human
***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 determine whether the use of oral hypoglycemic agents during early pregnancy is associated with a risk of congenital malformations in infants of mothers with non-insulin-dependent diabetes mellitus ( NIDDM ) independent of maternal metabolic control . RESEARCH DESIGN AND METHODS From a prospect ively collected data -base of pregnancies complicated by diabetes at a large urban medical center , we identified 332 consecutive infants born to women with NIDDM who did not participate in a preconceptional diabetes care program . Stepwise logistical regression was used to identify maternal characteristics that were independently associated with risks of major and minor congenital malformations in infants . RESULTS Overall , 56 ( 16.9 % ) of the 332 infants were born with congenital anomalies ( 11.7 % major anomalies and 5.1 % minor anomalies ) . Analysis of data from subgroups of women who were treated with diet therapy , exogenous insulin , or sulfonylurea compounds during the first 8 weeks of gestation did not reveal statistically significant differences in major or minor malformation rates among the three groups . Stepwise logistic regression analysis revealed two maternal characteristics that were independently associated with major malformations in infants : maternal HbA1c at initial presentation for care ( direct relationship ; P = 0.0007 ) and the maternal age at onset of diabetes ( inverse relationship ; P = 0.009 ) . The risk of major malformations was unrelated to the mode of antidiabetic therapy during early pregnancy . No relationship was found between maternal glycemia or treatment modality and rates of minor congenital anomalies . CONCLUSIONS These data indicate that , in the absence of special preconceptional care , NIDDM is associated with a risk for major congenital anomalies that is in the range reported for pregnancies complicated by insulin-dependent diabetes mellitus . Moreover , the risk in individual patients appears to be related to maternal glycemic control rather than to the mode of antidiabetic therapy during early pregnancy 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 OBJECTIVE To assess whether metformin safely reduced development of gestational diabetes in women with the polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve and retrospective study . SETTING Outpatient clinical research center . PATIENT(S ) The prospect i ve study included 33 nondiabetic women with PCOS who conceived while taking metformin and had live births ; of these , 28 were taking metformin through delivery . The retrospective study included 39 nondiabetic women with PCOS who had live birth pregnancies without metformin therapy .  INTERVENTION(S ) Metformin , 2.55 g/d , throughout pregnancy in women with PCOS . MAIN OUTCOME MEASURE(S ) Development of gestational diabetes in women with PCOS . RESULT ( S ) Before metformin therapy , after covariance adjustment for age , the two cohorts did not differ in height , weight , basal metabolic index , insulin , insulin resistance , or insulin secretion . Both cohorts had high fasting insulin , were insulin resistant , and had high insulin secretion . Among the 33 women who received metformin  , gestational diabetes developed in 1 of 33 ( 3 % ) pregnancies versus 8 of 12 ( 67 % ) of their previous pregnancies without metformin . Among the 39 women who did not take metformin  , gestational diabetes developed in 14 of 60 ( 23 % ) pregnancies . When all live births were combined , gestational diabetes occurred in 22 of 72 pregnancies ( 31 % ) in women who did not take metformin versus 1 of 33 pregnancies ( 3 % ) in those who took metformin . With gestational diabetes as the response variable and age at delivery and treatment group ( metformin or no metformin ) as explanatory variables , the odds ratio for gestational diabetes in women with metformin versus without metformin was 0.093 ( 95 % CI : 0.011 to 0.795 ) . With gestational diabetes in 93 pregnancies as the response variable and age at delivery and treatment group ( metformin no metformin ) as explanatory variables , the odds ratio of gestational diabetes in pregnancies in women taking metformin versus without metformin was 0.115 ( 95 % CI : 0.014 to 0.938 ) . CONCLUSION ( S ) In PCOS , use of metformin is associated with a 10-fold reduction in gestational diabetes ( 31 % to 3 % ) . It also reduces insulin resistance and insulin secretion , thus decreasing the secretory dem and s imposed on pancreatic beta-cells by insulin resistance and pregnancy BACKGROUND We sought to determine whether metformin , which had facilitated conception in 72 oligoamenorrhoeic women with polycystic ovary syndrome ( PCOS ) , would safely reduce the rate of first trimester spontaneous abortion ( SAB ) and increase the number of live births without teratogenicity . METHODS Seventy-two oligoamenorrheic women with PCOS conceived on metformin ( 2.55 g/day ) . They were prospect ively assessed in an outpatient clinical research centre . Outcome measures included number of first trimester SAB , live births , normal ongoing pregnancies > or=13 weeks , gestational diabetes ( GD ) , congenital defects ( CD ) , birthweight and height , as well as weight , height , and motor and social development during the first 6 months of life . RESULTS Of the 84 fetuses , to date there have been 63 normal live births without CD ( 75 % ) , 14 first trimester SAB ( 17 % ) , and seven ongoing pregnancies > or=13 weeks with normal sonograms without CD ( 8 % ) . Previously , without metformin , 40 of the 72 women had 100 pregnancies ( 100 fetuses ) with 34 ( 34 % ) live births and 62 ( 62 % ) first trimester SAB . In current pregnancies on metformin in these 40 women ( 46 pregnancies , 47 fetuses ) , there have been 33 live births ( 70 % ) , two pregnancies ongoing > /=13 weeks ( 4 % ) , and 12 SAB ( 26 % ) ( P < 0.0001 ) . There was no maternal lactic acidosis , and no maternal or neonatal hypoglycaemia . Fasting entry serum insulin was a significant explanatory variable for total ( previous and current ) first trimester SAB , odds ratio 1.32 ( for each 5 micro U/ml rise in insulin ) , 95 % CI 1.09 - 1.60 ( P = 0.005 ) . On metformin , GD developed in 4 % of pregnancies versus 26 % of previous pregnancies without metformin , P = 0.025 . There have been no major CD in the 63 live births or CD by sonography in the seven fetuses < or=13 weeks . In the 63 live births , neither weight nor height differed from the normal neonatal population . At 6 month follow-up , height was greater ( P = 0.008 ) and weight did not differ from the normal paediatric population ; motor and social development were normal . CONCLUSIONS Metformin therapy during pregnancy in women with PCOS was safely associated with reduction in SAB and in GD , was not teratogenic , and did not adversely affect birthweight or height , or height , weight , and motor and social development at 3 and 6 months of life 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 OBJECTIVE To evaluate the effect of metformin therapy on hyper and rogenism , insulin resistance , cervical scores , ovulation , and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled study . SETTING Infertility clinic of a tertiary referral center . PATIENT(S ) Fifty-six women with clomiphene citrate-resistant PCOS . INTERVENTION(S ) Two cycles of oral metformin therapy ( 850 mg , twice daily ) in group I and placebo therapy ( twice daily ) in group II . Clomiphene citrate ( 100 mg/day ) on cycle days 3 - 7 of the second cycle in both groups . MAIN OUTCOME MEASURE(S ) Insulin , T , DHEAS , FSH , LH , body mass index ( BMI ) , waist-to-hip ratio , endometrial thickness , cervical score , ovulation , and pregnancy rates in clomiphene-induced cycles after metformin therapy . RESULT ( S ) Metformin therapy result ed in a significant decrease in total T , LH level , LH/FSH ratio , insulin resistance , and mean BMI . No difference in waist-to-hip ratio , DHEAS level , and fasting insulin level was observed . Clomiphene citrate induction result ed in higher ovulation rates and thicker endometrium in the metformin group than in the placebo group . There was higher cumulative pregnancy 
    Output:
    
agent
***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 determine whether the use of oral hypoglycemic agents during early pregnancy is associated with a risk of congenital malformations in infants of mothers with non-insulin-dependent diabetes mellitus ( NIDDM ) independent of maternal metabolic control . RESEARCH DESIGN AND METHODS From a prospect ively collected data -base of pregnancies complicated by diabetes at a large urban medical center , we identified 332 consecutive infants born to women with NIDDM who did not participate in a preconceptional diabetes care program . Stepwise logistical regression was used to identify maternal characteristics that were independently associated with risks of major and minor congenital malformations in infants . RESULTS Overall , 56 ( 16.9 % ) of the 332 infants were born with congenital anomalies ( 11.7 % major anomalies and 5.1 % minor anomalies ) . Analysis of data from subgroups of women who were treated with diet therapy , exogenous insulin , or sulfonylurea compounds during the first 8 weeks of gestation did not reveal statistically significant differences in major or minor malformation rates among the three groups . Stepwise logistic regression analysis revealed two maternal characteristics that were independently associated with major malformations in infants : maternal HbA1c at initial presentation for care ( direct relationship ; P = 0.0007 ) and the maternal age at onset of diabetes ( inverse relationship ; P = 0.009 ) . The risk of major malformations was unrelated to the mode of antidiabetic therapy during early pregnancy . No relationship was found between maternal glycemia or treatment modality and rates of minor congenital anomalies . CONCLUSIONS These data indicate that , in the absence of special preconceptional care , NIDDM is associated with a risk for major congenital anomalies that is in the range reported for pregnancies complicated by insulin-dependent diabetes mellitus . Moreover , the risk in individual patients appears to be related to maternal glycemic control rather than to the mode of antidiabetic therapy during early pregnancy 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 OBJECTIVE To assess whether metformin safely reduced development of gestational diabetes in women with the polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve and retrospective study . SETTING Outpatient clinical research center . PATIENT(S ) The prospect i ve study included 33 nondiabetic women with PCOS who conceived while taking metformin and had live births ; of these , 28 were taking metformin through delivery . The retrospective study included 39 nondiabetic women with PCOS who had live birth pregnancies without metformin therapy .  