Advertisement

Diagnostic evaluation of women experiencing repeated in vitro fertilization failure

      Abstract

      Objective

      The aim of the study was to propose a set of tests to clarify the diagnosis of repeated implantation failure in patients undergoing in vitro fertilization (IVF).

      Study design

      Fifty-nine patients with at least two unsuccessful IVF attempts were included in the study. Blood samples were evaluated for the presence of underlying thyroid abnormalities, antiphospholipid antibodies (aPL), increased levels of natural killer cells (NK), inherited thrombophilia and mouse embryo assay factor (MEA-f). The same tests were performed on 20 normal fertile control patients.

      Results

      Seventy-six percent of IVF patients showed at least one abnormal result. This incidence was higher with respect to that found among control patients (45%). The prevalence of thyroid abnormalities, aPL and increased NK level was higher in IVF patients whereas no differences were observed in terms of prevalence of inherited thrombophilias and MEA-f.

      Conclusions

      A better understanding of reproductive failure mechanisms should allow an effective diagnostic flow chart and a focused therapeutic option for patients experiencing repeated IVF failure. With this objective in mind, our data provide two important results: thyroid abnormalities, aPL and increased NK levels are more prevalent in women experiencing IVF failure. No evidence was found for an association between inherited thrombophilia and MEA-f and failure to achieve pregnancy after IVF.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      References

        • Robert C.J.
        • Lowe C.R.
        Where have all the conceptions gone?.
        Lancet. 1975; I: 498-499
        • Zinaman M.J.
        • O’Connor J.
        • Clegg E.D.
        • et al.
        Estimates of human fertility and pregnancy loss.
        Fertil Steril. 1996; 65: 503-509
        • Macklon N.S.
        • Geraedts J.P.M.
        • Fauser B.C.J.M.
        Conception to ongoing pregnancy: the “black box” of early pregnancy.
        Hum Reprod Update. 2002; 4: 333-343
        • Roussev R.G.
        • Kaider B.D.
        • Price D.E.
        • et al.
        Laboratory evaluation of women experiencing reproductive failure.
        Am J Reprod Immunol. 1996; 35: 415-420
      1. Assisted reproductive technology in the United States: 2000 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. Fertil Steril 2004;81(5):1207–20.

