P-889: Adipocytokine expression in subcutaneous and visceral fat in ...

P-888 A HOMEOSTASIS MODEL ASSESSMENT (HOMA) CUT-OFF VALUE OF 1.7 IS USEFUL FOR SELECTING WOMEN THAT WILL RESPOND TO TREATMENT WITH METFORMIN IN A LATIN AMERICAN PCOS POPULATION. L. A. Sanchez, I. Centeno, M. Pe´rez, F. Ablan, D. Torassa, I. Campos. Caracas Fertility Center, Caracas, Venezuela; Clinica el Avila, Caracas, Venezuela; Hospital Vargas, Caracas, Venezuela. CONCLUSION: Although intensive diet and exercise involve a significant time commitment on the part of PCOS patients, even short-term participation over 5-7 wks produced significant improvements in anthropometric, nutritional, fitness, and reproductive outcomes. This pilot program is unique in its close supervision of patients, supportive environment exclusively for participants, and its carefully coordinated multidisciplinary approach. Further, the results show that favorable outcomes can be achieved in a community setting. Supported by: None

P-887 C-REACTIVE PROTEIN, BUT NOT TRIGLYCERIDE/HDL RATIO, CORRELATES WITH BODY MASS INDEX AND HOMEOSTATIC MARKERS OF INSULIN SENSITIVITY IN WOMEN WITH POLYCYSTIC OVARIAN SYNDROME (PCOS). M. Lydic. SUNY-Stony Brook, Stony Brook, NY. OBJECTIVE: Triglyceride/HDL cholesterol ratio has been described by McLaughlin et al.(Am J Cardiol. 2005 Aug 1;96(3):399-404) as a reliable predictor of Metabolic Syndrome diagnosed by NCEP/ATP III criteria. The objective of this study was to ascertain the relationships between triglyceride/HDL ratio and insulin sensitivity (by HOMA-IR), serum testosterone, body mass index (BMI), and other markers associated with cardiovascular disease in PCOS women. DESIGN: Retrospective chart review of patients from a university academic practice. MATERIALS AND METHODS: This study was approved by the investigational review board of SUNY-Stony Brook. Charts were reviewed of PCOS patients from the practice of the Division of Reproductive Endocrinology and Infertility at SUNY-Stony Brook. All PCOS subjects, ages 18-42 years, were diagnosed according to the ASRM/ESHRE Rotterdam criteria (2003). Data were collected for height and weight, lipid profile, fasting glucose and insulin, FSH, LH, C-reactive protein, homocysteine, AST, ALT,and androgens. Calculations for HOMA-IR, BMI, LH/FSH ratio,and triglyceride/HDL ratio were made. Data were statistically analyzed by descriptive statistics and Pearsson correlation using SPSS v 11.5 for Windows. Statistical significance was defined as P⬍ 0.5. RESULTS: Fifty two PCOS patient charts were reviewed and 12 were excluded due to incomplete data. Forty patients were included in the study. The mean ⫾ SE triglyceride/HDL ratio was 3.1 ⫾ 0.4 (range 0.4-12.8), and the mean BMI was 34.4 ⫾ 1.1 (range 21.9-48.0).The mean C-reactive protein was 1.1 ⫾ 0.3 mg/dL (range 0.1-6.6). Mean homocysteine was 6.3 ⫾ 0.3 ␮mol/L (range 3.4-10.3). Mean HOMA-IR was 3.7 ⫾ 0.5 (range 0-21.5), and mean total testosterone was 45.8 ⫾ 4.3 ng/dL(range 14-98). Mean FSH was 5.0 ⫾ 0.3 IU/L, and mean LH was 10.5 ⫾ 1.4 IU/L. Mean LH/FSH ratio was 2.1 ⫾ 0.3. There were no statistically significant correlations between triglyceride/HDL ratio and any other parameter. However, C-reactive protein significantly correlated with HOMA-IR (r ⫽ 0.45, P ⫽ 0.016) and BMI (r ⫽ 0.546, P ⫽ 0.004) by Pearrson correlation. No significant correlation existed between BMI and HOMA-IR. CONCLUSION: Triglyceride/HDL ratio does not significantly correlate with any of the common markers of insulin sensitivity or predictors of cardiovascular risk in PCOS subjects. Elevated triglyceride and low HDL are individual criteria of the Metabolic Syndrome and may not all be present in reproductive age women with PCOS until many years later after prolonged insulin resistance. However, C-reactive protein has a significant correlation with insulin sensitivity and BMI. Therefore, C-reactive protein may be more useful than triglyceride/HDL ratio in predicting risk of cardiovascular disease and metabolic syndrome in reproductive age women with PCOS. Further study with larger subject numbers is most desireable. Supported by: None

