***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE To evaluate whether morbidly obese women have an increased risk of pregnancy complications and adverse perinatal outcomes . METHODS In a prospect i ve population -based cohort study , 3,480 women with morbid obesity , defined as a body mass index ( BMI ) more than 40 , and 12,698 women with a BMI between 35.1 and 40 were compared with normal-weight women ( BMI 19.8 - 26 ) . The perinatal outcome of singletons born to women without insulin-dependent diabetes mellitus was evaluated after suitable adjustments . RESULTS In the group of morbidly obese mothers ( BMI greater than 40 ) as compared with the normal-weight mothers , there was an increased risk of the following outcomes ( adjusted odds ratio ; 95 % confidence interval ) : preeclampsia ( 4.82 ; 4.04 , 5.74 ) , antepartum stillbirth ( 2.79 ; 1.94 , 4.02 ) , cesarean delivery ( 2.69 ; 2.49 , 2.90 ) , instrumental delivery ( 1.34 ; 1.16 , 1.56 ) , shoulder dystocia ( 3.14 ; 1.86 , 5.31 ) , meconium aspiration ( 2.85 ; 1.60 , 5.07 ) , fetal distress ( 2.52 ; 2.12 , 2.99 ) , early neonatal death ( 3.41 ; 2.07 , 5.63 ) , and large-for-gestational age ( 3.82 ; 3.50 , 4.16 ) . The associations were similar for women with BMI s between 35.1 and 40 but to a lesser degree . CONCLUSION Maternal morbid obesity in early pregnancy is strongly associated with a number of pregnancy complications and perinatal conditions . LEVEL OF EVIDENCE BACKGROUND / AIMS Non-Alcoholic Steatohepatitis ( NASH ) is a chronic liver disease frequently associated with insulin resistance and type 2 diabetes mellitus ( T2DM ) . Pioglitazone reverses the metabolic and histological abnormalities of patients with impaired glucose tolerance or T2DM and NASH , but also leads to weight gain . To underst and the nature of weight gain associated with pioglitazone treatment in NASH we analyzed 35 patients who completed tests for determination of whole body fat ( WBF ) and total body water ( TBW ) .  METHODS Twenty-one patients received pioglitazone and 14 placebo in a double-blind , r and omized fashion for a period of 6 months . WBF and TBW were measured before and after treatment using DXA , a water dilution technique and bioimpedance . RESULTS Pioglitazone increased body weight ( from 93.6+/-4.2 to 96.1+/-4.5 kg , p<0.003 ) and WBF measured with DXA ( from 32.9+/-2.1 to 35.4+/-2.5 kg , p<0.002 ) while no changes were seen with placebo .  Total body water was not altered significantly either after pioglitazone ( from 45.4+/-2.3 to 45.6+/-2.7 l , p = NS ) or placebo . Muscle hydration and extracellular water were unchanged both by pioglitazone and placebo treatments . CONCLUSIONS Six months of pioglitazone  treatment in patients with NASH is associated with weight gain that is attributable to an increase in adipose tissue mass and not to water retention background Hyper and rogenism , hyperinsulinaemia and obesity play a key and coordinating roles in the pathogenesis of polycystic ovary syndrome ( PCOS ) , contributing in different ways to the clinical expression of the syndrome . Weight loss is beneficial , but the additional administration of insulin‐lowering drugs , such as metformin , and anti and rogens may produce further benefits , due to their different spectrum of action . The effects of long‐term metformin and flutamide , an anti and rogen drug , added alone or in combination with a low‐calorie diet , on body weight and fat distribution , and rogens , metabolic parameters and clinical status in obese women with PCOS were investigated Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome ( PCOS ) . Dietary-induced weight loss and the administration of insulin-lowering drugs , such as metformin , are usually followed by improved hyper and rogenism and related clinical abnormalities . This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight , fat distribution , the glucose-insulin system , and hormones in a group of 20 obese PCOS women [ body mass index ( BMI ) > 28 kg/m2 ] with the abdominal phenotype ( waist to hip ratio > 0.80 ) , and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS . At baseline , we measured sex hormone , sex hormone-binding globulin ( SHBG ) , and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography ( CT ) at the L4-L5 level , to measure sc adipose tissue area ( SAT ) and visceral adipose tissue area . All women were then given a low-calorie diet ( 1,200 - 1,400 kcal/day ) alone for one month , after which anthropometric parameters and CT scan were newly measured . While continuing dietary treatment , PCOS women and obese controls were subsequently placed , in a r and om order , on metformin ( 850 mg/os , twice daily ) ( 12 and 8 , respectively ) or placebo ( 8 and 12 , respectively ) , according to a double-blind design , for the following 6 months . Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment . During the treatment period , 3 women of the control group ( all treated with placebo ) were excluded because of noncompliance ; and 2 PCOS women , both treated with metformin , were also excluded because they became pregnant . Therefore , the women cohort available for final statistical analysis included 18 PCOS ( 10 treated with metformin and 8 with placebo ) and 17 control women ( 8 treated with metformin and 9 with placebo )  . The treatment was well tolerated . In the PCOS group , metformin therapy improved hirsutism and menstrual cycles significantly more than placebo .  Baseline anthropometric and CT parameters were similar in all groups . Hypocaloric dieting for 1 month similarly reduced BMI values and the waist circumference in both PCOS and control groups , without any significant effect on CT scan parameters . In both PCOS and control women , however , metformin treatment reduced body weight and BMI significantly more than placebo . Changes in the waist-to-hip ratio values were similar in PCOS women and controls , regardless of pharmacological treatment . Metformin treatment significantly decreased SAT values in both PCOS and control groups , although only in the latter group were SAT changes significantly greater than those observed during the placebo treatment . On the contrary , visceral adipose tissue area values significantly decreased during metformin treatment in both PCOS and control groups , but only in the former was the effect of metformin treatment significantly higher than that of placebo .  