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Der Gynäkologe

, Volume 51, Issue 4, pp 304–311 | Cite as

Diagnostik bei habituellem Abort

Sinn und Unsinn
  • Ruben-J. Kuon
  • Kilian Vomstein
  • Bettina Toth
Leitthema
  • 239 Downloads

Zusammenfassung

Hintergrund

Etwa 1–3 % aller Paare im reproduktiven Alter sind von habituellen Aborten betroffen. Ihre Betreuung stellt besondere Herausforderungen an den behandelnden Arzt, insbesondere da die Ursachen multifaktoriell sein können. Daher ist eine zielgerichtete Diagnostik von großer Bedeutung.

Ziel der Arbeit

Einordnung der verschiedenen diagnostischen Verfahren in evidenzbasierte und nichtevidenzbasierte Maßnahmen.

Material und Methoden

Anhand der bestehenden Literatur, die auch in der Neufassung der S2k-Leitlinie der AWMF (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften), „Diagnostik und Therapie beim wiederholten Spontanabort“ (015/50), und in der ESHRE(European Society of Human Reproduction and Embryology)-Leitlinie, „Guideline on the management of recurrent pregnancy loss“, berücksichtigt wurde, soll eine evidenzbasierte Diagnostik beschrieben werden.

Ergebnisse

Die Diagnostik bei Paaren mit habituellen Aborten umfasst den Ausschluss von genetischen, anatomischen, infektiologischen, psychologischen, hämostaseologischen und immunologischen Risikofaktoren. Eine Vielzahl weiterer möglicher Risikofaktoren wird derzeit unter Studienbedingungen untersucht.

Diskussion

Die Abklärung habitueller Aborte sollte im Rahmen eines standardisierten diagnostischen Vorgehens erfolgen. Aufgrund vieler neuer Risikofaktoren, die in der internationalen Literatur beschrieben werden, ist eine Abgrenzung zu evidenzbasiertem Vorgehen notwendig. Eine besondere Bedeutung kommt dem ärztlichen Gespräch zu; es muss mögliche diagnostische Schritte erläutern und auch überhöhte Erwartungen an eine nichtevidenzbasierte Diagnostik, welche innerhalb von Studien stattfinden sollte, einordnen.

Schlüsselwörter

Kürettage  Reproduktion Differenzialdiagnostik Hämostase Beratung Natürliche Killerzellen 

Diagnostic procedures in recurrent miscarriage

The rational and the irrational

Abstract

Background

Recurrent miscarriage affects around 1–3% of couples in reproductive age. Management of these patients represents a challenge for the treating physician, particularly because the causes may be multifactorial. Therefore, a standardized, evidence-based diagnostic approach is needed to give the patients the best treatment options.

Objective

Classification of different diagnostic procedures in evidence-based and non-evidence-based approaches.

Materials and methods

Based on the literature, which is also considered in the most recent version of the German S2k AWMF (“Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften”) guideline on diagnostics and treatment in recurrent miscarriage (“Diagnostik und Therapie beim wiederholten Spontanabort;” 015/50) as well as by the new European Society of Human Reproduction and Embryology (ESHRE) guideline on management of recurrent pregnancy loss, evidence-based diagnostic procedures are evaluated and discussed.

Results

Diagnostic workup in couples with recurrent miscarriage includes exclusion of genetic, anatomic, infectiologic, psychologic, hemostasiologic, and immunologic risk factors. A multitude of other possible risk factors are currently being investigated in studies.

Conclusion

The clarification of recurrent miscarriage should proceed within the framework of a standardized diagnostic pathway. Due to many new risk factors described in the international literature, a distinction from an evidence-based approach is necessary. The patient–physician consultation plays a particularly important role: possible diagnostic steps should be explained and overly high expectations of a non-evidenced-based diagnostic approach, which should take place within studies, can be realistically discussed.