INTERVENTION(S ) Metformin , 2.55 g/d , throughout pregnancy in women with PCOS . MAIN OUTCOME MEASURE(S ) Development of gestational diabetes in women with PCOS . RESULT ( S ) Before metformin therapy , after covariance adjustment for age , the two cohorts did not differ in height , weight , basal metabolic index , insulin , insulin resistance , or insulin secretion . Both cohorts had high fasting insulin , were insulin resistant , and had high insulin secretion . Among the 33 women who received metformin  , gestational diabetes developed in 1 of 33 ( 3 % ) pregnancies versus 8 of 12 ( 67 % ) of their previous pregnancies without metformin . Among the 39 women who did not take metformin  , gestational diabetes developed in 14 of 60 ( 23 % ) pregnancies . When all live births were combined , gestational diabetes occurred in 22 of 72 pregnancies ( 31 % ) in women who did not take metformin versus 1 of 33 pregnancies ( 3 % ) in those who took metformin . With gestational diabetes as the response variable and age at delivery and treatment group ( metformin or no metformin ) as explanatory variables , the odds ratio for gestational diabetes in women with metformin versus without metformin was 0.093 ( 95 % CI : 0.011 to 0.795 ) . With gestational diabetes in 93 pregnancies as the response variable and age at delivery and treatment group ( metformin no metformin ) as explanatory variables , the odds ratio of gestational diabetes in pregnancies in women taking metformin versus without metformin was 0.115 ( 95 % CI : 0.014 to 0.938 ) . CONCLUSION ( S ) In PCOS , use of metformin is associated with a 10-fold reduction in gestational diabetes ( 31 % to 3 % ) . It also reduces insulin resistance and insulin secretion , thus decreasing the secretory dem and s imposed on pancreatic beta-cells by insulin resistance and pregnancy BACKGROUND We sought to determine whether metformin , which had facilitated conception in 72 oligoamenorrhoeic women with polycystic ovary syndrome ( PCOS ) , would safely reduce the rate of first trimester spontaneous abortion ( SAB ) and increase the number of live births without teratogenicity . METHODS Seventy-two oligoamenorrheic women with PCOS conceived on metformin ( 2.55 g/day ) . They were prospect ively assessed in an outpatient clinical research centre . Outcome measures included number of first trimester SAB , live births , normal ongoing pregnancies > or=13 weeks , gestational diabetes ( GD ) , congenital defects ( CD ) , birthweight and height , as well as weight , height , and motor and social development during the first 6 months of life . RESULTS Of the 84 fetuses , to date there have been 63 normal live births without CD ( 75 % ) , 14 first trimester SAB ( 17 % ) , and seven ongoing pregnancies > or=13 weeks with normal sonograms without CD ( 8 % ) . Previously , without metformin , 40 of the 72 women had 100 pregnancies ( 100 fetuses ) with 34 ( 34 % ) live births and 62 ( 62 % ) first trimester SAB . In current pregnancies on metformin in these 40 women ( 46 pregnancies , 47 fetuses ) , there have been 33 live births ( 70 % ) , two pregnancies ongoing > /=13 weeks ( 4 % ) , and 12 SAB ( 26 % ) ( P < 0.0001 ) . There was no maternal lactic acidosis , and no maternal or neonatal hypoglycaemia . Fasting entry serum insulin was a significant explanatory variable for total ( previous and current ) first trimester SAB , odds ratio 1.32 ( for each 5 micro U/ml rise in insulin ) , 95 % CI 1.09 - 1.60 ( P = 0.005 ) . On metformin , GD developed in 4 % of pregnancies versus 26 % of previous pregnancies without metformin , P = 0.025 . There have been no major CD in the 63 live births or CD by sonography in the seven fetuses < or=13 weeks . In the 63 live births , neither weight nor height differed from the normal neonatal population . At 6 month follow-up , height was greater ( P = 0.008 ) and weight did not differ from the normal paediatric population ; motor and social development were normal . CONCLUSIONS Metformin therapy during pregnancy in women with PCOS was safely associated with reduction in SAB and in GD , was not teratogenic , and did not adversely affect birthweight or height , or height , weight , and motor and social development at 3 and 6 months of life 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 OBJECTIVE To evaluate the effect of metformin therapy on hyper and rogenism , insulin resistance , cervical scores , ovulation , and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled study . SETTING Infertility clinic of a tertiary referral center . PATIENT(S ) Fifty-six women with clomiphene citrate-resistant PCOS . INTERVENTION(S ) Two cycles of oral metformin therapy ( 850 mg , twice daily ) in group I and placebo therapy ( twice daily ) in group II . Clomiphene citrate ( 100 mg/day ) on cycle days 3 - 7 of the second cycle in both groups . MAIN OUTCOME MEASURE(S ) Insulin , T , DHEAS , FSH , LH , body mass index ( BMI ) , waist-to-hip ratio , endometrial thickness , cervical score , ovulation , and pregnancy rates in clomiphene-induced cycles after metformin therapy . RESULT ( S ) Metformin therapy result ed in a significant decrease in total T , LH level , LH/FSH ratio , insulin resistance , and mean BMI . No difference in waist-to-hip ratio , DHEAS level , and fasting insulin level was observed . Clomiphene citrate induction result ed in higher ovulation rates and thicker endometrium in the metformin group than in the placebo group . There was higher cumulative pregnancy 
    Output:
    