Thrombosis Research
Volume 121, Issue 6 , Pages 713-726 , 2008

The “ART” of thromboembolism: A review of assisted reproductive technology and thromboembolic complications

  • W.S. Chan

      Affiliations

    • Department of Medicine and Obstetrics & Gynecology, Women's College Hospital and Sunnybrook Health Sciences Centre, 76, Grenville Street, Toronto, Ontario, Canada M5S 1B2
    • Corresponding Author InformationCorresponding author.
  • ,
  • M.E. Dixon

      Affiliations

    • Department of Obstetrics & Gynecology, Sunnybrook and Women's College Fertility Centre, 790 Bay Street, Suite 1120, Toronto, ON, Canada M5G 1N8

Received 30 January 2007 ,Revised 30 January 2007 ,Accepted 29 May 2007.

References 

  1. International Committee for Monitoring Assisted Reproductive Technology Adamson GD, de Mouzon J, Lancaster P, Nygren KG, Sullivan E, Zegers-Hochschild F. World collaborative report on in vitro fertilization, 2000. Fertil Steril. Jun 2006;85(6):1586–1622[PMID: 16759920]
  2. Wright VC, Schieve LA, Reynolds MA, Jeng G. Assisted reproductive technology surveillance in United States, 2002. MMWR. June 2005;54(SS02):1–24
  3. Stewart JA, Hamilton PJ, Murdoch AP. Thromboembolic disease associated with ovarian stimulation and assisted conception techniques. Hum Reprod. 1997;12:2167–2173
  4. Baumann P, Diedrich K. Thromboembolic complications associated with reproductive endocrinologic procedures. Hematol/Oncol Clin North Am. April 2000;14(2):431–443
  5. Mancuso A, De Vivo A, Fanara G, Di Leo R, Toscano A. Upper body venous thrombosis associated with ovarian stimulation: case report and review of the literature. Clin. Exp. Obstet. Gynecol. 2005;32:149–154
  6. Whelan JG, Vlahos NF. The ovarian hyperstimulation syndrome. Fertil Steril. 2000;73:83–896
  7. Chan WS, Ginsberg JS. A review of upper extremity deep vein thrombosis in pregnancy: unmasking the ‘ART’ behind the clot. J Thromb Haemost. 2006;4(8):1673–1677
  8. Yen and Jaffe's reproductive endocrinology: physiology, pathophysiology, and clinical management. 5th Edition. W B Saunders Co; July 2004;
  9. Pritts EA, Atwood AK. Luteal phase support in infertility treatment: a meta-analysis of randomized trials. Hum Reprod. 2002;17(9):2287–2299
  10. Todros T, Carmazzi CM, Bontempo S, Gaglioti P, Donvito V, Massobrio M. Spontaneous ovarian hyperstimulation syndrome and deep vein thrombosis in pregnancy: case report. Hum Reprod. Sep 1999;14(9):2245–2248
  11. Golan A, Ron-el R, Herman A, Soffer Y, Weinraub Z, Caspi E. Ovarian hyperstimulation syndrome: an update review. Obstet Gynecol Surv. 1989;44:430–440
  12. Ong ACM, Eisen V, Rennie DP, Homburg R, Lachelin GCL, Jacobs HS, et al. The pathogenesis of the ovarian hyperstimulation syndrome (OHS): a possible role for ovarian rennin. Clin Endocrinol. 1991;34:43–49
  13. Levin ER, Rosen GF, Cassidenti DL, Yee B, Meldrum D, Wisot A, et al. Role of vascular endothelial cell growth factor in ovarian hyperstimulation syndrome. J Clin Invest. 1998;102:1978–1985
  14. Neulen J, Yan Z, Raczek S, Weindel K, Keck C, Weich HA, et al. Human chorionic gonadotropin-dependent expression of vascular endothelial growth factor/vascular permeability factor in human granulose cells: importance in ovarian hyperstimulation syndrome. J Clin Endocrinol Metab. 1995;80:1967–1971
