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Wiederholtes Implantationsversagen – diagnostische und therapeutische Ansätze

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Reproduktionsmedizin

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Zusammenfassung

Die Implantation als erfolgreicher Beginn einer sich etablierenden Schwangerschaft stellt das Ergebnis eines durch zahlreiche Faktoren von Embryo und Endometrium beeinflussten Zusammenspieles dar. Dabei lässt sich im Einzelnen oft nicht eruieren, was Ursache der wiederholt ausbleibenden Einnistung ist und ab wann Krankheitswert vorliegt. Für verschiedene therapeutische Ansätze zur Verbesserung der Implantation gibt es keine oder nur wenige Interventionsstudien, die bei der vermuteten Kausalität umgekehrt auch den Nutzen der Behandlung beweisen. Das Kapitel stellt den aktuellen Kenntnisstand der Diagnostik sowie der therapeutischen Möglichkeiten zur Verbesserung der Implantation dar.

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Literatur

  • Ban-Frangez H, Tomazevic T, Virant-Klun I, Verdenik I, Ribic-Pucelj M, Bokal EV (2009) The outcome of singleton pregnancies after IVF/ICSI in women before and after hysteroscopic resection of a uterine septum compared to normal controls. Eur J Obstet Gynecol Reprod Biol 146:184–187

    Article  CAS  PubMed  Google Scholar 

  • Bouet PE, El Hachem H, Monceau E, Gariépy G, Kadoch IJ, Sylvestre C (2016) Chronic endometritis in women with recurrent pregnancy loss and recurrent implantation failure: prevalence and role of office hysteroscopy and immunohistochemistry in diagnosis. Fertil Steril 105:106–110

    Article  PubMed  Google Scholar 

  • Cakmak H, Taylor HS (2011) Implantation failure: molecular mechanisms and clinical treatment. Hum Reprod Update 17:242–253

    Article  CAS  PubMed  Google Scholar 

  • Caseiro AL, Regalo A, Pereira E, Esteves T, Fernandes F, Carvalho J (2015) Implication of sperm chromosomal abnormalities in recurrent abortion and multiple implantation failure. Reprod Biomed Online 31:481–485

    Article  PubMed  Google Scholar 

  • Cermik D, Selam B, Taylor HS (2003) Regulation of HOXA-10 expression by testosterone in vitro and in the endometrium of patients with polycystic ovary syndrome. J Clin Endocrinol Metab 88:238–243

    Article  CAS  PubMed  Google Scholar 

  • Cicinelli E, De Ziegler D, Nicoletti R, Colafiglio G, Saliani N, Resta L, Rizzi D, De Vito D (2008) Chronic endometritis: correlation among hysteroscopic, histologic, and bacteriologic findings in a prospective trial with 2190 consecutive office hysteroscopies. Fertil Steril 89:677–684

    Article  PubMed  Google Scholar 

  • Cicinelli E, Matteo M, Tinelli R, Lepera A, Alfonso R, Indraccolo U, Marrocchella S, Greco P, Resta L (2015) Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy. Hum Reprod 30:323–330

    Article  PubMed  Google Scholar 

  • Coulam CB, Jeyendran RS, Fishel LA, Roussev R (2006) Multiple thrombophilic gene mutations are risk factors for implantation failure. Reprod Biomed Online 12:322–327

    Article  PubMed  Google Scholar 

  • Daftary GS, Kayisli U, Seli E, Bukulmez O, Arici A, Taylor HS (2007) Salpingectomy increases peri-implantation endometrial HOXA10 expression in women with hydrosalpinx. Fertil Steril 87:367–372

    Article  CAS  PubMed  Google Scholar 

  • Di Nisio M, Rutjes AW, Ferrante N, Tiboni GM, Cuccurullo F, Porreca E (2011) Thrombophilia and outcomes of assisted reproduction technologies: a systematic review and meta-analysis. Blood 118:2670–2678

    Article  CAS  PubMed  Google Scholar 

  • Donaghay M, Lessey BA (2007) Uterine receptivity: alterations associated with benign gynecological disease. Semin Reprod Med 25:461–475

    Article  CAS  PubMed  Google Scholar 

  • El-Toukhy T, Campo R, Khalaf Y, Tabanelli C, Gianaroli L, Gordts SS, Gordts S, Mestdagh G, Mardesic T, Voboril J, Marchino GL, Benedetto C, Al-Shawaf T, Sabatini L, Seed PT, Gergolet M, Grimbizis G, Harb H, Coomarasamy A (2016) Hysteroscopy in recurrent in-vitro fertilisation failure (TROPHY): a multicentre, randomised controlled trial. Lancet 387:2614–2621

    Article  PubMed  Google Scholar 

  • Fatemi HM, Popovic-Todorovic B (2013) Implantation in assisted reproduction: a look at endometrial receptivity. Reprod Biomed Online 27:530–538

    Article  CAS  PubMed  Google Scholar 

  • Franasiak JM, Scott RT (2017) Contribution of immunology to implantation failure of euploid embryos. Fertil Steril 107:1279–1283

    Article  CAS  PubMed  Google Scholar 

  • Grandone E, Colaizzo D, Lo Bue A, