***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 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 This study evaluated the results of a management protocol combining a number of investigations and interventions , previously proven beneficial in r and omized controlled trials in  IVF/intracytoplasmic sperm injection ( ICSI ) patients with apparently unexplained recurrent implantation failure ( defined as two or more previous failed cycles , during which at least six good- quality embryos were transferred ) . It was a prospect i ve cohort study and included 273 couples with previous recurrent implantation failure . Each patient ( all under 40 ) underwent a pre-treatment work-up , consisting of pelvic ultrasound scan for hydrosalpinx , hysteroscopy and screening for acquired and congenital thrombophilia . Detected abnormalities were dealt with accordingly : proximal occlusion for hydrosalpinx , hysteroscopic management for intrauterine pathology and thromboprophylaxis with daily low-molecular weight heparin from the day of embryo transfer for thrombophilia . The patients then underwent IVF/ICSI with laser-assisted hatching .  112 patients ( 41 % ; group 1 ) had abnormalities detected ( 17 hydrosalpinx , 11 intrauterine pathology , 63 congenital thrombophilia , 21 acquired thrombophilia ) and the remaining 161 ( 59 % ; group 2 ) had normal work-up . The pregnancy rates per cycle started for all patients , group 1 and group 2 were 47 % , 55 % and 41 % , respectively . This suggests that using the described management protocol in couples with previous recurrent implantation failure leads to a favourable chance of success 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 OBJECTIVE To evaluate the expression of syndecan-1 , -2 , -3 , and -4 in different phases of eutopic endometrium of normal cycling women . DESIGN Prospect i ve observational study . SETTING University-based research center for reproductive medicine . PATIENT(S ) Twenty-nine healthy ovulatory volunteers . INTERVENTION(S ) mRNA and protein expression of syndecan-1 to -4 in human endometrium . MAIN OUTCOME MEASURE(S ) Real-time polymerase chain reaction of syndecan members and further characterization of mRNA expression of syndecan-1 and -4 with multiprobe RNase protection assays of epithelial and stromal cells after purification with antibody-coated magnetic beads . For confirmation of results , protein expression and localization using immunohistochemistry for syndecan-1 and -4 was performed . RESULT ( S ) All syndecans were expressed within human endometrium . Syndecan-1 and -4 proved to be significantly upregulated in whole endometrium during the secretory phase ( 2.73-fold and 2.85-fold , respectively ) . Using multiprobe RNase protection assays , a significant upregulation of mRNA was noted in epithelial cells during the secretory phase for both syndecan-1 and -4 ( 7.46-fold and 2.52-fold , respectively ) and confirmed by immunohistochemistry . CONCLUSION ( S ) Cycle-dependent expression of syndecan-1 and -4 suggests that these adhesion proteins are involved in the regulation of the cycling endometrium BACKGROUND The quality of clinical trials has received increasing attention with the growth of evidence -based medicine and systematic review s. We aim ed to identify whether errors and omissions commonly encountered when undertaking Cochrane review s in this field are still passing peer review . METHODS We undertook a review of trials published in 2001 by two major journals . We selected from Medline only trials in which authors compared pregnancy rates under two interventions by allocating women to different groups . RESULTS We identified 39 trials meeting our criteria . Six trials were fatally flawed by design , either by inappropriate use of a cross-over design or by systematic allocation described by the authors as ' r and om ' . Only six reports cl aim ed to apply the intention-to-treat principle , and the principle was misunderstood by four of these . Only five trials reported live birth rates sufficiently to allow valid meta- analysis . Most trials ( 82 % ) included at least one ' unit of analysis ' error . CONCLUSIONS We selected simple trials from respected journals , assuming that our sample would represent trials of highest method ological quality in the field . Nevertheless , the st and ards of design , analysis and reporting of many subfertility trials are not sufficient to allow reliable interpretation of results , or inclusion in meta-analyses 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 Background Introduction : Recently , thrombophilia ( acquired and inherited ) has been implicated in recurrent IVF – ET failure . The objective of this study was to determine the effect and safety of thromboprophylaxis using low-molecular-weight heparin ( LMWH ) in women with recurrent in vitro fertilization (IVF)–embryo transfer ( ET ) failure and thrombophilia . Methods : Eighty-three women with history of three or more previous IVF failures and who had at least one thrombophilic defect were eligible for this study . Patients were r and omly allocated into two groups : Group A ( n = 42 ) received enoxaparin 40 mg/day , and group B ( n = 41 ) received placebo ( NaCl 0.9 % ) . Both treatments started on the day of ET and continued until delivery or foetal demise was diagnosed . The primary outcomes were the implantation , pregnancy and live birth rates . Results : Patients who received LMWH for thromboprophylaxis had a significant increase in the implantation and pregnancy rates compared with the placebo group ( 20.9 % vs. 6.1 % and 31 % vs. 9.6 % , respectively ; p < 0.001 and p < 0.05 , respectively ) . A significant increase in the live birth rate was observed in the heparin-treated group compared with placebo ( 23.8 % vs. 2.8 % , respectively ; p < 0.05 ) . The abortion rate was significantly higher in the placebo-treated group compared to the heparin-treated group ( p < 0.05 ) . The frequency of treatment complications did not differ between the two study groups . Conclusions : LMWH is a safe and effective thromboprophylactic treatment for women with thrombophilia and recurrent IVF – 
    Output:
    
There was also a significant improvement in the clinical pregnancy rate with use of LMWH ( OR 1.61 , 95 % CI 1.03 to 2.53 , three studies , 386 women , I(2 ) = 29 % , very low quality evidence with low heterogeneity).However these findings should be interpreted with extreme caution as they were dependent upon the choice of statistical method : they were no longer statistically significant when a r and om-effects model was used .
Adverse events were poorly reported in all included studies , with no comparative data available .
However , LMWH did cause adverse effects including bruising , ecchymosis , bleeding , thrombocytopenia and allergic reactions .
It appeared that these adverse effects were increased if heparin therapy was used over a longer duration .
The results of this Cochrane review of three r and omised controlled trials with a total of 386 women suggested that peri-implantation LMWH in assisted reproduction treatment ( ART ) cycles may improve the live birth rate in women undergoing assisted reproduction .
However , these results were dependent on small low quality studies with substantial heterogeneity , and were sensitive to the choice of statistical model .
There were side effects reported with use of heparin , including bruising and bleeding , and no reliable data on long-term effects .