Keywords

Curettage  Reproduction Diagnosis, differential Hemostasis Counseling Natural killer cells 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

R.-J. Kuon und B. Toth sind Gesellschafter der Reprognostics GbR. K. Vomstein gibt an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Literatur

  1. 1.
    ACOG (2002) ACOG practice bulletin. Management of recurrent pregnancy loss. Number 24, February 2001. (Replaces Technical Bulletin Number 212, September 1995). American College of Obstetricians and Gynecologists. Int J Gynecol Obstet 78:179–190CrossRefGoogle Scholar
  2. 2.
    Alijotas Reig J, Ferrer-Oliveras R, Ruffatti A et al (2015) The European Registry on Obstetric Antiphospholipid Syndrome (EUROAPS): a survey of 247 consecutive cases. Autoimmun Rev 14:387–395.  https://doi.org/10.1016/j.autrev.2014.12.010 CrossRefPubMedGoogle Scholar
  3. 3.
    Arachchillage DRJ, Machin SJ, Mackie IJ, Cohen H (2015) Diagnosis and management of non-criteria obstetric antiphospholipid syndrome. Thromb Haemost 113:13–19.  https://doi.org/10.1160/TH14-05-0416 CrossRefPubMedGoogle Scholar
  4. 4.
    Bayer-Garner IB, Korourian S (2001) Plasma cells in chronic endometritis are easily identified when stained with syndecan-1. Mod Pathol 14:877–879.  https://doi.org/10.1038/modpathol.3880405 CrossRefPubMedGoogle Scholar
  5. 5.
    Boots CE, Bernardi LA, Stephenson MD (2014) Frequency of euploid miscarriage is increased in obese women with recurrent early pregnancy loss. Fertil Steril 102:455–459.  https://doi.org/10.1016/j.fertnstert.2014.05.005 CrossRefPubMedGoogle Scholar
  6. 6.
    Bradley LA, Palomaki GE, Bienstock J et al (2012) Can Factor V Leiden and prothrombin G20210A testing in women with recurrent pregnancy loss result in improved pregnancy outcomes?: Results from a targeted evidence-based review. Genet Med 14:39–50.  https://doi.org/10.1038/gim.0b013e31822e575b CrossRefPubMedGoogle Scholar
  7. 7.
    Branch DW, Gibson M, Silver RM (2010) Clinical practice. Recurrent miscarriage. N Engl J Med 363:1740–1747CrossRefPubMedGoogle Scholar
  8. 8.
    Bustos D, Moret A, Tambutti M et al (2006) Autoantibodies in Argentine women with recurrent pregnancy loss. Am J Reprod Immunol 55:201–207CrossRefPubMedGoogle Scholar
  9. 9.
    Caliskan E, Ozkan S, Cakiroglu Y et al (2010) Diagnostic accuracy of real-time 3D sonography in the diagnosis of congenital Mullerian anomalies in high-risk patients with respect to the phase of the menstrual cycle. J Clin Ultrasound 38:123–127.  https://doi.org/10.1002/jcu.20662 PubMedGoogle Scholar
  10. 10.
    Carbone J, Sarmiento E, Gallego A et al (2016) Peripheral blood T‑ and B‑cell immunophenotypic abnormalities in selected women with unexplained recurrent miscarriage. J Reprod Immunol 113:50–53.  https://doi.org/10.1016/j.jri.2015.11.003 CrossRefPubMedGoogle Scholar
  11. 11.
    Chen X, Mariee N, Jiang L et al (2017) Measurement of uterine natural killer cell percentage in the periimplantation endometrium from fertile women and women with recurrent reproductive failure: establishment of a reference range. Am J Obstet Gynecol 217:680.e1–680.e6.  https://doi.org/10.1016/j.ajog.2017.09.010 CrossRefGoogle Scholar
  12. 12.
    Cicinelli E, Resta L, Nicoletti R et al (2005) Endometrial micropolyps at fluid hysteroscopy suggest the existence of chronic endometritis. Hum Reprod 20:1386–1389.  https://doi.org/10.1093/humrep/deh779 CrossRefPubMedGoogle Scholar
  13. 13.
    Cicinelli E, Matteo M, Tinelli R et al (2014) Chronic endometritis due to common bacteria is prevalent in women with recurrent miscarriage as confirmed by improved pregnancy outcome after antibiotic treatment. Reprod Sci 21:640–647CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Cocksedge KA, Saravelos SH, Wang Q et al (2008) Does free androgen index predict subsequent pregnancy outcome in women with recurrent miscarriage? Hum Reprod 23:797–802.  https://doi.org/10.1093/humrep/den022 CrossRefPubMedGoogle Scholar
