- Email: [email protected]
Simvastatin Improves Hyperandrogenism, Hyperandrogenemia, LH and Lipid Profile in Women With PCOS: A Randomized, Cross-over Study
ductive technology for primary infertility. A mock embryo transfer was performed by Wallace (Sims portex ltd., Hythe, Kent, UK) ET catheter, immediately followed by saline OH using a 2.7 mm hysteroscope. Hegar dilators or uterine sounds were not used. Hysteroscopic procedures were performed during the proliferative phase of the cycle after the cessation of menses. Outcomes measured were ease of transfer (easy; passing through cervix without resistance, moderately difficult; requiring use of outer rigid sheath, and very difficult; requiring the use of stilletes or tenaculum) and the presence of blood on the catheter tip. Endometrial damage was graded as follows: none, minor (superficial disturbance of endometrium with no bleeding), moderate (disturbance of endometrium with bleeding) or severe (significant disturbance of endometrium and/or significant bleeding/clots). Pearson Chi-Square test was used for statistical analysis. RESULTS: A statistically significant reciprocal relation was seen between the ease of ET catheter placement and the degree of endometrial damage (p⫽ 0.008), (Table). In the easy transfer group, 64,5% did not have any sign of endometrial damage, whereas about 30% of the women in the moderate and difficult transfer groups were observed to have no sign of endometrial damage. Three percentile of the women in the easy transfer group had moderate endometrial damage, while this rate was 11,3% and 29,4% in the moderate and difficult transfer groups, respectively. None of the groups had any sign of severe endometrial damage. It was also observed that there was a direct relation between presence of blood on the catheter tip and endometrial damage. In the group without blood on the catheter tip, 65% did not have endometrial damage finding, whereas this rate was 20% in the group with blood on the catheter tip. Of the women in whom there was no blood on the catheter tip, 2,5% were observed to have moderate endometrial damage, while the same rate in cases with blood was 22,9% (p⫽ 0.001), (Table).
test (PCT) with normal semen parameters and otherwise no factors that reduced fertility. These couples were randomly allocated between expectant management or IUI for six months. In the first three IUI cycles no controlled ovarian hyperstimulation (COH) was given. If these attempts failed subsequent IUI cycles were performed with COH. The primary endpoint was ongoing pregnancy within 6 months. The treatment effect was expressed as a relative risk and 95% confidence interval (CI). The analysis was performed according the intention to treat principle. We assumed a three times higher pregnancy rate in the couples treated with IUI. To detect this anticipated difference in ongoing pregnancy rates after 6 months, with an alpha of 5% and a power of 80%, 55 couples were required in each group. RESULTS: At present, 98 couples have been included (89%) and six months follow-up is available for 77 couples. In the expectant management group, 11 couples (31%) became pregnant of which 9 had an ongoing pregnancy (26%). In the IUI group, 18 couples (43%) became pregnant of which 16 had an ongoing pregnancy (38%). The relative risk of an ongoing pregnancy was 1.5 (95% CI 0.99 to 2.2). CONCLUSION: This trial suggest a beneficial effect of IUI in couples with an isolated cervical factor. This effect should be considered by those who plea against performance of the post-coital test. Supported by: This study was facilitated by grant 94512002 from ZonMW, The Netherlands Organization for Health Research and Development, The Hague, The Netherlands.
Monday, October 17, 2005 6:15 p.m. O-130 IVM of Oocytes Followed by IVF-ET in Patients With Delayed Follicular Growth During Controlled Ovarian Hyperstimulation. J. Yoon, J. Lim, K. Lim, S. Park, J. Jung, W. Lee. Maria Infertility Hospital, Seoul, Republic of Korea.
CONCLUSION: Clinical perception of ease of transfer and the presence of blood on the catheter tip correlate well with the degree of endometrial disruption. Findings obtained from trial ET applied before ART cycle may give an idea about the success of real ET catheterization application. Use of hysteroscopy offers a unique insight into the effects of ET on endometrial integrity. Supported by: None.
