***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: BACKGROUND Obese women with the polycystic ovary syndrome are relatively unresponsive to the induction of ovulation by clomiphene . We hypothesized that reducing insulin secretion by administering metformin would increase the ovulatory response to clomiphene . METHODS We performed oral glucose-tolerance tests before and after the administration of 500 mg of metformin or placebo three times daily for 35 days in 61 obese women with the polycystic ovary syndrome . Women who did not ovulate spontaneously were then given 50 mg of clomiphene daily for five days while continuing to take metformin or placebo .  Serum progesterone was measured on days 14 , 28 , 35 , 44 , and 53 , and ovulation was presumed to have occurred if the concentration exceeded 8 ng per milliliter ( 26 nmol per liter ) on any of these days . RESULTS Twenty-one women in the metformin group and 25 women in the placebo group were given clomiphene because they did not ovulate spontaneously during the first phase of the study . Among the 21 women given metformin plus clomiphene , the mean ( + /-SE ) area under the serum insulin curve after oral glucose administration decreased from 6745+/-2021 to 3479+/-455 microU per milliliter per minute ( 40.5+/-12.1 to 20.9+/-2.7 nmol per liter per minute , P=0.03 ) , but it did not change significantly in the 25 women given placebo plus clomiphene . Nineteen of the 21 women ( 90 percent ) who received metformin plus clomiphene  ovulated ( mean peak serum progesterone concentration , 23.8+/-3.4 ng per milliliter [ 7.6+/-10.9 nmol per liter ] ) . Two of the 25 women ( 8 percent ) who received placebo plus clomiphene  ovulated ( P<0.001 ) . Overall , 31 of the 35 women ( 89 percent ) treated with metformin  ovulated spontaneously or in response to clomiphene  , as compared with 3 of the 26 women ( 12 percent ) treated with placebo . CONCLUSIONS The ovulatory response to clomiphene can be increased in obese women with the polycystic ovary syndrome by decreasing insulin secretion with metformin BACKGROUND Medical induction of ovulation using clomiphene citrate ( CC ) as first line and exogenous gonadotrophins as second line forms the classical treatment algorithm in normogonadotrophic anovulatory infertility . Because the chances of success following classical ovulation induction are not well established , a shift in first-line therapy can be observed towards alternative treatment . The study aim was to : ( i ) reliably assess the probability of singleton live birth following classical induction of ovulation ; and ( ii ) construct a prediction model , based on individual patient characteristics assessed upon st and ardized initial screening , to help identify patients with poor chances of success . METHODS A total of 240 consecutive women visiting a specialist academic fertility unit with a history of infertility , oligomenorrhoea or amenorrhoea , and normal FSH and estradiol serum concentrations ( WHO group 2 ) was prospect ively followed . The women had not been previously treated with ovulation-inducing agents . All patients commenced with CC . Patients who did not ovulate within three treatment cycles of incremental daily doses up to 150 mg for 5 consecutive days or ovulatory CC patients who did not conceive within six cycles , subsequently underwent gonadotrophin induction of ovulation applying a step-down dose regimen . The main outcome measure was pregnancy result ing in singleton live birth . Cox regression was used to construct a multivariable prediction model . RESULTS Overall , there were 134 pregnancies ending in a singleton live birth ( 56 % of women ) . The cumulative pregnancy rate after 12 and 24 months of follow-up was 50 % and 71 % respectively . Polycystic ovary syndrome ( PCOS ) patients ( 49 % ) , clearly non-PCOS patients ( 13 % ) and the in-between group did not differ in prognosis ( P = 0.9 ) . The multivariable Cox regression model contained the woman 's age , the insulin : glucose ratio and duration of infertility . With a cut-off value of 30 % for low chance , the model predicted probabilities at 12 months lower than this cut-off for 25 out of 240 patients ( 10.4 % ) . CONCLUSIONS Classical ovulation induction produces very good results in normogonadotrophic anovulatory infertility . Alternative treatment options may not be indicated as first-line therapy in these patients , except for subgroups with poor prognosis . These women can be identified by older age , longer duration of infertility and higher insulin : glucose