Early trophoblast invasion and placentation in women with different PCOS phenotypes.

This study evaluated the impact of different phenotypes of polycystic ovary syndrome (PCOS) on early trophoblast invasion and placentation. Pregnant patients with different PCOS phenotypes and healthy pregnant women, matched for age and body mass index, were enrolled. Histological analysis of trophoblastic and decidual tissue and macroscopic and microscopic assessment of the placentas were performed. Implantation-site vessels with endovascular trophoblast differed significantly among PCOS phenotypes. Placental weight, thickness, density and fetal-placental weight ratio were significantly different in the full-blown and non-polycystic ovary (PCO) phenotypes versus the ovulatory and non-hyperandrogenic phenotypes. The incidence of macroscopic placental lesions was only significantly different between controls and the full-blown and non-PCO phenotypes. The overall incidence of microscopic placental lesions was significantly different among PCOS phenotypes and was significantly higher in the full-blown and non-PCO phenotypes than in the ovulatory and non-hyperandrogenic phenotypes. The rates of chorionic villitis and intervillositis were significantly higher in full-blown and non-PCO phenotypes than in ovulatory and non-hyperandrogenic phenotypes. In conclusion, alterations in early trophoblast invasion and placentation observed in PCOS vary widely according to phenotype.

A randomized controlled trial comparing three single-incision minislings for stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Studies have observed a significant heterogeneity in efficacy data for single-incision minislings (SIMS) as surgical treatment for female urinary incontinence (UI). Our study aim was to test the hypothesis that different vaginal kits for SIMS have different long-term outcomes. METHODS: One hundred and twenty women with stress (SUI) or mixed (MUI) UI were enrolled in a multicenter randomized clinical trial (registration number NCT00751088) and treated with three different SIMS (Ajust, MiniArc, or TVT Secur System). Duration of follow-up was at least 24 months from surgery. The primary outcome was the subjective cure rate at 24 months from surgery; secondary outcomes were rates of total failure and reoperations for UI. RESULTS: At study end, no difference was detected between groups in terms of total subjective cure rate [21 (52.5%) vs. 26 (65.0%) vs. 21 (52.5%), in Ajust, MiniArc, and TVT Secur System group, respectively; P = 0.412] or in terms of total failure rate [24 (60.0%) vs. 22 (55.0 %) vs. 27 (67.5 %), in Ajust, MiniArc, and TVT Secur System group, respectively; P = 0.432]. The proportion of patients who received a second surgery for UI was also not significantly different between groups [13 (32.5%) vs. 10 (25.0%) vs. 13 (32.5%), in Ajust, MiniArc, and TVT Secur System, respectively; P = 0.831]. CONCLUSION: The long-term efficacy of SIMS does not differ between the vaginal kits examined.

Single-incision mini-slings versus retropubic tension-free vaginal tapes: a multicenter clinical trial.

STUDY OBJECTIVE: To compare single-incision mini-slings (SIMSs) and retropubic tension-free vaginal tape (r-TVT) in terms of the long-term efficacy and safety for the treatment of female stress (SUI) or mixed urinary incontinence (MUI). DESIGN: Prospective multicenter cohort trial (registration number NCT00751088) (Canadian Task Force II). SETTINGS: Department of Obstetrics and Gynecology, Italy. PATIENTS: Two hundred-forty women with SUI/MUI. INTERVENTIONS: SIMS or r-TVT. MEASUREMENTS AND MAIN RESULTS: The operative time and the use of analgesic tablets were significantly (p < .001) higher and lower, respectively, in the r-TVT group versus the SIMS group. After 24 months of follow-up, no difference between the study arms was observed in terms of the complication rate (30/120 [25%] vs 19/120 [15.8%] for the r-TVT and SIMS arms, respectively; relative risk = 1.58; 95% confidence interval, 0.94-2.65; p = .083), whereas the subjective cure rate was significantly lower in the SIMS arm than in the r-TVT arm (57/103 [55.3%] vs 89/106 [84.0%] for the r-TVT and SIMS arms, respectively; relative risk = 0.66; 95% confidence interval, 0.54-0.80]; p < .001). The proportion of retreated patients for SUI/MUI was significantly higher in the SIMS arm than in the r-TVT arm (37/103 [34.9%] vs 12/106 [11.3%] for SIMS and r-TVT arm, respectively; p < .001). CONCLUSION: SIMS has no advantage in terms of safety over r-TVT and was found to be less effective than r-TVT. Thus, its use in the clinical practice should be questioned.

