Fertility and Sterility
Volume 86, Issue 2 , Pages 362-366 , August 2006

A randomized study of thromboprophylaxis in women with unexplained consecutive recurrent miscarriages

  • Mordechai Dolitzky, M.D.

      Affiliations

    • Department of Obstetrics & Gynecology, Sheba Medical Center, Tel Hashomer, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    • Drs. Mordechai Dolitzky and Aida Inbal are first authors.
    • ,
  • Aida Inbal, M.D.

      Affiliations

    • Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    • Drs. Mordechai Dolitzky and Aida Inbal are first authors.
    • ,
  • Yakov Segal, M.D.

      Affiliations

    • Department of Obstetrics & Gynecology, Sheba Medical Center, Tel Hashomer, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    • ,
  • Amir Weiss, M.D.

      Affiliations

    • Department of Obstetrics & Gynecology, Ha’Emek Medical Center, Afula, Israel
    • ,
  • Benjamin Brenner, M.D.

      Affiliations

    • Thrombosis and Hemostasis Unit, Rambam Medical Center, Haifa, Israel
    • ,
  • Howard Carp, M.B., B.S.

      Affiliations

    • Department of Obstetrics & Gynecology, Sheba Medical Center, Tel Hashomer, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    • Corresponding Author InformationReprint requests: Howard Carp, M.B., B.S., Department of Obstetrics & Gynecology, Sheba Medical Center, Tel Hashomer, 52621, Israel (FAX: 972-9-9574779).

Received 22 September 2005 ,Revised 30 December 2005 ,Accepted 30 December 2005.

