Tiziana Russo

Laparoscopic treatment for endometrial cancer: A meta-analysis of randomized controlled trials (RCTs)

OBJECTIVE To define, if any, type I clinical evidence regarding the safety and efficacy of the laparoscopic approach to endometrial cancer. METHODS Meta-analysis of randomized controlled trials (RCTs). RESULTS Four RCTs were identified and included in the final analysis. No significant difference between laparoscopic and laparotomic approaches to endometrial cancer in overall [odds ratio (OR)=0.80, 95%CI 0.37 to 1.70, P=0.695], disease-free (OR=0.76, 95%CI 0.34 to 1.72, P=0.655), and cancer-related (OR=0.89, 95%CI 0.19 to 4.13, P=0.815) survival was observed. Significantly longer operative time (OR=53.48, 95%CI 37.28 to 69.68, P=0.0002), lower intraoperative blood loss (OR=-266.86, 95%CI -454.82 to -78.90, P=0.005) and postoperative complications (OR=0.40, 95%CI 0.23 to 0.70, P=0.007) were associated to laparoscopy. No effect of laparoscopy on pelvic (OR=0.62, 95%CI -1.47 to 2.71, P=0.560) and para-aortic (OR=1.49, 95%CI -2.49 to 5.60, P=0.477) nodes yield, and intraoperative complications (OR=1.60, 95%CI 0.49 to 5.22, P=0.390) was observed. CONCLUSIONS Even if limited by few RCTs with short-term follow-up, our data suggest that laparoscopic approach should be considered an effective and safe procedure for patients with early stage endometrial cancer as well as laparotomic one. Notwithstanding the longer operative time, advantages of the laparoscopy over traditional laparotomy regard intraoperative blood loss and postoperative complications.

Laparoscopic surgery vs laparotomy for early stage endometrial cancer: long-term data of a randomized controlled trial.

OBJECTIVE The purpose of the study was to compare the long-term safety and efficacy of laparoscopic surgery and laparotomy approaches to early stage endometrial cancer. STUDY DESIGN This was a prospective long-term extension study of a randomized controlled study that included 84 patients with clinical stage I endometrial cancer (laparoscopic surgery group, 40 women; laparotomy group, 38 women). Safety and efficacy data were evaluated and analyzed by the intention-to-treat principle. RESULTS After a follow-up period of 78 months (interquartile range, 7; range, 19-84 months) and 79 months (interquartile range, 6; range, 22-84 months) for laparoscopic surgery and laparotomy groups, respectively, no difference in the cumulative recurrence rates (8/40 [20.0%] and 7/38 [18.4%]; P = .860) and deaths (7/40 [17.5%] and 6/38 [15.8%] patients; P = .839) was detected between groups. No significant differences in overall (P = .535) and disease-free (P = .512) survival were observed. CONCLUSION The laparoscopic surgery approach to early stage endometrial cancer is as safe and effective a procedure as the laparotomy approach.

Pregnancy in women with polycystic ovary syndrome: the effect of different phenotypes and features on obstetric and neonatal outcomes

OBJECTIVE To test the hypothesis that the risk of adverse obstetric or neonatal outcomes varies according to different phenotypes of polycystic ovary syndrome (PCOS), and to evaluate the clinical impact of the main features of PCOS. DESIGN Prospective controlled clinical study. SETTING Academic Departments of Obstetrics and Gynecology, and of Endocrinology, Italy. PATIENT(S) Ninety-seven pregnant women with PCOS and 73 healthy pregnant subjects were recruited as cases and controls, respectively. INTERVENTION(S) Clinical, biochemical, and ultrasonographic evaluations. MAIN OUTCOME MEASURE(S) Obstetric and neonatal outcomes. RESULT(S) The relative risk (RR) for adverse obstetric or neonatal outcomes was increased (1.7, 95% confidence interval [CI] 1.12-2.96) in patients with PCOS and varied according to the PCOS phenotype (1.93, 95% CI 1.12-2.96; 2.23, 95% CI 1.21-3.15; 0.54, 95% CI 0.09-1.63, and 0.48, 95% CI 0.31-0.78 for full-blown, nonpolycystic ovaries [PCO], nonhyperandrogenic, and ovulatory phenotypes, respectively). The RRs were 1.57 (95% CI 0.85-2.52) and 0.48 (95% CI 0.31-0.78) for oligoanovulatory and ovulatory patients with PCOS, respectively. The risk for adverse obstetric or neonatal outcomes was affected significantly by ovarian dysfunction and biochemical hyperandrogenism, whereas no significant effect was detected for clinical hyperandrogenism and PCO. CONCLUSION(S) The increased risk for adverse obstetric and neonatal outcomes that was observed in patients with PCOS varies widely according to the different phenotypes and features of PCOS.