        • Clark D.A.
        • Coulam C.B.
        • Daya S.
        • et al.
        Unexplained sporadic and recurrent miscarriage in the new millennium: a critical analysis of immune mechanisms and treatments.
        Hum Reprod Update. 2001; 7: 501-511
        • Gianaroli L.
        • Masgli C.
        • Ferraretti A.P.
        • et al.
        Preimplantation diagnosis for aneuploidies in patients undergoing in vitro fertilization with a poor prognosis: identification of the categories for which it should be proposed.
        Fertil Steril. 1999; 72: 837-844
        • Coulam C.B.
        • Roussev R.G.
        Correlation of NK cell activation and inhibition markers with NK cytotoxicity among women experiencing immunological implantation failure after in vitro fertilization and embryo transfer.
        J Assist Reprod Genet. 2003; 20: 58-62
        • Laird S.M.
        • Tuckerman E.M.
        • Cork B.A.
        • et al.
        A review of immune cells and molecules in women with recurrent miscarriage.
        Hum Reprod Update. 2003; 9: 163-174
        • Poppe K.
        • Glinoer D.
        Thyroid autoimmunity and hypothyroidism before and during pregnancy.
        Hum Reprod Update. 2003; 9: 49-61
        • Buchholz T.
        • Thaler C.J.
        Inherited thrombophilia: impact on human reproduction.
        Am J Reprod Immunol. 2003; 50: 20-32
        • McIntyre J.A.
        Antiphospholipid antibodies in implantation failures.
        Am J Reprod Immunol. 2003; 49: 221-229
        • Kaider A.S.
        • Kaider B.D.
        • Janowicz P.B.
        • et al.
        Immunodiagnostic evaluation in women with reproductive failure.
        Am J Reprod Immunol. 1999; 42: 335-346
        • Vaquero E.
        • Lazzarin N.
        • De Carolis C.
        • et al.
        Mild thyroid abnormalities and recurrent spontaneous abortion: diagnostic and therapeutical approach.
        Am J Reprod Immunol. 2000; 43: 204-208
        • Wilson W.A.
        • Gharavi A.E.
        • Koike T.
        • et al.
        International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome.
        Arthritis Rheum. 1999; 42: 1309-1311
        • Brenner B.
        • Hoffman R.
        • Blumenfeld Z.
        • et al.
        Gestational outcome in thrombophilic women with recurrent pregnancy loss treated by enoxaparin.
        Thromb Haemost. 2000; 83: 693-697
        • Vaquero E.
        • Lazzarin N.
        • Di Pierro G.
        • et al.
        Pregnancy outcome in women with inherited thrombophilias and recurrent spontaneous abortion treated with low molecular weight heparin: preliminary results.
        J Matern Fetal Neonatal Med. 2003; 13: 40-43
        • Singh A.
        • Nery Dantas Z.
        • Stone S.C.
        • et al.
        Presence of thyroid antibodies in early reproductive failure: biochemical versus clinical pregnancies.
        Fertil Steril. 1995; 63: 277-281
        • Bussen S.
        • Steck T.
        • Dietl J.
        Increased prevalence of thyroid antibodies in euthyroid women with history of recurrent in vitro fertilization.
        Hum Reprod. 2000; 15: 545-548
        • Matalon S.T.
        • Blank M.
        • Ornoy A.
        • et al.
        The association between anti thyroid antibodies and pregnancy loss.
        Am J Reprod Immunol. 2001; 45: 72-77
        • Bussen S.S.
        • 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
        • Pratt D.
        • Novotny M.
        • Kaberlein G.
        • et al.
        Antithyroid antibodies and the association with non-organ-specific antibodies in recurrent pregnancy loss.
        Am J Obstet Gynecol. 1993; 168: 837-841
        • Glinoer D.
        • Fernandez Soto M.
        • Bourdoux P.
        • et al.
        Pregnancy in patients with mild thyroid abnormalities maternal and neonatal repercussion.
        J Clin Endocrinol Metab. 1991; 73: 421-427
        • Lejeune B.
        • Grun J.P.
        • De Nayer P.
        • et al.
        Antithyroid antibodies underlying thyroid abnormalities and miscarriage or pregnancy induced hypertension.
        Br J Obstet Gynaecol. 1993; 100: 669-672
        • Ghazeeri G.S.
        • Kutteh H.
        Immunological testing and treatment in reproduction: frequency assessment of practice patterns at assisted reproduction clinics in the USA and Australia.
        Hum Reprod. 2001; 16: 2130-2135
        • Di Simone N.
        • Caliandro D.
        • Castellani R.
        • et al.
        Low molecular weight heparin restores in vitro trophoblast invasiveness and differentiation in presence of immunoglobulin G fractions obtained from patients with antiphospholipid syndrome.
        Hum Reprod. 1999; 14: 489-495
        • Gopel W.
        • Ludwig M.
        • Junge A.K.
        • et al.
        Selection pressure for the factor V Leiden mutation and embryo implantation.
        Lancet. 2001; 358: 1238-1239
        • Martinelli I.
        • Taioli
        • Ragni G.
        • et al.
        Embryo implantation after assisted reproductive procedures and maternal thrombophilia.
        Haematologica. 2003; 88: 731-732
        • Grandone E.
        • Colaizzo D.
        • Lo Bue A.
        • et al.
        Inherited thrombophilia and in vitro fertilization implantation failure.
        Fertil Steril. 2001; 76: 201-202
        • Coulam C.B.
        • Goodman C.
        • Roussev R.G.
        • et al.
        Systemic CD 56 can predict pregnancy outcome.
        Am J Reprod Immunol. 1995; 33: 40-46