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: We prospect ively estimated the prevalence of the polycystic ovary syndrome ( PCOS ) , as defined by the NIH/NICHHD 1990 endocrine criteria , in a population of 154 Caucasian women of reproductive age reporting spontaneously for blood donation .  Anthropometric data ; the presence of hirsutism , acne , and and rogenic alopecia ; and the menstrual history were recorded by a single investigator . In 145 women , blood sample s were also obtained for measurement of serum and rogen levels .  PCOS was defined by the presence of 1 ) oligomenorrhea , 2 ) clinical and /or biochemical hyper and rogenism , and 3 ) exclusion of hyperprolactinemia , thyroid disorders , and nonclassic 21-hydroxylase deficiency . Hirsutism was defined by a modified Ferriman-Gallwey score of 8 or more , acne was considered as a sign of hyper and rogenism when persistent after the second decade of life , and hyper and rogenemia was defined by an increase in circulating testosterone or dehydroepi and rosterone sulfate or an increase in the free and rogen index above the 95th percentile of the control values derived from the nonhirsute , nonacneic women having regular menses who were not receiving hormonal therapy . PCOS was present in 10(6.5 % ) , hirsutism was present in 11 ( 7.1 % ) , and acne was present in 19 ( 12.3 % ) of the 154 women . Our results demonstrate a 6.5 % prevalence of PCOS , as defined , in a minimally biased population of Caucasian women from Spain . The polycystic ovary syndrome , hirsutism , and acne are common endocrine disorders in women 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 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 Metformin appears to improve reproductive function in some women with polycystic ovary syndrome ( PCOS ) . We wished to explore the effect of metformin in women with PCOS undergoing IVF . METHODS A r and omized , placebo-controlled , double-blind study was carried out between 2001 and 2004 . Patients with PCOS undergoing IVF/ICSI treatment using a long GnRH agonist protocol were r and omized to receive metformin ( MET ) , 850 mg , or placebo ( PLA ) tablets twice daily from the start of the down-regulation process until the day of oocyte collection . The primary outcome was to be an improvement in the overall fertilization rate . RESULTS One-hundred and one IVF/ICSI cycles were r and omized to receive metformin ( 52 ) or to receive placebo ( 49 ) . There was no difference in the total dose of rFSH required per cycle ( median dose : MET = 1200 U , PLA = 1300 U ; P = 0.937 ) . The median number of oocytes retrieved per cycle ( MET = 17.2 , PLA = 16.2 ; P = 0.459 ) and the overall fertilization rates ( MET = 52.9 % , PLA = 54.9 % ; P = 0.641 ) did not differ . However , both the clinical pregnancy rates beyond 12 weeks gestation per cycle ( MET = 38.5 % , PLA = 16.3 % ; P = 0.023 ) and per embryo transfer ( MET = 44.4 % , PLA = 19.1 % ; P = 0.022 ) were significantly higher in those treated with metformin . Furthermore , a significant decrease in the incidence of severe ovarian hyperstimulation syndrome ( OHSS ) was observed ( MET = 3.8 % , PLA = 20.4 % ; P = 0.023 ) , and this was still significant after adjustment for BMI , total rFSH dose and age ( OR = 0.15 ; 95 % CI : 0.03 , 0.76 ; P = 0.022 ) . CONCLUSION Short-term co-treatment with metformin for patients with PCOS undergoing IVF/ICSI cycles does not improve the response to stimulation but significantly improves the pregnancy outcome and reduces the risk of OHSS We hypothesized that hyperinsulinemia contributes to early pregnancy loss in the polycystic ovary syndrome by adversely affecting endometrial function and environment . Serum glycodelin , a putative biomarker of endometrial function , is decreased in women with early pregnancy loss . Insulin-like growth factor-binding protein-1 may also play an important role in pregnancy by facilitating adhesion processes at the feto-maternal interface . We studied 48 women with polycystic ovary syndrome before and after 4 weeks of administration of 500 mg metformin ( n = 26 ) or placebo ( n = 22 ) 3 times daily . Oral glucose tolerance tests were performed , and serum glycodelin and insulin-like growth factor-binding protein-1 were measured during the follicular and clomiphene-induced luteal phases of menses . In the metformin group , the mean ( + /-SE ) area under the serum insulin curve after glucose administration decreased from 62 + /- 6 to 19 + /- 2 nmol/L.min ( P < 0.001 ) . Follicular phase serum glycodelin concentrations increased 20-fold from 150 + /- 46 to 2813 + /- 1192 pmol/L ( P < 0.001 ) , and serum insulin-like-growth factor-binding protein-1 concentrations increased from 936 + /- 152 to 2396 + /- 300 pmol/L ( P < 0.001 ) . Similarly , luteal phase serum glycodelin concentrations increased 3-fold from 3434 + /- 1299 to 10624 + /- 1803 pmol/L ( P < 0.001 ) , and serum insulin-like growth factor-binding protein-1 concentrations increased from 1220 + /- 136 to 4916 + /- 596 pmol/L ( P < 0.001 ) . Uterine vascular penetration also increased in the metformin group , as did blood flow of spiral arteries , as demonstrated by a 20 % decrease in the resistance index from 0.71 + /- 0.02 to 0.57 + /- 0.03 ( P < 0.001 ) . These variables did not change in the placebo group . We conclude that insulin reduction with metformin increases follicular and luteal phase serum glycodelin and insulin-like growth factor-binding protein-1 concentrations and enhances luteal phase uterine vascularity and blood flow in the polycystic ovary syndrome . These changes may reflect an improved endometrial milieu for the establishment and maintenance of pregnancy OBJECTIVE To determine whether metformin would safely reduce the rate of first-trimester spontaneous abortion without teratogenicity in 19 women with the polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve pilot study . SETTING Outpatient . PATIENT(S ) Twenty-two previously oligoamenorrheic , nondiabetic women with PCOS ; 125 women with PCOS who were not currently pregnant and who had > or = 1 previous pregnancy while they were not receiving metformin .  INTERVENTION(S ) Metformin , 1.5 - 2.55 g/day , throughout pregnancy . MAIN OUTCOME MEASURE(S ) Rates of first-trimester spontaneous abortion and teratogenicity . RESULT ( S ) Before metformin , 10 women had 22 previous pregnancies with 16  first-trimester spontaneous abortions ( 73 % ) . While receiving metformin , these 10 women had 6 normal live births ( 60 % ) , 1 spontaneous abortion ( 10 % ) , and 3 normal ongoing pregnancies ( 30 % ) ( all > or = 13 weeks ; median gestation , 23 weeks ) . Among women receiving metformin , including those with live births and normal pregnancy for at least the first trimester , 1 of 10 ( 10 % ) had first-trimester spontaneous abortion compared with 73 % in 22 previous pregnancies without metformin ( P<.002 ) . To date , the 19 women receiving metformin have had no adverse maternal side effects , and no birth defects have occurred ; 9 ( 47 % ) had normal term live births , 2 ( 11 % ) had normal and appropriate for gestational age births ( one at 33 and one at 35 
    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: We prospect ively estimated the prevalence of the polycystic ovary syndrome ( PCOS ) , as defined by the NIH/NICHHD 1990 endocrine criteria , in a population of 154 Caucasian women of reproductive age reporting spontaneously for blood donation .  Anthropometric data ; the presence of hirsutism , acne , and and rogenic alopecia ; and the menstrual history were recorded by a single investigator . In 145 women , blood sample s were also obtained for measurement of serum and rogen levels .  PCOS was defined by the presence of 1 ) oligomenorrhea , 2 ) clinical and /or biochemical hyper and rogenism , and 3 ) exclusion of hyperprolactinemia , thyroid disorders , and nonclassic 21-hydroxylase deficiency . Hirsutism was defined by a modified Ferriman-Gallwey score of 8 or more , acne was considered as a sign of hyper and rogenism when persistent after the second decade of life , and hyper and rogenemia was defined by an increase in circulating testosterone or dehydroepi and rosterone sulfate or an increase in the free and rogen index above the 95th percentile of the control values derived from the nonhirsute , nonacneic women having regular menses who were not receiving hormonal therapy . PCOS was present in 10(6.5 % ) , hirsutism was present in 11 ( 7.1 % ) , and acne was present in 19 ( 12.3 % ) of the 154 women . Our results demonstrate a 6.5 % prevalence of PCOS , as defined , in a minimally biased population of Caucasian women from Spain . The polycystic ovary syndrome , hirsutism , and acne are common endocrine disorders in women 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 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 Metformin appears to improve reproductive function in some women with polycystic ovary syndrome ( PCOS ) . We wished to explore the effect of metformin in women with PCOS undergoing IVF . METHODS A r and omized , placebo-controlled , double-blind study was carried out between 2001 and 2004 . Patients with PCOS undergoing IVF/ICSI treatment using a long GnRH agonist protocol were r and omized to receive metformin ( MET ) , 850 mg , or placebo ( PLA ) tablets twice daily from the start of the down-regulation process until the day of oocyte collection . The primary outcome was to be an improvement in the overall fertilization rate . RESULTS One-hundred and one IVF/ICSI cycles were r and omized