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


      Objective: To determine the effects of low-dose aspirin on ovarian response, uterine and ovarian blood flow velocity, and implantation and pregnancy rates in patients undergoing IVF.
      Design: Prospective, randomized, double-blind placebo-controlled assay.
      Setting: Department of Reproductive Medicine, CER Medical Institute, Buenos Aires, Argentina.
      Patient(s): Two hundred ninety-eight infertile patients (mean [± SD] age, 35.6 ± 4.09 years) undergoing IVF cycles.
      Intervention(s): In the treatment group, 149 patients underwent controlled ovarian hyperstimulation and received a daily dose of 100 mg of aspirin. In the control group, 149 patients underwent controlled ovarian hyperstimulation in association with placebo.
      Main Outcome Measure(s): Number of follicles, number of oocytes retrieved, serum E2 levels, uterine and ovarian pulsatility index, cancellation rate, number of embryos transferred, and implantation and pregnancy rates.
      Result(s): There were statistically significant differences between the treatment group and the control group, respectively, in the number of follicles (19.8 ± 7.2 versus 10.2 ± 5.3), number of oocytes retrieved (16.2 ± 6.7 versus 8.6 ± 4.6), serum E2 levels (2,923.8 ± 1,023.4 versus 1,614.3 ± 791.7 pg/mL), uterine pulsatility index (1.22 ± 0.34 versus 1.96 ± 0.58), ovarian pulsatility index (1.18 ± 0.31 versus 1.99 ± 0.56), pregnancy rate (45% versus 28%), and implantation rate (17.8% versus 9.2%).
      Conclusion(s): Low-dose aspirin treatment significantly improves ovarian responsiveness, uterine and ovarian blood flow velocity, and implantation and pregnancy rates in IVF patients.


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        • Vane R.J
        Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs.
        Nature. 1971; 231: 232-235
        • Williard J.E
        • Lage R
        • Hillis L.D
        The use of aspirin in ischemic heart disease.
        N Engl J Med. 1992; 327: 175-181
        • ISIS-2 (Second International Study of Infarct Survival) Collaborative Group
        Randomized trial of intravenous streptokinase, oral aspirin, both or neither among 17187 cases of suspected acute myocardial infarction.
        Lancet. 1988; 2: 349-360
        • ISIS-3 (Third International Study of Infarct Survival) Collaborative Group
        A randomized comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41299 cases of suspected acute myocardial infarction.
        Lancet. 1992; 339: 753-770
        • Meijer A
        • Verheugt F.W
        • Werter C.J
        • Lie K
        • van der Pol J.M
        • van Eenige M.J
        Aspirin versus coumadin in the prevention of reocclusion and recurrent ischemia after successful thrombolysis: a prospective placebo-controlled angiographic study. Results of the APRICOT study.
        Circulation. 1993; 87: 1524-1530
        • Fuster V
        • Dyken M.L
        • Vokonas P.S
        Aspirin as a therapeutic agent in cardiovascular disease.
        Circulation. 1993; 87: 659-675
        • Wallenberg H.C
        • Rotman S.N
        Prevention of recurrent idiopathic fetal growth retardation by low-dose aspirin and dipyridamole.
        Am J Obstet Gynecol. 1987; 157: 1230-1235
        • Yamaguchi M
        • Mori N
        6-Keto prostaglandin F1a, thromboxane B2 and 13-14 dihydro-15 keto prostaglandin F concentrations of normotensive and preeclamptic patients during pregnancy, delivery and the postpartum period.
        Am J Obstet Gynecol. 1985; 151: 121-123
        • Jouppilsa P
        • Kirkinen P
        • Koinla A
        • Ylikorkala O
        Failure of exogenous prostacyclin to change placental and fetal blood flow in preeclampsia.
        Am J Obstet Gynecol. 1985; 151: 661-665
        • Sher G
        • Feinmnan M
        • Zouves C
        • Kuttner G
        • Massarani G
        • Salem R
        • et al.
        High fecundity rates following in-vitro fertilization and embryo transfer in antiphospholipid antibody seropositive women treated with heparin and aspirin.
        Hum Reprod. 1994; 9: 2278-2283
        • Thun M.J
        • Namboodiri B.S
        • Heath C.W
        Aspirin use and reduced risk of fatal colon cancer.
        N Engl J Med. 1991; 325: 1593-1596
        • Giovannucci E
        • Egan K.M
        • Hunter D.J
        • Stampfer M.J
        • Colditz G.A
        • Willett W.C
        • et al.
        Aspirin and the risk of colorectal cancer in women.
        N Engl J Med. 1995; 333: 609-614
        • Polak de Fried E
        • Blanco L
        • Lancuba S
        • Asch R
        Improvement of clinical pregnancy rate and implantation rate of in-vitro fertilization-embryo transfer patients by using methylprednisone.
        Hum Reprod. 1993; 8: 393-395
        • Burch J.W
        • Majerus P.W
        The role of prostaglandins in platelet function.
