Low-molecular-weight heparin for women with unexplained recurrent pregnancy loss a multicenter trial with a minimization randomization scheme

Annals of Internal Medicine

Volumn 162, Issue 9, 2015, Pages 601-609

  Schleussner, Ekkehard ^a   Kamin, Gabriele ^b   Seliger, Gregor ^c   Rogenhofer, Nina ^d   Ebner, Susanne ^e   Toth, Bettina ^f   Schenk, Michael ^g   Henes, Melanie ^h   Michael, K Bohlmann ⁱ   Fischer, Thorsten ^j   Brosteanu, Oana ^k   Bauersachs, Rupert ^l   Petroff, David ^k   Beuter Winkler, Petra ^m   Bohlmann, Michael K ^m   Ckmann, Andreas Brü ^m   Dudenhausen, Joachim ^m   Grüner, Susanne ^m   Illing, Ruth ^m   Kemkes Matthes, Bettina ^m   Lachmann, Robert ^m   Lawrenz, Barbara ^m   Neuhaus, Petra ^m   Nitzsche, Katharina ^m   Scheler, Cerrie ^m   Seeger, Sven ^m   Seeliger, Christin ^m   Thaler, Christian ^m   more..

^a FRIEDRICH SCHILLER UNIVERSITY JENA   (Germany)

^b UNIVERSITY HOSPITAL CARL GUSTAV CARUS   (Germany)

^c MARTIN LUTHER UNIVERSITÄT HALLE WITTENBERG   (Germany)

^d UNIVERSITY OF MUNICH   (Germany)

^e Repro Medicine and Human Genetics   (Germany)

^f UNIVERSITY OF HEIDELBERG   (Germany)

^g Das Kinderwunsch Institut Schenk GmbH   (Austria)

^h UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

ⁱ UNIVERSITY HOSPITAL SCHLESWIG HOLSTEIN   (Germany)

^j UNIVERSITY OF SALZBURG   (Austria)

^k UNIVERSITY OF LEIPZIG   (Germany)

^l KLINIKUM DARMSTADT   (Germany)

^m NONE

more..

Author keywords

[No Author keywords available]

Indexed keywords

LOW MOLECULAR WEIGHT HEPARIN; MULTIVITAMIN; ANTICOAGULANT AGENT; DALTEPARIN; VITAMIN;

ADULT; ARTICLE; BLOOD SAMPLING; ECHOGRAPHY; FEMALE; FETUS DEATH; FETUS MALFORMATION; FOLLOW UP; HUMAN; HYPERTRANSAMINASEMIA; LIVE BIRTH; MEASUREMENT; OSTEOPOROSIS; PERINATAL CARE; PLACENTA INSUFFICIENCY; PREECLAMPSIA; PREGNANCY; PRIORITY JOURNAL; RANDOMIZATION; RECURRENT ABORTION; SPONTANEOUS ABORTION; THIRD TRIMESTER PREGNANCY; THROMBOCYTE COUNT; THROMBOEMBOLISM; UNIVERSITY HOSPITAL; VITAMIN SUPPLEMENTATION; ABORTION, HABITUAL; CLINICAL TRIAL; CONTROLLED STUDY; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL; SUBCUTANEOUS DRUG ADMINISTRATION;

ABORTION, HABITUAL; ANTICOAGULANTS; DALTEPARIN; FEMALE; HEPARIN, LOW-MOLECULAR-WEIGHT; HUMANS; INJECTIONS, SUBCUTANEOUS; LIVE BIRTH; PREGNANCY; VITAMINS;

EID: 84928919942     PISSN: 00034819     EISSN: 15393704     Source Type: Journal    
DOI: 10.7326/M14-2062     Document Type: Article

References (38)