to receive metformin ( 52 ) or to receive placebo ( 49 ) . There was no difference in the total dose of rFSH required per cycle ( median dose : MET = 1200 U , PLA = 1300 U ; P = 0.937 ) . The median number of oocytes retrieved per cycle ( MET = 17.2 , PLA = 16.2 ; P = 0.459 ) and the overall fertilization rates ( MET = 52.9 % , PLA = 54.9 % ; P = 0.641 ) did not differ . However , both the clinical pregnancy rates beyond 12 weeks gestation per cycle ( MET = 38.5 % , PLA = 16.3 % ; P = 0.023 ) and per embryo transfer ( MET = 44.4 % , PLA = 19.1 % ; P = 0.022 ) were significantly higher in those treated with metformin . Furthermore , a significant decrease in the incidence of severe ovarian hyperstimulation syndrome ( OHSS ) was observed ( MET = 3.8 % , PLA = 20.4 % ; P = 0.023 ) , and this was still significant after adjustment for BMI , total rFSH dose and age ( OR = 0.15 ; 95 % CI : 0.03 , 0.76 ; P = 0.022 ) . CONCLUSION Short-term co-treatment with metformin for patients with PCOS undergoing IVF/ICSI cycles does not improve the response to stimulation but significantly improves the pregnancy outcome and reduces the risk of OHSS We hypothesized that hyperinsulinemia contributes to early pregnancy loss in the polycystic ovary syndrome by adversely affecting endometrial function and environment . Serum glycodelin , a putative biomarker of endometrial function , is decreased in women with early pregnancy loss . Insulin-like growth factor-binding protein-1 may also play an important role in pregnancy by facilitating adhesion processes at the feto-maternal interface . We studied 48 women with polycystic ovary syndrome before and after 4 weeks of administration of 500 mg metformin ( n = 26 ) or placebo ( n = 22 ) 3 times daily . Oral glucose tolerance tests were performed , and serum glycodelin and insulin-like growth factor-binding protein-1 were measured during the follicular and clomiphene-induced luteal phases of menses . In the metformin group , the mean ( + /-SE ) area under the serum insulin curve after glucose administration decreased from 62 + /- 6 to 19 + /- 2 nmol/L.min ( P < 0.001 ) . Follicular phase serum glycodelin concentrations increased 20-fold from 150 + /- 46 to 2813 + /- 1192 pmol/L ( P < 0.001 ) , and serum insulin-like-growth factor-binding protein-1 concentrations increased from 936 + /- 152 to 2396 + /- 300 pmol/L ( P < 0.001 ) . Similarly , luteal phase serum glycodelin concentrations increased 3-fold from 3434 + /- 1299 to 10624 + /- 1803 pmol/L ( P < 0.001 ) , and serum insulin-like growth factor-binding protein-1 concentrations increased from 1220 + /- 136 to 4916 + /- 596 pmol/L ( P < 0.001 ) . Uterine vascular penetration also increased in the metformin group , as did blood flow of spiral arteries , as demonstrated by a 20 % decrease in the resistance index from 0.71 + /- 0.02 to 0.57 + /- 0.03 ( P < 0.001 ) . These variables did not change in the placebo group . We conclude that insulin reduction with metformin increases follicular and luteal phase serum glycodelin and insulin-like growth factor-binding protein-1 concentrations and enhances luteal phase uterine vascularity and blood flow in the polycystic ovary syndrome . These changes may reflect an improved endometrial milieu for the establishment and maintenance of pregnancy OBJECTIVE To determine whether metformin would safely reduce the rate of first-trimester spontaneous abortion without teratogenicity in 19 women with the polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve pilot study . SETTING Outpatient . PATIENT(S ) Twenty-two previously oligoamenorrheic , nondiabetic women with PCOS ; 125 women with PCOS who were not currently pregnant and who had > or = 1 previous pregnancy while they were not receiving metformin .  INTERVENTION(S ) Metformin , 1.5 - 2.55 g/day , throughout pregnancy . MAIN OUTCOME MEASURE(S ) Rates of first-trimester spontaneous abortion and teratogenicity . RESULT ( S ) Before metformin , 10 women had 22 previous pregnancies with 16  first-trimester spontaneous abortions ( 73 % ) . While receiving metformin , these 10 women had 6 normal live births ( 60 % ) , 1 spontaneous abortion ( 10 % ) , and 3 normal ongoing pregnancies ( 30 % ) ( all > or = 13 weeks ; median gestation , 23 weeks ) . Among women receiving metformin , including those with live births and normal pregnancy for at least the first trimester , 1 of 10 ( 10 % ) had first-trimester spontaneous abortion compared with 73 % in 22 previous pregnancies without metformin ( P<.002 ) . To date , the 19 women receiving metformin have had no adverse maternal side effects , and no birth defects have occurred ; 9 ( 47 % ) had normal term live births , 2 ( 11 % ) had normal and appropriate for gestational age births ( one at 33 and one at 35 
    Output:
    