***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: Twenty-two nulli- all primipara who had had previous repeated spontaneous abortions and who did not have anti-HLA antibodies for the partner , received immunological treatment consisting of a single transfusion of the partner 's lymphocytes in the third week of pregnancy , and giving natural progesterone supplements after the kinetic of Beta-HCG in the plasma had been assessed . The number of pregnancies which went to terme ( 94 % success ) was significantly better than those obtained in our first protocol which was to give one to three transfusions of the partner 's lymphocytes before the pregnancy started ( 58 % success rare after 24 treatments ) . Apart from obtaining much better results the second protocol made it possible to avoid giving a significant number of useless transfusions ( 22 % of pre-conceptual transfusions were not followed by a pregnancy at all ) Objective . To investigate whether active immunization with third party leukocytes improves pregnancy outcome in women with unexplained recurrent miscarriages Presented herein is a r and omized prospect i ve study performed to evaluate the efficacy of the addition of lymphocyte immunotherapy ( LI ) to progesterone ( P ) therapy ( LI/P ) for the prevention of spontaneous abortion ( SAB ) in primary aborters with a history of three SABs . The incidence of intrauterine pregnancies in four cycles was 23 of 35 ( 65.7 % ) patients for LI/P vs. 14 of 31 ( 45.1 % ) patients treated with progesterone alone .  SABs occurred in 6 of 23 ( 26.0 % ) LI/P-treated patients compared to 8 of 14 ( 57.1 % ) given progesterone alone . The mean number of previous abortions in both groups was 3.9 . The  mean age of the LI/P group was 34.1 vs. 33.6 years for the group treated with progesterone alone . These data could be interpreted to show that progesterone therapy and LI independently inhibit SAB or that LI/P acts synergistically to inhibit immune destruction .  LI/P therapy was found to be more effective than progesterone therapy alone To eluci date the mechanisms that facilitate tolerance at the maternal-fetal interface , we are investigating the role of genes that are involved in peripheral self-tolerance in couples with idiopathic recurrent miscarriage . CTLA-4 is a negative regulator of T-cell proliferation and has been associated with human autoimmune disease . An AT(n ) polymorphism in the 3'-untranslated region ( UTR ) of the human gene results in AT stretches that vary in length from 16 to 46 bp . We hypothesized that long stretches of AT repeats would result in mRNA instability , and reduced fetal survival in humans . We examined the transmission of AT(n ) alleles in 60 couples with a history of > or = 3 unexplained spontaneous abortions to their 51liveborn children and 10 abortuses . The shorter allele was transmitted from heterozygous mothers to 26 of 35 liveborn children ( chi2 = 8.3 , P = 0.0040 ) and to three of nine aborted fetuses ( chi2 = 1.0 , P = 0.317 ) . The shorter allele was transmitted from heterozygous fathers to 15 of 32 liveborn children ( chi2 = 0.12 , P=0.726 ) and to five of eight aborted fetuses ( chi2 = 0.5 , P = 0.480 ) . Furthermore , liveborn fetuses who inherited smaller alleles were more likely to represent the first successful pregnancy than liveborn fetuses who inherited larger maternal alleles ( Pexact = 0.044 ) and fetuses of first pregnancies that inherited the smaller allele were significantly more likely to survive to term ( Pexact = 0.0086 ) . The preferential transmission of maternally-inherited shorter alleles to liveborn children , but r and om transmission of paternally-inherited alleles , suggests that CTLA-4 may be imprinted in humans and that this gene may play a role in inducing or maintaining tolerance at the maternal-fetal interface The aim of this study was to evaluate the therapeutic efficacy of intravenous immunoglobulin ( IVIG ) in the prevention of recurrent spontaneous abortion ( RSA ) . In a double-blind , r and omized , placebo-controlled study , 41 women with a history of unexplained recurrent spontaneous abortion were treated with IVIG or saline infusions during pregnancy . The birth of a child was considered a successful outcome . The overall success rate was 77 % in the IVIG group compared with 79 % in the placebo group . For women with primary RSA the success rates were 82 ( IVIG ) and 89 % ( placebo ) , and for women with secondary RSA the rates were 73 ( IVIG ) and 70 % ( placebo ) . We found no statistically