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Abstracts

OBJECTIVE: To determine a level of insulin sensitivity as evaluated by HOMA model that may be useful in selecting women with PCOS who will respond to treatment with metformin. DESIGN: Prospective descriptive clinical trial. MATERIALS AND METHODS: Thirty three (33) consecutive subjects with diagnosis of PCOS were prospectively assigned to receive treatment with metformin for 12 weeks. All patients had, at least, 12 weeks without any hormonal treatment and normal levels of thyroid-stimulating hormone, and prolactin before entering the study protocol. The diagnosis of PCOS was established by the exclusion of other conditions that can cause chronic anovulation with associated hyperandrogenism: 21-OH-deficient-non classic adrenal hyperplasia, ovarian-adrenal tumors, and Cushing’s syndrome. A detailed physical examination was performed and registered at basal conditions and at the end of study period. Measured laboratory parameters included fasting glucose and insulin, plasminogen activator inhibitor 1 (PAI-1), area under the curve for glucose (AUCG) and insulin (AUCI). Serum samples for measuring androgens were also collected prior to and at week 12 of treatment, and were frozen at -20 °C. Statistical analysis was performed using KwikStat-4 Statistical Data Analysis Program (TexaSoft, Cedar Hill, TX). RESULTS: A total of 22 subjects completed the study. Subjects demonstrating an improvement in insulin sensitivity after treatment with metformin were classified as responders as oppose to non responders who had not improvement in insulin sensitivity. Responders had a mean HOMA initial value of 3.74 vs 1.74 in non reponders (P ⫽ 0.05). A cut-off HOMA initial value of 1.7 demonstrated to be useful in selecting patients who will respond to treatment with metformin. A total of 77% of women with HOMA initial value equal or above 1.7 responded to metformin treatment with an improvement in insulin sensitivity; alternatively, only 33% of those patients with initial values below 1.7 demonstrated an increased in insulin sensitivity (P ⫽ 0.04). There was an improvement of 25% in mean insulin sensitivity in those patients with HOMA values equal or above 1.7. This was significantly different from the group with values below 1.7 who had a decreased of 18% in mean insulin sensitivity in spite of treatment with metformin.Compared to subjects with HOMA below 1.7, those with HOMA equal or above 1.7 were significantly older (27 yrs vs 23.33 yrs) and had significantly higher values of BMI (30.13 Kg/m2 vs 22.89 Kg/m2), W/H ratio (0.84 vs 0.78), PAI (15.42 ng/mL vs 9.64 ng/mL), AUCG (12734 vs 10338), and AUCI (10348 vs 3693). There was a significant decrease in levels of DHEAS and menstrual cycle length in the group above 1.7 after treatment with metformin. The W/H ratio was the only parameter which improved in subject with HOMA below 1.7 after the treatment period. CONCLUSION: In this population of Latin American PCOS women, different levels of insulin resistance have been demonstrated. Additionally, we demonstrated that a cut-off HOMA level of 1.7 is useful for selecting PCOS women who may respond to treatment with metformin. Additional studies to confirm our findings are needed. Supported by: Institutional Financial Support

P-889 ADIPOCYTOKINE EXPRESSION IN SUBCUTANEOUS AND VISCERAL FAT IN WOMEN WITH POLYCYSTIC OVARY SYNDROME (PCOS) AND IN OVULATORY CONTROLS: RELATIONSHIPS TO SERUM LEVELS AND MARKERS OF INSULIN RESISTANCE. M. C. Chu, D. Tortoriello, P. Vardhana, C. Moran, E. Carmina, R. A. Lobo. North Shore Univ Hospital, Manhasset, NY; Columbia Univ, New York, NY; Mexican Institute of Social Security, Mexico City, Mexico.