Monday, October 17, 2005 6:00 p.m. O-129 A Randomized Clinical Trial Assessing the Effectiveness Of Intrauterine Insemination For Couples With an Isolated Cervical Factor. P. Steures, J. W. Van der Steeg, F. Van der Veen, P. G. Hompes, M. J. Eijkemans, B. W. Mol. Vrije Universiteit Medical Center, Amsterdam, Netherlands; Academic Medical Center, Amsterdam, Netherlands; Erasmus Medical Center, Rotterdam, Netherlands; Ma´xima Medical Center, Veldhoven, Netherlands. OBJECTIVE: To assess the effectiveness of intrauterine insemination (IUI) in cervical factor subfertility. The effectiveness of IUI is well established for male and unexplained subfertility. Data on IUI for cervical factor subfertility from five small clinical trials are conflicting. DESIGN: Randomized clinical trial. MATERIALS AND METHODS: We performed a randomized clinical trial in 17 Fertility Centers in The Netherlands. Couples were eligible if they had a cervical factor, diagnosed by a well-timed, non-progressive post-coital
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Abstracts
OBJECTIVE: To investigate the efficacy of immature oocyte retrieval followed by IVM and IVF-ET in the patients with delayed follicular development during controlled ovarian hyperstimulation DESIGN: Retrospective study MATERIALS AND METHODS: Between February 2001 and April 2004, 50 infertile patients underwent a total 55 cycles of COH for IVF-ET. Of the 50 patients, 5 women underwent 2 cycles. When there was no evidence of follicular growth ⬎ 10 mm after 7 or more days of ovarian stimulation, hCG 10,000 IU was administered and oocytes were retrieved 36 hours later, followed by IVM and IVF-ET. RESULTS: A total 641 viable immature oocytes from 55 cycles were obtained, and the mean number of oocytes recovered was 11.7⫾8.3 (range 2-48). Five hundred oocytes developed to MII (78.0%). A total 359 oocytes were fertilized by ICSI (71.8%). The duration of gonadotropin administration was 9.6 ⫾ 2.4 days (range 7-15). The total dose of gonadotropin was 1,847⫾890 IU (range 950-4,725). Embryo transfer was performed in 52 cycles. The mean number of transferred embryo was 3.9⫾1.1. Thirty-two gestational sacs were identified, and the implantation rate was 15.8%. Gestational sac(s) was identified in total 21 patients, and the clinical pregnancy rate was 40.4% per embryo transfer. CONCLUSION: When a patient poorly responds to ovarian stimulation and is on the brink of cycle cancellation due to delayed response to gonadotropin stimulation, immature oocyte retrieval followed by IVM and IVF-ET may provide an important alternative to cancellation of these cycles. Supported by: None.
PLENARY SESSION 3 Tuesday, October 18, 2005 8:45 a.m. O-131 Simvastatin Improves Hyperandrogenism, Hyperandrogenemia, LH and Lipid Profile in Women With PCOS: A Randomized, Cross-over Study. B. Banaszewska, L. Pawelczyk, R. Z. Spaczynski, J. Dziura, A. J. Duleba. Poznan University of Medical Sciences, Poznan, Poland; Yale University School of Medicine, New Haven, CT.
Vol. 84, Suppl 1, September 2005
OBJECTIVE: Statins inhibit HMG-Co-A reductase, a rate-limiting step of the pathway leading to cholesterol synthesis. Statins improve dyslipidemia and other cardiovascular risk factors such as systemic inflammation and oxidative stress. Our studies of theca-interstitial cells demonstrated that statins decrease growth (inhibit proliferation and induce apoptosis), reduce steroidogenesis (by decreasing expression of CYP11 and 3HSD), and may reduce oxidative stress by decreasing expression of NADPH subunits. Since polycystic ovary syndrome (PCOS) is associated with hyperandrogenism, dyslipidemia and oxidative stress, we proposed that statins improve endocrine and metabolic aspects of this condition. Recently (SGI 2005), we reported preliminary findings of a randomized trial of women with PCOS comparing the use of oral contraceptive pill (OCP) with OCP combined with simvastatin: at 12-weeks, there was a simvastatin-related improvement of testosterone, decrease of LH and improvement of lipid profile. This report presents the continuation of this study and demonstrates for the first time that simvastatin improves clinical endpoint: hirsutism. DESIGN: Prospective, randomized, cross-over clinical trial. MATERIALS AND METHODS: Forty-eight women with PCOS who did not receive any hormonal treatment for at least three months were evaluated: the patients age was 23.9 ⫾ 3.5 years (mean ⫾ SD) and BMI