significant difference in treatment results between IVIG and placebo It is still unclear whether i.v . immunoglobulins ( Ig ) can facilitate the reproductive prognosis of women who have suffered recurrent pregnancy loss . We report the results of a multicentre placebo-controlled study on the effect of Ig administration on pregnancy outcome in 46 women who had suffered at least three recurrent miscarriages . All were screened to exclude chromosomal or Müllerian abnormalities , the presence of antinuclear antibodies , lupus anticoagulant ( LA ) or elevated titres of anticardiolipin antibodies which may have revealed an underlying autoimmune problem . To avoid a selection bias towards ongoing pregnancies , i.v . Ig or placebo were administered between weeks 5 and 7 of gestation for 2 consecutive days as soon as each woman knew she was pregnant and before embryonic heart activity could be detected . A further infusion was administered at week 8 when ultrasonography confirmed an ongoing embryonic development . In all , 68 % of the women who received Ig  went to term versus 79 % of those who received a placebo ( not significant ) , with no significant differences in the pregnancy course or the perinatal outcome . These results suggest either that women with recurrent miscarriages who have no recognized cause of pregnancy loss have a good reproductive prognosis without any treatment or that the emotional care associated with the administration of a placebo can indirectly facilitate the progression of pregnancy The Recurrent Miscarriage ( REMIS ) study is a double-blind , multicenter , r and omized clinical trial design ed to evaluate the efficacy of immunization with paternal leukocytes in the prevention of miscarriages in women who have had three or more unexplained pregnancy losses . Women entering the study are immunized with their husb and 's leukocytes or with a saline control before they become pregnant . After becoming pregnant , they receive weekly ultrasound examinations and psychological support during the first trimester and are followed until a successful delivery or a miscarriage occurs . The primary analysis for the study will be an intent-to-treat analysis in which we shall compare the proportion of successes in the two groups , defining a " success " as a pregnancy achieved within 12 months of r and omization that results in a viable offspring . We shall count both miscarriages and nonpregnancies as failures , owing to the possibility of very early losses prior to the detection of pregnancy . In a secondary analysis , we shall exclude women who do not become pregnant within the alloted 12 month period . We compared the test size and power of these two approaches under various configurations for the true rates of nonpregnancy , miscarriage , and delivery in the two groups . Although the analysis excluding nonpregnant women achieves greater power for alternatives in which pregnancy rates are equal and live birth rates higher in the treated group , the rejection rate is not adequately controlled when pregnancy rates differ but live birth rates are unaffected by treatment . It can also lead to a reduction in power if the treatment prevents early as well as later losses . We conclude that the intent-to-treat analysis should remain the primary analysis for the trial ABSTRACT : The efficacy of immunotherapy for the treatment of recurrent spontaneous abortions was tested in patients selected from the same ethnically homogeneous population of Chinese in Taiwan in whom the immunogenetics of gestational trophoblastic tumors and of recurrent spontaneous abortion had been studied . The patients , who included both primary and secondary aborters , were r and omly assigned to three groups : those who were immunized with their own lymphocytes ( controls ) ( 49 ) ; those who were immunized with their husb and s ' lymphocytes ( 39 ) ; and those who were immunized with third party lymphocytes ( 11 )  . The data were analyzed individually for the primary and secondary aborters and collectively for both groups combined . The number of babies born , the number of current pregnancies , and the number of recurrent abortions were not statistically significantly different between the control and the immunized groups , and a similar small number of congenital abnormalities ( 4–9 % ) occurred in both the control and immunized groups . The increase in the blocking effect for the mixed lymphocyte reaction was not related to the success of the postimmunization pregnancies . Thus , this