  15. 15.
    Craig LB, Ke RW, Kutteh WH (2002) Increased prevalence of insulin resistance in women with a history of recurrent pregnancy loss. Fertil Steril 78:487–490CrossRefPubMedGoogle Scholar
  16. 16.
    Faridi RM, Agrawal S (2011) Killer immunoglobulin-like receptors (KIRs) and HLA-C allorecognition patterns implicative of dominant activation of natural killer cells contribute to recurrent miscarriages. Hum Reprod 26:491–497.  https://doi.org/10.1093/humrep/deq341 CrossRefPubMedGoogle Scholar
  17. 17.
    Gao Y, Wang PL (2015) Increased CD56(+) NK cells and enhanced Th1 responses in human unexplained recurrent spontaneous abortion. Genet Mol Res 14:18103–18109.  https://doi.org/10.4238/2015.December.22.36 CrossRefPubMedGoogle Scholar
  18. 18.
    GEEPGD (2017) ESHRE Guideline on the management of recurrent pregnancy loss, S 1–154Google Scholar
  19. 19.
    Goddijn M, Leschot NJ (2000) Genetic aspects of miscarriage. Baillieres Best Pract Res Clin Obstet Gynaecol 14:855–865.  https://doi.org/10.1053/beog.2000.0124 CrossRefPubMedGoogle Scholar
  20. 20.
    Goeckenjan M (2018) Modifikation von Risikofaktoren für frühe Fehlgeburten. Präkonzeptionelle Beratung und Lebensstiländerung. Gynäkologe.  https://doi.org/10.1007/s00129-018-4223-7 Google Scholar
  21. 21.
    Grimbizis GF, Gordts S, Di Spiezio Sardo A et al (2013) The ESHRE/ESGE consensus on the classification of female genital tract congenital anomalies. Hum Reprod 28:2032–2044.  https://doi.org/10.1093/humrep/det098 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Groot L de, Abalovich M, Alexander EK et al (2012) Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 97:2543–2565CrossRefPubMedGoogle Scholar
  23. 23.
    Hefler-Frischmuth K, Walch K, Hefler L et al (2017) Serologic markers of autoimmunity in women with recurrent pregnancy loss. Am J Reprod Immunol 77:e12635.  https://doi.org/10.1111/aji.12635 CrossRefGoogle Scholar
  24. 24.
    Hiby SE, Walker JJ, O’shaughnessy KM et al (2004) Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success. J Exp Med 200:957–965CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Hooker AB, Lemmers M, Thurkow AL et al (2014) Systematic review and meta-analysis of intrauterine adhesions after miscarriage: prevalence, risk factors and long-term reproductive outcome. Hum Reprod Update 20:262–278.  https://doi.org/10.1093/humupd/dmt045 CrossRefPubMedGoogle Scholar
  26. 26.
    Hooker AB, Aydin H, Brölmann HAM, Huirne JAF (2016) Long-term complications and reproductive outcome after the management of retained products of conception: a systematic review. Fertil Steril 105:156–164.e1–2.  https://doi.org/10.1016/j.fertnstert.2015.09.021 CrossRefPubMedGoogle Scholar
  27. 27.
    Johnston-MacAnanny EB, Hartnett J, Engmann LL et al (2010) Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization. Fertil Steril 93:437–441.  https://doi.org/10.1016/j.fertnstert.2008.12.131 CrossRefPubMedGoogle Scholar
  28. 28.
    Katano K, Suzuki S, Ozaki Y et al (2013) Peripheral natural killer cell activity as a predictor of recurrent pregnancy loss: a large cohort study. Fertil Steril 100:1629–1634.  https://doi.org/10.1016/j.fertnstert.2013.07.1996 CrossRefPubMedGoogle Scholar
  29. 29.
    Koo HS, Kwak-Kim J, Yi HJ et al (2015) Resistance of uterine radial artery blood flow was correlated with peripheral blood NK cell fraction and improved with low molecular weight heparin therapy in women with unexplained recurrent pregnancy loss. Am J Reprod Immunol 73:175–184CrossRefPubMedGoogle Scholar
  30. 30.