  15. Morris RS, Paulson RJ. Increased angiotensin-converting enzyme activity in a patient with severe ovarian hyperstimulation syndrome. Fertil Steril. Mar 1999;71(3):562–563
  16. Mozes M, Bogokowsky H, Antebi E, Lunenfeld B, Rabau E, Serr DM, et al. Thromboembolic phenomena after ovarian stimulation with human gonadotrophins. Lancet. Dec 11 1965;2(7424):1213–1215
  17. Kermode AG, Churchyard A, Carroll WM. Stroke complicating severe ovarian hyperstimulation syndrome. Aust N Z J Med. Apr 1993;23(2):219–220
  18. Inbar OJ, Levran D, Mashiach S, Dor J. Ischemic stroke due to induction of ovulation with clomiphene citrate and menotropins without evidence of ovarian hyperstimulation syndrome. Fertil Steril. Nov 1994;62(5):1075–1076
  19. Cluroe AD, Synek BJ. A fatal case of ovarian hyperstimulation syndrome with cerebral infarction. Pathology. Oct 1995;27(4):344–346
  20. Choktanasiri W, Rojanasakul A. Acute arterial thrombosis after gamete intrafallopian transfer: a case report. J Assist Reprod Genet. May 1995;12(5):335–337
  21. Aurousseau MH, Samama MM, Belhassen A, Herve F, Hugues JN. Risk of thromboembolism in relation to an in-vitro fertilization programme: three case reports. Hum Reprod. Jan 1995;10(1):94–97
  22. Germond M, Wirthner D, Thorin D, Ruchat P, Essinger A, De Grandi P. Aorto-subclavian thromboembolism: a rare complication associated with moderate ovarian hyperstimulation syndrome. Hum Reprod. Jun 1996;11(6):1173–1176
  23. El Sadek MM, Amer MK, Fahmy M. Acute cerebrovascular accidents with severe ovarian hyperstimulation syndrome. Hum Reprod. Jul 1998;13(7):1793–1795
  24. Aboulghar MA, Mansour RT, Serour GI, Amin YM. Moderate ovarian hyperstimulation syndrome complicated by deep cerebrovascular thrombosis. Hum Reprod. Aug 1998;13(8):2088–2091
  25. Hwang WJ, Lai ML, Hsu CC, Hou NT. Ischemic stroke in a young woman with ovarian hyperstimulation syndrome. J Formos Med Assoc. 1998;97:503–506
  26. Ludwig M, Tolg R, Richardt G, Katus HA, Diedrich K. Myocardial infarction associated with ovarian hyperstimulation syndrome. JAMA. Aug 18 1999;282(7):632–633
  27. Davies AJ, Patel B. Hyperstimulation—brain attack. Br J Radiol. Sep 1999;72(861):923–924
  28. Yoshii F, Ooki N, Shinohara Y, Uehara K, Mochimaru F. Multiple cerebral infarctions associated with ovarian hyperstimulation syndrome. Neurology. Jul 13 1999;53(1):225–227
  29. Turkistani IM, Ghourab SA, Al-Sheikh OH, Abuel-Asrar AM. Central retinal artery occlusion associated with severe ovarian hyperstimulation syndrome. Eur J Ophthalmol. Jul–Sep 2001;11(3):313–315
  30. Heinig J, Behre HM, Klockenbusch W. Occlusion of the ulnar artery in a patient with severe ovarian hyperstimulation syndrome. Eur J Obstet Gynecol Reprod Biol. May 2001;96(1):126–127
  31. Mancini A, Milardi D, Di Pietro ML, Giacchi E, Spagnolo AG, Di Donna V, et al. A case of forearm amputation after ovarian stimulation for in vitro fertilization-embryo transfer. Fertil Steril. Jul 2001;76(1):198–200
  32. Elford K, Leader A, Wee R, Stys PK. Stroke in ovarian hyperstimulation syndrome in early pregnancy treated with intra-arterial rt-PA. Neurology. Oct 22 2002;59(8):1270–1272
