Current concepts of efficient diagnosis and therapeutic options in patients with recurrent early abortions;Aktuelles zur rationellen diagnostik und therapie habitueller frühaborte

Geburtshilfe und Frauenheilkunde

Volumn 67, Issue 3, 2007, Pages 217-227

  Bohlmann, Michael K ^a   Schauf, B ^a   Luedders, D W ^b   Wallwiener, D ^a   Strowitzki, T ^c   Von Wolff, M ^c  

^a UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

^b Univ Frauenklinik Lübeck   (Germany)

^c UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

Author keywords

Early pregnancy; Efficient diagnosis; Idiopathic; Recurrent abortion; Therapeutic options

Indexed keywords

BLOOD CLOTTING FACTOR 5 LEIDEN; PROLACTIN; PROTHROMBIN; VITRONECTIN;

ABORTION; ANTIPHOSPHOLIPID SYNDROME; CHROMOSOME ABERRATION; DISEASE ASSOCIATION; DISEASE PREDISPOSITION; ENDOCRINE DISEASE; GENE MUTATION; HUMAN; IMMUNITY; INFECTION; LUTEAL INSUFFICIENCY; RECURRENT ABORTION; REVIEW; RISK FACTOR; SPONTANEOUS ABORTION;

EID: 34248659396     PISSN: 00165751     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2006-955970     Document Type: Review

References (143)

1. Breckwoldt M, Keck C. Störungen der Fruchtbarkeit. In: Pfleiderer A, Breckwoldt M, Martius G (Hrsg). Gynäkologie und Geburtshilfe, 3. Auflage. Stuttgart: Georg Thieme Verlag, 2000
2. Berry CW, Brambati B, Eskes TK, Exalto N, Fox H, Geraedts JP, Gerhard I, Gonzales Gomes F, Grudzinskas JG, Hustin J. The Euro-Team Early Pregnancy (ETEP) protocol for recurrent miscarriage. Hum Reprod 1995; 10: 1516-1520
3. Menge S, Müller-Lantzsch C, Keck C, Tempfer C. Recurrent spontaneous abortion: causes and therapeutic options. Geburtsh Frauenheilk 2004; 64: 574-583
4. Pandey MK, Rani R, Agrawal S. An update in recurrent spontaneous abortion. Arch Gynecol Obstet 2005; 272: 95-108
5. Rai R, Regan L. Recurrent miscarriage. Lancet 2006; 368: 601-611
6. Hassald TJ, Jacobs PA. Trisomy in man. Annu Rev Genet 1984; 18: 69-97
7. Edmonds DK, Lindsay KS, Miller JF, Williamson E, Wood PJ. Early embryonic mortality in women. Fertil Steril 1982; 38: 47-53
8. Creasy R. The cytogenetics of spontaneous abortion in humans. In: Beard RW, Sharp F (eds). Early Pregnancy Loss: Mechanisms and Treatment. London: Springer Verlag, 1988: 293-304
9. Ogasawara M, Aoki K, Okada S, Suzumori K. Embryonic karyotype of abortuses in relation to the number of previous miscarriages. Fertil Steril 2000; 73: 300-304
10. Voigt R, Axt-Fliedner R, Diedrich K, Schwinger E. Chromosomal findings in recurrent abortions. Gynäkol Endokrinol 2005; 3: 40-44
11. Stern JJ, Dorfmann AD, Gutierrez-Najar AJ, Cerrillo M, Coulam CB. Frequency of abnormal karyotypes among abortuses from women with and without a history of recurrent spontaneous abortion. Fertil Steril 1996; 65: 250-253
12. Carp H, Toder V, Aviram A, Daniely M, Mashiach S, Barkai G. Karyotype of the abortus in recurrent miscarriage. Fertil Steril 2001; 75: 678-682
13. Christiansen OB, Pedersen B, Rosgaard A, Husth M. A randomized, double-blind, placebo-controlled trial of intravenous immunoglobulin in the prevention of recurrent miscarriage: evidence for a therapeutic effect in women with secondary recurrent miscarriage. Hum Reprod 2002; 17: 809-816
14. Stephenson MD, Awartani KA, Robinson WP. Cytogenetic analysis of miscarriages from couples with recurrent miscarriage: a case-control study. Hum Reprod 2002; 17: 446-451