was 22.3 ⫾ 3.4. The subjects were randomized to Group A or B. Group A first received OCP alone (20 g ethinyl estradiol and 150 g desogestrel) and after 12 weeks OCP plus 20 mg simvastatin daily for 12 weeks more. Group B first received OCP plus 20 mg simvastatin daily and after 12 weeks OCP alone. Clinical, endocrine and metabolic evaluations were performed at baseline, at 12 weeks (cross-over) and at 24 weeks. Data were analyzed using a random effects model with tests for period and carryover effects, and adjustment for baseline values. RESULTS: Simvastatin induced a decrease of total testosterone by 18% below the effect of OCP (P⫽0.004); this effect was paralleled by a 16% decrease of free testosterone below the effect of OCP (P⫽0.09). A simvastatin-attributable decline of hirsutism was modestly but significantly greater than the effect of OCP alone (by 4%, P⫽0.02). Simvastatin increased odds of having no acne vs. OCP alone; however, this effect did not reach statistical significance (OR⫽3.9; P⫽0.09). Simvastatin, in comparison to OCP, also decreased LH by 24% (P⫽0.002) and LH: FSH ratio by 22% (P⫽0.01). Furthermore, simvastatin (vs. OCP) decreased total cholesterol by 12% (P⬍0.001), LDL by 21% (P⬍0.001), and triglycerides by 18% (P⫽0.003); HDL was comparable (increase by 3%, P⫽0.3). BMI was not significantly affected by either treatment. CONCLUSION: This is the first report that simvastatin improves a clinical end-point of treatment of PCOS: hirsutism. In addition, simvastatin significantly lowers total testosterone, decreases LH and LH: FSH ratio, and improves lipid profile. Supported by: This work was supported by NIH grant R01 HD 40207.
Tuesday, October 18, 2005 9:00 a.m. O-132 Increased Risk Of Depression In Women With Polycystic Ovary Syndrome. E. M. Hollinrake, A. Abreu, A. Sparks, B. Van Voorhis, A. Dokras. University of Iowa, Iowa City, IA. OBJECTIVE: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged women. PCOS confers an increased risk for insulin-resistance, type II diabetes mellitus, hypertension, dyslipidemia, atherosclerotic disease, and endometrial cancer. Few small studies have also suggested an increased risk of depression in women with PCOS. The goals of this study were to estimate the prevalence of depression in women with PCOS compared to controls using two separate standardized scoring systems for depression. In addition, we evaluated the correlation between depression and markers of PCOS such as obesity/insulin resistance and hyperandrogenism. DESIGN: Prospective case-control study. MATERIALS AND METHODS: Women with PCOS diagnosed by the Rotterdam criteria, were recruited from the Reproductive Endocrinology clinic at the University of Iowa. Women without PCOS attending the Gynecology clinic during the same time period for an annual exam were used as controls. We used the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire (PRIME-MD PHQ to diagnose Major Depressive Disorder and Other Depressive Syndromes. We used the Beck Depres-
FERTILITY & STERILITY威
sion Inventory (BDI) to score the severity of depression. We used chi-square and t-test to compare differences between women with PCOS and controls, and PCOS women with and without depression. This study was approved by the University of Iowa Institutional Review Board. RESULTS: A total of 95 women with PCOS and 42 controls completed the study. In the PCOS group 35% (33/95) of women were classified as depressed compared to 2.4% (1/42) of controls (p⬍0.001). The majority of women in both groups were white (⬎90%). The PCOS women had a higher BMI (35.2 ⫾8.7) compared to the controls (25.04⫾6.1, p⬍0.01). After adjusting for age and BMI, women with PCOS had an increased risk of depression (p⬍0.002). In the PCOS group, 13 subjects screened positive for Major Depressive Disorder, 8 for Other Depressive Syndromes. No control subjects met criteria for the above conditions. In addition 12 women with PCOS were on anti-depressants, while one control subject was on antidepressants. On examining the PCOS group further, the average BDI scores in the depressed (22.2⫾12) and non-depressed PCOS groups (6.68⫾6) were significantly different (p⬍0.0001). Factors known to influence the prevalence of depression, such as age, family history of depression, marital status and presence of infertility did not differ significantly between the two PCOS groups. PCOS women with depression however had a higher BMI (39.02⫾8.6) compared