  33. Akdemir R, Uyan C, Emiroglu Y. Acute myocardial infarction secondary thrombosis associated with ovarial hyperstimulation syndrome. Int J Cardiol. May 2002;83(2):187–189
  34. Koo EJ, Rha JH, Lee BI, Kim MO, Ha CK. A case of cerebral infarct in combined antiphospholipid antibody and ovarian hyperstimulation syndrome. J Korean Med Sci. Aug 2002;17(4):574–576
  35. Di Micco P, D'Uva M, Romano M, Di Marco B, Niglio A. Stroke due to left carotid thrombosis in moderate ovarian hyperstimulation syndrome. Thromb Haemost. Nov 2003;90(5):957–960
  36. Celebioglu B, Topatan B, Guler A, Aksu TA. Fatal mesenteric artery thrombus following oocyte retrieval. BJOG. Nov 2004;111(11):1301–1304
  37. Kaaja R, Siegberg R, Tiitinen A, Koskimies A. Severe hyperstimulation syndrome and deep venous thrombosis. Lancet. Oct 28 1989;2(8670):1043
  38. Fournet N, Surrey E, Kerin J. Internal jugular vein thrombosis after ovulation induction with gonadotropins. Fertil Steril. Aug 1991;56(2):354–356
  39. Rajah R, Boothroyd A, Lees WR. A pain in the neck!. Br J Radiol. Sep 1991;64(765):867–868
  40. Mills MS, Eddowes HA, Fox R, Wardle PG. Subclavian vein thrombosis: a late complication of ovarian hyperstimulation syndrome. Hum Reprod. Mar 1992;7(3):370–371
  41. Waterstone JJ, Summers BA, Hoskins MC, Berry J, Parsons JH. Ovarian hyperstimulation syndrome and deep cerebral venous thrombosis. Br J Obstet Gynaecol. May 1992;99(5):439–440
  42. Ayhan A, Urman B, Gurgan T, Tuncer ZS, Deren O. Thrombosis of the internal jugular vein associated with severe ovarian hyperstimulation syndrome. Aust N Z J Obstet Gynaecol. Nov 1993;33(4):436–437
  43. Hignett M, Spence JE, Claman P. Internal jugular vein thrombosis: a late complication of ovarian hyperstimulation syndrome despite mini-dose heparin prophylaxis. Hum Reprod. Dec 1995;10(12):3121–3123
  44. Hulinsky I, Smith HC. External jugular vein thrombosis: a complication of the ovarian hyperstimulation syndrome. Med J Aust. Mar 20 1995;162(6):335–336
  45. Kligman I, Noyes N, Benadiva CA, Rosenwaks Z. Massive deep vein thrombosis in a patient with antithrombin III deficiency undergoing ovarian stimulation for in vitro fertilization. Fertil Steril. Mar 1995;63(3):673–676
  46. Hollemaert S, Wautrecht JC, Capel P, Abramowicz MJ, Englert Y, Delbaere A. Thrombosis associated with ovarian hyperstimulation syndrome in a carrier of the factor V Leiden mutation. Thromb Haemost. Aug 1996;76(2):275–277
  47. Horstkamp B, Lubke M, Kentenich H, Riess H, Buscher U, Lichtenegger W. Internal jugular vein thrombosis caused by resistance to activated protein C as a complication of ovarian hyperstimulation after in-vitro fertilization. Hum Reprod. Feb 1996;11(2):280–282
  48. Moutos DM, Miller MM, Mahadevan MM. Bilateral internal jugular venous thrombosis complicating severe ovarian hyperstimulation syndrome after prophylactic albumin administration. Fertil Steril. Jul 1997;68(1):174–176
  49. Stewart JA, Hamilton PJ, Murdoch AP. Upper limb thrombosis associated with assisted conception treatment. Hum Reprod. Oct 1997;12(10):2174–2175
  50. Ellis MH, Nun IB, Rathaus V, Werner M, Shenkman L. Internal jugular vein thrombosis in patients with ovarian hyperstimulation syndrome. Fertil Steril. Jan 1998;69(1):140–142
