***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 To study the effect of metformin before and during assisted reproductive technology ( ART ) on the clinical pregnancy rate ( CPR ) in non-obese women with polycystic ovary syndrome ( PCOS ) . METHODS A multi-centre , prospect i ve , r and omized , double-blind study was conducted in eight IVF clinics in four Nordic countries . We enrolled 150 PCOS women with a body mass index < 28 kg/m(2 ) , and treated them with 2000 mg/day metformin or identical placebo tablets for ≥ 12 weeks prior to and during long protocol  IVF  or ICSI and until the day of pregnancy testing . The primary outcome measure was CPR . Secondary outcome measures included spontaneous pregnancy rates during the pretreatment period , and the live birth rate ( LBR ) . RESULTS Among IVF treated women ( n = 112 ) , biochemical pregnancy rates were identical in both groups ( 42.9 % ) , and there were no significant differences in the metformin versus the placebo group in CPR [ 39.3 versus 30.4 % ; 95 % confidence interval ( CI ) : -8.6 to 26.5 ] . The LBR was 37.5 versus 28.6 % ( 95 % CI : -8.4 to 26.3 ) . However , prior to IVF there were 15 ( 20.3 % ) spontaneous pregnancies in the metformin group and eight ( 10.7 % ) in the placebo group ( 95 % CI : -1.9 to 21.1 ; P = 0.1047 ) . According to intention to treat analyses ( n = 149 ) ; significantly higher overall CPR were observed in the metformin versus placebo group ( 50.0 versus 33.3 % ; 95 % CI : -1.1 to 32.3 ; P = 0.0391 ) . LBR was also significantly higher with use of metformin versus placebo ( 48.6 versus 32.0 ; 95 % CI : 1.1 to 32.2 ; P = 0.0383 ) . No major unexpected safety issues or multiple births were reported . More gastrointestinal side effects occurred in the metformin group ( 41 versus 12 % ; 95 % CI : 0.15 to 0.42 ; P < 0.001 ) . CONCLUSIONS Metformin treatment for 12 weeks before and during IVF or ICSI in non-obese women with PCOS significantly increases pregnancy and LBRs  compared with placebo . However , there was no effect on the outcome of ART per se . TRIAL REGISTRATION Clinical Trials.gov Identifier : NCT00159575 Estimates of the prevalence of the polycystic ovary syndrome ( PCOS )  in the general population have ranged from 2 - 20 % . The vast majority of these reports have studied White population s in Europe , used limited definitions of the disorder , and /or used bias population s , such as those seeking medical care . To estimate the prevalence of this disorder in the United States and address these limitations , we prospect ively determined the prevalence of PCOS in a reproductive-aged population of 369 consecutive women ( 174 White and 195 Black ; aged 18 - 45 yr ) , examined at the time of their preemployment physical .  Body measures  were obtained , and body hair was quantified by a modified Ferriman-Gallwey ( F-G ) method . All exams were initially performed by 2 trained nurses , and any subject with an F-G score above 3 was reexamined by a physician , the same for all patients . Of the 369 women , 277 ( 75.1 % ) also agreed to complete a question naire and have additional blood drawn . Subjects were studied regardless of current estrogen/progestin hormonal use ( 28.5 % ) . PCOS was defined as 1 ) oligoovulation , 2 ) clinical hyper and rogenism ( i.e. hirsutism ) and /or hyper and rogenemia , and 3 ) exclusion of other related disorders , such as hyperprolactinemia , thyroid abnormalities , and non-classic adrenal hyperplasia . Hirsutism was defined by a F-G score of 6 or more , and hyper and rogenemia was defined as a total or free testosterone , and rostenedione , and /or dehydroepi and rosterone sulfate level above the 95th percentile of control values [ i.e. all eumenorrheic women in the study , who had no hirsutism ( F-G < or = 5 ) or acne and were receiving no hormonal therapy ; n = 98 ] . Considering all 369 women studied , White and Black women had similar mean ages ( 29.4 + /- 7.1 and 31.1 + /- 7.8 yr , respectively ) , although White women had a lesser body mass than Black women ( 24.9 + /- 6.1 vs. 29.2 + /- 8.1 kg/m2 , respectively ; P < 0.001 ) . Of these 7.6 % , 4.6 % , and 1.9 % demonstrated a F-G score of 6 or more , 8 or 10 , respectively , and there was no significant racial difference , with hirsutism prevalences of 8.0 % , 2.8 % , and 1.6 % in Whites , and 7.1 % , 6.1 % , and 2.1 % in Blacks , respectively . Of the 277 women consenting to a history and hormonal evaluation , 4.0 % had PCOS as defined , 4.7 % ( 6 of 129 ) of Whites and 3.4 % ( 5 of 148 ) of Blacks . In conclusion , in our consecutive population of unselected women the prevalence of hirsutism varied from 2 - 8 % depending on the chosen cut-off F-G score , with no significant difference between White and Black women . Using an F-G score of 6 or more as indicative of hirsutism , 3.4 % of Blacks and 4.7 % of Whites had PCOS as defined . These data suggest that PCOS may be one of most common reproductive endocrinological disorders of women Gonadotrophin treatment in  clomiphene citrate resistant polycystic ovarian syndrome ( PCOS ) patients , using either low-dose step-up or low-dose step-down protocol s , is highly effective to achieve singleton live births . Concomitant use of gonadotrophin releasing hormone analogues ( GnRHa ) , which will block the endogenous feedback for monofollicular development during the low-dose step-up protocol , should not be employed . It is more difficult to induce ovulation in patients with more ' severe ' PCOS , characterized by obesity and insulin resistance . There is need for optimization of starting doses for both the low-dose step-up and step-down protocol s. Such optimization will prevent hyperstimulation due to a starting dose far above the FSH threshold , as well as minimize the time-consuming low-dose increments by starting with a higher dose in women with augmented FSH threshold . External validation of reported models for prediction of FSH response is warranted for tailoring and optimizing treatment for everyday clinical practice . Although preliminary , the partial cessation of follicular development , along with regression leading to atresia , lends support to the LH ceiling theory , emphasizing the delicate balance and need for both FSH and LH in normal follicular development . Future well- design ed r and omized controlled trials will reveal whether IVF with or without in-vitro maturation of the oocytes will improve safety and efficacy compared with classical ovulation induction strategies 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 recombinant FSH plus metformin or placebo tablets . MAIN OUTCOME MEASURE(S ) Primary end point : cancellation rate for low ovarian response . Secondary end-points : other clinical , biochemical , and reproductive data . RESULT ( S ) Enrollment was stopped after 88 participants had been r and omized and analyzed due to an unacceptable increased risk of poor ovarian response in the metformin arm . Statistically significant differences between the metformin and placebo groups were observed in the dose of gonadotropins used , peak estradiol levels , and the number of dominant follicles , retrieved oocytes , and metaphase II oocytes . CONCLUSION ( S ) In patients with PCOS and reduced ovarian reserve , metformin worsened the response to gonadotropins , and its administration should be stopped before the start of controlled ovarian hyperstimulation for IVF programs . CLINICAL TRIALS IDENTIFICATION NUMBER : NCT01208740 BACKGROUND Our aim was to investigate the effect of pre-treatment with metformin in women with polycystic ovary syndrome ( PCOS ) scheduled for IVF stimulation . METHODS Seventy-three oligo/amenorrhoeic women with polycystic ovaries and at least one of the following criteria : hyper and rogenaemia , elevated LH/FSH ratio , hyperinsulinism , decreased SHBG levels or hirsutism , were studied . Normal weight and overweight patients were r and omized separately in a prospect i ve , r and omized , double blind study . All patients were treated for at least 16 weeks with metformin ( 1000 mg bid ) or placebo ending on the day of HCG injection . RESULTS No differences were found in the primary end-points : duration of FSH stimulation 14.4 ( 13.1 - 15.7 ) versus 14.2 ( 12.6 - 15.7 ) days or estradiol on the day of HCG injection 6.8 ( 5.3 - 8.2 ) versus 7.6 ( 5.6 - 9.6 ) nmol/l in the metformin and placebo groups , respectively . The secondary end-points number of oocytes , fertilization rates , embryo quality , pregnancy rates and clinical pregnancy rates were equal . However , in the normal weight subgroup ( BMI < 28 kg/m(2 ) , n = 27 ) , pregnancy rates following IVF were 0.71 ( 0.63 - 0.79 ) versus 0.23 ( 0.15 - 0.31 ) in the metformin and placebo groups , respectively ( P = 0.04 ) . Overall clinical pregnancy rates were equal : 0.51 ( 0.34 - 0.68 ) versus 0.44 ( 0.27 - 0.62 ) in the metformin and placebo groups , respectively . However , in the normal weight subgroup , clinical pregnancy rates were 0.67 ( 0.43 - 0.91 ) and 0.33 ( 0.06 - 0.60 ) , respectively ( P = 0.06 ) . CONCLUSIONS Pre-treatment with metformin prior to conventional IVF/ICSI in women with PCOS does not improve stimulation or clinical outcome . However , among normal weight PCOS women , pre-treatment with metformin tends to improve pregnancy rates . Further studies in subgroups of PCOS women are required 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 , 
    Output:
    
This review found no conclusive evidence that metformin treatment before or during ART cycles improved live birth rates in women with PCOS .
However , the use of this insulin-sensitising agent increased clinical pregnancy rates and decreased the risk of OHSS