Association of common thrombophilias and antiphospholipid antibodies with success rate of in vitro fertilisation

Summary

Assisted reproductive technology (ART) is extensively used as a tool for pregnancy achievement in subfertile couples. Congenital and acquired thrombophilias have been suggested by some investigators to play a role in abnormal embryo implantation and placentation. The objective of this study was to assess the role of common thrombophilias in women with unexplained infertility undergoing <i>in vitro</i>fertilisation (IVF). We retrospectively analysed 594 women from a large healthcare maintenance organisation going through IVF and who had a thrombophilia workup, and compared them for prevalence of thrombophilia to two reference groups consisting of 637 fertile women from previous work and 17,337 women members of the same healthcare organisation with no history of venous thromboembolism. The mean age of the women at the first cycle of IVF was 30.9 years (SD: 4.1).The mean number of IVF cycles was 7.3 (SD: 5.0), and the mean fertility success rate per woman was 14.6% (SD: 19.0%). None of the common thrombophilias tested was found to be significantly associated with the number of IVF cycles or with lower fertility success rate. Rather, women who had APCR and /or factor V Leiden and lupus anticoagulant had significantly higher live birth rates (12.3% and 12.6%, respectively) in comparison to women who were tested negative (9.0% and 9.7%, respectively). Thus, hypercoagulability is not associated with failure to achieve pregnancy. These data suggest that neither screening for thrombophilia nor anticoagulant treatment is indicated in cases with unexplained reproductive failure.

Keywords

Thrombophilia - IVF - factor V Leiden - APCR - antiphospholipid antibodies

• References

• 1 Di Nisio M, Rutjes AW, Ferrante N. et al. Thrombophilia and outcomes of assisted reproduction technologies: a systematic review and meta-analysis. Blood 2011; 118: 670-678.
• 2 Fasouliotis SJ, Schenker JG. Failures in assisted reproductive technology: an overview. Eur J Obstet Gynecol 2003; 107: 4-18.
• 3 Kupferminc MJ, Eldor A, Steinman N. et al. Increased frequency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med 1999; 340: 9-13.
• 4 Azem F, Many A, Ben Ami I. et al. Increased rates of thrombophilia in women with repeated IVF failures. Hum Reprod 2004; 19: 368-370.
• 5 Grandone E, Colaizzo D, Lo Bue A. et al. Inherited thrombophilia and in vitro fertilization implantation failure. Fertil Steril 2001; 76: 201-202.
• 6 Urman B, Ata B, Yakin K. et al. Luteal phase empirical low molecular weight heparin administration in patients with failed ICSI embryo transfer cycles: a randomized open-labeled pilot trial. Hum Reprod 2009; 24: 1640-1647.
• 7 Berker B, Taşkin S, Kahraman K. et al. The role of low-molecular-weight heparin in recurrent implantation failure: a prospective, quasi-randomized, controlled study. Fertil Steril 2011; 95: 2499-2502.
• 8 Qublan H, Amarin Z, Dabbas M. et al. Low-molecular-weight heparin in the treatment of recurrent IVF-ET failure and thrombophilia: a prospective randomized placebo-controlled trial. Hum Fertil 2008; 11: 246-253.
• 9 Rodger MA, Betancourt MT, Clark P. et al. The association of factor V leiden and prothrombin gene mutation and placenta-mediated pregnancy complications: a systematic review and meta-analysis of prospective cohort studies. PLoS Med 2010; 7: e1000292.
• 10 Norrie G, Farquharson RG, Greaves M. Sceening and treatment for heritable thrombophilia in pregnancy faillure: inconsistencies among UK early pregnancy units. Br J Haematol 2009; 144: 241-244.
• 11 Girardi G, Redecha P, Salmon JE. Heparin prevents antiphospholipid antibody- induced fetal loss by inhibiting complement activation. Nature Med 2004; 10: 1222-1226.
• 12 Salomon O, Seligsohn U, Steinberg DM. et al. The common prothrombotic factors in nulliparous women do not compromise blood flow in the feto-maternal circulation and are not associated with preeclampsia or intrauterine growth restriction. Am J Obstet Gynecol 2004; 191: 2002-2009.
• 13 Salomon O, Steinberg DM, Zivelin A. et al. Single and combined prothrombotic factors in patients with idiopathic venous thromboembolism: prevalence and risk assessment. Arterioscler Thromb Vasc Biol 1999; 19: 511-518.
• 14 Baker VL, Jones CE, Cometti B. et al. Factors affecting success rates in two concurrent clinical IVF trials: an examination of potential explanations for the difference in pregnancy rates between the United States and Europe. Fertil Steril 2010; 94: 1287-1291.
• 15 Gleicher N, Weghofer A, Barad D. A formal comparison of the practice of assisted reproductive technologies between Europe and the USA. Hum Reprod 2006; 21: 1945-1960.
• 16 Malizia BA, Hacker MR, Penzias AS. Cumulative live -birth rates after in vitro fertilization. N Engl J Med 2009; 360: 236-243.
• 17 Göpel W, Ludwig M, Junge AK. et al. Selection pressure for the factor V Leiden mutation and embryo implantation. Lancet 2001; 358: 1238-1239.
• 18 Qublan HS, Eid SS, Ababneh HA. et al. Acquired and inherited thrombophilia: implication in recurrent IVF and embryo transfer failure. Hum Reprod 2006; 21: 2694-2698.
• 19 Simur A, Ozdemir S, Acar H. et al. Repeated in vitro fertilizayion failure and its relation with thrombophilia. Gynecol Obstet Invest 2009; 67: 109-112.
• 20 Vaquero E, Lazzarin N, Caserta D. et al. Diagnostic evaluation of women experiencing repeated in vitro fertilization failure. Eur J Obstet Gynecol Reprod Biol 2006; 125: 79-84.
• 21 Ricci G, Bogatti P, Fischer-Tamaro L. et al. Factor V Leiden and prothrombin gene G20210A mutation and in vitro fertilization: prospective cohort study. Hum Reprod 2011; 26: 3068-3077.
• 22 Chamley LW, Duncalf AM, Mitchell MD. et al. Action of anticardiolipin and antibodies to B2-glycoprotein on trophoblast proliferation as a mechanism for fetal death. Lancet 1998; 352: 1037-1038.
• 23 Birdsall MA, Lockwood GM, Ledger WL. et al. Antiphospholipid antibodies in women having in-vitro fertilization. Hum Reprod 1996; 11: 1185-1189.