***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 compare live birth rates after fresh embryo transfer ( ET ) and cumulative ongoing pregnancy rates after fresh ET and frozen-thawed ( ET ) between continents and overall after one treatment cycle with corifollitropin alfa or recombinant FSH . DESIGN Double-blind , multicenter , r and omized controlled trial . SETTING Fourteen centers in North America ( NA ) ; 20 in Europe ( EU ) . PATIENT(S ) 804 NA patients and 702 EU patients . INTERVENTION(S ) Patients > 60 kg received a single dose of corifollitropin alfa or daily rFSH for the first 7 days of controlled ovarian stimulation . MAIN OUTCOME MEASURE(S ) Live birth rates . RESULT ( S ) Within each continent no differences were noted between the two treatment groups ; however , between continents , the cumulative ongoing pregnancy rate and live birth rate were considerably higher in NA than in EU . The live birth rate in NA was 39.2 % in both treatment groups compared with 31.5 % and 28.8 % in EU after corifollitropin alfa and rFSH treatment , respectively . Considering the number of embryos transferred , the live birth rate per ET was still higher in NA than in EU ( 42.7 % v.s 36.8 % with corifollitropin alfa and 41.6 % vs. 30.9 % with rFSH ) . Overall live birth rates after fresh ET were 35.6 % and 34.4 % ( estimated difference 1.1 % [ 95 % confidence interval -3.7 - 5.8 ] ) , and the estimated cumulative live birth rates were 43.4 % and 41.3 % with corifollitropin alfa and rFSH , respectively . CONCLUSION ( S ) Live birth rates and cumulative pregnancy rates were higher in NA than in EU after treatment with either corifollitropin alfa or daily rFSH ; both treatment protocol s provided equal success rates . CLINICAL TRIALS.GOV IDENTIFIERS : NCT00703014 and NCT00702273 STUDY QUESTION Is treatment with corifollitropin alfa , a new recombinant gonadotrophin with sustained follicle-stimulating activity , safe in terms of perinatal complications and birth defects in infants conceived following corifollitropin alfa treatment for contolled ovarian stimulation ( COS ) ? SUMMARY ANSWER In terms of neonatal outcome and risk of malformations , treatment with a single dose of corifollitropin alfa during COS is as safe as treatment with daily recombinant FSH ( rFSH ) . WHAT IS KNOWN AND WHAT THIS PAPER ADDS This is the first pooled analysis of individual safety data in terms of neonatal outcome and major and minor congenital malformations collected following intervention trials of corifollitropin alfa . DESIGN Pregnancy and follow-up studies were conducted prospect ively and data were collected from all Phase II and III trials with corifollitropin alfa intervention , including two comparative r and omized controlled trials ( RCTs ) in which patients received either a single dose of corifollitropin alfa or daily rFSH for the first 7 days of COS .  Patients with ongoing pregnancies at 10 weeks after embryo transfer were followed up to labour and the health of the offspring was assessed up to 4 - 12 weeks after birth . PARTICIPANTS AND SETTING Following corifollitropin alfa treatment prior to IVF or ICSI , the health of 677 pregnant women , 838 fetuses and 806 live born infants was evaluated . MAIN RESULTS AND THE ROLE OF CHANCE Among 440 fetuses in the corifollitropin alfa arm and 381 fetuses in the rFSH arm of the two RCTs , there were 424 ( 96.4 % ) and 370 ( 98.7 % ) live births , respectively . Neonatal characteristics , the frequency of premature births and the incidence of infant adverse events were similar in both treatment arms . The overall incidence of any congenital malformations in live born infants was 16.3 and 17.0 % , with major malformation rates of 4.0 and 5.4 % in the corifollitropin alfa and rFSH groups , respectively [ odds ratio ( OR ) for major malformations , 0.71 ; 95 % confidence interval , 0.36 - 1.38 ] . From 838 fetuses assessed in all corifollitropin alfa intervention trials , there were 806 ( 96.2 % ) live births with a major malformation rate of 4.5 % in live born infants . BIAS , CONFOUNDING AND OTHER REASONS FOR CAUTION Both RCTs had a double-blind and active-controlled design and the adjudication of congenital malformations was also performed in a blinded fashion . As the total number of major malformations was limited ( 37 ) , the confidence interval around the OR was rather wide . GENERALISABILITY TO OTHER POPULATION S : The similarity of corifollitropin alfa and rFSH with respect to the incidence of congenital malformations was consistent across the RCTs and pregnancy type ( singleton , multiple ) . This suggests that this similarity could hold in general . Overall incidences , however , may depend on the definitions of malformations and rules to adjudicate these events as major or minor A single injection of corifollitropin alfa can replace seven daily injections of recombinant FSH ( rFSH ) using a gonadotrophin-releasing hormone antagonist protocol in ovarian stimulation prior to IVF or intracytoplasmic sperm injection . This double-blind r and omized controlled trial assessed the pharmacokinetics and pharmacodynamics of 150μg corifollitropin alfa versus daily 200IU rFSH in 1509 patients . Comparative analyses were performed on serum concentrations of FSH immunoreactivity ( pharmacokinetics ) , and the number and size of growing follicles , and inhibin B and oestradiol concentrations as biomarkers of ovarian response ( pharmacodynamics ) . The rate of follicular development was similar in both treatment groups . By stimulation day 8 , 33 % of patients treated with corifollitropin alfa reached the criterion for human chorionic gonadotrophin ( HCG ) injection . The number of follicles ⩾11 mm was slightly higher after corifollitropin alfa compared with daily rFSH at stimulation day 8 ( difference , 1.2 ; 95 % confidence interval ( CI ) 0.5 - 1.8 ; P<0.01 ) and on the day of HCG injection ( difference , 2.1 ; 95 % CI 1.4 - 2.8 ; P<0.01 ) . The rise of inhibin B and oestradiol concentrations was similar in both treatment groups . Although the pharmacokinetics of corifollitropin alfa and rFSH are quite different their pharmacodynamic profiles at the dosages used are similar . A single injection of corifollitropin alfa can replace seven daily injections of recombinant FSH ( rFSH ) using a gonadotrophin-releasing hormone antagonist protocol in ovarian stimulation prior to IVF or intracytoplasmic sperm injection . The objective of this study was to compare the pharmacokinetics and pharmacodynamics of corifollitropin alfa versus daily rFSH . A total of 1509 patients were r and omized in a double-blind , controlled trial to either a single injection of 150μg corifollitropin alfa or to daily injections of 200IU rFSH for the first 7 days of ovarian stimulation . Serum levels of FSH immunoreactivity were analysed ( pharmacokinetic analysis ) , together with the number and size of growing follicles and serum inhibin B and oestradiol concentrations as biomarkers of the ovarian response ( pharmacodynamic analysis ) . Serum FSH immunoreactivity levels were higher up to stimulation day 5 for corifollitropin alfa compared with the daily rFSH regimen but were similar from day 8 onwards , when patients started rFSH if the criteria for human chorionic gonadotrophin were not yet reached . Corifollitropin alfa treatment result ed in a similar growth rate of follicles though a slightly higher number of follicles were recruited compared with daily rFSH . It is concluded that the pharmacokinetics of corifollitropin alfa and rFSH are quite different but their induced pharmacodynamic effects at the dosages used are similar BACKGROUND This study primarily investigated the dose-response relationship of corifollitropin alfa to initiate multifollicular development for the first 7 days of controlled ovarian stimulation ( COS ) . METHODS Women aged 20 - 39 years undergoing COS for in vitro fertilization or intracytoplasmic sperm injection were r and omized to a single dose of corifollitropin alfa 60 , 120 or 180 microg , or daily injections of 150 IU recombinant follicle-stimulating hormone ( rFSH ) .  