***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: In this article we review the important statistical properties of the urn r and omization ( design ) for assigning patients to treatment groups in a clinical trial . The urn design is the most widely studied member of the family of adaptive biased-coin design s. Such design s are a compromise between design s that yield perfect balance in treatment assignments and complete r and omization which eliminates experimental bias . The urn design forces a small-sized trial to be balanced but approaches complete r and omization as the size of the trial ( n ) increases . Thus , the urn design is not as vulnerable to experimental bias as are other restricted r and omization procedures . In a clinical trial it may be difficult to postulate that the study subjects constitute a r and om sample from a well-defined homogeneous population . In this case , a r and omization model provides a preferred basis for statistical inference . We describe the large- sample permutational null distributions of linear rank statistics for testing the e quality of treatment groups based on the urn design . In general , these permutation tests may be different from those based on the population model , which is equivalent to assuming complete r and omization . Poststratified subgroup analyses can also be performed on the basis of the urn design permutational distribution . This provides a basis for analyzing the subset of patients with observed responses when some patients ' responses can be assumed to be missing-at-r and om . For multiple mutually exclusive strata , these tests are correlated . For this case , a combined covariate-adjusted test of treatment effect is described . Finally , we show how to generalize the urn design to a prospect ively stratified trial with a fairly large number of strata A r and omised double-blind placebo-controlled trial concerning the treatment of threatened premature labour was undertaken using the following methodology : beta-mimetics were given intravenously to all patients ( 44 ) and micronised progesterone or the placebo were prescribed orally after r and omisation ( 22 patients in each group ) . The mean index of prolongation of pregnancy was similar in both groups . However , the mean duration of the intravenous infusion and the mean dose of beta-mimetics administered intravenously were significantly lower in the oral progesterone group ( p less than 0.01 ) . Similarly , there was a significant ( less than 0.05 ) decrease in the mean duration of hospitalisation . The cost and risks of treatment are thus significantly reduced when beta-mimetics and oral progesterone are used in combination A prior report suggested that active-duty pregnant women are at increased risk for low-birth weight infants and a higher perinatal mortality rate . The present double-blind investigation was design ed to prospect ively evaluate that risk and to test the efficacy of 17 alpha-hydroxyprogesterone caproate to prevent reported complications . Three groups of active-duty women were studied , beginning between 16 and 20 weeks ' gestation . They were similar for parity , previous abortion , race , cigarette smoking , and marital status . Of these , 80 were given 17 alpha-hydroxyprogesterone caproate , 88 received placebo , and 78 declined to participate in the protocol . There was no significant differences in the three groups when comparisons were made for low-birth weight infants and for perinatal mortality . However , when comparison was made to a military dependent population , they had a significantly worse outcome with regard to both perinatal mortality ( p = 0.001 ) and infants with a birth weight less than 2,500 gm ( p = 0.01 ) . We concluded that pregnant military personnel were at increased risk for adverse pregnancy outcome , but that this risk was not altered by therapy with 17 alpha-hydroxyprogesterone caproate In France , prescription of micronized progesterone at high doses of 900 to 1200 mg/day is common practice in the case of preterm delivery , even though this is neither an indication nor a posology given for marketing authorisation . A few cases of gestational pruritus have been reported during such use , associated with cholestasic and /or cytolytic hepatic disorders . We report here the results of a controlled , double-blind study versus a placebo , aim ed at assessing the effects on the liver of micronized progesterone administered orally at high doses ( 900 - 1200 mg/day ) , conducted in a population of 201 women presenting moderate menace of preterm delivery during the third trimester of pregnancy . 