15. Nawroth F, Strehler E, Sterzik K, Ludwig M. Habituelle Aborte - Diagnostik und Therapie. Frauenarzt 2006; 47: 300-304
16. Clifford K, Rai R, Regan L. Future pregnancy outcome in unexplained recurrent first trimester miscarriage. Hum Reprod 1997; 12: 387-389
17. Nybo Andersen AM, Wohlfahrtf Christens P, Olsen J, Melbye M. Maternal age and fetal loss: population based register linkage study. BMJ 2000; 320: 1708-1712
18. Stirrat GM. Recurrent miscarriage. Lancet 1990; 336: 673-675
19. Steck T, Bussen S, Marzusch K. Strategien zur Abortprophylaxe bei einer Vorgeschichte mit wiederholten Fehlgeburten. I. Epidemiologie, genetische und anatomische Abortursachen. Fertilitat 1997; 13: 7-16
20. von Wolff M, Strowitzki T. Recurrent miscarriages - a multifactorial disease. Gynakol Endokrinol 2005; 3: 7-17
21. Robinson WP, McFadden DE, Stephenson MD. The origin of abnormalities in recurrent aneuploidy/polyploidy. Am J Hum Genet 2001; 69: 1245-1254
22. 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
23. Clifford K, Rai R, Watson H, Regan L. An informative protocol for the investigation of recurrent miscarriage: preliminary experience of 500 consecutive cases. Hum Reprod 1994; 9: 1328-1332
24. Royal College of Obstetricians and Gynaecologists (RCOG). Guideline No. 17. The management of recurrent miscarriage. London: Royal College of Obstetricians and Gynaecologists, 1998
25. American College of Obstetricians and Gynecologists. Management of recurrent early pregnancy loss. ACOG practice bulletin. Washington DC: American College of Obstetricians and Gynecologists, 2001
26. Deutsche Gesellschaft für Gynäkologie und Geburtshilfe e.V., Arbeitsgemeinschaft Immunologie in Gynäkologie und Geburtshilfe. Diagnostik und Therapie des wiederholten Spontanabortes (WSA), Leitlinien, Empfehlungen, Stellungnahmen, Stand September 2006, http://dggg.de/leitlinien- 2006/pdf-2006/3-endo-fpm/3-2-3.wsa.pdf
27. Franssen MT, Korevaar JC, Leschot NJ, Bossuyt PM, Knegt AC, GerssenSchoorl KB, Wouters CH, Hansson KB, Hochstenbach R, Madan K, van der Veen F, Goddijn M. Selective chromosome analysis in couples with two or more miscarriages: case-control study. BMJ 2005; 331: 137-141
28. Christiansen OB, Andersen AMN, Bosch E, Daya S, Delves PJ, Hviid TV, Kutteh WH, Laird SM, Li TC, van der Ven K. Evidenced-based investigations and treatments of recurrent pregnancy loss. Fertil Steril 2005; 83: 821-839
29. Goldenberg M, Sivan E, Sharabi Z, Mashiach S, Lipitz S, Seidman DS. Reproductive outcome following hysteroscopic management of intra-uterine septum and adhesions. Hum Reprod 1995; 10: 2663-2665
30. Hickok LR. Hysteroscopic treatment of the uterine septum: a clinician's experience. Am J Obstet Gynecol 2000; 182: 1414-1420
31. Makino T, Umeuchi M, Nakada K, Nozawa S, Iizuka R. Incidence of congenital uterine anomalies in repeated reproductive wastage and prognosis for pregnancy after metroplasty. Int J Fertil 1992; 37: 167-170
32. Li TC, Makris M, Tomsu M, Tuckerman E, Laird S. Recurrent miscarriage: aetiology, management and prognosis. Human Reprod Update 2002; 8: 463-481
33. Wölfler MM, Rimbach S. Morphologic uterine disorders in association with recurrent pregnancy loss. Gynäkol Endokrinol 2005; 3: 18-24
