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: BACKGROUND Investigation of a possible effect of metformin on and rogen levels in pregnant women with polycystic ovary syndrome ( PCOS ) . METHODS A prospect i ve , r and omized , double-blind , placebo-controlled pilot study was conducted . Forty pregnant women with PCOS received diet and lifestyle counselling  and were r and omized to either metformin 850 mg twice daily or placebo . Primary outcome measures were changes in serum levels of dehydroepi and rosterone sulphate , and rostenedione , testosterone , sex hormone-binding globulin , and free testosterone index . Secondary outcome measures were pregnancy complications and outcome . Two-tailed t-tests and chi2-tests were used . RESULTS Maternal and rogen levels were unaffected by metformin treatment in pregnant women with PCOS . While none of the 18 women in the metformin group experienced a severe pregnancy or post-partum complication , seven of the 22 ( 32 % ) women experienced severe complications in the placebo group ( P = 0.01 ) . CONCLUSIONS Metformin treatment did not reduce maternal and rogen levels in pregnant women with PCOS . In the metformin-treated group we observed a reduction of severe , pregnancy and post-partum complications .  Metformin treatment of pregnant PCOS women may reduce complications during pregnancy and in the post-partum period This study was conducted to assess the effect of noninsulin-dependent diabetes mellitus ( NIDDM ) and gender on the pharmacokinetics of metformin and to investigate whether or not metformin exhibits dose-dependent pharmacokinetics . The pharmacodynamic effects ( on plasma glucose and insulin ) of metformin in patients with NIDDM and in healthy subjects also were assessed . Nine patients with NIDDM and 9 healthy subjects received 4 single-blind single-dose treatments of metformin HCL ( 850 mg , 1,700 mg , 2,550 mg , and placebo ) and a multiple-dose treatment of 850 mg metformin HCL ( 3 times daily for 19 doses ) . After each single-dose treatment and the final dose of the multiple-dose phase , multiple plasma and urine sample s were collected for 48 hours and assayed for  metformin levels . Plasma sample s were also assayed for glucose and insulin levels . There were no significant differences in  metformin kinetics in patients with NIDDM compared with healthy subjects , in men compared with women , or during multiple-dose treatment versus single-dose treatment . Plasma concentrations of metformin  increase less than proportionally to dose , most likely due to a decrease in percent absorbed . In patients with NIDDM , single doses of 1,700-mg or higher of metformin significantly decrease postpr and ial , but not prepr and ial , glucose concentrations and do not influence insulin concentrations . With multiple doses , both prepr and ial and postpr and ial glucose concentrations and prepr and ial insulin concentrations were significantly lower than with placebo . The effect of metformin on glucose level is correlated with the average fasting plasma glucose level without drug . In healthy subjects , single and multiple doses of metformin showed no effect on plasma glucose , but significantly attenuated the rise in immediate postpr and ial insulin levels Please cite this paper as : Ijäs H , Vääräsmäki M , Morin‐Papunen L , Keravuo R , Ebeling T , Saarela T , Raudaskoski T. Metformin should be considered in the treatment of gestational diabetes : a prospect i ve r and omised study . BJOG 2011;118:880–885 AIM The objective of this study was to explore the result of pretreatment and concomitant use of metformin with clomiphene citrate ( CC ) and rFSH for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome ( PCOS ) . MATERIAL AND METHODS This r and omized controlled trial was done in the Dhaka Medical College and Hospital and the Infertility Care and Research Centre , Dhaka , Bangladesh . A total of 165 infertile patients with CC-resistant PCOS who attended for treatment were the target population for this study . Patients were divided into three groups : groups A and B were given metformin and group C was the control . Along with metformin , group A received CC and group B received rFSH . Group C was