    Koopman LA, Kopcow HD, Rybalov B et al (2003) Human decidual natural killer cells are a unique NK cell subset with immunomodulatory potential. J Exp Med 198:1201–1212.  https://doi.org/10.1084/jem.20030305 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Kumar A, Meena M, Begum N et al (2011) Latent celiac disease in reproductive performance of women. Fertil Steril 95:922–927CrossRefPubMedGoogle Scholar
  32. 32.
    Kuon RJ, Schaumann J, Goeggl T et al (2015) Patients with idiopathic recurrent miscarriage show higher levels of DR+ activated T‑cells that are less responsive to mitogens. J Reprod Immunol 112:82–87.  https://doi.org/10.1016/j.jri.2015.08.006 CrossRefPubMedGoogle Scholar
  33. 33.
    Kuon RJ, Vomstein K, Weber M et al (2017) The “killer cell story” in recurrent miscarriage: association between activated peripheral lymphocytes and uterine natural killer cells. J Reprod Immunol 119:9–14.  https://doi.org/10.1016/j.jri.2016.11.002 CrossRefPubMedGoogle Scholar
  34. 34.
    Kuon RJ, Weber M, Heger J et al (2017) Uterine natural killer cells in patients with idiopathic recurrent miscarriage. Am J Reprod Immunol.  https://doi.org/10.1111/aji.12721 PubMedGoogle Scholar
  35. 35.
    Kurien BT, Scofield RH (2006) Autoantibody determination in the diagnosis of systemic lupus erythematosus. Scand J Immunol 64:227–235CrossRefPubMedGoogle Scholar
  36. 36.
    Kwak-Kim JYH, Chung-Bang HS, Ng SC et al (2003) Increased T helper 1 cytokine responses by circulating T cells are present in women with recurrent pregnancy losses and in infertile women with multiple implantation failures after IVF. Hum Reprod 18:767–773CrossRefPubMedGoogle Scholar
  37. 37.
    Lachapelle MH, Miron P, Hemmings R, Roy DC (1996) Endometrial T, B, and NK cells in patients with recurrent spontaneous abortion. Altered profile and pregnancy outcome. J Immunol 156:4027–4034PubMedGoogle Scholar
  38. 38.
    Lash GE, Bulmer JN (2011) Do uterine natural killer (uNK) cells contribute to female reproductive disorders? J Reprod Immunol 88:156–164CrossRefPubMedGoogle Scholar
  39. 39.
    Lash GE, Schiessl B, Kirkley M et al (2006) Expression of angiogenic growth factors by uterine natural killer cells during early pregnancy. J Leukoc Biol 80:572–580CrossRefPubMedGoogle Scholar
  40. 40.
    Laurino MY, Bennett RL, Saraiya DS et al (2005) Genetic evaluation and counseling of couples with recurrent miscarriage: recommendations of the National Society of Genetic Counselors. J Genet Couns 14:165–181CrossRefPubMedGoogle Scholar
  41. 41.
    Lee SK, Kim JY, Hur SE et al (2011) An imbalance in interleukin-17-producing T and Foxp3+ regulatory T cells in women with idiopathic recurrent pregnancy loss. Hum Reprod 26:2964–2971.  https://doi.org/10.1093/humrep/der301 CrossRefPubMedGoogle Scholar
  42. 42.
    Lyall F, Robson SC, Bulmer JN (2013) Spiral artery remodeling and trophoblast invasion in preeclampsia and fetal growth restriction: relationship to clinical outcome. Hypertension 62:1046–1054CrossRefPubMedGoogle Scholar
  43. 43.
    McQueen DB, Bernardi LA, Stephenson MD (2014) Chronic endometritis in women with recurrent early pregnancy loss and/or fetal demise. Fertil Steril 101:1026–1030.  https://doi.org/10.1016/j.fertnstert.2013.12.031 CrossRefPubMedGoogle Scholar
  44. 44.
    Metwally M, Cheong YC, Horne AW (2012) Surgical treatment of fibroids for subfertility. Cochrane Database Syst Rev.  https://doi.org/10.1002/14651858.CD003857.pub3 PubMedGoogle Scholar
  45. 45.
    Miyakis S, Lockshin MD, Atsumi T et al (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4(2):295–306CrossRefPubMedGoogle Scholar
  46. 46.
    Molazadeh M, Karimzadeh H, Azizi MR (2014) Prevalence and clinical significance of antinuclear antibodies in Iranian women with unexplained recurrent miscarriage. Iran J Reprod Med 12:221–226PubMedPubMedCentralGoogle Scholar
  47. 47.