References 

  1. Coulam CB . Recurrent pregnancy loss (foreward) . In:  Greenshaw C editors. Clinical obstetrics and gynecology . Philadelphia: Harper and Row; 1986;p. 863
  2. Salat-Baroux J . Recurrent spontaneous abortions . Reprod Nutr Dev . 1988;28:1555–1568
  3. Wheeler JM . Epidemiologic aspects of recurrent pregnancy loss . Infertil Reprod Med Clin North Am . 1991;2:1–17
  4. Reginald PW , Beard RW , Chapple J , Forbes PB , Liddell HS , Mowbray JF , et al.   Outcome of pregnancies progressing beyond 28 weeks gestation in women with a history of recurrent miscarriage . Br J Obstet Gynaecol . 1987;94:643
  5. Jivraj S , Anstie B , Cheong YC , Fairlie FM , Laird SM , Li TC . Obstetric and neonatal outcome in women with a history of recurrent miscarriage (a cohort study) . Hum Reprod . 2001;16:102–106
  6. Seidman DS , Gale R , Ever-Hadani P , Slater PE , Stevenson DK . Reproductive complications after previous spontaneous abortions . Pediatr Rev Commun . 1990;5:1–10
  7. Bowie EJW , Thompson JH , Pascuzzi CA . Thrombosis in systemic lupus erythematosus despite circulating anticoagulants . J Lab Clin Med . 1963;62:416–432
  8. Preston FE , Rosendaal FR , Walker ID , Briot E , Berntorp E , Conard J , et al.   Increased fetal loss in women with heritable thrombophilia . Lancet . 1996;348:913–916
  9. Grandone E , Margaglione M , Colaizzo D , D’Addedda M , Cappucci G , Vecchione G , et al.   Factor V Leiden is associated with repeated and recurrent unexplained fetal losses . Thromb Haemost . 1997;77:822–824
  10. Rai R , Regan L , Hadley E , Dave M , Cohen H . Second-trimester pregnancy loss is associated with activated C resistance . Br J Haematol . 1996;92:489–490
  11. Martinelli I , Taioli E , Cetin I , Marinoni A , Gerosa S , Villa MV , et al.   Mutations in coagulation factors in women with unexplained late fetal loss . N Engl J Med . 2000;343:1015–1018
  12. Tal J , Schliamser LM , Leibovitz Z , Ohel G , Attias D . A possible role for activated protein C resistance in patients with first and second trimester pregnancy failure . Hum Reprod . 1999;14:1624–1627
  13. Rey E , Kahn SR , David M , Shrier I . Thrombophilic disorders and fetal loss (a meta-analysis) . Lancet . 2003;361:901–908
  14. Brenner B , Hoffman R , Blumenfeld Z , Weiner Z , Youris JS . Gestational outcome in thrombophilic women with recurrent pregnancy loss treated by enoxaparin . Thromb Haemost . 2000;83:693–697
  15. Grandone E , Brancaccio V , Colaizzo D , Scianname N , Pavone G , Di Minno G , et al.   Preventing adverse obstetric outcomes in women with genetic thrombophilia . Fertil Steril . 2002;78:371–375
  16. Kupferminc MJ , Fait G , Many A , Lessing JB , Yair D , Bar-Am A , et al.   Low-molecular-weight heparin for the prevention of obstetric complications in women with thrombophilias . Hypertens Pregnancy . 2001;20:35–44
  17. Riyazi N , Leeda M , de Vries JI , Huijgens PC , van Geijn HP , Dekker GA . Low-molecular-weight heparin combined with aspirin in pregnant women with thrombophilia and a history of preeclampsia or fetal growth restriction (a preliminary study) . Eur J Obstet Gynecol Reprod Bio . 1998;80:49–54
  18. Gris JC , Mercier E , Quere I , Lavigne-Lissalde G , Cochery-Nouvellon E , Hoffet M , et al.   Low-molecular-weight heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder . Blood . 2004;103:3695–3699
  19. Carp HJA , Dolitzky M , Inbal A . Thromboprophylaxis improves the live birth rate in women with consecutive recurrent miscarriages and hereditary thrombophilia . Thrombosis and Hemost . 2003;1:433–438
  20. Stirling Y , Woolf L , North WR , Seghatchian MJ , Meade TW . Haemostasis in normal pregnancy . Thromb Haem . 1984;52:176–182
  21. Comp PC , Thurnau GR , Welsh J , Esmon CT . Functional and immunologic protein S levels are decreased during pregnancy . Blood . 1986;68:881–885
  22. Kruithof EK , Tran-Thang C , Gudinchet A , Hauert J , Nicoloso G , Genton C , et al.   Fibrinolysis in pregnancy (a study of plasminogen activator inhibitors) . Blood . 1987;69:460–466
  23. Tzafettas J , Mamopoulos A , Anapliotis A , Loufopoulos A , Psarra A , Klearchou N , et al.   Thromboprophylaxis throughout pregnancy in women with previous history of recurrent miscarriages of unknown aetiology . Clin Exp Obstet Gynecol . 2002;29:267–270
  24. Bates SM , Greer IA , Hirsh J , Ginsberg JS . Use of antithrombotic agents during pregnancy (the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy) . (Review) Chest . 2004;126:627S–644S
  25. Carp HJA . Investigation and treatment for recurrent pregnancy loss . In:  Rainsbury P ,  Vinniker D editor. A practical guide to reproductive medicine. Lancs. . UK: Parthenon & Co; 1997;p. 337–362
  26. Knudsen UB , Hansen V , Juul S , Secher NJ . Prognosis of a new pregnancy following previous spontaneous abortions . Eur J Obstet Gynecol Reprod Biol . 1991;39:31–36
  27. Kupferminc MJ , Peri H , Zwang E , Yaron Y , Wolman I , Eldor A . High prevalence of the prothrombin gene mutation in women with intrauterine growth retardation, abruptio placentae and second trimester loss . Acta Obstet Gynecol Scand . 2000;79:963–967
  28. Alfirevic Z , Roberts D , Martlew V . How strong is the association between maternal thrombophilia and adverse pregnancy outcome? A systematic review . Eur J Obstet Gynecol Reprod Biol . 2002;101:6–14
  29. Baram D , Rashkovsky M , Hershkoviz R , Drucker I , Reshef T , Ben-Shitrit S , et al.   Inhibitory effects of low molecular weight heparin on mediator release by mast cells (preferential inhibition of cytokine production and mast cell-dependent cutaneous inflammation) . Clin Exp Immunol . 1997;110:485–491
  30. Downing LJ , Strieter RM , Kadell AM , Wilke CA , Greenfield LJ , Wakefield TW . Low-dose low-molecular-weight heparin is anti-inflammatory during venous thrombosis . J Vasc Surg . 1998;28:848–854
  31. Carp HJA . Cytokines in recurrent miscarriage . Lupus . 2004;13:630–634
  32. Rai R , Backos M , Baxter N , Chilcott I , Regan L . Recurrent miscarriage-an aspirin a day? . Hum Reprod . 2000;15:2220–2223
  33. Daya S . Recurrent spontaneous early pregnancy loss and low dose aspirin . (Review) Minerva Ginecol . 2003;55:441–449
  34. Pattison NS , Chamley LW , Birdsall M , Zanderigo AM , Liddell HS , McDougall J . Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? A randomized controlled trial . Am J Obstet Gynecol . 2000;183:1008–1012
  35. Clark DA , Daya S , Coulam CB , Gunby J  The Recurrent Miscarriage Immunotherapy Trialists Group . Implication of abnormal human trophoblast karyotype for the evidence-based approach to the understanding, investigation, and treatment of recurrent spontaneous abortion . Am J Reprod Immunol . 1996;35:495–498
  36. Lepercq J , Conard J , Borel-Derlon A , Darmon JY , Boudignat O , Francoual C , et al.   Venous thromboembolism during pregnancy (a retrospective study of enoxaparin safety in 624 pregnancies) . BJOG . 2001;108:1134–1140

 This study was funded by a nonrestrictive grant in aid from Aventis Pharma Ltd.

PII: S0015-0282(06)00688-1

doi: 10.1016/j.fertnstert.2005.12.068

Fertility and Sterility
Volume 86, Issue 2 , Pages 362-366 , August 2006

Article Tools