Fasting insulin significantly decreased in both PCOS women and controls , regardless of treatment , whereas glucose-stimulated insulin significantly decreased only in PCOS women and controls treated with metformin . Neither metformin or placebo significantly modified the levels of LH , FSH , dehydroepi and rosterone sulphate , and progesterone in any group , whereas testosterone concentrations decreased only in PCOS women treated with metformin .  SHBG concentrations remained unchanged in all PCOS women ; whereas in the control group , they significantly increased after both metformin and placebo .  Leptin levels decreased only during metformin treatment in both PCOS and control groups . ( ABSTRACT TRUNCATED BACKGROUND Insulin resistance and increased ovarian cytochrome P450c17 alpha activity are both features of the polycystic ovary syndrome . P450c17 alpha , which is involved in and rogen bio synthesis , has both 17 alpha-hydroxylase and 17,20-lyase activities . Increased activity of this enzyme results in exaggerated conversion of progesterone to 17 alpha-hydroxyprogesterone in response to stimulation by gonadotrophin . We hypothesized that hyperinsulinemia stimulates ovarian P450c17 alpha activity . METHODS We measured fasting serum steroid concentrations and the response of serum 17 alpha-hydroxyprogesterone to leuprolide , a gonadotrophin-releasing hormone agonist , and performed oral glucose-tolerance tests before and after oral administration of either metformin ( 500 mg three times daily ) or placebo for four to eight weeks in 24 obese women with the polycystic ovary syndrome . RESULTS In the 11 women given metformin , the mean ( + /- SE ) area under the serum insulin curve after oral glucose administration decreased from 9303 + /- 1603 to 4982 + /- 911 microU per milliliter per minute ( 56 + /- 10 to 30 + /- 6 nmol per liter per minute ) ( P = 0.004 ) . This decrease was associated with a reduction in the basal serum 17 alpha-hydroxyprogesterone concentration from 135 + /- 21 to 66 + /- 7 ng per deciliter ( 4.1 + /- 0.6 to 2.0 + /- 0.2 nmol per liter ) ( P = 0.01 ) and a reduction in the leuprolide-stimulated peak serum 17 alpha-hydroxyprogesterone concentration from 455 + /- 54 to 281 + /- 52 ng per deciliter ( 13.7 + /- 1.6 to 8.5 + /- 1.6 nmol per liter ) ( P = 0.01 ) . The serum 17 alpha-hydroxyprogesterone values increased slightly in the placebo group . In the metformin group , the basal serum luteinizing hormone concentration decreased from 8.5 + /- 2.2 to 2.8 + /- 0.5 mlU per milliliter ( P = 0.01 ) , the serum free testosterone concentration decreased from 0.34 + /- 0.07 to 0.19 + /- 0.05 ng per deciliter ( 12 + /- 3 to 7 + /- 2 pmol per liter ) ( P = 0.009 ) , and the serum sex hormone-binding globulin concentration increased from 0.8 + /- 0.2 to 2.3 + /- 0.6 microgram per deciliter ( 29 + /- 7 to 80 + /- 21 nmol per liter ) ( P < 0.001 ) . None of these values changed significantly in the placebo group . CONCLUSIONS In obese women with the polycystic ovary syndrome , decreasing serum insulin concentrations with metformin reduces ovarian cytochrome P450c17 alpha activity and ameliorates hyper and rogenism Severe insulin resistance is a key abnormality in obese women with polycystic ovary syndrome ( PCOS ) . The purpose of this study was to evaluate whether pioglitazone decreases insulin resistance ( IR ) and hyper and rogenism to the same extent as metformin in obese women with PCOS who have not received any previous treatment . Fifty-two women with PCOS were r and omly allocated to receive either pioglitazone ( 30 mg/d , n = 25 ) or metformin ( 850 mg three times daily , n = 27 ) and were assessed before and after 6 months . Body weight , body mass index , and waist to hip ratio increased significantly ( P < /= 0.05 ) after pioglitazone treatment but not after metformin treatment . Fasting serum insulin concentration ( P < 0.001 for both drugs ) and the area under the insulin curve during a 2-h oral glucose tolerance test decreased after pioglitazone ( P < 0.002 ) or metformin ( P < 0.05 ) treatment . IR ( homeostasis model of assessment -IR index ) decreased and insulin sensitivity ( elevation of the quantitative insulin sensitivity check index and the fasting glucose to insulin ratio ) increased ( P < /= 0.008 ) after treatment with either drug . Hirsutism ( P < 0.05 ) and serum concentrations of free testosterone ( P < 0.02 ) and and rostenedione ( P < 0.01 ) declined to a similar extent after treatment with the drugs . Treatment with pioglitazone or metformin was associated with the occurrence of pregnancy ( n = 5 and n = 3 , respectively ) . These results suggest that pioglitazone is as effective as metformin in improving insulin sensitivity and hyper and rogenism , despite an increase in body weight , body mass index , and the waist to hip ratio associated with pioglitazone BACKGROUND Our aim was to investigate the effect of pre-treatment with metformin in women with polycystic ovary syndrome ( PCOS ) scheduled for IVF stimulation 
    Output:
    
There was some indication of greater effect with high-dose metformin ( > 1500 mg/day ) and longer duration of therapy ( > 8 weeks ) .
A structured lifestyle modification programme to achieve weight loss should still be the first line treatment in obese women with or without PCOS .
Adequately powered RCTs are required to confirm the findings of this review and to assess whether the addition of high-dose metformin therapy to a structured lifestyle modification programme might contribute to more weight loss