treated with only rFSH . Metformin was given 1500 mg daily for 4 weeks . Afterwards CC or rFSH were added for induction of ovulation along with metformin . Six ovulatory cycles were assessed . Treatment was terminated when there was no response with maximum dose of CC and rFSH or after six ovulatory cycles without pregnancy or after achieving pregnancy . A P-value of < 0.5 was considered as significant . RESULTS Ovulation ( 89.09 % ) and pregnancy ( 54.55 % ) rates were higher in group B. Ovulation ( 74.55 % ) and pregnancy ( 29.09 % ) rates were also satisfactory in group C but a dose of rFSH requirement was significantly higher ( P = 0.000 ) . In group A , both ovulation and pregnancy rate were much lower than the other two groups ( 27.27 % and 12.73 % , respectively ) . CONCLUSIONS Use of metformin increases the response of ovulation-inducing agents and can be used safely in PCOS OBJECTIVE To evaluate ovulation and pregnancy predictors in infertile polycystic ovary syndrome ( PCOS ) patients who received clomiphene citrate ( CC ) and metformin as first-line ovulation inductors . DESIGN Prospect i ve controlled study . SETTING Departments of Obstetrics and Gynecology , Universities Magna Graecia of Catanzaro and Federico II of Naples , Italy . PATIENT(S ) Eighty infertile anovulatory PCOS patients allocated in two groups matched for body mass index ( BMI ) and age . INTERVENTION(S ) Metformin ( 1700 mg/day for 6 months ) or CC ( 50 mg/day , increasing doses up to 250 mg/day ) . MAIN OUTCOME MEASURE(S ) Baseline clinical and biochemical parameters categorized according to interventions response . RESULT ( S ) The BMI was statistically significantly lower in patients who ovulated under both treatments . Insulin sensitivity indexes were statistically significantly worse in patients who ovulated under metformin and statistically significantly better in patients who ovulated under CC . And rogen levels and free and rogen index ( FAI ) were statistically significantly lower in ovulatory patients than in anovulatory ones who received CC . Age , BMI , infertility duration , and insulin sensitivity indexes were statistically significantly different between patients who achieved and those who did not achieve a pregnancy under both treatments . And rogens levels and FAI were statistically significantly lower in patients who achieved a pregnancy under CC . CONCLUSION ( S ) Insulin-resistant PCOS patients with low BMI are more likely to respond to metformin whereas CC treatment is more effective in less hyper and rogenic and insulin-resistant PCOS patients with low BMI BACKGROUND There are few data in the literature regarding the utility of metfomin before and during gonadotrophin administration in women with polycystic ovary syndrome ( PCOS ) . The aim of the present study was to assess the effect of the pre-treatment and co-administration of metformin in infertile PCOS women treated with controlled ovarian stimulation ( COS ) followed by timed intercourse ( TI ) or intrauterine insemination ( IUI ) . METHODS Seventy insulin-resistant primary infertile women with PCOS were r and omized to receive metformin cloridrate ( 850 mg twice daily ; group A ) or placebo tablets ( two tablets daily ; group B ) for 3 months . Three trials of COS using highly purified urinary FSH ( hpFSH ) plus TI/IUI were performed . Number of ampoules of gonadotrophin used , duration of the ovarian stimulation , cycle cancellation , ovulation , pregnancy , abortion , live birth , mono-ovulatory cycles , multiple pregnancies and ovarian hyperstimulation syndrome ( OHSS ) rates were assessed . RESULTS No difference between groups was detected in ovulation , cycle cancellation , pregnancy , abortion , live birth , multiple pregnancies and OHSS rates . The mono-ovulatory cycle rates were significantly ( P = 0.002 ) more frequent in group A than in group B , whereas the days of stimulation for non-cancelled cycles and the number of vials of gonadotrophins used were significantly ( P < 0.001 ) higher in group A than in group B. CONCLUSION In insulin-resistant women with PCOS  , metformin pre-treatment and co-administration with hpFSH increases the mono-ovulatory cycles BACKGROUND We conducted a r and