Angela Falbo

Evidence-based and potential benefits of metformin in the polycystic ovary syndrome: a comprehensive review.

Metformin is an insulin sensitizer widely used for the treatment of patients affected by type 2 diabetes mellitus. Because many women with polycystic ovary syndrome (PCOS) are insulin resistant, metformin was introduced in clinical practice to treat these patients also. Moreover, metformins effect has other targets beside its insulin-sensitizing action. The present review was aimed at describing all evidence-based and potential uses of metformin in PCOS patients. In particular, we will analyze the uses of metformin not only for the treatment of all PCOS-related disturbances such as menstrual disorders, anovulatory infertility, increased abortion, or complicated pregnancy risk, hyperandrogenism, endometrial, metabolic and cardiovascular abnormalities, but also for the prevention of the syndrome.

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 complications in women with polycystic ovary syndrome

BACKGROUND The great majority of studies performed so far concerning women diagnosed with polycystic ovary syndrome (PCOS) have focused on diagnosis, menstrual cycle abnormalities, hirsutism and infertility. Although progress has been made in developing methods for achieving a pregnancy and reducing multiple gestations in women with PCOS, little attention has been paid to pregnancy complications and subsequent child outcomes. This review aims to summarize current knowledge regarding the clinical and pathophysiological features of pregnancy and children in women with PCOS. METHODS A literature search up to April 2015 was performed in PubMed, Medline, the Cochrane Library and Web of Science without language restriction. All articles were initially screened for title and abstract and full texts of eligible articles were subsequently selected. Systematic reviews with meta-analysis were initially included for each specific subject. Recent randomised controlled trials (RCTs), which were not included in the systematic reviews, were also included. In addition to evidence from meta-analyses or RCTs, we used non-randomized prospective, uncontrolled prospective, retrospective and experimental studies. When specific data for patients with PCOS were lacking, results from general population studies were reported. RESULTS Women with PCOS exhibit a clinically significant increased risk of pregnancy complications compared with controls. Data which were not adjusted for BMI or other confounders demonstrated in PCOS a 3-4-fold increased risk of pregnancy-induced hypertension and pre-eclampsia, a 3-fold increased risk of gestational diabetes and 2-fold higher chance for premature delivery. Features characteristic of PCOS, such as hyperandrogenism, obesity, insulin resistance and metabolic abnormalities, may contribute to the increased risk of obstetric and neonatal complications. Limited available data suggest that offspring of women with PCOS have an increased risk for future metabolic and reproductive dysfunction. Underlying pathophysiological mechanisms of pregnancy complications along with its association with health of offspring remain uncertain. To date, the strategies for prevention and management of pregnancy complications in women with PCOS, and whether long-term health of these women is influenced, and to what extent, by pregnancy and/or pregnancy complications, remain to be elucidated. CONCLUSIONS Women with PCOS show an increased risk of pregnancy complications. Heterogeneous aetiological factors involved in PCOS and associated co-morbidities may all be involved in compromised pregnancy and child outcomes. In women with PCOS, a possible relationship with genetic, environmental, clinical and biochemical factors involved in this complex condition, as well as with pregnancy complications and long-term health for both mother and child, remains to be established.

Effect of preconceptional metformin on abortion risk in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials

OBJECTIVE To evaluate the effect of pregestational metformin administration on abortion risk in polycystic ovary syndrome (PCOS) patients. DESIGN Systematic review and meta-analysis. SETTING Academic Department of Obstetrics and Gynecology in Italy. PATIENT(S) Women affected by PCOS receiving pregestational metformin. INTERVENTION(S) Systematic review of randomized controlled trials (RCTs) published up to June 2008 and subsequent meta-analysis. MAIN OUTCOME MEASURE(S) Abortion rate. RESULT(S) Seventeen RCTs were included in the final analysis. Overall, no effect of the metformin administration was detected on the abortion risk. No statistically significant effect of metformin on the abortion risk was observed in any comparison when subgrouping the RCTs according to received treatment. CONCLUSION(S) Metformin has no effect on the abortion risk in PCOS patients when administered before pregnancy.

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.

Effects of metformin in women with polycystic ovary syndrome treated with gonadotrophins for in vitro fertilisation and intracytoplasmic sperm injection cycles: a systematic review and meta‐analysis of randomised controlled trials

Metformin is widely used for treating women with polycystic ovary syndrome (PCOS), and many patients with PCOS who are infertile receive gonadotrophins while being treated with metformin.

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.

Safety of laparoscopy vs laparotomy in the surgical staging of endometrial cancer: a systematic review and metaanalysis of randomized controlled trials

The aim of the current study was to compare the safety of the laparoscopic vs abdominal approach to staging endometrial cancer. A search was conducted for randomized controlled trials that reported data from women with histologically confirmed endometrial cancer who underwent laparoscopic or abdominal surgery. An additional metaanalysis was performed. The primary endpoints were the rates of intraoperative and postoperative complications. A total of 8 original randomized controlled trials were included in the final analysis. No significant difference was observed in the relative risk (RR) for intraoperative complications between laparoscopy and laparotomy (RR, 1.25; 95% confidence interval, 0.99-1.56; P = .062). In contrast, a significant advantage of laparoscopy over laparotomy was obtained in terms of postoperative complications (RR, 0.71; 95% confidence interval, 0.63-0.79; P = .016). In comparison with abdominal surgery, the safety of the laparoscopic approach for surgical staging of endometrial cancer is similar in terms of intraoperative complications but results in fewer postoperative complications.