Low-dose aspirin does not improve ovarian stimulation, endometrial response, or pregnancy rates for in vitro fertilization

  • Bradley S Hurst
  • Jennifer T Bhojwani
  • Paul B Marshburn
  • Margaret A Papadakis
  • Terry A Loeb
  • Michelle L Matthews
Open Access



The purpose of this study is to determine if low-dose aspirin improved ovarian stimulation, endometrial response, or IVF pregnancy rates in our program.


Retrospective analysis of 316 consecutive IVF cycles from 1995 through 2001. Aspirin 80 mg daily was initiated at the start of luteal leuprolide in 72 cycles. The 244 controls received no aspirin during treatment.


The live birth rate in aspirin users was 29%, slightly lower compared to 41% in the no aspirin control group (p = 0.07). Implantation rates were 21% with aspirin and 30% in the control population (p = 0.01). There was no difference in the maximal endometrial thickness between aspirin and non-aspirin groups. The two groups were similar regarding age, gonadotropin ampules, embryos, number of embryos transferred, prior parity, diagnosis, use of intracytoplasmic sperm injection, and stimulation protocol.


Low-dose aspirin was not beneficial to IVF patients in our program. Aspirin does not enhance endometrial thickness, augment the ovarian response, or improve pregnancy rates.


aspirin embryo transfer endometrium fertilization in vitro infertility 



We thank Howell Sasser, Ph.D., Director of Research Epidemiology, Dickson Institute at Carolinas Medical Center for his assistance with statistical evaluation.