34. Grimbizis G, Camus M, Tarlatzis BC, Bontis JN, Devroey P. Clinical implications of uterine malformations and hysteroscopic treatment results. Hum Reprod Update 2001; 7: 161-174
35. Salim R, Regan L, Woelfer B, Backos M, Jurkovic D. A comparative study of the morphology of congenital uterine anomalies in women with and without a history of recurrent first trimester miscarriage. Hum Reprod 2003; 18: 162-166
36. Fedele L, Bianchi S, Marchini M, Mezzopane R, Di Nola G, Tozzi L. Residual uterine septum of less than 1 cm after hysteroscopic metroplasty does not impair reproductive outcome. Hum Reprod 1996; 11: 727-729
37. Marchionni M, Fambrini M, Zammbelli V, Scarselli G, Susini T. Reproductive performance before and after abdominal myomectomy: a retrospective analysis. Fertil Steril 2004; 82: 154-159
38. Plesinac S, Plecas D, Babovic I. Influence of uterine myomas on course and outcome of pregnancy. Geburtsh Frauenheilk 2006; 66: 674-676
39. Römer T. Post-abortion hysteroscopy - a method of early diagnosis of congenital and acquired intrauterine causes of abortions. Eur J Obstet Gynecol Reprod Biol 1994; 57: 171-173
40. Dalton CF, Laird SM, Serle E, Saravelos H, Warren MA, Li TC, Bolton AE. The measurement of CA 125 and placental protein 14 in uterine flushings in women with recurrent miscarriage; relation to endometrial morphology. Hum Reprod 1995; 10: 2680-2684
41. Lessey BA, Castelbaum AJ, Sawin AJ, Sun J. Integrins as markers of uterine receptivity in women with primary unexplained infertility. Fertil Steril 1995; 63: 535-542
42. Aplin JD, Hey NA, Li TC. MUC1 as a cell surface and secretory component of endometrial epithelium: reduced levels in recurrent miscarriage. Am J Reprod Immunol 1996; 35: 261-266
43. Hambartsoumian E. Endometrial leukemia inhibitory factor (LIF) as a possible cause of unexplained infertility and multiple failures of implantation. Am J Reprod Immunol 1998; 39: 137-143
44. Clifford K, Flanagan AM, Regan L. Endometrial CD56+ natural killer cells in women with recurrent miscarriage: a histomorphometric study. Hum Reprod 1999; 14: 2727-2730
45. Lim KJ, Odukoya OA, Ajjan RA, Li TC, Weetman AP, Cooke ID. The role of T-helper cytokines in human reproduction. Fertil Steril 2000; 73: 136-142
46. von Wolff M, Thaler CJ, Strowitzki T, Broome J, Stolz W, Tabibzadeh S. Regulated expression of cytokines in human endometrium throughout the menstrual cycle: dysregulation in habitual abortion. Mol Hum Reprod 2000; 6: 627-634
47. 3-integrin - mRNA and protein expression in human endometrium. Fertil Steril 2001; 76: 775-781
48. von Wolff M, Walter S, Jauckus J, Kern A, Strowitzki T. Glucose transporter proteins (GLUT) in human endometrium - does GLUT1 play a role in the endometrial preparation for the implanting embryo? Hum Reprod 2002; 17: 131
49. Quenby S, Kalumbi C, Bates M, Farquharson R, Vince G. Prednisolone reduces preconceptual endometrial natural killer cells in women with recurrent miscarriage. Fertil Steril 2005; 84: 980-984
50. Kujovich JL. Thrombophilia and pregnancy complications. Am J Ob Gyn 2004; 191: 412-424
51. de Wolf F, Carreras LO, Moennan P. Decidual vasculopathy and extensive placental infarction in a patient with repeated thromboembolic accidents, recurrent fetal loss, and a lupus anticoagulant. Am J Obstet Gynecol 1982; 142: 829-834