Pervasive developmental disorders in children of hyperandrogenic women with polycystic ovary syndrome: a longitudinal case-control study.

OBJECTIVE: Foetal exposure to high testosterone concentrations seems to be involved in the development of mammalian brain and related to pervasive developmental disorders (PDDs). The aim of the current study was to test the hypothesis that children born from hyperandrogenic women with polycystic ovary syndrome (PCOS) are at higher risk of PDDs. DESIGN: Longitudinal case-control study. PATIENTS: Thirty pregnant PCOS patients with hyperandrogenaemia and other 45 pregnant healthy women were followed during pregnancy. All women had a healthy baby. MEASUREMENTS: Clinical evaluations and biochemical assays of the mothers during pregnancy and after delivery were performed. The children's versions of the Autism-Spectrum Quotient (AQ-C), the Empathy Quotient (EQ-C) and Systemizing Quotient (SQ-C) tests were administered. RESULTS: Total AQ-C and communication scores were significantly higher for children of PCOS patients. Stratifying our population according to sex, total AQ-C, communication and attention switching subscores were significantly higher only for daughters of PCOS patients. EQ-C and SQ-C scores resulted in significantly lower and higher scores, respectively, only in daughters of PCOS patients in comparison with those of healthy non-PCOS controls. AQ-C, EQ-C and SQ-C scores, irrespective of the studied group and/or subclassification by gender, were significantly influenced by amniotic testosterone levels. CONCLUSIONS: Daughters of mothers affected by hyperandrogenic PCOS seem to have a higher risk for PDDs probably due to an unbalanced prenatal exposure to high levels of testosterone.

Metformin administration in patients with polycystic ovary syndrome who receive gonadotropins for in vitro fertilization cycles: 10-year experience in a large infertile population.

The study aim was to evaluate our personal experience regarding the use and the reproductive effect of metformin administration in a large population of infertile patients with polycystic ovary syndrome (PCOS) undergoing gonadotropins ovarian stimulation for in vitro fertilization (IVF). Infertile patients with PCOS undergoing gonadotropins ovarian stimulation with (metformin group, n = 191) or without (control group, n = 187) metformin and IVF were evaluated. Treatment characteristics, patients' data and reproductive outcomes were evaluated. In all cases, metformin with an immediate-release formulation was administered, and in most of cases it was given as pre- and co-treatment (74.9%) and at a dosage of 1700 mg/day (59.7%). Stimulation length and gonadotropins doses were significantly (p < 0.05) higher in metformin group than in control group. The number of dominant follicles on day of ovarian maturation triggering and peak oestradiol levels were significantly (p < 0.05) lower in metformin group than in control group. Cycle cancellation rate under metformin resulted significantly influenced by interaction with body mass index (BMI), age and basal follicle-stimulating hormone (FSH) levels. Notwithstanding, metformin use in infertile PCOS patients who receive gonadotropins for IVF is not standardized, it seems to modulate the ovarian response to stimulation. This effect may benefit or harm on the basis of ovarian reserve and patients' characteristics.

Systemic and local effects of metformin administration in patients with polycystic ovary syndrome (PCOS): relationship to the ovulatory response.

