***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: This study evaluated whether heparin administration could affect IVF outcome .  A total of 172 women , aged < 40years , without laboratory findings of thrombophilia and undergoing their first IVF cycle , were r and omly allocated to treatment ( n=86 ) and control ( n=86 ) groups . Patients allocated to the treatment group received low-molecular-weight heparin dalteparin sodium 2500IU s.c . daily , in addition to routine luteal phase support , from oocyte retrieval up to the day of the pregnancy test or up to the ninth week of pregnancy in the cases of positive human chorionic gonadotrophin . From the day after the oocyte retrieval , all patients began st and ard supplementation with vaginal progesterone 200 mg twice a day . At the sixth week of pregnancy , patients underwent an ultrasound scan to assess the number/viability of gestational sacs . Implantation rates were 15 % and 12 % in the dalteparin and control groups , respectively . The clinical pregnancy rates/embryo transfers were 26 % ( 19/73 ) and 20 % ( 16/80 ) , in the dalteparin and control groups , respectively , with live birth rates/embryo transfer of 21 % ( 15/73 ) and 16 % ( 13/80 ) . Despite the lack of statistical significance , the increase in pregnancies observed in the treatment group may be considered as an important clinical point in the optimization of IVF clinical outcome OBJECTIVE We attempted to compare the use of low-dose heparin with a st and ard dose of 40 mg prednisone daily ( both plus low-dose aspirin ) for treatment of pregnant women with antiphospholipid antibody-associated recurrent fetal loss with respect to maternal and perinatal morbidity and efficacy in prevention of fetal death . STUDY DESIGN A multicenter r and omized trial included 20 patients . Generalizability of results from r and omized patients was evaluated by means of additional data from 13 women refusing and 12 women ineligible for r and omization . Data from study groups were compared with Fisher 's exact test , and generalizability was evaluated with a chi 2 test for trend . RESULTS Live birth rates were the same ( 75 % ) with either treatment , but " serious " maternal morbidity and the frequency of preterm delivery were significantly higher among women r and omly assigned to prednisone ( p = 0.02 vs p = 0.006 ) . Preterm delivery among prednisone-treated women was usually associated with premature rupture of the membranes or preeclampsia . These results could be generalized to the other groups of women ascertained during the course of the study . CONCLUSIONS Low-dose heparin should be preferred to prednisone when treatment is indicated for high-risk pregnant women with antiphospholipid antibodies OBJECTIVE The purpose of this study was to compare the use of low-dose aspirin alone with heparin and low-dose aspirin in the treatment of the antiphospholipid antibody syndrome . STUDY DESIGN A prospect i ve , single-center trial included 50 patients who were alternately assigned to treatment . Each patient had at least three consecutive spontaneous pregnancy losses , positive antiphospholipid antibodies on two occasions , and a complete evaluation . Data were compared by chi(2 ) analysis and Fisher 's exact test . RESULTS Viable infants were delivered of 11 of 25 ( 44 % ) women treated with aspirin and 20 of 25 ( 80 % ) women treated with heparin and aspirin ( p < 0.05 ) . There were no significant differences between the low-dose aspirin and the heparin plus low-dose aspirin groups with respect to gestational age at delivery ( 37.8 + /- 2.1 vs 37.2 + /- 3.4 weeks ) , number of cesarean sections ( 18 % vs 20 % ) , or complications . CONCLUSION Heparin plus low-dose aspirin provides a significantly better pregnancy outcome than low-dose aspirin alone does for antiphospholipid antibody-associated recurrent pregnancy loss Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more PROBLEMS : 1 ) Does the administration of heparin and aspirin ( H/A ) in combination with intravenous immunoglobulin G ( IVIG ) improve in vitro fertilization ( IVF ) implantation and birth rates in patients with recurrent IVF failures ? 2 ) Is the effect of such treatment related to the antiphospholipid antibody ( APA ) status of the patients concerned BACKGROUND The role of thrombophilia and thyroid autoimmunity in unexplained infertility ( UI ) , implantation failure ( IF ) and recurrent spontaneous abortion ( RSA ) is controversial and poorly understood . METHODS From March , 2004 to January , 2007 , 119 women were prospect ively included : 32 oocyte donors , 31 patients with UI , 26 with IF and 30 with RSA .  The IF and RSA groups presented normal preimplantation genetic screening . Protein C , protein S , antithrombin III , lupus anticoagulant , activated protein C resistance ( APCR ) , immunoglobulin M and G anticardiolipin antibodies , homocystine , Factor V Leiden , prothrombin G20210A mutation , methylentetrahydrofolate reductase C677 T mutation , thyroid-stimulating hormone ( TSH ) , free thyroxine , anti-thyroid peroxidase ( TPO ) and anti-thyroglobulin ( TG ) antibodies were assessed . RESULTS The prevalence of thrombophilia was high and similar among groups . In the IF group , the prevalence of APCR ( 15.4 % ) , lupus anticoagulant ( 11.5 % ) and combined thrombophilia ( 19.2 % ) was higher , but not significantly different , than the other three groups . The prevalence of thyroid autoimmunity in women with IF ( anti-TPO antibodies , P = 0.009 ; anti-TPO plus anti-TG antibodies , P = 0.04 ) and UI ( anti-TPO , P = 0.002 ; anti-TG , P = 0.019 ; anti-TPO plus anti-TG antibodies , P = 0.005 ) was significantly increased in comparison to those with RSA . There was also a trend towards a higher prevalence of thyroid autoimmunity in the UI and IF groups than in the control group . TSH and free thyroxine levels all remained within a normal range . CONCLUSIONS When embryo aneuploidy is ruled out , thrombophilia could constitute an etiologic factor in IF . Furthermore , thyroid autoimmunity is strongly related to UI and IF PROBLEM : The effect of mini‐dose heparin/aspirin ( H/A ) alone vs. combined intravenous immunoglobulin G ( IVIg ) and H/A on in vitro fertilization ( IVF ) birthrates in women who test seropositive for antiphospholipid antibodies ( APA+ ) was evaluated , as was the question of whether outcome is influenced by the gammaglobulin isotype(s ) or the phospholipid ( PL ) epitope(s ) to which the APAs are directed BACKGROUND Heparin and low molecular weight heparin ( LMWH ) are used widely to improve the pregnancy outcome in women with thrombophilia , miscarriage , recurrent miscarriage and fetal death . This study was design ed to investigate the effects of heparin and LMWHs , enoxaparin and tinzaparin , on E-cadherin and laminin expression in placental and decidual tissues in rat pregnancy . METHODS Wistar albino female rats ( n = 48 ) were r and omly assigned to four study groups ( normal saline , heparin , enoxaparin and tinzaparin ) in the preconceptional period . Tissue sections of placenta and decidua were immunohistochemically examined for the expression of E-cadherin and laminin . RESULTS E-cadherin placental staining score of heparin group was significantly lower and E-cadherin decidual staining score of heparin and enoxaparin groups were significantly lower than control group . There were no significant differences in placental and decidual laminin staining scores among the study groups . CONCLUSIONS Heparin and enoxaparin can reduce E-cadherin expression but not laminin expression in rat pregnancy . They might modulate trophoblast invasion . We suggest that this is the possible underlying mechanism involving in improvement of trophoblast invasion by the use of heparin and LMWH in patients with the history of miscarriage OBJECTIVE To investigate whether heparin and low-dose aspirin increase the pregnancy rate in antiphospholipid antibody or antinuclear antibody-seropositive women with IVF implantation failure . DESIGN A double-blind , r and omized , transfer-by-transfer of fresh or cryopreserved embryos , crossover trial . A hospital infertility clinic and associated IVF service . PATIENT(S ) Women seropositive for at least one antiphospholipid ( APA ) , antinuclear ( ANA ) , or beta(2 ) glycoprotein I autoantibody and > or=10 embryos transferred without achieving pregnancy ( n = 143 ) . INTERVENTION(S ) Subcutaneous unfractionated heparin ( 5000 IU b.i.d . ) and aspirin ( 100 mg daily ) ( 158 transfers of 296 embryos ) or placebo ( 142 transfers of 259 embryos ) from the day of embryo transfer . MAIN OUTCOME MEASURE(S ) Fetal heart per embryo transferred ( implantation rate ) . RESULT ( S ) There was no significant difference in pregnancy rates or implantation rates between treated and placebo cycles ; for example , fetal hearts per embryo transferred implantation rates were 6.8 % ( 20/296 ) and 8.5 % ( 22/259 ) , respectively , and the generalized estimating equation covariate adjusted relative pregnancy rate was 0.65 ( 95 % confidence interval , 0.33 - 1.28 ) . The implantation rate for seropositive trial participants ( 42/555 , 7.6 % ) compared favorably with that for IVF implantation-failure patients continuing treatment outside the trial ( 147/3237 , 4.5 % ) . CONCLUSION ( S ) Heparin and aspirin did not improve pregnancy or implantation rates for APA-positive or ANA-positive patients with IVF implantation failure BACKGROUND The pathology underlying recurrent implantation failures ( RIF ) is not clear and treatment options proposed are generally not evidence based . Although the effect of heparin on trophoblast biology has not been studied extensively , given the available data suggesting a possible beneficial effect of heparin on embryo implantation , we decided to undertake this pilot study . METHODS One hundred and fifty women with > or = 2 failed assisted reproduction treatment cycles were included in this r and omized open-label pilot trial . Participants underwent controlled ovarian stimulation with the long protocol and were r and omly allocated to receive 1 mg/kg/day low molecular weight heparin ( LMWH ) or no treatment in addition to routine luteal phase support ( LPS ) on the day after oocyte retrieval . LPS and LMWH was continued up to the 12th gestational week in pregnant participants . RESULTS There were 26 ( 34.7 % ) live births in the LMWH group , and 20 ( 26.7 % ) in the control group ( absolute difference 8.0 % , 95 % CI -4.2 to 24.9 % , P = 0.29 ) . There were 34 ( 45.3 % ) and 29 ( 38.7 % ) clinical pregnancies in the LMWH and control groups , respectively ( absolute difference 6.6 % , 95 % CI -9.0 to 21.8 % , P = 0.41 ) . Implantation rates were 24.5 and 19.8 % in the LMWH and control groups , respectively ( absolute difference 4.7 % , 95 % CI -4.7 to 14.1 % , P = 0.33 ) . CONCLUSION Despite lack of statistical significance , observed relative increase by 30 % in live birth rates with LMWH may be regarded as a clinical ly significant trend necessitating further research on the use of empirical LMWH in women with RIF and possibly in all women undergoing assisted reproduction treatment . Failure to demonstrate statistical significance of the observed treatment difference may be due to limited sample size of this pilot study Abstract Objective : To determine whether treatment with low dose aspirin and heparin leads to a higher rate of live births than that achieved with low dose aspirin alone in women with a history of recurrent miscarriage associated with phospholipid antibodies ( or antiphospholipid antibodies ) , lupus anticoagulant , and cardiolipin antibodies ( or anticardiolipin antibodies ) . Design : R and omised controlled trial . Setting : Specialist clinic for recurrent miscarriages . Subjects : 
    Output:
    
However , the beneficial effect of LMWH was not significant when only studies with unexplained RIF were pooled .