52. Out HJ, Kooijman CD, Bruinse HW, Derksen RH. Histopathological findings in placentae from patients with intra-uterine fetal death and antiphospholipid antibodies. Eur J Obstet Gynecol Reprod Biol 1991; 41: 179-186
53. Bane AL, Gillan JE. Massive perivillous fibrinoid causing recurrent placental failure. BJOG 2003; 110: 292-295
54. Rey E, Kahn SR, David M, Shrier I. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet 2003; 361: 901-908
55. Robertson L, Wu O, Langhorne P, Twaddle S, Clark P, Lowe GD, Walker ID, Greaves M, Brenkel I, Regan L, Greer IA. The Thrombosis: Risk and Economic Assessment of Thrombophila Screening (TREATS) Study. Thrombophilia in pregnancy: a systematic review. Br J Haematol 2006; 132: 171-196
56. Ogasawara MS, Aoki K, Katano K, Ozaki Y, Suzumori K. Factor XII but not protein C, protein S, antithrombin III, or factor XIII is a predictor of recurrent miscarriage. Fertil Steril 2001; 75: 916-919
57. Pauer HU, Burfeind P, Kostering H, Emons G, Hinney B. Factor XII deficiency is strongly associated with primary recurrent abortions. Fertil Steril 2003; 80: 590-594
58. Gris JC, Quere I, Dechaud H, Mercier E, Pincon C, Hoffet M, Vasse M, Mares P. High frequency of protein Z deficiency in patients with unexplained early fetal loss. Blood 2002; 99: 2606-2608
59. Marietta M, Facchinetti F, Sgarbi L, Simoni L, Bertesi M, Torelli G, Volpe A. Elevated plasma levels of factor VIII in women with early recurrent miscarriage. J Thromb Haemost 2003; 1: 2536-2539
60. Dossenbach-Glaninger A, van Trotsenburg M, Krugluger W, Dossenbach MR, Oberkanins C, Ruber J, Hopmeier P. Elevated coagulation factor VIII and the risk for recurrent early pregnancy loss. Thromb Haemost 2004; 91: 694-699
61. Willeke A, Gerdsen F, Bauersachs R, Lindhoff-Last E. Rationelle Thrombophiliediagnostik. Dtsch Ärztebl 2002; 99: A2111-A2118
62. Buchholz T, Thaler CJ. Inherited thrombophilia: impact on human reproduction. AJRI 2003; 50: 20-32
63. Rai R, Tuddenham E, Backos M, Jivraj S, El'Gaddal S, Choy S, Cork B, Regan L. Thromboelastography, whole-blood haemostasis and recurrent miscarriage. Hum Reprod 2003; 18: 2540-2543
64. Boushey CJ, Beresford SAA, Omenn GS Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA 1995; 274: 1049-1057
65. Hübner U, Koch I, Retzke U, Herrmann W. Die Bedeutung der Hyperhomocysteinämie für Embryonalentwicklung und Schwangerschaftskomplikationen. Geburtsh Frauenheilk 2003; 63: 990-998
66. Makris M. Hyperhomocysteinemia and thrombosis. Clin Lab Haematol 2000; 22: 133-143
67. Nelen WL, Blom HJ, Steegers EA, den Heijer M, Eskes TK. Hyperhomocysteinemia and recurrent early pregnancy loss: a meta-analysis. Fertil Steril 2000; 74: 1196-1199
68. Bohlmann MK, von Wolff M, Rossmann H, Deckner C, Galler-Weber J, Strowitzki T. MTHFR-Polymorphismen und Homocysteinspiegel bei Paaren mit habituellen Aborten. Arch Gyn Obstet 2004; 270: FV-E 1.2; S 13
69. Bohlmann MK, Luedders DW, von Wolff M. Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage. Hum Reprod 2007; 22: 309
70. 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: 433-438
71. Hills FA, Abrahams VM, Gonzalez-Timon B, Francis J, Cloke B, Hinkson L, Rai R, Mor G, Regan L, Sullivan M, Lam EW, Brosens JJ. Heparin prevents programmed cell death in human trophoblast. Mol Hum Reprod 2006; 12: 237-243
