Fibrinolytic defects and recurrent miscarriage: a systematic review and meta-analysis.
OBJECTIVE
To systematically review evidence of the association between fibrinolytic defects and recurrent miscarriage.


METHODS
MEDLINE, EMBASE, and references of retrieved articles (last update September 2006) were used.


METHODS
Studies comparing the prevalence of fibrinolytic defects in patients with recurrent miscarriage and control women were reviewed. Of 111 potentially relevant studies, data from 14 were integrated with meta-analytic techniques and were presented as odds ratios (ORs).


RESULTS
Plasminogen activator inhibitor-1 4G/5G polymorphism (OR 1.65, 95% confidence interval [CI] 0.92-2.95) and increased plasminogen activator inhibitor activity were not significantly associated with recurrent miscarriage, although the latter showed profound heterogeneity across studies. Although factor XII C46T polymorphism is not associated with recurrent miscarriage (OR 1.07, 95% CI 0.52-2.22), factor XII deficiency is significantly associated (five studies, 1,096 women; OR 18.11, 95% CI 5.52-59.39), with minimal heterogeneity across studies. Factor XIII Val34Leu and Tyr204Phe polymorphisms were not associated with recurrent miscarriage (OR 1.24, 95% CI 0.46-3.34 and OR 2.61, 95% CI 0.45-15.16, respectively). There were no eligible studies found for the rest of the factors searched (urokinase-type plasminogen activator, tissue-type plasminogen activator, kallicrein, a2-antiplasmin, a2-macroglobulin, thrombin-activated thrombolysis inhibitor, and factor XI). Only a small minority of studies ascertained miscarriage according to specific criteria, and none of the studies provided equal examination for confounders in cases and controls.


CONCLUSIONS
Factor XII deficiency is associated with recurrent miscarriage. Data on the other factors either fail to show association or are quite limited.
Sotiriadis
Alexandros
A
Department of Obstetrics and Gynecology, University Hospital of Ioannina, Greece. asotir@gmail.com
Makrigiannakis
Antonis
A
Stefos
Theodor
T
Paraskevaidis
Evangelos
E
Kalantaridou
Sophia N
SN
D000026:Abortion, Habitual / Q000503:physiopathology*; D016022:Case-Control Studies; D002648:Child; D005174:Factor XII / Q000032:analysis* / Q000235:genetics; D005175:Factor XII Deficiency / Q000453:epidemiology / Q000503:physiopathology; D005176:Factor XIII / Q000235:genetics; D005260:Female; D005342:Fibrinolysis / Q000502:physiology*; D005865:Gestational Age; D006801:Humans; D016017:Odds Ratio; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D011110:Polymorphism, Genetic; D011247:Pregnancy
D017395:Plasminogen Activator Inhibitor 1; D005174:Factor XII; D005176:Factor XIII