omized clinical trial to determine whether treatment of women with gestational diabetes mellitus reduced the risk of perinatal complications . METHODS We r and omly assigned women between 24 and 34 weeks ' gestation who had gestational diabetes to receive dietary advice , blood glucose monitoring , and insulin therapy as needed ( the intervention group ) or routine care . Primary outcomes included serious perinatal complications ( defined as death , shoulder dystocia , bone fracture , and nerve palsy ) , admission to the neonatal nursery , jaundice requiring phototherapy , induction of labor , cesarean birth , and maternal anxiety , depression , and health status . RESULTS The rate of serious perinatal complications was significantly lower among the infants of the 490 women in the intervention group than among the infants of the 510 women in the routine-care group ( 1 percent vs. 4 percent ; relative risk adjusted for maternal age , race or ethnic group , and parity , 0.33 ; 95 percent confidence interval , 0.14 to 0.75 ; P=0.01 ) . However , more infants of women in the intervention group were admitted to the neonatal nursery ( 71 percent vs. 61 percent ; adjusted relative risk , 1.13 ; 95 percent confidence interval , 1.03 to 1.23 ; P=0.01 ) . Women in the intervention group had a higher rate of induction of labor than the women in the routine-care group ( 39 percent vs. 29 percent ; adjusted relative risk , 1.36 ; 95 percent confidence interval , 1.15 to 1.62 ; P<0.001 ) , although the rates of cesarean delivery were similar ( 31 percent and 32 percent , respectively ; adjusted relative risk , 0.97 ; 95 percent confidence interval , 0.81 to 1.16 ; P=0.73 ) . At three months post partum , data on the women 's mood and quality of life , available for 573 women , revealed lower rates of depression and higher scores , consistent with improved health status , in the intervention group . CONCLUSIONS Treatment of gestational diabetes reduces serious perinatal morbidity and may also improve the woman 's health-related quality of life AIMS We compared metformin with insulin as treatment of gestational diabetes mellitus ( GDM ) . Furthermore , we aim ed to characterize  metformin-treated patients needing additional insulin to achieve prespecified glucose targets . METHODS We conducted a single centre r and omized controlled study with non-inferiority design comparing metformin and insulin in the treatment of 217 GDM patients having birth weight as primary outcome variable . RESULTS There were no significant differences in mean birth weight expressed in grams [ + 15 ( 90 % confidence interval ( CI ) : -121 to 89 ) ] or SD units [ + 0.04 ( 90 % CI : -0.27 to 0.18 ) ] between the metformin and insulin groups . There were no significant differences in neonatal or maternal data between the groups . Only 23 ( 20.9 % ) of the 110 patients in the metformin group needed additional insulin .  Compared with the patients on metformin only , those needing additional insulin  were older ( p = 0.04 ) , their oral glucose tolerance test had been performed earlier and diabetes therapy started earlier in gestation ( p = 0.01 and p = 0.004 , respectively ) . The risk for additional insulin was 4.6-fold in women with baseline serum fructosamine concentration above median compared with those below median . CONCLUSIONS Metformin is an effective alternative to insulin in the treatment of GDM patients . Serum fructosamine may help in predicting the adequacy of metformin treatment alone OBJECTIVE To evaluate the effects of metformin on the ovarian response to gonadotropins given for in vitro fertilization ( IVF ) programs in patients with polycystic ovary syndrome ( PCOS ) and reduced ovarian reserve . DESIGN Prospect i ve , parallel , r and omized , double-blind , placebo-controlled clinical trial . SETTING Academic departments of obstetrics and gynecology , and a private IVF center . PATIENT(S ) Primary infertile patients with PCOS older than 35 years and /or with a basal follicle-stimulating hormone ( FSH ) level higher than 10 IU/L who were scheduled for IVF cycles . INTERVENTION(S ) Gonadotropin-releasing hormone agonist flare-up protocol and high starting doses of recom 