72. Gris JC, Mercier E, Quere I, Lavigne-Lissalde G, Cochery-Nouvellon E, Hoffet M, Ripart-Neveu S, Tailland ML, Dauzat M, Mares P. Low-molecular-weight heparin versus lowdose aspirin in women with one fetal loss and a constitutional thrombophilic disorder. Blood 2004; 103: 3695-3699
73. Brenner B, Hoffman R, Carp H, Dulitsky M, Younis J, UVE-ENOX Investigators. Efficacy and safety of two doses of enoxaparin in women with thrombophilia and recurrent pregnancy loss: the LIVE-ENOX study. J Thromb Haemost 2005; 3: 227-229
74. Heilmann L, Rath W, von Tempfelhoff GF, Harenberg J, Breddin HK, Riess H, Schramm W. Niedermolekulare Heparine in der Schwangerschaft. Dtsch Ärztebl 2002; 99: A424-432
75. Rath W, Heilmann L. Thrombophile Risikofaktoren und Schwangerschaftskomplikationen. Frauenarzt 2002; 43: 537-546
76. Meytes D, Ayalon H, Virag I, Weisbort, Zakut H. Heparin-induced thrombocytopenia and recurrent thrombosis in pregnancy. A case report. J Reprod Med 1986; 31: 993-996
77. Copplestone A, Oscier DG. Heparin-induced thrombocytopenia in pregnancy. Br J Haematol 1987; 65: 248
78. Greinacher A, Eckardt T, Mussmann J, Mueller-Eckardt C. Pregnancy complicated by heparin-associated thrombocytopenia: management by a prospectively in vitro selected heparinoid (ORG 10172). Thromb Res 1993; 71: 123-126
79. Ginsberg JS, Hirsh J. Anticoagulans during pregnancy. Ann Rev Med 1989; 40: 79-86
80. Schinzel H, Bahlmann F, Peetz D, Savvidis S, Himmrich L, Klotz M. Prevention of thromboembolism with low-molecular weight heparin (Dalteparin-Na) in risk pregnancy. Med Klin 2002; 97: 193-203
81. Shefras J, Farquharson RG. Bone-densitity studie in pregnant women receiving heparin. Eur J Obstet Gynecol Reprod Biol 1996; 65: 171-174
82. Perrild V, Kaaja R, Leinonen P, Ekblad V, Kataja M, Ikkala E. Thrombophylaxis with low-molecular weight heparin (Dalteparin) in pregnancy. Thromb Res 1999; 96: 275-282
83. 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; 2: CD002859
84. Ogasawara MS, Iinuma Y, Aoki K, Katano K, Ozaki Y, Suzumori K. Lowdose aspirin is effective for treatment of recurrent miscarriage in patients with decreased coagulation factor XII. Fertil Steril 2001; 76: 203-204
85. Kozer E, Nikfar S, Costei A, Boskovic R, Nulman I, Koren G. Aspirin consumption during the first trimester of pregnancy and congenital anomalies: a meta-analysis. Am J Obstet Gynecol 2002; 187: 1623-1630
86. Slone D, Siskind V, Heinonen OP, Monson RR, Kaufman DW, Shapiro S. Aspirin and congenital malformations. Lancet 1976; 26: 1373-1375
87. Briggs S. Drugs in Pregnancy and Lactation: a Reference Guide to Fetal and Neonatal Risk. 5th ed. Baltimore, MD: Williams and Wilkins, 1998; 73-81
88. Nielsen GL, Sorensen HT, Larsen H, Pedersen L. Risk of adverse birth outcome and miscarriage in pregnant users of non-steroidal anti-inflammatory drugs: population based observational study and case-control study. BMJ 2001; 322: 266-270
89. Li DK, Liu L, Odouli R. Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study. BMJ 2003; 327: 368
90. Stanger O, Herrmann W, Pietrzik K Fowler B, Geisel J, Dierkes J, Weger M, DACH-UGA Homocystein e.V., DACH-LIGA homocystein (German, Austrian and Swiss homocysteine society). Consensus paper on the rational clinical use of homocysteine, folic acid and B-vitamins in cardiovascular and thrombotic diseases: guidelines and recommendations. Clin Chem Lab Med 2003; 41: 1392-1403