  51. Tang OS, Ng EH, Wai Cheng P, Chung Ho P. Cortical vein thrombosis misinterpreted as intracranial haemorrhage in severe ovarian hyperstimulation syndrome: case report. Hum Reprod. Sep 2000;15(9):1913–1916
  52. Ludwig M, Felberbaum RE, Diedrich K. Deep vein thrombosis during administration of HMG for ovarian stimulation. Arch Gynecol Obstet. Feb 2000;263(3):139–141
  53. Loret de Mola JR, Kiwi R, Austin C, Goldfarb JM. Subclavian deep vein thrombosis associated with the use of recombinant follicle-stimulating hormone (Gonal-F) complicating mild ovarian hyperstimulation syndrome. Fertil Steril. Jun 2000;73(6):1253–1256
  54. Lamon D, Chang CK, Hruska L, Kerlakian G, Smith JM. Superior vena cava thrombosis after in vitro fertilization: case report and review of the literature. Ann Vasc Surg. May 2000;14(3):283–285
  55. Schanzer A, Rockman CB, Jacobowitz GR, Riles TS. Internal jugular vein thrombosis in association with the ovarian hyperstimulation syndrome. J Vasc Surg. Apr 2000;31(4):815–818
  56. Sobande AA, Archibong EI, Albar HM. Ovarian hyperstimulation syndrome and deep vein thrombosis. Saudi Med J. Aug 2000;21(8):783–784
  57. Tavmergen E, Ozcakir HT, Levi R, Adakan F, Ulukus M, Terek MC. Bilateral jugular venous thromboembolism and pulmonary emboli in a patient with severe ovarian hyperstimulation syndrome. J Obstet Gynaecol Res. Aug 2001;27(4):217–220
  58. Belaen B, Geerinckx K, Vergauwe P, Thys J. Internal jugular vein thrombosis after ovarian stimulation. Hum Reprod. Mar 2001;16(3):510–512
  59. Arya R, Shehata HA, Patel RK, Sahu S, Rajasingam D, Harrington KF, et al. Internal jugular vein thrombosis after assisted conception therapy. Br J Haematol. Oct 2001;115(1):153–155
  60. Thomas RV, Reid W, Perry DJ. Internal jugular vein thrombosis following in-vitro fertilization in a woman with protein S deficiency and heterozygosity for the prothrombin 3′ UTR mutation, despite anticoagulation with heparin. Blood Coagul Fibrinolysis. Sep 2001;12(6):487–489
  61. Hirano Y, Kasashima F, Abe Y, Matsumoto Y, Endo M, Sasaki H, et al. The use of a Greenfield filter to treat a pregnant woman for internal jugular venous thrombosis: report of a case. Surg Today. 2002;32(7):635–637
  62. Berker B, Demiral C, Satiroglu H. Internal jugular vein thrombosis as a late complication of ovarian hyperstimulation syndrome in an ICSI patient. Arch Gynecol Obstet. Nov 2004;270(3):197–198[Electronic publication 2003 May 23]
  63. McGowan BM, Kay LA, Perry DJ. Deep vein thrombosis followed by internal jugular vein thrombosis as a complication of in vitro fertilization in a woman heterozygous for the prothrombin 3′ UTR and factor V Leiden mutations. Am J Hematol. Aug 2003;73(4):276–278
  64. Ulug U, Aksoy E, Erden H, Bayazit N, Bahceci M. Bilateral internal jugular venous thrombosis following successful assisted conception in the absence of ovarian hyperstimulation syndrome. Eur J Obstet Gynecol Reprod Biol. Aug 15 2003;109(2):231–233
  65. Jesudason WV, Small M. Internal jugular vein thrombosis following ovarian hyperstimulation. J Laryngol Otol. Mar 2003;117(3):222–223
  66. Ou YC, Kao YL, Lai SL, Kung FT, Huang FJ, Chang SY, et al. Thromboembolism after ovarian stimulation: successful management of a woman with superior sagittal sinus thrombosis after IVF and embryo transfer: case report. Hum Reprod. Nov 2003;18(11):2375–2381