    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: BACKGROUND Investigation of a possible effect of metformin on and rogen levels in pregnant women with polycystic ovary syndrome ( PCOS ) . METHODS A prospect i ve , r and omized , double-blind , placebo-controlled pilot study was conducted . Forty pregnant women with PCOS received diet and lifestyle counselling  and were r and omized to either metformin 850 mg twice daily or placebo . Primary outcome measures were changes in serum levels of dehydroepi and rosterone sulphate , and rostenedione , testosterone , sex hormone-binding globulin , and free testosterone index . Secondary outcome measures were pregnancy complications and outcome . Two-tailed t-tests and chi2-tests were used . RESULTS Maternal and rogen levels were unaffected by metformin treatment in pregnant women with PCOS . While none of the 18 women in the metformin group experienced a severe pregnancy or post-partum complication , seven of the 22 ( 32 % ) women experienced severe complications in the placebo group ( P = 0.01 ) . CONCLUSIONS Metformin treatment did not reduce maternal and rogen levels in pregnant women with PCOS . In the metformin-treated group we observed a reduction of severe , pregnancy and post-partum complications .  Metformin treatment of pregnant PCOS women may reduce complications during pregnancy and in the post-partum period This study was conducted to assess the effect of noninsulin-dependent diabetes mellitus ( NIDDM ) and gender on the pharmacokinetics of metformin and to investigate whether or not metformin exhibits dose-dependent pharmacokinetics . The pharmacodynamic effects ( on plasma glucose and insulin ) of metformin in patients with NIDDM and in healthy subjects also were assessed . Nine patients with NIDDM and 9 healthy subjects received 4 single-blind single-dose treatments of metformin HCL ( 850 mg , 1,700 mg , 2,550 mg , and placebo ) and a multiple-dose treatment of 850 mg metformin HCL ( 3 times daily for 19 doses ) . After each single-dose treatment and the final dose of the multiple-dose phase , multiple plasma and urine sample s were collected for 48 hours and assayed for  metformin levels . Plasma sample s were also assayed for glucose and insulin levels . There were no significant differences in  metformin kinetics in patients with NIDDM compared with healthy subjects , in men compared with women , or during multiple-dose treatment versus single-dose treatment . Plasma concentrations of metformin  increase less than proportionally to dose , most likely due to a decrease in percent absorbed . In patients with NIDDM , single doses of 1,700-mg or higher of metformin significantly decrease postpr and ial , but not prepr and ial , glucose concentrations and do not influence insulin concentrations . With multiple doses , both prepr and ial and postpr and ial glucose concentrations and prepr and ial insulin concentrations were significantly lower than with placebo . The effect of metformin on glucose level is correlated with the average fasting plasma glucose level without drug . In healthy subjects , single and multiple doses of metformin showed no effect on plasma glucose , but significantly attenuated the rise in immediate postpr and ial insulin levels Please cite this paper as : Ijäs H , Vääräsmäki M , Morin‐Papunen L , Keravuo R , Ebeling T , Saarela T , Raudaskoski T. Metformin should be considered in the treatment of gestational diabetes : a prospect i ve r and omised study . BJOG 2011;118:880–885 AIM The objective of this study was to explore the result of pretreatment and concomitant use of metformin with clomiphene citrate ( CC ) and rFSH for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome ( PCOS ) . MATERIAL AND METHODS This r and omized controlled trial was done in the Dhaka Medical College and Hospital and the Infertility Care and Research Centre , Dhaka , Bangladesh . A total of 165 infertile patients with CC-resistant PCOS who attended for treatment were the target population for this study . Patients were divided into three groups : groups A and B were given metformin and group C was the control . Along with metformin , group A received CC and group B received rFSH . Group C was treated