***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 Clomiphene is the current first-line infertility treatment in women with the polycystic ovary syndrome , but aromatase inhibitors , including letrozole , might result in better pregnancy outcomes . METHODS In this double-blind , multicenter trial , we r and omly assigned 750 women , in a 1:1 ratio , to receive letrozole or clomiphene for up to five treatment cycles , with visits to determine ovulation and pregnancy , followed by tracking of pregnancies . The polycystic ovary syndrome was defined according to modified Rotterdam criteria ( anovulation with either hyper and rogenism or polycystic ovaries ) . Participants were 18 to 40 years of age , had at least one patent fallopian tube and a normal uterine cavity , and had a male partner with a sperm concentration of at least 14 million per milliliter ; the women and their partners agreed to have regular intercourse with the intent of conception during the study . The primary outcome was live birth during the treatment period . RESULTS Women who received letrozole had more cumulative live births than those who received clomiphene ( 103 of 374 [ 27.5 % ] vs. 72 of 376 [ 19.1 % ] , P=0.007 ; rate ratio for live birth , 1.44 ; 95 % confidence interval , 1.10 to 1.87 ) without significant differences in overall congenital anomalies , though there were four major congenital anomalies in the letrozole group versus one in the clomiphene group ( P=0.65 ) . The cumulative ovulation rate was higher with letrozole than with clomiphene ( 834 of 1352 treatment cycles [ 61.7 % ] vs. 688 of 1425 treatment cycles [ 48.3 % ] , P<0.001 ) . There were no significant between-group differences in pregnancy loss ( 49 of 154 pregnancies in the letrozole group [ 31.8 % ] and 30 of 103 pregnancies in the clomiphene group [ 29.1 % ] ) or twin pregnancy ( 3.4 % and 7.4 % , respectively ) . Clomiphene was associated with a higher incidence of hot flushes , and letrozole was associated with higher incidences of fatigue and dizziness . Rates of other adverse events were similar in the two treatment groups . CONCLUSIONS As compared with clomiphene , letrozole was associated with higher live-birth and ovulation rates among infertile women with the polycystic ovary syndrome . ( Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others ; Clinical Trials.gov number , NCT00719186 . ) OBJECTIVE To determine the serum concentrations of enclomiphene and zuclomiphene across consecutive cycles of clomiphene citrate treatment in anovulatory infertile women . DESIGN Prospect i ve cohort . SETTING Tertiary institutional infertility clinic . PATIENT(S ) Fourteen consenting anovulatory infertile women receiving st and ardized , cyclic , incremental treatment with clomiphene citrate for ovulation induction . INTERVENTION(S ) Clomiphene citrate treatment ( 50 - 150 mg/d , cycle days 5 - 9 ) , titrated to the minimum effective ovulation-inducing dose , was administered for three to six total cycles . Blood sample s were obtained on cycle days 3 and 10 in each treatment cycle . MAIN OUTCOME MEASURE(S ) Serum concentrations of enclomiphene and zuclomiphene . RESULT ( S ) Cycle day 3 zuclomiphene levels were below assay limits in all initial cycles , increased progressively across three consecutive cycles , and thereafter plateaued . Cycle day 3 enclomiphene concentrations were uniformly undetectable . Cycle day 10  enclomiphene levels increased with dose administered , but these observations were not statistically significant . CONCLUSION ( S ) Clomiphene citrate induction of ovulation results in an isomer-specific systemic accumulation of zuclomiphene across consecutive cycles of treatment . The combined maximum concentration of enclomiphene and zuclomiphene attained in practice approximates 100 nmol/L and is generally well below levels previously demonstrated to have adverse effects in vitro Letrozole was compared with clomiphene citrate ( CC ) as a first-line treatment for ovulation induction in women with polycystic ovaries ( PCOs ) . A total of 106 women with primary infertility and a diagnosis of PCOs were r and omized to receive either 100 mg CC ( n = 55 ) or 2.5 mg letrozole ( n = 51 ) daily for 5 days . Human chorionic gonadotrophin ( hCG ) at a dose of 10 000 IU was administered when at least one follicle with a mean diameter ≥ 18 mm was observed using transvaginal ultrasound . The number of mature follicles was significantly lower , but endometrial thickness and ovulation and pregnancy rates were significantly higher in the letrozole group than in the CC group . In conclusion , letrozole is associated with a higher pregnancy rate than CC in PCO patients and may have a role as a first-line treatment for anovulatory patients with PCOs OBJECTIVE To use aromatase inhibition for induction of ovulation in women in whom clomiphene citrate ( CC ) treatment was unsuccessful . DESIGN Prospect i ve trial in infertility patients treated with CC .  