BACKGROUND: Several data have demonstrated the efficacy of metformin in inducing ovulation in patients with polycystic ovary syndrome (PCOS), however, the exact mechanism by which this drug acts remains unknown. The aim of the present study was to evaluate whether the efficacy of the drug in patients with PCOS is related to a systemic hormonal-metabolic improvement, or to a local action on the ovary. METHODS: Twenty-four normal weight patients with PCOS, who were treated with metformin, were enrolled. Of these, 12 subjects were anovulatory (Group A1), whereas the other 12 were ovulatory but had failed to conceive (Group A2). A further 24 untreated subjects who were scheduled for laparoscopic surgery were enrolled as controls, 12 anovulatory patients with PCOS scheduled for laparoscopic myomectomy (Group B1) and a further 12 non-PCOS participants were scheduled for diagnostic laparoscopy (Group B2). Clinical assessments and biochemical evaluations in blood and antral follicular fluid were performed in each participant. RESULTS: In 1/12 and 9/12 participants from Groups A1 and A2, respectively, the ovarian morphology was changed, and a significant (P < 0.05) reduction in the ovarian dimensions was observed only in Group A2. In both of these groups, and without difference between them, serum androgens and indices of insulin resistance improved significantly (P < 0.05) after metformin treatment. On the other hand, significant differences (P < 0.05) between the two groups were detected with respect to the same biochemical parameters in antral follicular fluid. In Groups A1 and A2, levels of androgens and indices of insulin resistance in the antral follicular fluid were significantly (P < 0.05) better than in Group B1, but worse than in Group B2. CONCLUSIONS: Irrespective of its systemic effects, the efficacy of metformin in the induction of ovulation is probably due to a direct action on the ovary, and the ovulatory response to the drug seems to be related to local sensitivity or resistance to the drug.

Ultra-conservative fertility-sparing strategy for bilateral borderline ovarian tumours: an 11-year follow-up.

BACKGROUND: This is a prospective long-term extension study of a randomized controlled trial aimed to assess the risk-benefit ratio of an ultra-conservative fertility-sparing approach in patients with bilateral borderline ovarian tumours (BOTs). METHODS: The experimental group (n = 15) was treated with an ultra-conservative surgical approach consisting of bilateral cystectomy, whereas the control group (n = 17) received a less conservative surgery consisting of oophorectomy plus controlateral cystectomy alone. All patients received a complete laparoscopic staging followed by a fertility enhancement programme. Patients who completed childbearing were treated with a non-conservative standard treatment at the first recurrence. RESULTS: After a follow-up period of 128 (9 interquartile range (IQR); 115-150 range) and 132 (7 IQR; 117-152 range) months for the experimental and control groups, respectively (P = 0.25), the time to first baby-in-arm (P < 0.02) and the relative rate (RR) of baby-in-arm (8.05 [95% confidence interval (CI), 1.20-9.66; P < 0.01]) were significantly lower and higher, respectively, for the experimental compared with the control group. Although the time to first recurrence was significently (P < 0.01) shorter for the experimental group, in the regression analysis the difference did not reach the statistic significance (P = 0.14), and the RR of recurrence (1.23 [95% CI, 0.62-3.17; P = 0.41]) was not significant. Finally the number needed to treat for pregnancy was three, the number needed to harm for radical surgery was only two. CONCLUSIONS: The ultra-conservative fertility-sparing approach is more effective than the standard approach in terms of reproductive outcomes, but presents a higher oncological risk.

Laparoscopic ovarian diathermy vs clomiphene citrate plus metformin as second-line strategy for infertile anovulatory patients with polycystic ovary syndrome: a randomized controlled trial.

OBJECTIVE: The purpose of this study was to compare the effectiveness of laparoscopic ovarian diathermy (LOD) vs clomiphene citrate (CC) plus metformin in infertile patients with CC-resistant polycystic ovary syndrome (PCOS). STUDY DESIGN: Fifty primary infertile patients with CC-resistant PCOS were assigned randomly to receive LOD followed by a 6-month observation (group A) or 6-cycle course of CC plus metformin (group B). Reproductive and safety outcomes were analyzed. RESULTS: No significant difference between 2 groups in pregnancy (15/92 women [16.3%] vs 14/107 women [13.1%]; P = .521) and live-birth (13/92 women [14.1%] vs 12/107 women [11.2%]; P = .536) rates per cycle was observed. With the use of a Cox regression analysis, patients under medical treatment, compared with patients who received surgical treatment, had a relative risk of pregnancy of 1.2 (95% confidence interval, 0.61-2.44; P = .582) and a relative risk of live-birth of 1.4 (95% confidence interval, 0.63-2.96; P = .425). CONCLUSION: LOD and CC plus metformin seem to be 2 effective approaches to treat infertility in patients with CC-resistant PCOS.

Effectiveness of risedronate in osteoporotic postmenopausal women with inflammatory bowel disease: a prospective, parallel, open-label, two-year extension study.