1. Brenner B, Hoffman R, Blumenfeld Z, Weiner Z, Younis JS. Gestational outcome in thrombophilic women with recurrent pregnancy loss treated by enoxaparin. Thromb Haemost. 2000;83:693-7. [PMID: 10823264]
2. Sarto A, Rocha M, Geller M, Capmany C, Martínez M, Quintans C, et al. [Treatment with enoxaparin adapted to the fertility programs in women with recurrent abortion and thrombophilia]. Medicina (B Aires). 2001;61:406-12. [PMID: 11563168]
3. Carp H, Dolitzky M, Inbal A. Thromboprophylaxis improves the live birth rate in women with consecutive recurrent miscarriages and hereditary thrombophilia. J Thromb Haemost. 2003;1:433-8. [PMID: 12871446]
4. Grandone E, Brancaccio V, Colaizzo D, Sciannamé N, Pavone G, Di Minno G, et al. Preventing adverse obstetric outcomes in women with genetic thrombophilia. Fertil Steril. 2002;78:371-5. [PMID: 12137876]
5. Rai R, Regan L. Recurrent miscarriage. Lancet. 2006;368:601-11. [PMID: 16905025]
6. Kupferminc MJ, Eldor A. Inherited thrombophilia and gestational vascular complications. Semin Thromb Hemost. 2003;29:185-94. [PMID: 12709922]
7. Bauersachs RM, Dudenhausen J, Faridi A, Fischer T, Fung S, Geisen U, et al; EThIG Investigators. Risk stratification and heparin prophylaxis to prevent venous thromboembolism in pregnant women. Thromb Haemost. 2007;98:1237-45. [PMID: 18064320]
8. Badawy AM, Khiary M, Sherif LS, Hassan M, Ragab A, Abdelall I. Low-molecular weight heparin in patients with recurrent early miscarriages of unknown aetiology. J Obstet Gynaecol. 2008;28:280-4. [PMID: 18569468] doi:10.1080/01443610802042688
9. Fawzy M, Shokeir T, El-Tatongy M, Warda O, El-Refaiey AA, Mosbah A. Treatment options and pregnancy outcome in women with idiopathic recurrent miscarriage: a randomized placebo-controlled study. Arch Gynecol Obstet. 2008;278:33-8. [PMID: 18071727]
10. Clark P, Walker ID, Langhorne P, Crichton L, Thomson A, Greaves M, et al; Scottish Pregnancy Intervention Study (SPIN) collaborators. SPIN (Scottish Pregnancy Intervention) study: a multicenter, randomized controlled trial of low-molecular-weight heparin and low-dose aspirin in women with recurrent miscarriage. Blood. 2010;115:4162-7. [PMID: 20237316] doi:10.1182/blood-2010-01 -267252
11. Kaandorp SP, Goddijn M, van der Post JA, Hutten BA, Verhoeve HR, Hamulyák K, et al. Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. N Engl J Med. 2010;362:1586-96. [PMID: 20335572] doi:10.1056/NEJMoa1000641
12. Visser J, Ulander VM, Helmerhorst FM, Lampinen K, Morin-Papunen L, Bloemenkamp KW, et al. Thromboprophylaxis for recurrent miscarriage in women with or without thrombophilia. HABENOX: a randomised multicentre trial. Thromb Haemost. 2011; 105:295-301. [PMID: 21103659] doi:10.1160/TH10-05-0334
13. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295-306. [PMID: 16420554]
14. Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics. 1975;31:103-15. [PMID: 1100130]
15. Voigt M, Schneider KT, Jährig K. [Analysis of a 1992 birth sample in Germany. 1: New percentile values of the body weight of newborn infants]. Geburtshilfe Frauenheilkd. 1996;56:550-8. [PMID: 9036070]
16. Robertson L, Wu O, Langhorne P, Twaddle S, Clark P, Lowe GD, et al; Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Thrombophilia in pregnancy: a systematic review. Br J Haematol. 2006;132:171-96. [PMID: 16398652]
17. Krause M, Sonntag B, Klamroth R, Heinecke A, Scholz C, Langer C, et al. Lipoprotein (a) and other prothrombotic risk factors in Caucasian women with unexplained recurrent miscarriage. Results of a multicentre case-control study. Thromb Haemost. 2005;93:867-71. [PMID: 15886801]
18. Stirrat GM. Recurrent miscarriage. Lancet. 1990;336:673-5. [PMID: 1975862]
19. Wilson EB. Probable inference, the law of succession, and statistical inference. J Am Stat Assoc. 1927;22:209-12.
20. Newcombe RG. Interval estimation for the difference between independent proportions: comparison of eleven methods. Stat Med. 1998;17:873-90. [PMID: 9595617]