    Moleski SM, Lindenmeyer CC, Veloski JJ et al (2015) Increased rates of pregnancy complications in women with celiac disease. Ann Gastroenterol 28:236–240PubMedPubMedCentralGoogle Scholar
  48. 48.
    Ng SC, Gilman-Sachs A, Thaker P et al (2002) Expression of intracellular Th1 and Th2 cytokines in women with recurrent spontaneous abortion, implantation failures after IVF/ET or normal pregnancy. Am J Reprod Immunol 48:77–86CrossRefPubMedGoogle Scholar
  49. 49.
    Oppelt P, von Have M, Paulsen M et al (2007) Female genital malformations and their associated abnormalities. Fertil Steril 87:335–342CrossRefPubMedGoogle Scholar
  50. 50.
    Ormesher L, Simcox LE, Tower C, Greer IA (2017) “To test or not to test”, the arguments for and against thrombophilia testing in obstetrics. Obstet Med 10:61–66.  https://doi.org/10.1177/1753495X17695696 CrossRefPubMedGoogle Scholar
  51. 51.
    Plaisier M, Dennert I, Rost E et al (2009) Decidual vascularization and the expression of angiogenic growth factors and proteases in first trimester spontaneous abortions. Hum Reprod 24:185–197.  https://doi.org/10.1093/humrep/den296 CrossRefPubMedGoogle Scholar
  52. 52.
    Practice Committee of the American Society for Reproductive Medicine (2012) Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril 98:1103–1111.  https://doi.org/10.1016/j.fertnstert.2012.06.048 CrossRefGoogle Scholar
  53. 53.
    Quenby S, Bates M, Doig T et al (1999) Pre-implantation endometrial leukocytes in women with recurrent miscarriage. Hum Reprod 14:2386–2391CrossRefPubMedGoogle Scholar
  54. 54.
    Quenby S, Nik H, Innes B et al (2009) Uterine natural killer cells and angiogenesis in recurrent reproductive failure. Hum Reprod 24:45–54.  https://doi.org/10.1093/humrep/den348 CrossRefPubMedGoogle Scholar
  55. 55.
    Raga F, Casañ EM, Bonilla-Musoles F (2009) Expression of vascular endothelial growth factor receptors in the endometrium of septate uterus. Fertil Steril 92:1085–1090CrossRefPubMedGoogle Scholar
  56. 56.
    RCOG G‑T (2011) The investigation and treatment of couples with recurrent first-trimester and second-trimester miscarriage. Guideline no 17. RCOG G‑T, LondonGoogle Scholar
  57. 57.
    Robberecht C, Pexsters A, Deprest J et al (2012) Cytogenetic and morphological analysis of early products of conception following hystero-embryoscopy from couples with recurrent pregnancy loss. Prenat Diagn 32:933–942.  https://doi.org/10.1002/pd.3936 CrossRefPubMedGoogle Scholar
  58. 58.
    Roberts LN, Patel RK, Arya R (2009) Venous thromboembolism and ethnicity. Br J Haematol 146:369–383.  https://doi.org/10.1111/j.1365-2141.2009.07786.x CrossRefPubMedGoogle Scholar
  59. 59.
    Robertson MJ, Ritz J (1990) Biology and clinical relevance of human natural killer cells. Blood 76:2421–2438PubMedGoogle Scholar
  60. 60.
    Robson A, Harris LK, Innes BA et al (2012) Uterine natural killer cells initiate spiral artery remodeling in human pregnancy. Faseb J 26:4876–4885CrossRefPubMedGoogle Scholar
  61. 61.
    Rocca C la, Carbone F, Longobardi S, Matarese G (2014) The immunology of pregnancy: regulatory T cells control maternal immune tolerance toward the fetus. Immunol Lett 162:41–48.  https://doi.org/10.1016/j.imlet.2014.06.013 CrossRefPubMedGoogle Scholar
  62. 62.
    Rodger MA, Langlois NJ (2015) Is thrombophilia associated with placenta-mediated pregnancy complications? A prospective cohort study: reply. J Thromb Haemost 13:1536–1537.  https://doi.org/10.1111/jth.13015 CrossRefPubMedGoogle Scholar
  63. 63.
    Rodger MA, Betancourt MT, Clark P et al (2010) 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 7:e1000292.  https://doi.org/10.1371/journal.pmed.1000292 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Rudnik-Schöneborn S, Swoboda M, Zschocke J (2018) Genetische Untersuchungen bei wiederholten Spontanaborten – Aktuelle Empfehlungen unter besonderer Berücksichtigung der Präimplantationsdiagnostik. Gynäkologe.  https://doi.org/10.1007/s00129-018-4205-9 Google Scholar