OBJECTIVE: To evaluate long-term efficacy of risedronate in osteoporotic postmenopausal patients with inflammatory bowel disease (IBD). DESIGN: A prospective, parallel, open-label, 2-year extension study of a randomized, double-blind, 1-year clinical trial. Eighty-one osteoporotic postmenopausal women with IBD were treated with risedronate (n = 40) or placebo (n = 41). Bone mineral density (BMD), biochemical bone turnover markers, and vertebral and nonvertebral fractures were assessed throughout the study. Data were analyzed using the intent-to-treat principle. RESULTS: Significant (P < 0.05) differences were observed between risedronate and placebo groups at 1-, 2-, and 3-year follow-up visits in bone turnover markers and in lumbar spine, trochanter, and femoral neck BMD. In participants treated with risedronate, the percentage of changes from baseline in bone turnover markers and in lumbar spine, trochanter, and femoral neck BMD were significantly (P < 0.05) higher at 2- and 3-year follow-up in comparison with baseline and 1-year follow-up, with a significant (P < 0.05) difference between the 2- and 3-year follow-up visits. At the end of the study, the cumulative risk of vertebral and nonvertebral fractures was significantly (P < 0.05) lower in the risedronate group than in the placebo group. The relative risk for new vertebral fractures was 0.456 (95% CI: 0.134-1.559, P = 0.211) and 0.296 (95% CI: 0.121-0.721, P = 0.007) and was 0.209 (95% CI: 0.023-1.867, P = 0.161) and 0.137 (95% CI: 0.030-0.620, P = 0.010), respectively, for new nonvertebral fractures after 2 and 3 years of risedronate treatment. CONCLUSIONS: In postmenopausal osteoporotic women with IBD, long-term treatment with risedronate is effective in increasing BMD and reducing vertebral and nonvertebral fracture risk.

Clomiphene citrate versus metformin as first-line approach for the treatment of anovulation in infertile patients with polycystic ovary syndrome.

CONTEXT: Clomiphene citrate (CC) and metformin are two effective drugs used to induce ovulation in patients with polycystic ovary syndrome (PCOS), even if it is still unclear which compound between them should be initially administered. OBJECTIVE: The aim of the study was to compare in a clinical setting the efficacy of CC and metformin as first-line approaches for treating anovulation in infertile PCOS patients. DESIGN: This study was a multicenter, nonrandomized, prospective, controlled study. SETTING: The study was conducted at the Department of Obstetrics and Gynecology, Universities "Magna Graecia" of Catanzaro and "Federico II" of Naples, Italy. PATIENTS: Patients included 80 infertile anovulatory patients with PCOS allocated in two body mass index- and age-matched groups (experimental and control groups). INTERVENTIONS: Six months of 1700 mg/d metformin treatment (experimental group) or CC was administered using a traditional incremental-dose protocol (control group). In both groups, patients who ovulated under treatment continued the therapy for a total of 6 months. MAIN OUTCOME MEASURES: Reproductive outcomes were measured. RESULTS: Experimental and control groups were studied for a total of 204 and 169 cycles, respectively. No difference between the two groups was observed in ovulation (55.4 vs. 59.8%, respectively; P = 0.396), pregnancy (10.8 vs. 11.2%, respectively; P = 0.888), and abortion (19.5 vs. 26.3%, respectively; P = 0.530) rates. The cumulative pregnancy rate was not different between groups (62.9 vs. 48.6%, respectively; P = 0.225). CONCLUSION: A 6-month course of 1700 mg/d metformin treatment and CC administered in an escalation protocol are two effective first-line approaches for improving fertility in anovulatory PCOS women.

Insulin sensitivity after metformin suspension in normal-weight women with polycystic ovary syndrome.

CONTEXT: To date, the metabolic effects of the long-term metformin administration in anovulatory patients with polycystic ovary syndrome (PCOS) are known, whereas few data are available on the effects of its suspension. OBJECTIVE: The objective of the study was to evaluate the effects of metformin suspension on insulin sensitivity in PCOS patients. DESIGN: This was a prospective, randomized, placebo-controlled study. SETTING: The study was conducted at the University "Magna Graecia" of Catanzaro, Italy. PATIENTS: Patients included 30 normal-weight anovulatory PCOS women and 10 age- and body mass index-matched healthy controls. INTERVENTION: PCOS patients were randomized to receive 1700 mg daily metformin (metformin group) or placebo tables (placebo group) for 12 months, whereas no treatment was administered in healthy women (control group). MAIN OUTCOME MEASURES: Clinical, endocrine, and metabolic profile and clamp insulin sensitivity index were evaluated at study entry and after 6, 12, 18, and 24 months. RESULTS: At baseline, the clamp insulin sensitivity index resulted significantly different (P < 0.05) in PCOS patients in comparison with healthy controls, without difference between metformin and placebo groups. During treatment, the clamp insulin sensitivity index was significantly improved (P < 0.05) in the metformin group in comparison with baseline and placebo group, without significant differences between the 6- and 12-month assessments. At 6 and 12 months after treatment suspension, in the metformin group, insulin sensitivity index significantly (P < 0.05) worsened in comparison with that observed at baseline and during treatment and with that observed in the placebo and control groups. CONCLUSION: In normal-weight anovulatory PCOS patients, long-term metformin administration exerts beneficial effects on peripheral insulin sensitivity. Furthermore, this effect disappears at treatment suspension.

Metformin administration improves leukocyte count in women with polycystic ovary syndrome: a 6-month prospective study.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common disorder associated with a wide range of endocrine and metabolic abnormalities. Low-grade chronic inflammation is a related complication recently observed in PCOS. Increased white blood cell (WBC) count was previously reported in PCOS women. OBJECTIVE: To evaluate the effects of six months metformin administration on WBC count in PCOS women. PATIENTS AND METHODS: Fifty normal-weight PCOS women without additional metabolic or cardiovascular diseases were enrolled and treated with metformin (850 mg twice daily) for 6 months in a prospective baseline-controlled clinical study. At baseline and after treatment, WBC count and C-reactive protein (CRP) were evaluated in each patient. The whole hormonal profile, serum insulin and glucose levels (at fasting and during a 75 g 2-h oral glucose tolerance test), serum lipid profile were also assessed. RESULTS: A significant difference was observed in WBC count (7050 +/- 552 vs 6080 +/- 577 cell/mm(3) +/- s.d., P<0.001) and CRP levels (1.8 +/- 0.9 vs 1.1 +/- 0.6 mg/l +/- s.d., P<0.001) after metformin treatment in comparison with baseline values. SHBG levels and the free androgen index also changed significantly (P<0.001). Finally, high-density lipoproteins and the area under curve for glucose/area under curve for insulin ratio also significantly increased (P<0.001), whereas low-density lipoproteins and area under curve for insulin were significantly reduced (P<0.001). No other change was found in any of the biochemical parameters evaluated. CONCLUSION: A six-month course of metformin reduces WBC count in PCOS women.

Cardiopulmonary impairment in young women with polycystic ovary syndrome.

CONTEXT: Insulin resistance is a feature of polycystic ovary syndrome (PCOS), and it is related to mitochondrial function, particularly with maximal oxygen consumption (VO(2max)). At the moment, no evaluation of cardiopulmonary functional capacity in young patients with PCOS has been performed. OBJECTIVE: Our objective was to assess cardiopulmonary functional capacity in young PCOS overweight patients. DESIGN AND SETTING: We conducted a prospective baseline-controlled clinical study at University Federico II of Naples, School of Medicine (Naples, Italy). PATIENTS: Forty-five PCOS patients were matched with 45 healthy women for age (mean +/- sd, 21.3 +/- 2.0 vs. 21.6 +/- 1.9 yr, respectively) and body mass index (29.4 +/- 3.6 vs. 29.0 +/- 3.4 kg/m(2), respectively). MEAN OUTCOME MEASURES: We assessed hormonal and metabolic pattern and functional capacity by cardiopulmonary exercise testing to evaluate maximal oxygen consumption (VO(2max)), oxygen consumption at anaerobic threshold (VO(2AT)), and the maximal workload at peak exercise. RESULTS: VO(2max) (17.0 +/- 3.7 vs. 26.8 +/- 3.5 ml/kg.min), oxygen consumption at anaerobic threshold (13.9 +/- 3.0 vs. 21.2 +/- 3.8 ml/kg.min), and maximal workload at peak exercise (101.3 +/- 25.2 vs. 135 +/- 22.6 W) were significantly (P < 0.001) reduced in PCOS subjects compared with healthy women. The multiple linear regression analysis showed that only homeostasis model assessment appears to have a strong negative linear relation with VO(2max) in PCOS. No relation was found in controls. CONCLUSIONS: Our data demonstrate a reduced cardiopulmonary functional capacity in young PCOS patients.