  67. Chang FW, Chan CC, Yin CS, Wu GJ. Predicted value or renin activity in a woman who has severe ovarian hyperstimulation syndrome with internal jugular vein thrombosis. Feril Steril. 2004;82:937–939
  68. Rao AK, Chitkara U, Milki AA. Subclavian vein thrombosis following IVF and ovarian stimulation and IVF: a case report. Hum Reprod. Aug–Dec 2005;20(12):3307–3312
  69. Mara M, Koryntova D, Rezabek K, Kapral A, Drbohlav P, Jirsova S, et al. Thromboembolic complications in patients undergoing in vitro fertilization: retrospective clinical study. Ceska Gynekol. Jul 2004;69(4):312–316[Czech]
  70. Lindquist P, Dahlback B, Marsal K. Thrombotic risk during pregnancy: A population study. Obstet Gynecol. 1999;94:595–599
  71. Douketis JD, Ginsberg JS, Holbrook A, Crowther M, Duku EK, Burrows RF. A reevaluation of the risk for venous thromboembolism with the use of oral contraceptives and hormone replacement therapy. Arch Intern Med. Jul 28 1997;157(14):1522–1530[Review]
  72. Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from The Women's Health Initiative Randomized Controlled Trial. JAMA. 2002;288:321–333
  73. In:  Chernecky CC,  Berger BJ editor. Laboratory tests and diagnostic procedures. 4th ed.. Philadelphia: Saunders; 2004;
  74. Kierkegaard A. Incidence and diagnosis of deep vein thrombosis associated with pregnancy. Acta Obstet Gynecol Scand. 1983;62:239–243
  75. Mitwally M, Bhakoo H, Crickard K, Sullivan M, Batt R. Yeh Estradiol production during controlled ovarian hyperstimulation correlates with treatment outcome in women undergoing in vitro fertilization-embryo transfer. Fertil Steril. Sep 2006;86(3):588–596
  76. Anderson BS, Steffensen FH, Sorensen HT, Nielson GL, Olsen J. The cummulative incidence of venous thromboembolism during pregnancy and puerperium-an 11 year Danish population based study of 63300 pregnancies. Acta Obstet Gynecol Scand. 1998;77:110–113
  77. Biron C, Galtier-Dereure F, Rabesandratana H, Bernard I, Aguilar-Martinez P, Schved JF, et al. Hemostasis parameters during ovarian stimulation for in vitro fertilization: results of a prospective study. Fertil Steril. Jan 1997;67(1):104–109
  78. Kim HC, Kemmann E, Shelden RM, Saidi P. Response of blood coagulation parameters to elevated endogenous 17 beta-estradiol levels induced by human menopausal gonadotropins. Am J Obstet Gynecol. 1981 Aug 1;140(7):807–810
  79. Aune B, Hoie KE, Oian P, Holst N, Osterud B. Does ovarian stimulation for in-vitro fertilization induce a hypercoagulable state?. Hum Reprod. Aug 1991;6(7):925–927
  80. Rice VC, Richard-Davis G, Saleh AA, Ginsburg KA, Mammen EF, Moghissi K, et al. Fibrinolytic parameters in women undergoing ovulation induction. Am J Obstet Gynecol. Dec 1993;169(6):1549–1553
  81. Aune B, Oian P, Osterud B. Enhanced sensitivity of the extrinsic coagulation system during ovarian stimulation for in-vitro fertilization. Hum Reprod. Sep 1993;8(9):1349–1352
  82. Bremme K, Wramsby H, Andersson O, Wallin M, Blomback M. Do lowered factor VII levels at extremely high endogenous oestradiol levels protect against thrombin formation?. Blood Coagul Fibrinolysis. Apr 1994;5(2):205–210