85 patients received micronized progesterone and 116 the placebo .  The increase above normal levels of total biliary acids ( TBA ) and aminotransferases ( ASAT , ALAT ) , was significantly more frequent in the micronized progesterone than in the placebo group . Among the 26 patients ( 14 % ) with a level of TBA superior to 10 mumoles/l during treatment , 18 belonged to the progesterone and 8 to the placebo group ( p = 0.004 ) ; the 6 patients ( 3.4 % ) with increased ASAT were all under micronized progesterone ( p < 0.001 ) , as were the 10 patients ( 5.6 % ) with increased ALAT ( p < 0.001 ) . However , there is no statistically significant difference between the two groups regarding the occurrence of clinical manifestations ( icterus , pruritus ) which could be attributed to gravid cholestasis . We may conclude from this prospect i ve study that , during the third trimester of pregnancy , micronized progesterone is associated with a significant risk of biological cholestasis . This would suggest that in patients genetically predisposed towards gravid cholestasis , micronized progesterone could be a factor favoursing this disease OBJECTIVE The purpose of this study was to evaluate whether 17-alpha-hydroxyprogesterone caproate ( 17P ) treatment affect changes in cervical length . STUDY DESIGN Women with singleton pregnancy , between 25 and 33 + 6 weeks of gestation , who were hospitalized for preterm labor were included . Patients with rupture of membranes and /or signs of chorioamnionitis were excluded . Sixty undelivered patients were allocated r and omly to either observation or to receive 341 mg of 17P intramuscularly , twice each week until gestational week 36 . Cervical length was measured by transvaginal  ultrasound scanning at discharge and at day 7 and 21 after discharge . Statistical comparisons were done with analysis of variance and chi-square test . RESULTS Shortening of the cervix in the observation group ( 30 cases ) was higher than in the 17P group ( 30 cases ) both at day 7 ( 2.37 + /- 2.0 mm vs 0.83 + /- 1.74 mm ; P = .002 ) and day 21 ( 4.60 + /- 2.73 mm vs 2.40 + /- 2.46 mm ; P = .002 ) . Treatment with 17P was associated with both a reduction in the risk of cervical shortening of > or = 4 mm ( odds ratio , 0.18 ; 95 % CI , 0.04 - 0.66 ) and in the risk of preterm delivery ( odds ratio , 0.15 ; 95 % CI , 0.04 - 0.58 ) . CONCLUSION Undelivered patients after preterm labor undergo progressive shortening of the cervix , which is attenuated by 17P treatment OBJECTIVE The purpose of this study was to evaluate the effect of prophylactic vaginal progesterone in decreasing preterm birth rate in a high-risk population . STUDY DESIGN A r and omized , double-blind , placebo-controlled study included 142 high-risk singleton pregnancies .  Progesterone ( 100 mg ) or placebo was administered daily by vaginal suppository and all patients underwent uterine contraction monitoring with an external tocodynamometer once a week for 60 minutes , between 24 and 34 weeks of gestation . Progesterone ( n = 72 ) and placebo ( n = 70 ) groups were compared for epidemiologic characteristics , uterine contraction frequency , and incidence of preterm birth . Data were compared by chi(2 ) analysis and Fisher exact test . RESULTS The preterm birth rate was 21.1 % ( 30/142 ) . Differences in uterine activity were found between the progesterone and placebo groups ( 23.6 % vs 54.3 % , respectively ; P < .05 ) and in preterm birth between progesterone and placebo ( 13.8 % vs 28.5 % , respectively ; P < .05 ) . More women were delivered before 34 weeks in the placebo group ( 18.5 % ) than in the progesterone group ( 2.7 % ) ( P < .05 ) . CONCLUSION Prophylactic vaginal progesterone reduced the frequency of uterine contractions and the rate of preterm delivery in women at high risk for prematurity BACKGROUND Women who have had a spontaneous preterm delivery are at greatly increased risk for preterm delivery in subsequent pregnancies . The results of several small trials have suggested that 17 alpha-hydroxyprogesterone caproate ( 17P ) may reduce the risk of preterm delivery . METHODS We conducted a double-blind , placebo-controlled trial involving pregnant women with a documented history of spontaneous preterm delivery . Women were enrolled at 19 clinical centers at 16 to 20 weeks of gestation and r and omly assigned by a central data center , in a 2:1 ratio , to receive either weekly injections