Six weeks of structured exercise training and hypocaloric diet increases the probability of ovulation after clomiphene citrate in overweight and obese patients with polycystic ovary syndrome: a randomized controlled trial

BACKGROUND Clomiphene citrate (CC) is the first-line therapy for the induction of ovulation in infertile women with polycystic ovary syndrome (PCOS), but ∼20% of patients are unresponsive. The aim of the current study was to test the hypothesis that a 6-week intervention that consisted of structured exercise training (SET) and hypocaloric diet increases the probability of ovulation after CC in overweight and obese CC-resistant PCOS patients. METHODS A cohort of 96 overweight and obese CC-resistant PCOS patients was enrolled consecutively in a three-arm randomized, parallel, controlled, assessor-blinded clinical trial. The three interventions were: SET plus hypocaloric diet for 6 weeks (Group A); 2 weeks of observation followed by one cycle of CC therapy (Group B); and SET plus hypocaloric diet for 6 weeks, with one cycle of CC after the first 2 weeks (Group C). The primary end-point was the ovulation rate. Other reproductive data, as well as anthropometric, hormonal and metabolic data, were also collected and considered as secondary end points. RESULTS After 6 weeks of SET plus hypocaloric diet, the ovulation rate was significantly (P =0.008) higher in Group C [12/32 (37.5%)] than in Groups A [4/32 (12.5%)] and B [3/32 (9.4%)] with relative risks of 3.9 [95% confidence interval (CI) 1.1-8.3; P = 0.035] and 4.0 (95% CI 1.2-12.8; P = 0.020) compared with Groups A and B, respectively. Compared with baseline, in Groups A and C, a significant improvement in clinical and biochemical androgen and insulin sensitivity indexes was observed. In the same two groups, the insulin sensitivity index was significantly (P < 0.05) better than that in Group B. CONCLUSIONS In overweight and obese CC-resistant PCOS patients, a 6-week intervention of SET and a hypocaloric diet was effective in increasing the probability of ovulation under CC treatment. The study was registered at Clinicaltrials.gov:NCT0100468.

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

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.

Is plasminogen activator inhibitor-1 a cardiovascular risk factor in young women with polycystic ovary syndrome?

This study aimed to evaluate plasminogen activator inhibitor-1 (PAI-1) activity in PCOS. Thirty women with PCOS - 15 normal-weight and 15 obese - and 30 healthy women matched as a group for age and body mass index (BMI) were recruited. The homeostasis model assessment (HOMA) score was significantly elevated in obese compared with normal-weight women, in both PCOS women and controls. HOMA score was significantly higher in both PCOS groups relative to controls. After further adjustment for BMI, PAI-1 activity (IU/ml +/- SD) was significantly higher in the PCOS groups compared with controls. A significant positive correlation was found between HOMA score and BMI in PCOS and control groups. Serum PAI-1 activity was significantly related to BMI and HOMA score. When considering two BMI subgroups, there was no significant difference in the relationship between serum PAI-1 activity and HOMA score in both the control and PCOS groups. No other significant relationship was found between serum PAI-1 activity and any other hormonal or metabolic parameter. In conclusion, women with PCOS have significantly elevated PAI-1 activity independent of obesity, and it is speculated that elevated PAI-1 activity may be a factor in the increased cardiovascular morbidity seen in PCOS.