  83. Andersson O, Blomback M, Bremme K, Wramsby H. Prediction of changes in levels of haemostatic variables during natural menstrual cycle and ovarian hyperstimulation. Thromb Haemost. May 1997;77(5):901–904
  84. Richard-Davis G, Montgomery-Rice V, Mammen EF, Alshameeri RS, Morgan D, Moghissi KS. In vitro platelet function in controlled ovarian hyperstimulation cycles. Fertil Steril. May 1997;67(5):923–927
  85. Lox C, Canez M, Prien S. The influence of hyperestrogenism during in vitro fertilization on the fibrinolytic mechanism. Int J Fertil Womens Med. Jan–Feb 1998;43(1):34–39
  86. Magnani B, Tsen L, Datta S, Bader A. In vitro fertilization. Do short-term changes in estrogen levels produce increased fibrinolysis?. Am J Clin Pathol. Oct 1999;112(4):485–491
  87. Curvers J, Nap AW, Thomassen MC, Nienhuis SJ, Hamulyak K, Evers JL, et al. Effect of in vitro fertilization treatment and subsequent pregnancy on the protein C pathway. Br J Haematol. 2001;115:400–407
  88. Harnett MJ, Bhavani-Shankar K, Datta S, Tsen LC. In vitro fertilization-induced alterations in coagulation and fibrinolysis as measured by thromboelastography. Anesth Analg. Oct 2002;95(4):1063–1066
  89. Bar J, Orvieto R, Lahav J, Hod M, Kaplan B, Fisch B. Effect of urinary versus recombinant follicle-stimulating hormone on platelet function and other hemostatic variables in controlled ovarian hyperstimulation. Fertil Steril. 2004 Dec;82(6):1564–1569
  90. Phillips LL, Gladstone W, vande Wiele R. Studies of the coagulation and fibrinolytic systems in hyperstimulation syndrome after administration of human gonadotropins. J Reprod Med. Apr 1975;14(4):138–143
  91. Kodama H, Fukuda J, Karube H, Matsui T, Shimizu Y, Tanaka T. Characteristics of blood hemostatic markers in a patient with ovarian hyperstimulation syndrome who actually developed thromboembolism. Fertil Steril. Dec 1995;64(6):1207–1209
  92. Kodama H, Fukuda J, Karube H, Matsui T, Shimizu Y, Tanaka T. Status of the coagulation and fibrinolytic systems in ovarian hyperstimulation syndrome. Fertil Steril. Sep 1996;66(3):417–424
  93. Ogawa S, Minakami H, Araki S, Ohno T, Motoyama M, Shibahara H, et al. A rise of the serum level of von Willebrand factor occurs before clinical manifestation of the severe form of ovarian hyperstimulation syndrome. J Assist Reprod Genet. Feb 2001;18(2):114–119
  94. Rogolino A, Coccia ME, Fedi S, Gori AM, Cellai AP, Scarselli GF, et al. Hypercoagulability, high tissue factor and low tissue factor pathway inhibitor levels in severe ovarian hyperstimulation syndrome: possible association with clinical outcome. Blood Coagul Fibrinolysis. Apr 2003;14(3):277–282
  95. Brill-Edwards P, Ginsberg JS, Gent M, Hirsh J, Burrows R, Kearon C, et al. Safety of withholding heparin in pregnant women with a history of venous thromboembolism. Recurrence of Clot in This Pregnancy Study Group. N Engl J Med. Nov 16 2000;343(20):1439–1444
  96. Pabinger I, Grafenhofer H, Kaider A, Kyrle PA, Quehenberger P, Mannhalter C, et al. Risk of pregnancy-associated recurrent venous thromboembolism in women with a history of venous thrombosis. J Thromb Haemost. May 2005;3(5):949–954

PII: S0049-3848(07)00238-1

doi: 10.1016/j.thromres.2007.05.023

Thrombosis Research
Volume 121, Issue 6 , Pages 713-726 , 2008