Patients treated with corifollitropin alfa  started fixed daily treatment with 150 IU rFSH on stimulation Day 8 . Patients received a GnRH antagonist ( ganirelix 0.25 mg/day ) from stimulation Day 5 until the day of human chorionic gonadotrophin . RESULTS Pharmacokinetics of corifollitropin alfa were dose-proportional . The main reason for not having embryo transfer was insufficient ovarian response in 30.8 , 2.6 , 3.8 and 7.4 % of patients in the corifollitropin alfa 60 , 120 , 180 microg and rFSH groups , respectively . On Day 8 , the mean ( st and ard deviation ) number of follicles > or=11 mm was 6.8 ( 4.4 ) , 10.1 ( 6.1 ) and 12.8 ( 7.5 ) , respectively . The number of cumulus-oocyte complexes retrieved showed a clear dose-response relationship ( P < 0.0001 ) , being 5.2 ( 5.5 ) , 10.3 ( 6.3 ) and 12.5 ( 8.0 ) in the three dose groups , respectively . CONCLUSIONS A single injection of corifollitropin alfa induces dose-related increase in multifollicular development and in the number of retrieved oocytes . The optimal dose for a 1-week interval is higher than 60 microg and lower than 180 microg and will be selected based on modelling and simulation taking into account insufficient stimulation as well as overstimulation . Clinical Trials gov : NCT00598208 Background We sought to determine the impact of treatment flexibility on clinical outcomes in either a corifollitropin alfa or recombinant follicle-stimulating hormone ( rFSH ) protocol . Methods Post hoc analysis of a prospect i ve , multicenter , r and omized , double-blind , double-dummy non-inferiority clinical trial ( Engage ) . Efficacy outcomes were assessed on patients from the Engage trial who started treatment on menstrual cycle day 2 versus menstrual cycle day 3 , patients who received rFSH step-down or fixed-dose rFSH , patients who received rFSH on the day of human chorionic gonadotropin ( hCG ) compared with those who did not , and patients who received hCG when the criterion was reached versus those with a 1-day delay .  Results The effect of each of the treatment flexibility options on ongoing pregnancy rate was not significant . The estimated difference ( 95 % confidence interval ) in ongoing pregnancy rate was -4.3 % ( -9.4 % , 0.8 % ) for patients who started ovarian stimulation on cycle day 2 versus day 3 , 1.8 % ( -4.1 % , 7.6 % ) for patients who received hCG on the day the hCG criterion was met versus 1 day after , 3.2 % ( -2.1 % , 8.6 % ) for patients who received rFSH on the day of hCG administration versus those who did not , and -5.8 % ( -13.0 % , 1.4 % ) for patients who received a reduced versus fixed-dose of rFSH from day 8 . Conclusions Treatment flexibility of ovarian stimulation does not substantially affect the clinical outcome in patients ’ treatment following initiation of ovarian stimulation with either corifollitropin alfa or with daily rFSH in a gonadotropin-releasing hormone antagonist protocol .Trial registration Trial was registered under Clinical Trials.gov identifier NCT00696800 BACKGROUND One injection of corifollitropin alfa replaces the first seven daily FSH injections in controlled ovarian stimulation ( COS ) cycles . Repeated treatment with therapeutic proteins may cause immune responses or hypersensitivity reactions . We assessed the immunogenicity and safety of corifollitropin alfa treatment in up to three COS cycles . METHODS In this multicentre , phase III uncontrolled trial , patients ( > 60 kg ) started treatment with one injection of 150 µg corifollitropin alfa on cycle Day 2 or 3 of menses and 0.25 mg ganielix on stimulation Day 5 or 6 . Primary outcome measures were antibody formation against corifollitropin alfa ( using highly sensitive radioimmunopreci 
    Output:
    
The use of a medium dose ( 150 to 180 μg ) of long-acting FSH is a safe treatment option and equally effective compared to daily FSH in women with unexplained subfertility .
There was evidence of reduced live birth rate in women receiving a low dose ( 60 to 120 μg ) of long-acting FSH compared to daily FSH .