to those that screened negative (33.2⫾8.4, p⬍0.003). Fasting glucose levels were significantly higher (p⬍0.01), while glucose/insulin ratio was decreased in PCOS women with depression (p⬍0.003) compared to non-depressed women. Total and free testosterone were not significantly different between these two groups. CONCLUSION: In this pilot study, we report a significantly increased risk of depression in women with PCOS. Therefore, women with PCOS may need to be screened for depression. Depression in women with PCOS appears to be associated with high BMI and insulin resistance but does not correlate with serum androgen levels. The effects of weight loss and improvement in glucose tolerance on depression scores in this population need to be further investigated. Supported by: University of Iowa Medical Student Research Program
PRIZE PAPER CANDIDATES Tuesday, October 18, 2005 10:45 a.m. O-133 The Incidence of Molecular/Genetic Markers in Testis Tissue From Severely and Mildly Oligospermic Men With Varicoceles and Infertility. J. Rosenthal, J. L. Marmar, S. Benoff. Robert Wood Johnson Medical School at Camden, Camden, NJ; North Shore- LIJ Research Institute, Manhassett, NY. OBJECTIVE: Genetic abnormalities in men with varicoceles may influence fertility and effect varicocelectomy outcome.In WBCs and sperm , these abnormalities occur more often in men with severe oligospermia (⬍ 5 mil sperm/ml),but the overall incidence seems low(abnormal karyotype5,6%,Y chromosome microdeletions-6.0%,CF mutations-1.2%,androgen receptor defects-1.1%,high sperm DNA damage-10.0%). In contrast,we studied molecular/genetic markers in testis tissue from infertile men with varicoceles. We present data on the incidence of testis markers in severely versus moderately oligospermic patients and report the influence on varicocelectomy outcome. DESIGN: A retrospective study on the incidence molecular/genetic markers in testis tissue that correlate with apoptosis,and their ability to predict varicocelectomy outcome. MATERIALS AND METHODS: Percutanous testis aspiration biopsies with ultrasonic control were obtained at varicocelectomy (n ⫽ 119) or at sperm retrieval for ICSI in men with prior vasectomy and normal spermatogenesis (n ⫽ 5). Varicocele patients were divided into two groups (Group 1: ⬍5 million/ml, n ⫽ 47; Group 2: ⬎ 5 million/ml, n ⫽ 72). Markers were examined by different techniques: [1] microscopy ( BL thickness, germ cell count/tubule), [2] atomic absorption spectroscopy/autometallography (testicular Cd), [3] TUNEL (apoptosis), [4] RT-PCR (mRNAs for L-VDCC exons 6-9, CREM␣ and CREM), and [5] immunocytochemistry (L-VDCC, FasL, CD34, VEGF). Semen and marker data were available from 78 post varicocelectomy patients.A 50% increase in post op sperm density was considered sucessful, because men who achieved natural pregnancy after varicocelectomy demonstrated this level of increase.
S55
test (PCT) with normal semen parameters and otherwise no factors that reduced fertility. These couples were randomly allocated between expectant management or IUI for six months. In the first three IUI cycles no controlled ovarian hyperstimulation (COH) was given. If these attempts failed subsequent IUI cycles were performed with COH. The primary endpoint was ongoing pregnancy within 6 months. The treatment effect was expressed as a relative risk and 95% confidence interval (CI). The analysis was performed according the intention to treat principle. We assumed a three times higher pregnancy rate in the couples treated with IUI. To detect this anticipated difference in ongoing pregnancy rates after 6 months, with an alpha of 5% and a power of 80%, 55 couples were required in each group. RESULTS: At present, 98 couples have been included (89%) and six months follow-up is available for 77 couples. In the expectant management group, 11 couples (31%) became pregnant of which 9 had an ongoing pregnancy (26%). In the IUI group, 18 couples (43%) became pregnant of which 16 had an ongoing pregnancy (38%). The relative risk of an ongoing pregnancy was 1.5 (95% CI 0.99 to 2.2). CONCLUSION: This trial suggest a beneficial effect of IUI in couples with an isolated cervical factor. This effect should be considered by those who plea against performance of the post-coital test. Supported by: This study was facilitated by grant 94512002 from ZonMW, The Netherlands Organization for Health Research and Development, The Hague, The Netherlands.
