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Verbesserung der Implantation bei IVF/ICSI-Patientinnen

Endokrinologische und immunmodulierende Maßnahmen

Improved implantation in IVF/ICSI patients

Endocrinological and immunomodulating treatment options

  • Leitthema
  • Published:
Gynäkologische Endokrinologie Aims and scope

Zusammenfassung

Wesentliche Ziele der assistierten Reproduktion sind das Erreichen von qualitativ hochwertigen und entwicklungsfähigen Embryonen sowie die Verbesserung der Implantations- und Lebendgeburtenrate. Insbesondere bei Paaren mit rezidivierendem Implantationsversagen (RIF) stellt sich die Frage, inwieweit der Einsatz neuer Therapienmodalitäten zu einer Verbesserung der Schwangerschaftsrate beiträgt. Bei dem Embryo handelt es sich um die Sonderform eines semiallogenen Transplantats, das im Endometrium normalerweise nicht abgestoßen wird. Entscheidend ist hierbei, dass das mütterliche Immunsystem, und hier insbesondere die immunkompetenten Zellen im Bereich des Endometriums, den Embryo nicht abstoßen. Daher fokussieren sich neue Therapieansätze auf eine Beeinflussung der immunkompetenten Zellen an der fetomaternalen Grenzzone im Sinne einer Herunterregulierung der mütterlichen Immunantwort. Anhand der aktuellen Datenlage wollen wir uns in diesem Übersichtsbeitrag auf den Einsatz von Gestagenen, Östrogenen, Kortikosteroiden und TNF-α-Blockern bei Patientinnen unter IVF/ICSI-Behandlung konzentrieren.

Abstract

Assisted reproduction focuses on developing new methods of controlled ovarian stimulation, obtaining high-quality embryos and improving implantation rates. Treatment options during the luteal phase are part of ongoing research, especially in patients with recurrent implantation failure (RIF). Although human embryos are semiallogenic allografts, they are not rejected by the endometrium. Implantation is determined by the maternal immune system, mainly the cellular and humoral immune responses at the fetomaternal interphase. New treatment strategies in assisted reproduction are therefore directed at the maternal immune system in an attempt to optimize the implantation process. This review highlights recent studies on gestagens, estrogens, corticosteroids and tumor necrosis factor α (TNF α) inhibitors in patients during controlled ovarian hyperstimulation for IVF/ICSI.

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Literatur

  1. Edmonds DK, Lindsay KS, Miller JF et al (1982) Early embryonic mortality in women. Fertil Steril 38(4):447–453

    PubMed  CAS  Google Scholar 

  2. Choudhury SR, Knapp LA (2001) Human reproductive failure I: immunological factors. Hum Reprod Update 7(2):113–134

    Article  PubMed  CAS  Google Scholar 

  3. van Mourik MSM, Heijnen CJ, Macklon NS (2008) Embryonic implantation: cytokines, adhesion molecules and immune cells in establishing an implantation environment. J Leukocyte Biol (e pub ahead of print)

  4. Szekeres-Bartho J (2008) Regulation of NK cell cytotoxicity during pregnancy. Reprod Biomed Online 16(2):211–217

    Article  PubMed  CAS  Google Scholar 

  5. Szekeres-Bartho J, Balasch J (2008) Progestagen therapy for recurrent miscarriage. Hum Reprod Update 14(1):27–35

    Article  PubMed  CAS  Google Scholar 

  6. Boomsma CM, Macklon NS (2008) Does glucocorticoid therapy in the peri-implantation period have an impact on IVF outcomes? Curr Opin Obstet Gynecol 20(3):249–256

    Article  PubMed  Google Scholar 

  7. Kwak-Kim JY, 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(4):767–773

    Article  PubMed  CAS  Google Scholar 

  8. Fasouliotis SJ, Spandorfer SD, Witkin SS et al (2004) Maternal serum levels of interferon-gamma and interleukin-2 soluble receptor-alpha predict the outcome of early IVF pregnancies. Hum Reprod 19(6):1357–1363

    Article  PubMed  CAS  Google Scholar 

  9. Kalu E, Bhaskaran S, Thum MY et al (2008) Serial estimation of Th1:th2 cytokines profile in women undergoing in-vitro fertilization-embryo transfer. Am J Reprod Immunol 59(3):206–211