91. Quere I, Mercier E, Bellet H, Janbon C, Mares P, Gris JC. Vitamin supplementation and pregnancy outcome in women with recurrent early pregnancy loss and hyperhomocysteinemia. Fertil Steril 2001; 75: 823-825
92. Rai RS, Regan L, Clifford K, Pickering W, Dave M, Mackie I, Mcinally T, Cohen H. Antiphospholipid antibodies and beta 2-glycoprotein-I in 500 women with recurrent miscarriage: result of a comprehensive screening approach. Hum Reprod 1995; 10: 2001-2005
93. Fialova L, Mikulikova L, Matous-Malbohan I, Benesova O, Zwinger A. Prevalence of various antiphospholipid antibodies in pregnant women. Physiol Res 2000; 49: 299-305
94. Bizzaro N, Tonutti E, Villalta D, Tampoia M, Tozzoli R. Prevalence and clinical correlation of anti-phospholipid-binding protein antibodies in anticardiolipin-negative patients with systemic lupus erythematosus and women with unexplained recurrent miscarriages. Arch Pathol Lab Med 2005; 129: 61-68
95. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, De Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4: 295-306
96. Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette JC, Brey R, Derksen R, Harris EN, Hughes GR, Triplett DA, Khamashta MA. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 1999; 42: 1309-1311
97. Greaves M. Antiphospholipid antibodies and thrombosis. Lancet 1999; 353: 1348-1353
98. Luong TH, Rand JH, Wu XX, Godbold JH, Gascon-Lema M, Tuhrim S. Seasonal distribution of antiphospholipid antibodies. Stroke 2001; 32: 1707-1711
99. Sebire NJ, Backos M, El Gaddal S, Goldin RD, Regan L. Placental pathology, antiphospholipid antibodies, and pregnancy outcome in recurrent miscarriage patients. Obstet Gynecol 2003; 101: 258-263
100. Bose P, Black S, Kadyrov M, Bartz C, Shlebak A Regan L, Huppertz B. Adverse effects of lupus anticoagulant positive blood sera on placental viability can be prevented by heparin in vitro. Am J Obstet Gynecol 2004; 191: 2125-2131
101. Bose P, Black S, Kadyrov M, Weissenborn U, Neulen J, Regan L, Huppertz B. Heparin and aspirin attenuate placental apoptosis in vitro: implications for early pregnancy failure. Am J Obstet Gynecol 2005; 192: 23-30
102. Mak IY, Brosens JJ, Christian M, Hills FA, Chamley L, Regan L, White JO. Regulated expression of signal transducer and activator of transcription, Stat5, and its enhancement of PRL expression in human endometrial stromal cells in vitro. J Clin Endocrinol Metab 2002; 87: 2581-2588
103. Rai R, Clifford K, Cohen H, Regan L. High prospective fetal loss rate in untreated pregnancies of women with recurrent miscarriage and antiphospholipid antibodies. Hum Reprod 1995; 10: 3301-3304
104. Rai R, Cohen H, Dave M, Regan L. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ 1997; 314: 253-257
105. di Simone N, Caliandro D, Castellani R, Ferrazzani S, de Carolis S, Caruso A. Low-molecular weight heparin restores invasiveness and differentiation in presence of immunoglobulin G fractions obtained from patients with antiphospholipid syndrome. Hum Reprod 1999; 14: 489-495
106. Empson M, Lassere M, Craig JC, Scott JR. Recurrent pregnancy loss with antiphospholipid antibody: a systematic review of therapeutic trials. Obstet Gynecol 2002; 99: 135-144
107. Sapir T, Blank M, Shoenjeld Y. Immunomodulatory effects of intravenous immunoglobulins as a treatment for autoimmune diseases, cancer, and recurrent pregnancy loss. Ann N Y Acad Sci 2005; 1051: 743-778