Monday, October 17, 2005 6:15 p.m. O-130 IVM of Oocytes Followed by IVF-ET in Patients With Delayed Follicular Growth During Controlled Ovarian Hyperstimulation. J. Yoon, J. Lim, K. Lim, S. Park, J. Jung, W. Lee. Maria Infertility Hospital, Seoul, Republic of Korea.
CONCLUSION: Clinical perception of ease of transfer and the presence of blood on the catheter tip correlate well with the degree of endometrial disruption. Findings obtained from trial ET applied before ART cycle may give an idea about the success of real ET catheterization application. Use of hysteroscopy offers a unique insight into the effects of ET on endometrial integrity. Supported by: None.
Monday, October 17, 2005 6:00 p.m. O-129 A Randomized Clinical Trial Assessing the Effectiveness Of Intrauterine Insemination For Couples With an Isolated Cervical Factor. P. Steures, J. W. Van der Steeg, F. Van der Veen, P. G. Hompes, M. J. Eijkemans, B. W. Mol. Vrije Universiteit Medical Center, Amsterdam, Netherlands; Academic Medical Center, Amsterdam, Netherlands; Erasmus Medical Center, Rotterdam, Netherlands; Ma´xima Medical Center, Veldhoven, Netherlands. OBJECTIVE: To assess the effectiveness of intrauterine insemination (IUI) in cervical factor subfertility. The effectiveness of IUI is well established for male and unexplained subfertility. Data on IUI for cervical factor subfertility from five small clinical trials are conflicting. DESIGN: Randomized clinical trial. MATERIALS AND METHODS: We performed a randomized clinical trial in 17 Fertility Centers in The Netherlands. Couples were eligible if they had a cervical factor, diagnosed by a well-timed, non-progressive post-coital
S54
Abstracts
OBJECTIVE: To investigate the efficacy of immature oocyte retrieval followed by IVM and IVF-ET in the patients with delayed follicular development during controlled ovarian hyperstimulation DESIGN: Retrospective study MATERIALS AND METHODS: Between February 2001 and April 2004, 50 infertile patients underwent a total 55 cycles of COH for IVF-ET. Of the 50 patients, 5 women underwent 2 cycles. When there was no evidence of follicular growth ⬎ 10 mm after 7 or more days of ovarian stimulation, hCG 10,000 IU was administered and oocytes were retrieved 36 hours later, followed by IVM and IVF-ET. RESULTS: A total 641 viable immature oocytes from 55 cycles were obtained, and the mean number of oocytes recovered was 11.7⫾8.3 (range 2-48). Five hundred oocytes developed to MII (78.0%). A total 359 oocytes were fertilized by ICSI (71.8%). The duration of gonadotropin administration was 9.6 ⫾ 2.4 days (range 7-15). The total dose of gonadotropin was 1,847⫾890 IU (range 950-4,725). Embryo transfer was performed in 52 cycles. The mean number of transferred embryo was 3.9⫾1.1. Thirty-two gestational sacs were identified, and the implantation rate was 15.8%. Gestational sac(s) was identified in total 21 patients, and the clinical pregnancy rate was 40.4% per embryo transfer. CONCLUSION: When a patient poorly responds to ovarian stimulation and is on the brink of cycle cancellation due to delayed response to gonadotropin stimulation, immature oocyte retrieval followed by IVM and IVF-ET may provide an important alternative to cancellation of these cycles. Supported by: None.
PLENARY SESSION 3 Tuesday, October 18, 2005 8:45 a.m. O-131 Simvastatin Improves Hyperandrogenism, Hyperandrogenemia, LH and Lipid Profile in Women With PCOS: A Randomized, Cross-over Study. B. Banaszewska, L. Pawelczyk, R. Z. Spaczynski, J. Dziura, A. J. Duleba. Poznan University of Medical Sciences, Poznan, Poland; Yale University School of Medicine, New Haven, CT.