Laparoscopic uterine nerve ablation versus vaginal uterosacral ligament resection in postmenopausal women with intractable midline chronic pelvic pain: a randomized study.

OBJECTIVE: To assess and compare the laparoscopic uterine nerve ablation (LUNA) and the vaginal uterosacral ligament resection (VUSR) in postmenopausal women with chronic pelvic pain (CPP). STUDY DESIGN: Eighty postmenopausal women with intractable and severe midline CPP were randomized to undergo LUNA or VUSR. Costs of two surgical procedures were assesses. Cure rate, severity of CPP, and deep dyspareunia were also evaluated after 6 and 12 months from surgery. RESULTS: The mean cost of LUNA resulted significantly higher in comparison with VURS (2078+/-637 versus 1497+/-297, P<0.001). The cure rate was not significantly different between the two groups at 6 (33/40, 82.5% versus 35/40, 87.5% for groups A and B, respectively; P=0.530; RR 0.94, 95% CI 0.78-1.13), and 12 months (27/36, 75.0% versus 28/38, 73.7%, for groups A and B, respectively; P=0.901; RR 0.90, 95% CI 0.78-1.33) of follow-up. At same times, a significant (P<0.01) decrease in severity of CPP and deep dyspareunia was observed in both groups with no difference between them. CONCLUSIONS: Both LUNA and VUSR are equally effective surgical treatments in postmenopausal women with central CPP but VUNR is significantly cheaper than LUNA.

Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome.

CONTEXT: Although metformin has been shown to be effective in the treatment of anovulation in women with polycystic ovary syndrome (PCOS), clomiphene citrate (CC) is still considered to be the first-line drug to induce ovulation in these patients. OBJECTIVE: The goal of this study was to compare the effectiveness of metformin and CC administration as a first-line treatment in anovulatory women with PCOS. DESIGN: We describe a prospective parallel randomized, double-blind, double-dummy controlled clinical trial. SETTING: The study was conducted at the University "Magna Graecia" of Catanzaro, Catanzaro, Italy. PATIENTS: One hundred nonobese primary infertile anovulatory women with PCOS participated. INTERVENTIONS: We administered metformin cloridrate (850 mg twice daily) plus placebo (group A) or placebo plus CC (150 mg for 5 d from the third day of a progesterone withdrawal bleeding) (group B) for 6 months each. MEAN OUTCOME MEASURES: The main outcome measures were ovulation, pregnancy, abortion, and live-birth rates. RESULTS: The subjects of groups A (n = 45) and B (n = 47) were studied for a total of 205 and 221 cycles, respectively. The ovulation rate was not statistically different between either treatment group (62.9 vs. 67.0%, P = 0.38), whereas the pregnancy rate was significantly higher in group A than group B (15.1 vs. 7.2%, P = 0.009). The difference found between groups A and B regarding the abortion rate was significant (9.7 vs. 37.5%, P = 0.045), whereas a positive trend was observed for the live-birth rate (83.9 vs. 56.3%, P = 0.07). The cumulative pregnancy rate was significantly higher in group A than group B (68.9 vs. 34.0%, P < 0.001). CONCLUSIONS: Six-month metformin administration is significantly more effective than six-cycle CC treatment in improving fertility in anovulatory nonobese PCOS women.

Improvement in endothelial structure and function after metformin treatment in young normal-weight women with polycystic ovary syndrome: results of a 6-month study.