Long-term Effectiveness of Presacral Neurectomy for the Treatment of Severe Dysmenorrhea Due to Endometriosis

STUDY OBJECTIVE To assess the long-term effectiveness of presacral neurectomy (PSN) in women with severe dysmenorrhea due to endometriosis treated with conservative laparoscopic surgical intervention. DESIGN Randomized, controlled trial (Canadian Task Force classification I). SETTING University-affiliated department of obstetrics and gynecology. PATIENTS One hundred forty-one sexually active women of reproductive age. INTERVENTION Conservative laparoscopic surgery without (group A) or with (group B) PSN. MEASUREMENTS AND MAIN RESULTS At entry and 24-months after surgical procedures, cure rates; frequency and severity of dysmenorrhea, dyspareunia, and chronic pelvic pain; and quality of life were evaluated. At follow-up visit, the cure rate was significantly (P<0.05) higher in group B (83.3%) than in group A (53.3%). The frequency and severity of dysmenorrhea, dyspareunia, and chronic pelvic pain were significantly (P<0.05) lower in both groups compared with baseline values, and only severity was significantly (P<0.05) lower in group B. A significant (P<0.05) improvement in quality of life was observed after surgery in both groups and was significantly (P<0.05) increased in group B compared with group A. CONCLUSION PSN improves long-term cure rates and quality of life in women treated with conservative laparoscopic surgery for severe dysmenorrhea due to endometriosis.

Decidual Endovascular Trophoblast Invasion in Women with Polycystic Ovary Syndrome: An Experimental Case-Control Study

CONTEXT Previous experimental and clinical data suggest impaired decidual trophoblast invasion in patients with polycystic ovarian syndrome (PCOS). OBJECTIVE The objective of the study was to test the hypothesis that decidual endovascular trophoblast invasion in pregnant patients with PCOS is impaired and to clarify the potential mechanisms involved. DESIGN This was an experimental case-control study. SETTING The study was conducted at the academic Departments of Obstetrics and Gynecology and the Unit of Pathology (Italy). PATIENTS Forty-five pregnant subjects screened from a wide population of women waiting for legal pregnancy termination were included in the final analysis. Specifically, 15 pregnant patients with PCOS were enrolled as cases and another 30 age- and body mass index (BMI)-matched healthy pregnant women without any feature of PCOS were enrolled as the controls. INTERVENTION Interventions included the collection of trophoblastic and decidual tissue at the 12th week of gestation. MAIN OUTCOME MEASURES Clinical, ultrasonographic, and biochemical data as well as the histological analysis of decidual endovascular trophoblast invasion. RESULTS The rate of implantation site vessels with endovascular trophoblast invasion (ratio between total number of implantation site vessels and total number of vessels with endovascular trophoblast invasion) and the extent of endovascular trophoblast invasion (proportion between immunoreactive areas to cytokeratin 7 and to CD34) were significantly lower in patients with PCOS compared with healthy non-PCOS controls. Endovascular trophoblast invasion data were significantly and indirectly related to the markers of insulin resistance and testosterone concentrations in PCOS patients. CONCLUSIONS Pregnant patients with PCOS patients have impaired decidual trophoblast invasion. Further studies are needed to evaluate the exact mechanisms through which insulin resistance and hyperandrogenemia exert this effect.

Effects of metformin with or without supplementation with folate on homocysteine levels and vascular endothelium of women with polycystic ovary syndrome

OBJECTIVE To evaluate whether the administration of metformin exerts any effects on serum homocysteine (Hcy) levels in patients with polycystic ovary syndrome (PCOS) and whether supplementation with folate enhances the positive effects of metformin on the structure and function of the vascular endothelium. RESEARCH DESIGN AND METHODS A total of 50 patients affected by PCOS, without additional metabolic or cardiovascular diseases, were enrolled in a prospective nonrandomized placebo-controlled double-blind clinical study. They were grouped into two treatment arms that were matched for age and BMI. Patients were treated with a 6-month course of metformin (1,700 mg daily) plus folic acid (400 μg daily; experimental group, n = 25) or placebo (control group, n = 25). Complete hormonal and metabolic patterns, serum Hcy, folate, vitamin B12, endothelin-1 levels, brachial artery diameter at the baseline (BAD-B) and after reactive hyperemia (BAD-RH), flow-mediated dilation, and intima-media thickness in both common carotid arteries were evaluated. RESULTS After treatment, a significant increase in serum Hcy levels was observed in the control group compared with the baseline values and the experimental group. A beneficial effect was observed in the concentrations of BAD-B, BAD-RH, flow-mediated dilation, intima-media thickness, and serum endothelin-1 in both groups. However, the results were improved more significantly in the experimental group than in the control subjects. CONCLUSIONS Metformin exerts a slight but significant deleterious effect on serum Hcy levels in patients with PCOS, and supplementation with folate is useful to increase the beneficial effect of metformin on the vascular endothelium.

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.