  1. 1.
    Wada I, Hsu CC, Williams G, Macnamee MC, Brinsden PR: The benefits of low-dose aspirin therapy in women with impaired uterine perfusion during assisted conception. Hum Reprod. 1994, 9: 1954-7.CrossRefGoogle Scholar
  2. 2.
    Rubinstein M, Marazzi A, Polak de Fried E: Low-dose aspirin treatment improves ovarian responsiveness, uterine and ovarian blood flow velocity, implantation, and pregnancy rates in patients undergoing in vitro fertilization: a prospective, randomized, double-blind placebo-controlled assay. Fertil Steril. 1999, 71: 825-9. 10.1016/S0015-0282(99)00088-6.CrossRefGoogle Scholar
  3. 3.
    Weckstein LN, Jacobson A, Galen D, Hampton K, Hammel J: Low-dose aspirin for oocyte donation recipients with a thin endometrium: prospective, randomized study. Fertil Steril. 1997, 68: 927-30. 10.1016/S0015-0282(97)00330-0.CrossRefGoogle Scholar
  4. 4.
    Urman B, Mercan R, Alatas C, Balaban B, Isiklar A, Nuhoglu A: Low-dose aspirin does not increase implantation rates in patients undergoing intracytoplasmic sperm injection: a prospective randomized study. J Assisted Reprod Genet. 2000, 17: 586-90. 10.1023/A:1026491426423.CrossRefGoogle Scholar
  5. 5.
    Polak de Fried E: Errata. Fertil Steril. 1999, 72: 755-10.1016/S0015-0282(99)00351-9.CrossRefGoogle Scholar
  6. 6.
    Hsieh YY, Tsai HD, Chang CC, Lo HY, Chen CL: Low-dose aspirin for infertile women with thin endometrium receiving intrauterine insemination: a prospective, randomized study. J Assist Reprod Genet. 2000, 17: 174-7. 10.1023/A:1009474307376.CrossRefPubMedCentralPubMedGoogle Scholar
  7. 7.
    Waldenstrom U, Hellberg D, Nilsson S: Low-dose aspirin in a short regimen as standard treatment in in vitro fertilization: a randomized, prospective study. Fertil Steril. 2004, 81: 1560-4. 10.1016/j.fertnstert.2004.02.082.CrossRefGoogle Scholar
  8. 8.
    Sher G, Zouves C, Feinman M, Maassarani G, Matzner W, Chong P, Ching W: A rational basis for the use of combined heparin/aspirin and IVIG immunotherapy in the treatment of recurrent IVF failure associated with antiphospholipid antibodies. Am J Reprod Immunol. 1998, 39: 391-4.CrossRefGoogle Scholar
  9. 9.
    Hasegawa I, Hamanoto Y, Suzuki M, Murakawa H, Kurabayshi T, Takakuwa K, Tanaka K: Prednisolone plus low-dose aspirin improves the implantation rate in women with autoimmune conditions who are undergoing in vitro fertilization. Fertil Steril. 1998, 70: 1044-8. 10.1016/S0015-0282(98)00343-4.CrossRefGoogle Scholar
  10. 10.
    Sher G, Matzner W, Feinman M, Maassarani G, Zouves C, Chong P, Ching W: The selective use of heparin/aspirin therapy, alone or in combination with intravenous immunoglobulin G, in the management of antiphospholipid antibody-positive women undergoing in vitro fertilization. Am J Reprod Immunol. 1998, 40: 74-82.CrossRefGoogle Scholar
  11. 11.
    Sher G, Maassarani G, Zouves C, Feinman M, Sohn S, Matzner W, Chong P, Ching W: The use of combined heparin/aspirin and immunoglobulin G therapy in the treatment of in vitro fertilization patients with antithyroid antibodies. Am J Reprod Immunol. 1998, 39: 223-5.CrossRefGoogle Scholar
  12. 12.
    Sher G, Feinman M, Zouves C, Kuttner G, Maassarani G, Salem R, Matzner W, Ching W, Chong P: High fecundity rates following in-vitro fertilization and embryo transfer in antiphospholipid antibody seropositive women treated with heparin and aspirin. Hum Reprod. 1994, 9: 2278-83.CrossRefGoogle Scholar
  13. 13.
    Geva E, Amit A, Lerner-Geva L, Yaron Y, Daniel Y, Schwartz T, Azem F, Yovel I, Lessing JB: Prednisone and aspirin improve pregnancy rate in patients with reproductive failure and autoimmune antibodies: a prospective study. Am J Reprod Immunol. 2000, 43: 36-40. 10.1111/j.8755-8920.2000.430107.x.CrossRefGoogle Scholar
  14. 14.
    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. Am J Obstet Gynecol. 2005, 192: 23-30. 10.1016/j.ajog.2004.09.029.CrossRefPubMedGoogle Scholar
  15. 15.
    Stern C, Chamley L, Norris H, Hale L, Baker HW: A randomized, double-blind, placebo-controlled trial of heparin and aspirin for women with in vitro fertilization implantation failure and antiphospholipid or antinuclear antibodies. Fertil Steril. 2003, 80: 376-83. 10.1016/S0015-0282(03)00610-1.CrossRefPubMedGoogle Scholar
  16. 16.
    Check JH, Dietterich C, Lurie D, Nazari A, Chuong J: A matched study to determine whether low-dose aspirin without heparin improves pregnancy rates following frozen embryo transfer and/or affects endometrial sonographic parameters. J Assist Reprod Genet. 1998, 15: 579-82. 10.1023/A:1020373009043.CrossRefPubMedCentralPubMedGoogle Scholar