    Article  PubMed  CAS  Google Scholar 

  10. von Wolff M, Thaler CJ, Strowitzki T et al (2000) Regulated expression of cytokines in human endometrium throughout the menstrual cycle: dysregulation in habitual abortion. Mol Hum Reprod 6(7):627–634

    Article  Google Scholar 

  11. Winger EE, Reed JL, Ashoush S et al (2009) Treatment with adalimumab (Humira) and intravenous immunoglobulin improves pregnancy rates in women undergoing IVF. Am J Reprod Immunol 61(2):113–120

    Article  PubMed  CAS  Google Scholar 

  12. Daya S, Gunby J (2004) Luteal phase support in assisted reproduction cycles. Cochrane Database Syst Rev (3):CD004830

    Google Scholar 

  13. Chakravarty BN, Shirazee HH, Dam P et al (2005) Oral dydrogesterone versus intravaginal micronised progesterone as luteal phase support in assisted reproductive technology (ART) cycles: results of a randomised study. J Steroid Biochem Mol Biol 97(5):416–420

    Article  PubMed  CAS  Google Scholar 

  14. Straczek C, Oger E, Yon de Jonage-Canonico MB et al (2005) Prothrombotic mutations, hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration. Circulation 112(22):3495–3500

    Article  PubMed  CAS  Google Scholar 

  15. Gorkemli H, Ak D, Akyurek C et al (2004) Comparison of pregnancy outcomes of progesterone or progesterone + estradiol for luteal phase support in ICSI-ET cycles. Gynecol Obstet Invest 58(3):140–144

    Article  PubMed  CAS  Google Scholar 

  16. Fatemi HM, Camus M, Kolibianakis EM et al (2007) The luteal phase of recombinant follicle-stimulating hormone/gonadotropin-releasing hormone antagonist in vitro fertilization cycles during supplementation with progesterone or progesterone and estradiol. Fertil Steril 87(3):504–508

    Article  PubMed  CAS  Google Scholar 

  17. Fatemi HM, Popovic-Todorovic B, Papanikolaou E et al (2007) An update of luteal phase support in stimulated IVF cycles. Hum Reprod Update 13(6):581–590

    Article  PubMed  CAS  Google Scholar 

  18. Boomsma CM, Keay SD, Macklon NS (2007) Peri-implantation glucocorticoid administration for assisted reproductive technology cycles. Cochrane Database Syst Rev (1):CD005996

    Google Scholar 

  19. Ando T, Suganuma N, Furuhashi M et al (1996) Successful glucocorticoid treatment for patients with abnormal autoimmunity on in vitro fertilization and embryo transfer. J Assist Reprod Genet 13(10):776–781

    Article  PubMed  CAS  Google Scholar 

  20. Bider D, Blankstein J, Levron J, Tur-Kaspa I (1997) Gonadotropins and glucocorticoid therapy for „low responders“ – a controlled study. J Assist Reprod Genet 14(6):328–331

    Article  PubMed  CAS  Google Scholar 

  21. Fridstrom M, Carlstrom K, Sjoblom P, Hillensjo T (1999) Effect of prednisolone on serum and follicular fluid androgen concentrations in women with polycystic ovary syndrome undergoing in-vitro fertilization. Hum Reprod 14(6):1440–1444

    Article  PubMed  CAS  Google Scholar 

  22. Rein MS, Jackson KV, Sable DB et al (1996) Dexamethasone during ovulation induction for in-vitro fertilization: a pilot study. Hum Reprod 11(2):253–255

    PubMed  CAS  Google Scholar 

  23. Seckl JR (2004) Prenatal glucocorticoids and long-term programming. Eur J Endocrinol 151 (Suppl 3):U49–U62

    Article  PubMed  CAS  Google Scholar 

  24. Ashkar AA, Di Santo JP, Croy BA (2000) Interferon gamma contributes to initiation of uterine vascular modification, decidual integrity, and uterine natural killer cell maturation during normal murine pregnancy. J Exp Med 192(2):259–270