ratio 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 BACKGROUND This study aims to evaluate the impact of metformin on ovarian response when co-administered during recombinant (r)FSH using the low-dose step-up protocol in clomiphene citrate-resistant polycystic ovarian syndrome ( PCOS ) patients with normal glucose tolerance . METHODS AND RESULTS Thirty-two patients were r and omized to metformin  ( n = 16 ) and placebo  ( n = 16 ) groups . Hormonal assessment , a 75 g oral glucose tolerance test ( OGTT ) and a frequently sample d i.v . glucose tolerance test ( FSIGTT ) were performed before and after oral administration of metformin ( 850 mg twice daily ) or placebo for 6 weeks . Recombinant FSH treatment was undertaken , thereafter , in women who did not ovulate on metformin ( n = 10 ) or placebo ( n = 15 ) . There was no significant change in all insulin sensitivity indices in both groups . The only change noted was a decline in mean serum free testosterone concentration in the metformin group ( P = 0.049 ) . One patient on placebo and six patients on metformin  ovulated spontaneously ( P < 0.05 ) . All parameters of ovarian response were comparable between the two groups during rFSH treatment . Combining the 6 week placebo or metformin-only period with a single rFSH treatment cycle , the overall ovulation rates were 75 and 94 % in the placebo and metformin groups respectively ( P > 0.05 ) . The respective figures for pregnancy were 6.3 and 31.3 % ( P > 0.05 ) . CONCLUSIONS Metformin may restore ovulation with no improvement on insulin resistance in clomiphene citrate-resistant PCOS patients with normal glucose tolerance , but has no significant effect on ovarian response during rFSH treatment In 43 amenorrheic women with polycystic ovary syndrome ( PCOS ) , 31 ( 74 % ) with fasting hyperinsulinemia ( > or = 20 microU/mL ) , our aim was to determine whether Metformin ( Bristol-Myers Squibb , Princeton , NJ ) , which reduces hyperinsulinemia , would reverse the endocrinopathy of PCOS , allowing resumption of regular normal menses . A second aim was to assess the effects of weight loss versus other Metformin-induced effects on ovarian function , and to determine if there were different responses to Metformin between those who lost weight and those who did not . A third aim was to assess associations between PCOS , 4G/5 G polymorphism in the promoter sequence of the plasminogen activator inhibitor-1 gene ( PAI-1 gene ) , and PAI activity ( PAI-Fx ) . Of the 43 women , 40 ( 93 % ) had normal fasting blood glucose and 37 had normal hemoglobin A1C ( HgA1C ) ; onlythree ( 7 % ) had type 2 diabetes mellitus .  Metformin ( 1.5 to 2.25 g/d ) was given for 6.1+/-5.1 months ( range , 1.5 to 24 ) , to 16 patients for less than 3 months , to 12 for 3 to 6 months , and to 15 for at least 6 months . On Metformin , 39 of 43 patients ( 91 % ) resumed normal menses . The percentage of women resuming normal menses did not differ among treatment duration groups ( P<.1 ) or among dose groups ( P>.1 ) . The body mass index ( BMI ) decreased from 36.4 + 7 Kg/m2 at study entry to 35.1+/-6.7 on Metformin ( P=.0008 ) . Of 43 patients , 28 ( 67 % ) lost weight ( 1 to 69 pounds ) , with nine ( 21 % ) losing at least 12 pounds . On Metformin , the median fasting serum insulin decreased from 26 microU/mL to 22 ( P=.019 ) , testosterone decreased from 61 ng/dL to 47 ( P=.003 ) , and estradiol increased from 41 pg/mL to 71 ( P=.0001 ) . Metformin-induced  improvements in ovarian function were independent of weight loss ( testosterone decrease , P<.002 ; estradiol increase , P<.0004 ) . The change in response variables on Metformin did not differ ( P>.05 ) between those who lost weight and those who did not , excepting Lp(a ) , which increased 4 mg/dL in those who lost weight and decreased 9 mg/dL in those who did not ( P = .003 ) . The change in response variables on Metformin did not differ among the five quintiles of weight loss , excepting fasting glucose ( P<.05 ) , which increased 6 mg/dL in those who lost the least weight on Metformin versus those in the 60th to 80th percentile for weight loss , in whom glucose decreased 33 mg/dL. Although the pretreatment fasting serum insulin was not significantly correlated with testosterone ( r=.24 , P=.13 ) or and rostenedione ( r=.27 , P=.09 ) , on Metformin , the change 
    Output:
    
Metformin is effective for ovulation induction and cycle regulation in this group of patients .
Metformin plus CC appears to be very effective for achievement of pregnancy compared to CC alone .