with only rFSH . Metformin was given 1500 mg daily for 4 weeks . Afterwards CC or rFSH were added for induction of ovulation along with metformin . Six ovulatory cycles were assessed . Treatment was terminated when there was no response with maximum dose of CC and rFSH or after six ovulatory cycles without pregnancy or after achieving pregnancy . A P-value of < 0.5 was considered as significant . RESULTS Ovulation ( 89.09 % ) and pregnancy ( 54.55 % ) rates were higher in group B. Ovulation ( 74.55 % ) and pregnancy ( 29.09 % ) rates were also satisfactory in group C but a dose of rFSH requirement was significantly higher ( P = 0.000 ) . In group A , both ovulation and pregnancy rate were much lower than the other two groups ( 27.27 % and 12.73 % , respectively ) . CONCLUSIONS Use of metformin increases the response of ovulation-inducing agents and can be used safely in PCOS OBJECTIVE To evaluate ovulation and pregnancy predictors in infertile polycystic ovary syndrome ( PCOS ) patients who received clomiphene citrate ( CC ) and metformin as first-line ovulation inductors . DESIGN Prospect i ve controlled study . SETTING Departments of Obstetrics and Gynecology , Universities Magna Graecia of Catanzaro and Federico II of Naples , Italy . PATIENT(S ) Eighty infertile anovulatory PCOS patients allocated in two groups matched for body mass index ( BMI ) and age . INTERVENTION(S ) Metformin ( 1700 mg/day for 6 months ) or CC ( 50 mg/day , increasing doses up to 250 mg/day ) . MAIN OUTCOME MEASURE(S ) Baseline clinical and biochemical parameters categorized according to interventions response . RESULT ( S ) The BMI was statistically significantly lower in patients who ovulated under both treatments . Insulin sensitivity indexes were statistically significantly worse in patients who ovulated under metformin and statistically significantly better in patients who ovulated under CC . And rogen levels and free and rogen index ( FAI ) were statistically significantly lower in ovulatory patients than in anovulatory ones who received CC . Age , BMI , infertility duration , and insulin sensitivity indexes were statistically significantly different between patients who achieved and those who did not achieve a pregnancy under both treatments . And rogens levels and FAI were statistically significantly lower in patients who achieved a pregnancy under CC . CONCLUSION ( S ) Insulin-resistant PCOS patients with low BMI are more likely to respond to metformin whereas CC treatment is more effective in less hyper and rogenic and insulin-resistant PCOS patients with low BMI BACKGROUND There are few data in the literature regarding the utility of metfomin before and during gonadotrophin administration in women with polycystic ovary syndrome ( PCOS ) . The aim of the present study was to assess the effect of the pre-treatment and co-administration of metformin in infertile PCOS women treated with controlled ovarian stimulation ( COS ) followed by timed intercourse ( TI ) or intrauterine insemination ( IUI ) . METHODS Seventy insulin-resistant primary infertile women with PCOS were r and omized to receive metformin cloridrate ( 850 mg twice daily ; group A ) or placebo tablets ( two tablets daily ; group B ) for 3 months . Three trials of COS using highly purified urinary FSH ( hpFSH ) plus TI/IUI were performed . Number of ampoules of gonadotrophin used , duration of the ovarian stimulation , cycle cancellation , ovulation , pregnancy , abortion , live birth , mono-ovulatory cycles , multiple pregnancies and ovarian hyperstimulation syndrome ( OHSS ) rates were assessed . RESULTS No difference between groups was detected in ovulation , cycle cancellation , pregnancy , abortion , live birth , multiple pregnancies and OHSS rates . The mono-ovulatory cycle rates were significantly ( P = 0.002 ) more frequent in group A than in group B , whereas the days of stimulation for non-cancelled cycles and the number of vials of gonadotrophins used were significantly ( P < 0.001 ) higher in group A than in group B. CONCLUSION In insulin-resistant women with PCOS  , metformin pre-treatment and co-administration with hpFSH increases the mono-ovulatory cycles BACKGROUND We conducted a r and omized