CONTEXT: Recent data indicate that women affected by the polycystic ovary syndrome (PCOS) are at greater risk for cardiovascular disease and that metformin may improve the metabolic alterations in these patients. OBJECTIVE: The objective of this study was to evaluate the effects of 6 months of metformin administration on endothelial structure and function in women with PCOS. DESIGN: This was a prospective, baseline-controlled, clinical study. SETTING: The study was performed at University Federico II (Naples, Italy). PATIENTS: Thirty young normal-weight women with PCOS without additional metabolic or cardiovascular diseases were studied. INTERVENTIONS: Metformin (850 mg daily) was administered for 6 months. MEAN OUTCOME MEASURES: The main outcome measures were complete hormonal profile, including total testosterone, SHBG, dehydroepiandrosterone sulfate, prolactin, and gonadotropin levels; serum insulin and glucose levels during a 75-g 2-h oral glucose tolerance test; plasma endothelin-1 concentrations (picomoles per liter +/- sd); serum lipid profile; brachial artery baseline diameter (millimeters +/- sd), diameter after reactive hyperemia (millimeters +/- sd), and flow-mediated dilation (percentage +/- sd); and the intima media thickness (millimeters +/- sd) on both common carotid arteries. RESULTS: After treatment, SHBG levels and the free androgen index changed significantly (P < 0.001). High-density lipoproteins and the area under curve for glucose/area under curve for insulin ratio also significantly (P < 0.001) increased, whereas low-density lipoproteins and plasma endothelin-1 levels were significantly (P < 0.001) reduced. No other change was found in any of the biochemical parameters evaluated. A significant difference was observed in brachial artery baseline diameter (3.24 +/- 0.30 vs. 3.0 +/- 0.30), flow-mediated dilation (14.30 +/- 1.90 vs. 15.70 +/- 1.50) (P < 0.01, each), diameter after reactive hyperemia (3.70 +/- 0.30 vs. 3.55 +/- 0.10) (P < 0.05), and intima media thickness (0.53 +/- 0.09 vs. 0.40 +/- 0.07) (P < 0.001) after metformin treatment in comparison with baseline values. CONCLUSIONS: A 6-month course of metformin improves endothelial structure and function in young, normal-weight women with PCOS.

A prospective randomized comparison between laparoscopic and laparotomic approaches in women with early stage endometrial cancer: a focus on the quality of life.

OBJECTIVE: This study was undertaken to compare the quality of life (QoL) in women with early stage endometrial cancer treated with 2 different surgical approaches. STUDY DESIGN: Eighty-four women with clinical stage I endometrial cancer were enrolled in a prospective randomized controlled trial design and treated with laparoscopic or laparotomic approach. Another 40 women matched for demographic characteristics were studied as controls. In patients, before and after surgery, and in their matched controls, QoL was evaluated by using the Short-Form Healthy Survey (SF-36) and the climacteric symptoms using the Kupperman Index (KI). RESULTS: After randomization, no difference was detected in data recorded between the groups. At entry, QoL was similar in both treatment groups but significantly (P < .05) worse in comparison with controls. Throughout the study, QoL was significantly (P < .05) higher in laparoscopic group versus laparotomic group. After KI adjustment our data did not change. CONCLUSION: In early stage endometrial cancer, the laparoscopic approach provides significant benefits compared with laparotomy in terms of QoL.

Metformin administration versus laparoscopic ovarian diathermy in clomiphene citrate-resistant women with polycystic ovary syndrome: a prospective parallel randomized double-blind placebo-controlled trial.

At present, it is unclear what the role is of laparoscopic ovarian diathermy (LOD) and of metformin administration as second-line treatments for ovulation induction in women with polycystic ovary syndrome (PCOS) after failure of clomiphene citrate (CC) treatment. The aim of the present study was to compare in a randomized double-blind placebo-controlled fashion the effectiveness of LOD with metformin administration in the treatment of CC-resistant women with PCOS. A total of 120 overweight primary infertile anovulatory CC-resistant women with PCOS were enrolled and randomized into two groups of treatment. Group A underwent diagnostic laparoscopy, whereas group B underwent LOD. At hospital discharge, the patients were treated for 6 months with metformin cloridrate (group A; 850 mg twice daily) or with multivitamins (group B). The ovulation, pregnancy, abortion, and live-birth rates were evaluated. At the end of the study, the total ovulation rate was not statistically different between both treatment groups (54.8 vs. 53.2% [correction] in groups A and B, respectively), whereas the pregnancy (21.8 [correction] vs. 13.4%), the abortion (9.3 [correction] vs. 29.0%), and the live-birth (86.0 [correction] vs. 64.5%) rates were significantly (P < 0.05) different between the two groups. Our data show that metformin administration is more effective than LOD in overall reproductive outcomes in overweight infertile CC-resistant women with PCOS.