  65. 65.
    Saccone G, Berghella V, Maruotti GM et al (2017) Antiphospholipid antibody profile based obstetric outcomes of primary antiphospholipid syndrome: the PREGNANTS study. Am J Obstet Gynecol 216:525.e1–525.e12.  https://doi.org/10.1016/j.ajog.2017.01.026 CrossRefGoogle Scholar
  66. 66.
    Salim R, Regan L, Woelfer B et al (2003) A comparative study of the morphology of congenital uterine anomalies in women with and without a history of recurrent first trimester miscarriage. Hum Reprod 18:162–166CrossRefPubMedGoogle Scholar
  67. 67.
    Sarikaya E, Tokmak A, Aksoy RT et al (2017) The association between serological markers of celiac disease and idiopathic recurrent pregnancy loss. Fetal Pediatr Pathol 36:373–379.  https://doi.org/10.1080/15513815.2017.1346018 CrossRefPubMedGoogle Scholar
  68. 68.
    Seshadri S, Sunkara SK (2014) Natural killer cells in female infertility and recurrent miscarriage: a systematic review and meta-analysis. Hum Reprod Update 20:429–438CrossRefPubMedGoogle Scholar
  69. 69.
    Sugiura-Ogasawara M, Ozaki Y, Katano K et al (2011) Uterine anomaly and recurrent pregnancy loss. Semin Reprod Med 29:514–521CrossRefPubMedGoogle Scholar
  70. 70.
    Tang AW, Alfirevic Z, Quenby S (2011) Natural killer cells and pregnancy outcomes in women with recurrent miscarriage and infertility: a systematic review. Hum Reprod 26:1971–1980CrossRefPubMedGoogle Scholar
  71. 71.
    Thangaratinam S, Tan A, Knox E et al (2011) Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. BMJ 342:d2616CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Tian L, Shen H, Lu Q et al (2007) Insulin resistance increases the risk of spontaneous abortion after assisted reproduction technology treatment. J Clin Endocrinol Metab 92:1430–1433.  https://doi.org/10.1210/jc.2006-1123 CrossRefPubMedGoogle Scholar
  73. 73.
    Ticconi C, Rotondi F, Veglia M et al (2010) Antinuclear autoantibodies in women with recurrent pregnancy loss. Am J Reprod Immunol 64:384–392.  https://doi.org/10.1111/j.1600-0897.2010.00863.x CrossRefPubMedGoogle Scholar
  74. 74.
    Toth B, Jeschke U, Rogenhofer N et al (2010) Recurrent miscarriage: current concepts in diagnosis and treatment. J Reprod Immunol 85:25–32CrossRefPubMedGoogle Scholar
  75. 75.
    Wischmann T (2018) Psychologische Aspekte bei Frühabort. Gynäkologe.  https://doi.org/10.1007/s00129-017-4180-6 Google Scholar
  76. 76.
    Yuan J, Li J, Huang S‑Y, Sun X (2015) Characterization of the subsets of human NKT-like cells and the expression of Th1/Th2 cytokines in patients with unexplained recurrent spontaneous abortion. J Reprod Immunol 110:81–88.  https://doi.org/10.1016/j.jri.2015.05.001 CrossRefPubMedGoogle Scholar
  77. 77.
    Zhang C, Deng X, Zhang X et al (2016) Association between serum TNF-α levels and recurrent spontaneous miscarriage: a meta-analysis. Am J Reprod Immunol 75:86–93.  https://doi.org/10.1111/aji.12447 CrossRefPubMedGoogle Scholar
  78. 78.
    Zolghadri J, Momtahan M, Aminian K et al (2011) The value of hysteroscopy in diagnosis of chronic endometritis in patients with unexplained recurrent spontaneous abortion. Eur J Obstet Gynecol Reprod Biol 155:217–220.  https://doi.org/10.1016/j.ejogrb.2010.12.010 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2018

Authors and Affiliations

  1. 1.Abteilung für Gynäkologische Endokrinologie und FertilitätsstörungenUniversitätsfrauenklinik HeidelbergHeidelbergDeutschland
  2. 2.Gynäkologische Endokrinologie und ReproduktionsmedizinMedizinische Universität InnsbruckInnsbruckÖsterreich

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