clinical trial to determine whether treatment of women with gestational diabetes mellitus reduced the risk of perinatal complications . METHODS We r and omly assigned women between 24 and 34 weeks ' gestation who had gestational diabetes to receive dietary advice , blood glucose monitoring , and insulin therapy as needed ( the intervention group ) or routine care . Primary outcomes included serious perinatal complications ( defined as death , shoulder dystocia , bone fracture , and nerve palsy ) , admission to the neonatal nursery , jaundice requiring phototherapy , induction of labor , cesarean birth , and maternal anxiety , depression , and health status . RESULTS The rate of serious perinatal complications was significantly lower among the infants of the 490 women in the intervention group than among the infants of the 510 women in the routine-care group ( 1 percent vs. 4 percent ; relative risk adjusted for maternal age , race or ethnic group , and parity , 0.33 ; 95 percent confidence interval , 0.14 to 0.75 ; P=0.01 ) . However , more infants of women in the intervention group were admitted to the neonatal nursery ( 71 percent vs. 61 percent ; adjusted relative risk , 1.13 ; 95 percent confidence interval , 1.03 to 1.23 ; P=0.01 ) . Women in the intervention group had a higher rate of induction of labor than the women in the routine-care group ( 39 percent vs. 29 percent ; adjusted relative risk , 1.36 ; 95 percent confidence interval , 1.15 to 1.62 ; P<0.001 ) , although the rates of cesarean delivery were similar ( 31 percent and 32 percent , respectively ; adjusted relative risk , 0.97 ; 95 percent confidence interval , 0.81 to 1.16 ; P=0.73 ) . At three months post partum , data on the women 's mood and quality of life , available for 573 women , revealed lower rates of depression and higher scores , consistent with improved health status , in the intervention group . CONCLUSIONS Treatment of gestational diabetes reduces serious perinatal morbidity and may also improve the woman 's health-related quality of life AIMS We compared metformin with insulin as treatment of gestational diabetes mellitus ( GDM ) . Furthermore , we aim ed to characterize  metformin-treated patients needing additional insulin to achieve prespecified glucose targets . METHODS We conducted a single centre r and omized controlled study with non-inferiority design comparing metformin and insulin in the treatment of 217 GDM patients having birth weight as primary outcome variable . RESULTS There were no significant differences in mean birth weight expressed in grams [ + 15 ( 90 % confidence interval ( CI ) : -121 to 89 ) ] or SD units [ + 0.04 ( 90 % CI : -0.27 to 0.18 ) ] between the metformin and insulin groups . There were no significant differences in neonatal or maternal data between the groups . Only 23 ( 20.9 % ) of the 110 patients in the metformin group needed additional insulin .  Compared with the patients on metformin only , those needing additional insulin  were older ( p = 0.04 ) , their oral glucose tolerance test had been performed earlier and diabetes therapy started earlier in gestation ( p = 0.01 and p = 0.004 , respectively ) . The risk for additional insulin was 4.6-fold in women with baseline serum fructosamine concentration above median compared with those below median . CONCLUSIONS Metformin is an effective alternative to insulin in the treatment of GDM patients . Serum fructosamine may help in predicting the adequacy of metformin treatment alone OBJECTIVE To evaluate the effects of metformin on the ovarian response to gonadotropins given for in vitro fertilization ( IVF ) programs in patients with polycystic ovary syndrome ( PCOS ) and reduced ovarian reserve . DESIGN Prospect i ve , parallel , r and omized , double-blind , placebo-controlled clinical trial . SETTING Academic departments of obstetrics and gynecology , and a private IVF center . PATIENT(S ) Primary infertile patients with PCOS older than 35 years and /or with a basal follicle-stimulating hormone ( FSH ) level higher than 10 IU/L who were scheduled for IVF cycles . INTERVENTION(S ) Gonadotropin-releasing hormone agonist flare-up protocol and high starting doses of recom 
    Output:
    