Low-grade chronic inflammation in pregnant women with polycystic ovary syndrome: a prospective controlled clinical study.

CONTEXT: Polycystic ovary syndrome (PCOS) and pregnancy are conditions characterized by an increased low-grade chronic inflammation state. A higher incidence of pregnancy complications has been detected in pregnant PCOS women. OBJECTIVE: The objective of the study was to test the hypothesis that the low-grade chronic inflammation state typical of PCOS patients persists during gestation and is exacerbated by pregnancy and contributes to the increased risk of obstetric/neonatal complications. DESIGN: This was a prospective controlled clinical study. SETTING: The study was conducted at the Academic Department of Obstetrics and Gynecology of the "Pugliese-Ciaccio" Hospital of Catanzaro (Catanzaro, Italy). PATIENTS: One hundred fifty pregnant PCOS women and 150 age- and body mass index-matched healthy pregnant controls participated in the study. INTERVENTIONS: INTERVENTIONS included serial clinical, biochemical, and ultrasonographic assessments before and throughout pregnancy. MAIN OUTCOME MEASURES: Serum levels of white blood cell count (WBC), C-reactive protein (CRP), and ferritin were measured. RESULTS: Pregnant women with PCOS had higher WBC, CRP, and ferritin levels at study entry and at all gestational ages than controls. Changes in serum WBC and ferritin levels were significantly higher in PCOS than in controls starting from the 12th week of gestation whereas those in CRP from the 20th week of gestation. By multivariable Cox proportional hazard analysis, in the PCOS group, a significant association with the risk of adverse obstetric/neonatal outcomes was found for WBC [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.31-1.64; P = .010], CRP (HR 1.19, 95% CI 1.06-1.34; P = .019), and ferritin levels (HR 1.12, 95% CI 1.03-1.26; P = .011). CONCLUSIONS: In PCOS patients, the low-grade chronic inflammation persists during gestation and is exacerbated by pregnancy, and it is associated with adverse pregnancy outcomes.

Lipid profile in nonobese pregnant women with polycystic ovary syndrome: a prospective controlled clinical study.

Alterations in lipid pattern and increased risk for obstetric/neonatal complications have been observed in patients with polycystic ovary syndrome (PCOS). Pregnancy leads to physiologic changes in lipoprotein metabolism, and alterations in lipid profile have been related with adverse pregnancy outcomes. Based on these considerations, the aim of the present prospective controlled clinical study was to test the hypothesis that the changes in the lipid profile in patients with PCOS during pregnancy are characteristic and potentially related to the increased risk of obstetric/neonatal complications. One hundred and fifty nonobese PCOS women and 150 age- and body mass index (BMI)-matched healthy controls were enrolled. Serum lipids, glucose, insulin, and androgens levels were serially assayed in all subjects before and throughout pregnancy. Serum low-density lipoprotein (LDL) and triglyceride (TG) concentrations were significantly (P<0.05) higher in PCOS group than in healthy controls at each assessment. Throughout pregnancy, serum LDL and TG levels increased significantly (P<0.05) in both groups, although the change from pre-pregnancy values was significantly (P<0.05) greater in PCOS patients than in healthy controls. A significant (P<0.05) relationship was observed between serum LDL and TG changes and changes in both insulin sensitivity indexes and androgen levels in PCOS patients alone. After adjusting for maternal age, pre-pregnancy BMI and lipid levels, body weight gain, and insulin-resistance markers, serum TG concentrations during pregnancy were directly and independently associated with obstetric complications in both groups, whereas serum LDL levels only in PCOS patients. We can conclude that nonobese PCOS patients had specific changes in lipid profile during pregnancy, and that the lipid pattern typical of PCOS may account for the more frequent adverse pregnancy outcomes. PCOS-related hormonal and metabolic features, such as insulin resistance and high androgen levels, may mediate this phenomenon.