108. Ober C, Karrison T, Odem RR, Barnes RB, Branch DW, Stephenson MD, Baron B, Walker MA, Scott JR, Schreiber JR. Mononuclear-cell immunisation in prevention of recurrent miscarriages: a randomised trial. Lancet 1999; 354: 365-369
109. Scott JR. Immunotherapy for recurrent miscarriage. Cochrane Database Syst Rev 2003; 1: CD000112
110. Porter T, Lacoursiere Y, Scott JR. Immunotherapy for recurrent miscarriage. Cochrane Database Syst Rev 2006; 19: CD000112
111. Shakhar K, Rosenne E, Loewenthal R, Shakhar G, Carp H, Ben-Eliyahu S. High NK cell activity in recurrent miscarriage: what are we really measuring? Hum Reprod 2006; 21: 2421-2425
112. Moffett A, Regan L, Braude P. Natural killer cells, miscarriage, and infertility. BMJ 2004; 329: 1283-1285
113. Mills JL, Simpson JL, Driscoll SG, Jovanovic-Peterson L, Van Allen M, Aarons JH, Metzger B, Bieber FR, Knopp RH, Holmes LB et al. Incidence of spontaneous abortion among normal women and insulin-dependent diabetic women whose pregnancies were identified within 21 days of conception. N Engl J Med 1988; 319: 1617-1623
114. Rosenn B, Miodovnik M, Combs CA, Khoury J, Siddiqi TA. Glycemic thresholds for spontaneous abortion and congenital malformations in insulin-dependent diabetes mellitus. Obstet Gynecol 1994; 84: 515-520
115. Hunger-Dathe W, Kohn B, Kloos C, Müller UA, Wolf G, Schleußner E. Prävalenz kindlicher Fehlbildungen bei Frauen mit einem präexistenten Diabetes mellitus in Abhängigkeit von der Stoffwechseleinstellung. Geburtsh Frauenheilk 2005; 65: 1147-1155
116. Lashen H, Fear K, Sturdee DW. Obesity is associated with increased risk of first trimester and recurrent miscarriage: matched case-control study. Hum Reprod 2004; 19: 1644-1646
117. Clark AM, Thomley B, Tomlinson L, Gattetley C, Norman RJ. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum Reprod 1998; 13: 1502-1505
118. Morikawa M, Yamada H, Kato EH, Shimada S, Yamada T, Minakami H. Embryo loss pattern is predominant in miscarriages with normal chromosome karyotype among women with repeated miscarriage. Hum Reprod 2004; 19: 2644-2647
119. Jauniaux E, Farquharson RG, Christiansen OB, Exalto N. Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage. Hum Reprod 2006; 21: 2216-2222
120. Ludwig M, Schulte HM. Thyroid gland in infertility patients, pregnancy and lactation. Gynakol Endokrinol 2005; 3: 45-54
121. Roberts CP, Murphy AA. Endocrinopathies associated with recurrent pregnancy loss. Semin Reprod Med 2000; 18: 357-362
122. Vaquero E, Lazzarin N, De Carolis C, Valensise H, Moretti C, Ramanini C. Mild thyroid abnormalities and recurrent spontaneous abortion: diagnostic and therapeutical approach. Am J Reprod Immunol 2000; 43: 204-208
123. Abalovich M, Gutierrez S, Alcaraz G, Maccallini G, Garcia A, Levalle O. Overt and subclinical hypothyroidism complicating pregnancy. Thyroid 2002; 12: 63-68
124. Bussen SS, Steck T. Thyroid antibodies and their relation to antithrombin antibodies, anticardiolipin antibodies and lupus anticoagulant in women with recurrent spontaneous abortions (antithyroid, anticardiolipin and antithrombin autoantibodies and lupus anticoagulant in habitual aborters). Eur J Obstet Gynecol Reprod Biol 1997; 74: 139-143