    Article  PubMed  CAS  Google Scholar 

  25. Bulla R, Bossi F, Radillo O et al (2003) Placental trophoblast and endothelial cells as target of maternal immune response. Autoimmunity 36(1):11–18

    Article  PubMed  CAS  Google Scholar 

  26. Salamonsen LA, Hannan NJ, Dimitriadis E (2007) Cytokines and chemokines during human embryo implantation: roles in implantation and early placentation. Semin Reprod Med 25(6):437–444

    Article  PubMed  CAS  Google Scholar 

  27. Hill JA, Haimovici F, Anderson DJ (1987) Products of activated lymphocytes and macrophages inhibit mouse embryo development in vitro. J Immunol 139(7):2250–2254

    PubMed  CAS  Google Scholar 

  28. Wegmann TG, Lin H, Guilbert L, Mosmann TR (1993) Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol Today 14(7):353–356

    Article  PubMed  CAS  Google Scholar 

  29. Raghupathy R (1997) Th1-type immunity is incompatible with successful pregnancy. Immunol Today 18(10):478–482

    Article  PubMed  CAS  Google Scholar 

  30. Clark DA, Chaouat G (1989) What do we know about spontaneous abortion mechanisms? Am J Reprod Immunol 19(1):28–37

    PubMed  CAS  Google Scholar 

  31. Whiteside TL (1994) Cytokine measurements and interpretation of cytokine assays in human disease. J Clin Immunol 14(6):327–339

    Article  PubMed  CAS  Google Scholar 

  32. Abrahams VM, Aldo PB, Murphy SP et al (2008) TLR6 modulates first trimester trophoblast responses to peptidoglycan. J Immunol 180(9):6035–6043

    PubMed  CAS  Google Scholar 

  33. Aluvihare VR, Kallikourdis M, Betz AG (2004) Regulatory T cells mediate maternal tolerance to the fetus. Nat Immunol 5(3):266–271

    Article  PubMed  CAS  Google Scholar 

  34. Saito S, Sasaki Y, Sakai M (2005) CD4(+)CD25high regulatory T cells in human pregnancy. J Reprod Immunol 65(2):111–120

    Article  PubMed  CAS  Google Scholar 

  35. 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(2):77–86

    Article  PubMed  Google Scholar 

  36. Smitz J, Bourgain C, Van Waesberghe L et al (1993) A prospective randomized study on oestradiol valerate supplementation in addition to intravaginal micronized progesterone in buserelin and HMG induced superovulation. Hum Reprod 8(1):40–45

    PubMed  CAS  Google Scholar 

  37. Farhi J, Weissman A, Steinfeld Z et al (2000) Estradiol supplementation during the luteal phase may improve the pregnancy rate in patients undergoing in vitro fertilization-embryo transfer cycles. Fertil Steril 73(4):761–766

    Article  PubMed  CAS  Google Scholar 

  38. Lukaszuk K, Liss J, Lukaszuk M, Maj B (2005) Optimization of estradiol supplementation during the luteal phase improves the pregnancy rate in women undergoing in vitro fertilization-embryo transfer cycles. Fertil Steril 83(5):1372–1376

    Article  PubMed  CAS  Google Scholar 

  39. Lewin A, Benshushan A, Mezker E et al (1994) The role of estrogen support during the luteal phase of in vitro fertilization-embryo transplant cycles: a comparative study between progesterone alone and estrogen and progesterone support. Fertil Steril 62(1):121–125

    PubMed  CAS  Google Scholar 

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  1. Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Klinikum der Universität München-Campus Großhadern, Gynäkologische Endokrinologie und Reproduktionsmedizin , Marchioninistraße 15, 81377, München, Deutschland

    N. Rogenhofer , R. Ochsenkühn &  B. Toth

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  1. N. Rogenhofer
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  2. R. Ochsenkühn
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  3. B. Toth
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Correspondence to B. Toth.

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Rogenhofer , N., Ochsenkühn, R. & Toth, B. Verbesserung der Implantation bei IVF/ICSI-Patientinnen. Gynäkologische Endokrinologie 7, 63–67 (2009). https://doi.org/10.1007/s10304-008-0295-0

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  • DOI: https://doi.org/10.1007/s10304-008-0295-0

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