        Semin Hematol. 1979; 16: 196-207
        • Burch J.W
        • Stanford P.W
        Inhibition of platelet prostaglandin synthetase by oral aspirin.
        J Clin Invest. 1979; 61: 314-319
        • Lorenz R.L
        • Boehlig B
        • Vedelhoven W.M
        • Weber P.C
        Superior antiplatelet action of alternative day pulsed dosing versus split dose administration of aspirin.
        Am J Cardiol. 1989; 64: 1185-1188
        • Clarke R.J
        • Mayo G
        • Price P
        • Fitzgerald G.A
        Suppression of thromboxane A2 but not of systemic prostacyclin by controlled-release aspirin.
        N Engl J Med. 1991; 325: 1137-1141
        • Majerus P.W
        Arachidonate metabolism in vascular disorders.
        J Clin Invest. 1983; 72: 1521-1525
        • Weksler B.B
        • Pett S.B
        • Alonso D
        • Richter R.C
        • Stelzer P
        Differential inhibition by aspirin of vascular and platelet prostaglandin synthesis in atherosclerotic patients.
        N Engl J Med. 1983; 308: 800-805
        • Burch J.W
        Sensitivity of fatty acid cyclooxygenase from human aorta to acetylation by aspirin.
        Proc Natl Acad Sci USA. 1978; 75: 5181-5184
        • Moncada S
        • Vane J.R
        Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2 and prostacyclin.
        Pharmacol Rev. 1978; 30: 293-331
        • Moncada S
        • Vane J.R
        Mode of action of aspirin-like drugs.
        in: Stollerman G.H Cardiovascular drugs. Vol. 24. Adis Press, New York1982: 25-47
        • Smith J.B
        • Willis A.L
        Aspirin selectively inhibits prostaglandin production in human platelets.
        Nature (New Biol). 1971; 231: 235-237
        • Patrignani P
        • Filabozzi P
        Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects.
        J Clin Invest. 1982; 69: 1366-1372
        • Moncada S
        • Vane J.R
        Arachidonic acid metabolites and the interactions between platelets and blood vessel walls.
        N Engl J Med. 1979; 300: 1142-1147
      1. Gilman A.G Rall T.W Nies A.S Goodman and Gilman’s the pharmacologic basis of therapeutics. 8th ed. Pergamon, New York1991
      2. Vane J.R Botting R.M Aspirin and other salicylates. Chapman & Hall Medical, London1992
        • Wada I
        • Hsu C.C
        • Williams G
        • Macnamee M.C
        • Brindsen P.R
        The benefits of low-dose aspirin therapy in women with impaired uterine perfusion during assisted conception.
        Hum Reprod. 1994; 9: 1954-1957
        • Battaglia C
        • Artini P
        • Giulini S
        • Salvatori M
        • Maxia N
        • Petraglia F
        • et al.
        Colour Doppler changes and thromboxane production after ovarian stimulation with gonadotrophin-releasing hormone agonist.
        Hum Reprod. 1997; 12: 2477-2482
        • Steer C.V
        • Lin Tan S
        • Dillon D
        • Mason B.A
        • Cambell S
        Vaginal color Doppler assessment of uterine artery impedance correlates with immunohistochemical markers of endometrial receptivity required for the implantation of an embryo.
        Fertil Steril. 1995; 63: 101-108
        • Weckstein L.N
        • Jacobson A
        • Galen D
        • Hampton K
        • Hammel J
        Low dose aspirin for oocyte donation recipients with a thin endometrium.
        Fertil Steril. 1997; 68: 927-930
        • Deutinger J
        • Reinthaller A
        • Bernaschek G
        Transvaginal pulsed Doppler measurement of blood flow velocity in the ovarian arteries during cycle stimulation and after follicle puncture.
        Fertil Steril. 1989; 51: 466-470
        • Edwards R.G
        The adult ovary.
        in: Edwards R.G Conception in the human female. Academic Press, London1980: 89-110
        • Taylor K.J
        • Burns P.N
        • Wells P.N
        • Conway D.I
        Ultrasound Doppler flow studies of the ovarian and uterine arteries.
        Br J Obstet Gynaecol. 1985; 92: 240-246
        • Ford S.P
        • Reynolds L.P
        • Farley D.B
        Interaction of ovarian steroids and periarterial alpha-1-adrenergic receptors in altering uterine blood flow during the estrous cycle of gilts.
        Am J Obstet Gynecol. 1984; 150: 480-484
        • Battaglia C
        • Larocca E
        • Lanzani A
        Doppler ultrasound studies of the uterine arteries in spontaneous and IVF stimulated ovarian cycles.
        Gynecol Endocrinol. 1990; 4: 245-250
        • Goswamy R.K
        • Williams G
        • Steptoe P.C
        Decreased uterine perfusion—a cause of infertility.
        Hum Reprod. 1988; 3: 955-958
        • Steer C.V
        • Campbell S
        • Tan S.L
        The use of transvaginal color flow imaging after in vitro fertilization to identify optimum uterine conditions before embryo transfer.
        Fertil Steril. 1992; 57: 372-376