of 250 mg of 17P or weekly injections of an inert oil placebo ; injections were continued until delivery or to 36 weeks of gestation . The primary outcome was preterm delivery before 37 weeks of gestation . Analysis was performed according to the intention-to-treat principle . RESULTS Base-line characteristics of the 310 women in the progesterone group and the 153 women in the placebo group were similar . Treatment with 17P significantly reduced the risk of delivery at less than 37 weeks of gestation ( incidence , 36.3 percent in the progesterone group vs. 54.9 percent in the placebo group ; relative risk , 0.66 [ 95 percent confidence interval , 0.54 to 0.81 ] ) , delivery at less than 35 weeks of gestation ( incidence , 20.6 percent vs. 30.7 percent ; relative risk , 0.67 [ 95 percent confidence interval , 0.48 to 0.93 ] ) , and delivery at less than 32 weeks of gestation ( 11.4 percent vs. 19.6 percent ; relative risk , 0.58 [ 95 percent confidence interval , 0.37 to 0.91 ] ) . Infants of women treated with 17P had significantly lower rates of necrotizing enterocolitis , intraventricular hemorrhage , and need for supplemental oxygen . CONCLUSIONS Weekly injections of 17P result ed in a substantial reduction in the rate of recurrent preterm delivery among women who were at particularly high risk for preterm delivery and reduced the likelihood of several complications in their infants Cytotoxic activity and progesterone binding capacity of lymphocytes obtained from women with threatened preterm labour were tested before and during treatment with acetylsalicylic acid or 17-hydroxyprogesterone caproate .  Cytotoxic activity of the lymphocytes significantly decreased ( p less than 0.001 ) , while progesterone binding capacity significantly increased ( p less than 0.001 ) following the introduction of the treatments . No changes in these parameters were observed on lymphocytes of untreated women .  Preterm delivery occurred more frequently among untreated women than among women treated with acetylsalicylic acid ( p less than 0.01 ) or those treated with 17-hydroxyprogesterone caproate ( p less than 0.05 ) AIM To compare the success rates and gestational ages at delivery of nifedipine , proluton depot administration as a tocolytic agent and bed rest groups to pregnant women with threatened preterm labor . MATERIAL AND METHODS A total of 150 pregnant women with threatened preterm labor between 28 and 35 weeks of gestation were enrolled in the study . All women underwent contraction inhibition r and omly sorted into three groups . The first and second groups were inhibited with nifedipine and proluton depot , respectively . The third group was admitted for bed rest . RESULTS Nifedipine , proluton depot and bed rest can be used to inhibit contraction in threatened preterm labor . However , when time-to-event test was used , nifedipine took the shortest time for contraction inhibition with statistical significance . CONCLUSION Nifedipine , proluton depot and bed rest can be used successfully to inhibit contraction in threatened preterm labor . However , nifedipine took the shortest time to inhibit uterine contraction in threatened preterm labor The potential tocolytic effect of natural progesterone administration on premature  labor  was investigated in a double-blind study . An oral progesterone formulation was used because its ability to increase both plasma and myometrial concentration of progesterone in pregnant women had been previously demonstrated . Furthermore , no commercial intravenous or intramuscular natural progesterone formulation is currently available in France . Fifty-seven patients in two obstetric clinics , admitted because of the risk of premature delivery , were included in the study , and uterine contractility and fetal cardiac rhythm were monitored in all of them . At r and om and after 30 minutes ' rest , 29 women absorbed four capsules of 100 mg of progesterone each and 28 women absorbed four capsules of a placebo .  Plasma progesterone levels were evaluated in all 
    Output:
    
There are some data suggesting that the use of progestational agents results in a reduction of preterm deliveries at less than 37 weeks of gestation and an increase in birthweight .
The use of a progestational agent may also reduce the frequency of uterine contractions , prolong pregnancy and attenuate the shortening of cervical length .
AUTHORS ' CONCLUSIONS There is insufficient evidence to advocate progestational agents as a tocolytic for women presenting with preterm labour