Vol. 84, Suppl 1, September 2005
OBJECTIVE: Statins inhibit HMG-Co-A reductase, a rate-limiting step of the pathway leading to cholesterol synthesis. Statins improve dyslipidemia and other cardiovascular risk factors such as systemic inflammation and oxidative stress. Our studies of theca-interstitial cells demonstrated that statins decrease growth (inhibit proliferation and induce apoptosis), reduce steroidogenesis (by decreasing expression of CYP11 and 3HSD), and may reduce oxidative stress by decreasing expression of NADPH subunits. Since polycystic ovary syndrome (PCOS) is associated with hyperandrogenism, dyslipidemia and oxidative stress, we proposed that statins improve endocrine and metabolic aspects of this condition. Recently (SGI 2005), we reported preliminary findings of a randomized trial of women with PCOS comparing the use of oral contraceptive pill (OCP) with OCP combined with simvastatin: at 12-weeks, there was a simvastatin-related improvement of testosterone, decrease of LH and improvement of lipid profile. This report presents the continuation of this study and demonstrates for the first time that simvastatin improves clinical endpoint: hirsutism. DESIGN: Prospective, randomized, cross-over clinical trial. MATERIALS AND METHODS: Forty-eight women with PCOS who did not receive any hormonal treatment for at least three months were evaluated: the patients age was 23.9 ⫾ 3.5 years (mean ⫾ SD) and BMI was 22.3 ⫾ 3.4. The subjects were randomized to Group A or B. Group A first received OCP alone (20 g ethinyl estradiol and 150 g desogestrel) and after 12 weeks OCP plus 20 mg simvastatin daily for 12 weeks more. Group B first received OCP plus 20 mg simvastatin daily and after 12 weeks OCP alone. Clinical, endocrine and metabolic evaluations were performed at baseline, at 12 weeks (cross-over) and at 24 weeks. Data were analyzed using a random effects model with tests for period and carryover effects, and adjustment for baseline values. RESULTS: Simvastatin induced a decrease of total testosterone by 18% below the effect of OCP (P⫽0.004); this effect was paralleled by a 16% decrease of free testosterone below the effect of OCP (P⫽0.09). A simvastatin-attributable decline of hirsutism was modestly but significantly greater than the effect of OCP alone (by 4%, P⫽0.02). Simvastatin increased odds of having no acne vs. OCP alone; however, this effect did not reach statistical significance (OR⫽3.9; P⫽0.09). Simvastatin, in comparison to OCP, also decreased LH by 24% (P⫽0.002) and LH: FSH ratio by 22% (P⫽0.01). Furthermore, simvastatin (vs. OCP) decreased total cholesterol by 12% (P⬍0.001), LDL by 21% (P⬍0.001), and triglycerides by 18% (P⫽0.003); HDL was comparable (increase by 3%, P⫽0.3). BMI was not significantly affected by either treatment. CONCLUSION: This is the first report that simvastatin improves a clinical end-point of treatment of PCOS: hirsutism. In addition, simvastatin significantly lowers total testosterone, decreases LH and LH: FSH ratio, and improves lipid profile. Supported by: This work was supported by NIH grant R01 HD 40207.