Vol. 86, Suppl 2, September 2006

OBJECTIVE: Polycystic ovary syndrome (PCOS) is an extremely prevalent disorder in which elevated blood markers of cardiovascular risk, including insulin resistance (IR) and adipocytokines, have been found. Since obesity is closely linked to IR, this study was designed to determine if direct adipose expression of adipocytokines may be more reflective of IR than traditional parameters. DESIGN: A prospective study of fourteen young women with PCOS (age: 28.9 ⫾ 1.2, body mass index [BMI]: 34.3 ⫾ 3.0), 6 matched ovulatory controls (age: 37.5 ⫾ 1.9, BMI: 33.8 ⫾ 4.8), and 7 lean ovulatory controls (age: 32.6 ⫾ 2.1, BMI: 22 ⫾ 0.5) was performed. MATERIALS AND METHODS: Subcutaneous and omental fat samples were obtained for RNA extraction. Expression of adiponectin, leptin and TNF␣ were determined by real-time PCR. Blood was obtained for measures of fasting glucose, insulin, adiponectin, and leptin. Traditional indices of insulin sensitivity, homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI), were calculated based on fasting glucose and insulin values. In women with PCOS, transabdominal ultrasound determination of visceral and subcutaneous fat was performed. RESULTS: Compared to both lean and obese controls, women with PCOS had increased HOMA (p ⬍ 0.05) and decreased QUICKI (p ⬍ 0.05). As shown previously, serum adiponectin levels in PCOS were lower (9.0 ⫾ 4.4 ␮g/ml) and leptin levels were higher (123.8 ⫾ 34.2 ng/ml). In subcutaneous tissue, leptin expression was .82 ⫾ .16 (range 0.15 to 1.90) in PCOS, compared to 440.06 ⫾ 328.97 (range 0.28 to 2369.23) in controls, and adiponectin expression was 1.69 ⫾ 0.28 (range 0.44 to 2.97) in PCOS, compared to 468.44 ⫾ 187.44 (range 0.26 to 1100.02) in controls. In omental tissue, leptin expression was 1.86 ⫾ 0.14 (range 0.24 to 6.29) in PCOS, compared with 2.78 ⫾ 1.03 (range 0.24 to 5.85), and adiponectin expression was 3.35 ⫾ 0.99 (range 0.28 to 11.94) in PCOS, compared with 10.56 ⫾ 10.51 (range 0.01 to 31.57). Overall, leptin and adiponectin expression was higher in subcutaneous tissue than in omentum. Also there was a trend for lower expression of these adipocytokines in PCOS fat compared to control fat. There was a poor correlation between adipose tissue expression and blood levels in PCOS. Serum leptin in PCOS correlated with BMI (r ⫽ 0.66, p ⬍ 0.05) and subcutaneous fat mass (r ⫽ 0.74, p ⬍ 0.01). There were no significant correlations between serum levels or fat expression of adipocytokines and markers of IR. There was no correlation between adiponectin and leptin. CONCLUSION: These data suggest that expression of adipocytokines is higher in subcutaneous than in omental fat. In PCOS, fat expression of adiponectin and leptin appears to be lower compared to controls, while there is poor correlation between tissue expression and blood levels. Although there was a lack of significant correlation between leptin and adiponectin production and markers of IR, the correlation of serum leptin with body fat and the altered expression of adipocytokines in subcutaneous and visceral fat in PCOS suggest that adipose tissue expression of adipocytokines, although possibly perturbed, may be an important determinant of IR in PCOS. Supported by: None.

P-890 THE USE OF BIOCHEMICAL AND HORMONAL FACTORS AS PREDICTIVE FACTORS FOR PREGNANCY OUTCOME OF INFERTILE PATIENTS WITH POLYCYSTIC OVARIAN SYNDROME (PCOS) UNDERGOING INVITRO FERTILIZATION (IVF). F. Kwarteng, O. Adeyiga, B. Ahluwalia, P. Asmar, D. Broomfield. Howard Univ Hospital, Washington, DC; Washington Fertility Center, Annandale, VA. OBJECTIVE: To determine if Biochemical and Hormonal Factors can be use as Predictive Factors for Pregnancy Outcome of Infertile Patients with Polycystic Ovarian Syndrome ( PCOS) Undergoing In Vitro Fertilization (IVF). DESIGN: Retrospective Study MATERIALS AND METHODS: Chart review from January 2004 to December 2005 (2 years), of 33 patients age 26-40 with a history of primary infertility who were diagnosed with PCOS by WHO criteria. All IVF patients were treated with metformin for minimum period of 6 weeks followed by gonadotropin injections for an average number of 10 days. Baseline serum levels of estradiol (E2), Luteinizing Hormone (LH), Follic-

