.68 6 1.31 ng./ml. and 1.62 6 1.21 ng./ml., respectively, (p,0.001). The overall pregnancy rate was 43.2% (48 of 111 women) for a mean (6SD) duration of 6.47 (65.22) months of treatment. The pregnancy rates for only dexamethasone and dexamethasone plus clomiphene citrate and/or gonadotropin treatment groups were 34.5% and 51.8%, respectively. But, there was no statistically significant difference between the two groups with respect to pregnancy rates (p.0.05). Also, the mean time to pregnancy (8.1 months for only dexamethasone group vs. 11.5 months dexamethasone plus clomiphene citrate and/or gonadotropin group) were not statistically different between the two groups (p.0.05). For the entire group, the mean FT levels before and after dexamethasone suppression and the mean duration of treatment were not significantly different between pregnant and non-pregnant subjects. Although, the presence of other relative infertility factors (endometriosis, tubal/peritoneal, etc) besides hyperandrogenism has no negative impact on pregnancy rates (47.4% vs. 34.3%, p.0.05), male subfertility has a significant negative impact on outcome; 49.4% vs. 29.4% pregnancy rates, (p50.05). The age of woman and the duration of infertility are the most powerful demographic predictors of the outcome. Higher pregnancy rates were achieved when the age was younger and the duration of infertility was shorter (p,0.01). Conclusion: Low-dose dexamethasone without additional ovulatory agents is a reasonable alternative to the treatment of hyperandrogenic infertility, with comparable results without high medical costs and additional complications of hyperstimulation, multipl pregnancy and increased abortion.
P-155 Low-Dose Gonadotropins plus Intrauterine Insemination Treatment in Patients with Clomiphene Resistant Polycystic Ovary Syndrome. R. Pabuc¸cu, N. K. Duru, E. Orhon, T. Ku¨c¸u¨k, M. C. Yenen. GATA School of Medicine, Ankara, Turkey. Objectives: Ovulation induction (OI) with gonadotropins is widely accepted as the second-line treatment in clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). Low-dose step-up regimen was suggested to have comparable pregnancy rates (PR) with minimal risk of multiple pregnancy and ovarian hyperstimulation syndrome. This study was designed to determine the effect of intrauterine insemination (IUI) added to low-dose gonadotropins in patients with CC-resistant PCOS.
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