21. Koopman PAR. Confidence intervals for the ratio of two binomial proportions. Biometrics. 1984;40:513-7.
22. Schleuβner E. The prevention, diagnosis and treatment of premature labor. Dtsch Arztebl Int. 2013;110:227-35; quiz 236. [PMID: 23596503] doi:10.3238/arztebl.2013.0227
23. Kupferminc MJ, Eldor A, Steinman N, Many A, Bar-Am A, Jaffa A, et al. Increased frequency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med. 1999;340:9-13. [PMID: 9878639]
24. Walker MC, Ferguson SE, Allen VM. Heparin for pregnant women with acquired or inherited thrombophilias. Cochrane Database Syst Rev. 2003:CD003580. [PMID: 12804477]
25. Mantha S, Bauer KA, Zwicker JI. Low molecular weight heparin to achieve live birth following unexplained pregnancy loss: a systematic review. J Thromb Haemost. 2010;8:263-8. [PMID: 19912516] doi: 10.1111/j.1538-7836.2009.03687.x
26. de Jong PG, Kaandorp S, Di Nisio M, Goddijn M, Middeldorp S. Aspirin and/or heparin for women with unexplained recurrent miscarriage with or without inherited thrombophilia. Cochrane Database Syst Rev. 2014;7:CD004734. [PMID: 24995856] doi:10.1002 /14651858.CD004734.pub4
27. Empson M, Lassere M, Craig J, Scott J. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. Cochrane Database Syst Rev. 2005:CD002859. [PMID: 15846641]
28. Arias F, Romero R, Joist H, Kraus FT. Thrombophilia: a mechanism of disease in women with adverse pregnancy outcome and thrombotic lesions in the placenta. J Matern Fetal Med. 1998;7:277-86. [PMID: 9848693]
29. Buchholz T, Thaler CJ. Inherited thrombophilia: impact on human reproduction. Am J Reprod Immunol. 2003;50:20-32. [PMID: 14506925]
30. Pandey MK, Rani R, Agrawal S. An update in recurrent spontaneous abortion. Arch Gynecol Obstet. 2005;272:95-108. [PMID: 15906053]
31. Luxembourg B, Krause M, Lindhoff-Last E. Blood clotting disorders. Dtsch Arztebl. 2007;104:1489-1498.
32. Baumann K, Beuter-Winkler P, Hackethal A, Strowitzki T, Toth B, Bohlmann MK. Maternal factor V Leiden and prothrombin mutations do not seem to contribute to the occurrence of two or more than two consecutive miscarriages in Caucasian patients. Am J Reprod Immunol. 2013;70:518-21. [PMID: 23795816] doi:10.1111/aji.12144
33. von Depka M, Nowak-Göttl U, Eisert R, Dieterich C, Barthels M, Scharrer I, et al. Increased lipoprotein (a) levels as an independent risk factor for venous thromboembolism. Blood. 2000;96:3364-8. [PMID: 11071628]
34. American College of Obstetricians and Gynecologists. ACOG practice bulletin. Management of recurrent pregnancy loss. Number 24, February 2001. (Replaces Technical Bulletin Number 212, September 1995). American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 2002;78:179-90. [PMID: 12360906]
35. D'Ippolito S, Di Nicuolo F, Marana R, Castellani R, Stinson J, Tersigni C, et al. Emerging nonanticoagulant role of low molecular weight heparins on extravillous trophoblast functions and on heparin binding-epidermal growth factor and cystein-rich angiogenic inducer 61 expression. Fertil Steril. 2012;98:1028-36.e1-2. [PMID: 22818289] doi:10.1016/j.fertnstert.2012.06.042
36. De Braekeleer M, Dao TN. Cytogenetic studies in couples experiencing repeated pregnancy losses. Hum Reprod. 1990;5:519-28. [PMID: 2203803]
37. Rodger MA, Carrier M, Le Gal G, Martinelli I, Perna A, Rey E, et al; Low-Molecular-Weight Heparin for Placenta-Mediated Pregnancy Complications Study Group. Meta-analysis of low-molecularweight heparin to prevent recurrent placenta-mediated pregnancy complications. Blood. 2014;123:822-8. [PMID: 24357725] doi: 10.1182/blood-2013-01-478958
38. Rodger MA, Hague WM, Kingdom J, Kahn SR, Karovitch A, Sermer M, et al; TIPPS Investigators. Antepartum dalteparin versus no antepartum dalteparin for the prevention of pregnancy complications in pregnant women with thrombophilia (TIPPS): a multinational open-label randomised trial. Lancet. 2014;384:1673-83. [PMID: 25066248] doi:10.1016/S0140-6736(14)60793-5