study does not show any significant improvement in the rate of livebirths in women immunized with their husb and s ' lymphocytes or with third party lymphocytes compared to that in a placebo‐controlled group of women BACKGROUND Couples with unexplained recurrent miscarriage may have an alloimmune abnormality that prevents the mother from developing immune responses essential for the survival of the genetically foreign conceptus . Immunisation with paternal mononuclear cells is used as a treatment for such alloimmune-mediated pregnancy losses . However , the published results on this treatment are conflicting . In this study ( the Recurrent Miscarriage [ REMIS ] Study ) , we investigated whether paternal mononuclear cell immunisation improves the rate of successful pregnancies . METHODS Women who had had three or more spontaneous abortions of unknown cause were enrolled in a double-blind , multicentre , r and omised clinical trial . 91 were assigned immunisation with paternal mononuclear cells ( treatment ) and 92 immunisation with sterile saline ( control ) . The primary outcomes were the inability to achieve pregnancy within 12 months of r and omisation , or a pregnancy which terminated before 28 weeks of gestation ( failure ) ; and pregnancy of 28 or more weeks of gestation ( success ) . Two analyses were done : one included all women ( intention to treat ) , and the other included only those who became pregnant . FINDINGS Two women in each group received no treatment , and eight ( three treatment , five control ) were censored after an interim analysis . In the analysis of all r and omised women who completed the trial , the success rate was 31/86 ( 36 % ) in the treatment group and 41/85 ( 48 % ) in the control group ( odds ratio 0.60 [ 95 % CI 0.33 - 1.12 ] , p=0.108 ) . In the analysis of pregnant women only , the corresponding success rates were 31/68 ( 46 % ) and 41/63 ( 65 % ; odds ratio 0.45 [ 0.22 - 0.91 ] , p=0.026 ) . The results were unchanged after adjustment for maternal age , number of previous miscarriages , and whether or not the couple had had a previous viable pregnancy . Similar results were obtained in a subgroup analysis of 133 couples with no previous livebirth . INTERPRETATION Immunisation with paternal mononuclear cells does not improve pregnancy outcome  in women with unexplained recurrent miscarriage . This therapy should not be offered as a treatment for pregnancy loss PROBLEM : The efficacy of intravenous immunoglobulin ( IVIG ) for treatment of  unexplained recurrent spontaneous abortion  was assessed in a prospect i ve , r and omized , double‐blinded , and placebo‐controlled study PROBLEM : Recurrent spontaneous abortion ( RSA ) is the cause of childlessness in 2–5 % of reproducing couples . Immunological mechanisms have been proposed as an etiology in some cases of RSA . Various forms of immunotherapy have been attempted in individuals thought to have an immunologic mechanism associated with RSA . Intravenous immunoglobulin ( IVIG ) has been used in a pilot study to successfully treat women with RSA We conducted a r and omized trial comparing expectant management versus immunotherapy with paternal leukocytes to improve obstetric outcome in women with unexplained recurrent abortion . Eligible for the study were women with unexplained recurrent abortion ( three or more miscarriages and no live birth ) , negative findings of immunological screening and no inhibition of the mixed lymphocyte culture . These women were seen for the first time between October 1988 and March 1991 in a network of obstetric departments in Northern Italy . Subjects positive for HLA DR3 or with a partner positive for hepatitis virus B antigen were not eligible . A total of 44 women entered the study . Patients were r and omly allocated to immunotherapy ( 22 women ) or expectant management ( 22 women ) . Women allocated to immunotherapy were given 200 x 10(6 ) purified paternal lymphocytes before pregnancy . Median follow-up was 24 months ( range 10 - 39 ) in the immunotherapy group and 25 months ( range 11 - 38 ) in the expectant management group . Out of the 22 women r and omized to immunotherapy , 16 became pregnant and the corresponding value was 14 in the expectant management group . Spontaneous abortion occurred in six out of the 16 pre 
    Output:
    
REVIEW ER 'S CONCLUSIONS Paternal cell immunization , third party donor leukocytes , trophoblast membranes , and IVIG provide no significant beneficial effect over placebo in preventing further miscarriages