  17. 17.
    Kutteh WH, Yetman DL, Chantilis SJ, Crain J: Effect of antiphospholipid antibodies in women undergoing in-vitro fertilization: role of heparin and aspirin. Hum Reprod. 1997, 12: 1171-5. 10.1093/humrep/12.6.1171.CrossRefGoogle Scholar
  18. 18.
    Lok IH, Yip SK, Cheung LP, Yin Leung PH, Haines CJ: Adjuvant low-dose aspirin therapy in poor responders undergoing in vitro fertilization: a prospective, randomized, double-blind, placebo-controlled trial. Fertil Steril. 2004, 81: 556-61. 10.1016/j.fertnstert.2003.07.033.CrossRefGoogle Scholar
  19. 19.
    Triolo G, Ferrante A, Ciccia F, Accardo-Palumbo A, Perino A, Castelli A, Giarratano A, Licata G: Randomized study of subcutaneous low molecular weight heparin plus aspirin versus intravenous immunoglobulin in the treatment of recurrent fetal loss associated with antiphospholipid antibodies. Arthritis Rheum. 2003, 48: 728-31. 10.1002/art.10957.CrossRefPubMedGoogle Scholar
  20. 20.
    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 phospholipids antibodies (or antiphospholipid antibodies). BMJ. 1997, 314 (7076): 253-7.CrossRefPubMedGoogle Scholar
  21. 21.
    Kutteh WH: Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone. Am J Obstet Gynecol. 1996, 174: 1584-9.CrossRefGoogle Scholar
  22. 22.
    Farquharson RG, Quenby S, Greaves M: Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstet Gynecol. 2002, 100: 408-13. 10.1016/S0029-7844(02)02165-8.CrossRefGoogle Scholar
  23. 23.
    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: 1008-12. 10.1067/mob.2000.106754.CrossRefGoogle Scholar
  24. 24.
    Laskin CA, Bombardier C, Hannah ME, Mandel FP, Ritchie JW, Farewell V, Farine D, Spitzer K, Fielding L, Soloninka CA, Yeung M.: Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss. NEJM. 1997, 337: 148-53. 10.1056/NEJM199707173370302.CrossRefGoogle Scholar
  25. 25.
    Silver RK, MacGregor SN, Sholl JS, Hobart JM, Neerhof MG, Ragin A: Comparative trial of prednisone plus aspirin versus aspirin alone in the treatment of anticardiolipin antibody-positive obstetric patients. Am J Obstet Gynecol. 1993, 169: 1411-7.CrossRefGoogle Scholar
  26. 26.
    Practice Committee Report: Antiphospholipid antibodies do not affect IVF success. American Society for Reproductive Medicine. 1999Google Scholar
  27. 27.
    Rock JA, Hurst BS: Clinical significance of prostanoid concentration in women with endometriosis. Prog Clin Biol Res. 1990, 23: 61-80.Google Scholar
  28. 28.
    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 (7411): 368-10.1136/bmj.327.7411.368.CrossRefPubMedCentralPubMedGoogle Scholar
  29. 29.
    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: 1623-30. 10.1067/mob.2002.127376.CrossRefGoogle Scholar
  30. 30.
    Kozer E, Costei AM, Boskovic R, Nulman I, Nikfar S, Koren G: Effects of aspirin consumption during pregnancy on pregnancy outcomes: meta-analysis. Devel Reprod Toxicology. 2003, 68: 70-84. 10.1002/bdrb.10002.CrossRefGoogle Scholar
  31. 31.
    Leonhardt A, Bernert S, Watzer B, Schmitz-Zeigler G, Seyberth HW: Low-dose aspirin in pregnancy: maternal and neonatal aspirin concentrations and neonatal prostanoid formation. Pediatrics. 2003, 111: e77-81. 10.1542/peds.111.1.e77.CrossRefGoogle Scholar
  32. 32.
    Sibai BM, Caritis SN, Thom E, Klebanoff M, NcNellis D, Rocco L, Paul RH, Romero R, Witter F, Rosen M, et al: Prevention of preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. NEJM. 1993, 329: 1213-8. 10.1056/NEJM199310213291701.CrossRefGoogle Scholar
  33. 33.
    Golding J: A randomized trial of low dose aspirin for primiparae in pregnancy. The Jamaica Low Dose Aspirin Study Group. Br J Obstet Gynaecol. 1998, 105: 293-9.CrossRefGoogle Scholar
  34. 34.
    Centers for Disease Control and Prevention: Pregnancy-related death associated with heparin and aspirin treatment for infertility, 1996. JAMA. 1998, 279: 1860-1. 10.1001/jama.279.23.1860.CrossRefGoogle Scholar

Copyright information

© Hurst et al; licensee BioMed Central Ltd. 2005

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Authors and Affiliations

  • Bradley S Hurst
    • 1
  • Jennifer T Bhojwani
    • 1
  • Paul B Marshburn
    • 1
  • Margaret A Papadakis
    • 1
  • Terry A Loeb
    • 1
  • Michelle L Matthews
    • 1
  1. 1.Department of Obstetrics and GynecologyCarolinas Medical CenterCharlotteUSA

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