FERTILITY & STERILITY威

ular Stimulating Hormone (FSH), Testosterone, Dihydroepiandrosterone sulfate (DHEAS), Insulin, and Glucose were obtained before administration of metformin. Body Mass Index (BMI) was also measured. RESULTS: Pregnancy rates were greatest in patients with normal insulin levels, specifically less than 12 (p⬍0.005). Although insulin levels between 12 and 17 are within normal limits, there were no pregnancies achieved in patients with insulin levels ⬎ 15.5. Patients with serum testosterone levels ⬍ 40.0ng/dl had a higher pregnancy rate as compared to patients with testosterone levels above 40ng/dl. There were no pregnancies in patients with testosterone levels above 50ng/dl (p⬍ 0.003). Patients with BMI ⬍ 32kg/m2 had higher pregnancy rate of 56% (p⬍0.009). There were no pregnancies in patients with BMI above 37kg/m2. CONCLUSION: Pregnancy rates for patients with PCOS undergoing IVF were higher in patients with low serum insulin, glucose and testosterone levels as compared to those with elevated levels. Pregnancy outcome is not correlated with the quality or number of blastocyst transferred nor the dosage of gonadotropins in PCOS patients. Supported by: None

P-891 CLINICAL PROFILE OF INSULIN RESISTANT PCOS SUBJECTS. CHARACTERIZATION OF A LATIN AMERICAN POPULATION. L. A. Sanchez, I. Centeno, M. Perez, F. Ablan. Caracas Fertility Center, Caracas, Venezuela; Clinica el Avila, Caracas, Venezuela; Hospital Vargas, Caracas, Venezuela. OBJECTIVE: To determine the clinical and laboratory profile of those subjects having the more elevated levels of insulin resistance according to the homeostasis model assessment (HOMA) in a population of Latin American PCOS subjects. DESIGN: Prospective descriptive clinical trial. MATERIALS AND METHODS: Thirty three (33) consecutive subjects with diagnosis of PCOS were prospectively recruited. All patients had, at least, 12 weeks without any hormonal treatment and normal levels of thyroid-stimulating hormone, and prolactin before entering the study protocol. The diagnosis of PCOS was established by the exclusion of other conditions chronic anovulation with associated hyperandrogenism: 21-OHdeficient-non classic adrenal hyperplasia, ovarian-adrenal tumors, and Cushing’s syndrome. A detailed physical examination was performed and registered. We measured Body Mass Index (BMI), Ferriman Galwey score (FG), Waist to Hip ratio (W/H), ovarian volume (OV) by ultrasound and menstrual cycle length. Additional laboratory assessment was obtained including fasting glucose and insulin, and plasminogen activator inhibitor 1 (PAI-1). Serum samples for measuring androgens at the end of recuitment period were also collected and were frozen at -20 °C. Statistical analysis was performed using KwikStat-4 Statistical Data Analysis Program (TexaSoft, Cedar Hill, TX). We did obtain a mean HOMA value for entire study population; we then classified those subjects having HOMA values above the mean as insulin resistant and those with HOMA values below the mean as non insulin resistant. RESULTS: A total of 24 subjects completed the clinical and laboratory protocol. The mean HOMA value for the entire study population was 2.43. Ten from 24 (41.6%) subjects had values higher than the general mean, and constituted the insulin resistant group. Mean age of insulin resistant group was higher compared to non insulin resistant subjects (28.8 vs 24.62) but without reaching statistical significance. Overall, the insulin resistant group had a more severe clinical condition as it is suggested by the fact that they had statistically significant higher values of BMI (30.52 Kg/m2 vs 24.40 Kg/m2), W/H ratio (0.84 vs 0.78), menstrual cycle length (72.50 days vs 49.64 days), PAI (18.13 ng/mL vs 10.39 ng/mL), and A4 (4.11 ng/mL vs 3.33 ng/mL). Of note insulin resistant women had significantly lower values of DHEAS (154 ug/dL vs 208 ug/dL) CONCLUSION: In this population of Latin American PCOS women, we have demonstrated that PCOS subjects with higher insulin resistant state have a more severe disease, being older, with a major degree of obesity, elevated levels of PAI-1 and poorer menstrual function. Unexpectedly, adrenal androgens were lower in the insulin resistant group. Supported by: Institutional

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