SETTING Two tertiary-referral infertility clinics associated with the Division of Reproductive Sciences , University of Toronto . PATIENT(S ) Twelve patients with anovulatory polycystic ovary syndrome ( PCOS ) and 10 patients with ovulatory infertility , all of whom had previously received CC with an inadequate outcome ( no ovulation and /or endometrial thickness of < or = 0.5 cm ) . INTERVENTION(S ) The aromatase inhibitor letrozole was given orally in a dose of 2.5 mg on days 3 - 7 after menses . MAIN OUTCOME MEASURE(S ) Occurrence of ovulation , endometrial thickness , and pregnancy rates . RESULT ( S ) With CC treatment in patients with PCOS , ovulation occurred in 8 of 18 cycles ( 44.4 % ) , and all ovulatory cycles for the women included in this study had endometrial thickness of < or = 0.5 cm . In 10 ovulatory patients , 15 CC cycles result ed in a mean number of 2.5 mature follicles , but all cycles had endometrial thickness of < or = 0.5 cm on the day of hCG administration . With letrozole treatment in the same patients with PCOS , ovulation occurred in 9 of 12 cycles ( 75 % ) and pregnancy was achieved in 3 patients ( 25 % ) . In the 10 patients with ovulatory infertility , letrozole treatment result ed in a mean number of 2.3 mature follicles and mean endometrial thickness of 0.8 cm . Pregnancy was achieved in 1 patient ( 10 % ) . CONCLUSION ( S ) Oral administration of the aromatase inhibitor letrozole is effective for ovulation induction in anovulatory infertility and for increased follicle recruitment in ovulatory infertility . Letrozole appears to avoid the unfavorable effects on the endometrium frequently seen with antiestrogen use for ovulation induction BACKGROUND This study revisited the ultrasonographic diagnostic criteria of polycystic ovary syndrome ( PCOS ) and studied the relationship between the major hormonal and metabolic features of PCOS and the follicle number per ovary ( FNPO ) . METHODS This prospect i ve study included 214 women with PCOS compared with 112 women with normal ovaries . Main clinical , biological and ultrasonographic markers of PCOS were assessed during the early follicular phase . RESULTS The mean FNPO of follicles 2 - 5 mm in size was significantly higher in polycystic ovaries than in controls , while it was similar within the 6 - 9 mm range . Setting the threshold at 12 for the 2 - 9 mm FNPO offered the best compromise between specificity ( 99 % ) and sensitivity ( 75 % ) . Within the 2 - 5 mm follicular range , we found significant positive relationships between the FNPO and and rogens . The FNPO within the 6 - 9 mm range was significantly and negatively related to body mass index and fasting insulin serum level . CONCLUSIONS We propose to modify the definition of polycystic ovaries by adding the presence of > or = 12 follicles measuring 2 - 9 mm in diameter ( mean of both ovaries ) . Also , our findings strengthen the hypothesis that the intra-ovarian hyper and rogenism promotes excessive early follicular growth and that further progression can not proceed normally because of hyperinsulinism and /or other metabolic influence linked to obesity Background . Letrozole ( CGS 20267 ) , a triazole derivative , is a new , once‐daily , oral nonsteroidal inhibitor of aromatase activity OBJECTIVE To establish whether initial screening characteristics of normogonadotropic anovulatory infertile women can aid in predicting live birth after induction of ovulation with clomiphene citrate ( CC ) . DESIGN Prospect i ve longitudinal single-center study . SETTING Specialist academic fertility unit . PATIENT(S ) Two hundred fifty-nine couples with a history of infertility , oligoamenorrhea , and normal follicle-stimulating hormone ( FSH ) concentrations who have not been previously treated with any ovulation-induction medication . INTERVENTION(S ) 50 , 100 , or 150 mg of oral CC per day , for 5 subsequent days per cycle . MAIN OUTCOME MEASURE(S ) Conception leading to live birth after CC administration . RESULT ( S ) After receiving CC , 98 ( 38 % ) women conceived , leading to live birth . The cumulative live birth rate within 12 months was 42 % for the total study population and 56 % for the ovulatory women who had received CC . Factors predicting the chances for live birth included free and rogen index ( testosterone/sex hormone-binding globulin ratio ) , body mass index , cycle history ( oligomenorrhea versus amenorrhea ) , and the woman 's age . CONCLUSION ( S ) It is possible to predict the individual chances of live birth after CC administration using two distinct prediction models combined in a nomogram . Applying this nomogram in the clinic may be a step forward in optimizing the decision-making process in the treatment of normogonadotropic anovulatory infertility . Alternative first line of treatment options could be considered for some women who have limited chances for success Letrozole is a new non‐steroidal inhibitor of the aromatase enzyme system . It is currently under development for the treatment of postmenopausal women with advanced breast cancer .  Absolute bioavailability of letrozole when given orally as one 2·5 mg film‐coated tablet in comparison to the same dose given intravenously as a bolus injection was studied in 12 healthy postmenopausal women .  Letrozole  absolute systemic bioavailability after p.o . administration was 99·9±16·3 % . Elimination of letrozole was slow . Total‐body clearance of letrozole from plasma after i.v . administration was low ( 2.21 L h−1 ) . The calculated distribution volume at steady state ( 1.87 L kg−1 ) suggests a rather high tissue distribution . Biotransformation of letrozole is the main elimination mechanism with the glucuronide conjugate of the secondary alcohol metabolite being the predominant species found in urine . The two study treatments were tolerated equally well . © 1997 John Wiley & Sons , The present prospect i ve follow-up study was design ed to identify whether clin 
    Output:
    
WHAT IS KNOWN ALREADY According to a recent Cochrane systematic review ( 2014 ) , letrozole appears to improve live-birth ( LB ) and pregnancy rates in anovulatory women with PCOS , compared to CC .
However , with its robust design , the current RCT provides more valid and compelling evidence for the superiority of letrozole over CC as a primary ovulation induction agent in PCOS women with 40 % increase in pregnancy rates and with a shorter time-to-pregnancy .
Furthermore , the participants in this RCT are a good representation of subfertile PCOS population receiving fertility treatment in Europe and worldwide .