Tuesday, October 18, 2005 9:00 a.m. O-132 Increased Risk Of Depression In Women With Polycystic Ovary Syndrome. E. M. Hollinrake, A. Abreu, A. Sparks, B. Van Voorhis, A. Dokras. University of Iowa, Iowa City, IA. OBJECTIVE: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged women. PCOS confers an increased risk for insulin-resistance, type II diabetes mellitus, hypertension, dyslipidemia, atherosclerotic disease, and endometrial cancer. Few small studies have also suggested an increased risk of depression in women with PCOS. The goals of this study were to estimate the prevalence of depression in women with PCOS compared to controls using two separate standardized scoring systems for depression. In addition, we evaluated the correlation between depression and markers of PCOS such as obesity/insulin resistance and hyperandrogenism. DESIGN: Prospective case-control study. MATERIALS AND METHODS: Women with PCOS diagnosed by the Rotterdam criteria, were recruited from the Reproductive Endocrinology clinic at the University of Iowa. Women without PCOS attending the Gynecology clinic during the same time period for an annual exam were used as controls. We used the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire (PRIME-MD PHQ to diagnose Major Depressive Disorder and Other Depressive Syndromes. We used the Beck Depres-
FERTILITY & STERILITY威
sion Inventory (BDI) to score the severity of depression. We used chi-square and t-test to compare differences between women with PCOS and controls, and PCOS women with and without depression. This study was approved by the University of Iowa Institutional Review Board. RESULTS: A total of 95 women with PCOS and 42 controls completed the study. In the PCOS group 35% (33/95) of women were classified as depressed compared to 2.4% (1/42) of controls (p⬍0.001). The majority of women in both groups were white (⬎90%). The PCOS women had a higher BMI (35.2 ⫾8.7) compared to the controls (25.04⫾6.1, p⬍0.01). After adjusting for age and BMI, women with PCOS had an increased risk of depression (p⬍0.002). In the PCOS group, 13 subjects screened positive for Major Depressive Disorder, 8 for Other Depressive Syndromes. No control subjects met criteria for the above conditions. In addition 12 women with PCOS were on anti-depressants, while one control subject was on antidepressants. On examining the PCOS group further, the average BDI scores in the depressed (22.2⫾12) and non-depressed PCOS groups (6.68⫾6) were significantly different (p⬍0.0001). Factors known to influence the prevalence of depression, such as age, family history of depression, marital status and presence of infertility did not differ significantly between the two PCOS groups. PCOS women with depression however had a higher BMI (39.02⫾8.6) compared to those that screened negative (33.2⫾8.4, p⬍0.003). Fasting glucose levels were significantly higher (p⬍0.01), while glucose/insulin ratio was decreased in PCOS women with depression (p⬍0.003) compared to non-depressed women. Total and free testosterone were not significantly different between these two groups. CONCLUSION: In this pilot study, we report a significantly increased risk of depression in women with PCOS. Therefore, women with PCOS may need to be screened for depression. Depression in women with PCOS appears to be associated with high BMI and insulin resistance but does not correlate with serum androgen levels. The effects of weight loss and improvement in glucose tolerance on depression scores in this population need to be further investigated. Supported by: University of Iowa Medical Student Research Program
PRIZE PAPER CANDIDATES Tuesday, October 18, 2005 10:45 a.m. O-133 The Incidence of Molecular/Genetic Markers in Testis Tissue From Severely and Mildly Oligospermic Men With Varicoceles and Infertility. J. Rosenthal, J. L. Marmar, S. Benoff. Robert Wood Johnson Medical School at Camden, Camden, NJ; North Shore- LIJ Research Institute, Manhassett, NY. OBJECTIVE: Genetic abnormalities in men with varicoceles may influence fertility and effect varicocelectomy outcome.In WBCs and sperm , these abnormalities occur more often in men with severe oligospermia (⬍ 5 mil sperm/ml),but the overall incidence seems low(abnormal karyotype5,6%,Y chromosome microdeletions-6.0%,CF mutations-1.2%,androgen receptor defects-1.1%,high sperm DNA damage-10.0%). In contrast,we studied molecular/genetic markers in testis tissue from infertile men with varicoceles. We present data on the incidence of testis markers in severely versus moderately oligospermic patients and report the influence on varicocelectomy outcome. DESIGN: A retrospective study on the incidence molecular/genetic markers in testis tissue that correlate with apoptosis,and their ability to predict varicocelectomy outcome. MATERIALS AND METHODS: Percutanous testis aspiration biopsies with ultrasonic control were obtained at varicocelectomy (n ⫽ 119) or at sperm retrieval for ICSI in men with prior vasectomy and normal spermatogenesis (n ⫽ 5). Varicocele patients were divided into two groups (Group 1: ⬍5 million/ml, n ⫽ 47; Group 2: ⬎ 5 million/ml, n ⫽ 72). Markers were examined by different techniques: [1] microscopy ( BL thickness, germ cell count/tubule), [2] atomic absorption spectroscopy/autometallography (testicular Cd), [3] TUNEL (apoptosis), [4] RT-PCR (mRNAs for L-VDCC exons 6-9, CREM␣ and CREM), and [5] immunocytochemistry (L-VDCC, FasL, CD34, VEGF). Semen and marker data were available from 78 post varicocelectomy patients.A 50% increase in post op sperm density was considered sucessful, because men who achieved natural pregnancy after varicocelectomy demonstrated this level of increase.
S55