125. Rushworth FH, Backos M, Rai R, Chilcott IT, Baxter N, Regan L. Prospective pregnancy outcome in untreated recurrent miscarriers with thyroid autoantibodies. Hum Reprod 2000; 15: 1637-1639
126. Hirahara F, Andoh N, Sawai K, Hirabuki T, Uemura T, Minaguchi H. Hyperprolactinemic recurrent miscarriage and results of randomized bromocriptine treatment trials. Fertil Steril 1998; 70: 246-252
127. Balasch J, Vanrell JA. Corpus luteum insufficiency and fertility: a matter of controversy. Hum Reprod 1987; 2: 557-567
128. Daya S, Ward S, Burrows E. Progesterone profiles in luteal phase defect cycles and outcome of progesterone treatment in patients with recurrent spontaneous abortion. Am J Obstet Gynecol 1988; 158: 225-232
129. McNeely MJ, Soules MR. The diagnosis of luteal phase deficiency: a critical review. Fertil Steril 1988; 50: 1-15
130. Oates-Whitehead RM, Haas DM, Carrier JA. Progestogen for preventing miscarriage. Cochrane Database Syst Rev 2003; 4: CD003511
131. Rai R, Backos M, Rushworth F, Regan L. Polycystic ovaries and recurrent miscarriage - a reappraisal. Hum Reprod 2000; 15: 612-615
132. Clifford K, Rai R, Watson H, Franks S, Regan L. Does suppressing luteinising hormone secretion reduce the miscarriage rate? Results of a randomised controlled trial. BMJ 1996; 312: 1508-1511
133. Craig LB, Ke RW, Kutteh WH. Increased prevalence of insulin resistance in women with a history of recurrent pregnancy loss. Fertil Steril 2002; 78: 487-490
134. Jakubowicz DJ, Iuorno MJ, Jakubowicz S, Roberts KA, Nestler JE. Effects of metformin on early pregnancy loss in the polycystic ovary syndrome. J Clin Endocrinol Metab 2002; 87: 524-529
135. Vanky E, Salvesen KA, Heimstad R, Fougner HJ, Romundstad P, Carlson SM. Metformin reduces pregnancy complications without affecting androgen levels in pregnant polycystic ovary syndrome women: results of a randomized study. Hum Reprod 2004; 19: 1734-1740
136. Glueck CJ, Awadalla SG, Phillips H, Cameron D, Wang P, Fontaine RN. Polycystic ovary syndrome, infertility, familial thrombophilia, familial hypofibrinolysis, recurrent loss of in vitro fertilized embryos, and miscarriage. Fertil Steril 2000; 74: 394-397
137. Steck T, Bussen S, Marzusch K. Strategien zur Abortprophylaxe bei einer Vorgeschichte mit wiederholten Aborten. II. Infektionen, metabolische und endokrine Storungen, Schadstoffe und Gerinnungsdefekte. Fertilität 1997; 13: 17-26
138. Horne AW, Alexander CI. Recurrent miscarriage. J Fam Plann Reprod Health Care 2005; 31: 103-107
139. Vgwumade A, Manyonda I, Reid F, Hay P. Effect of early oral clindamycin on late miscarriage and preterm delivery in asymptomatic women with abnormal vaginal flora and bacterial vaginosis. Lancet 2003; 361: 983-998
140. Stray-Pedersen B, Stray-Pedersen S. Etiologic factors and subsequent reproductive performance in 195 couples with a prior history of habitual abortion. Am J Obstet Gynecol 1984; 148: 140-146
141. Sugiura-Ogasawara M, Furukawa TA, Nakano Y, Hori S, Aoki K, Kitamura T. Depression as a potential causal factor in subsequent miscarriage in recurrent spontaneous aborters. Hum Reprod 2002; 17: 2580-2584
142. Arck P. Stress and embryo implantation. J Gynecol Obstet Biol Reprod (Paris) 2004; 33: S40-S42
143. Liddell HS, Pattison NS, Zanderigo A. Recurrent miscarriage-outcome after supportive care in early pregnancy. Aust N Z J Obstet Gynaecol 1991; 31: 320-322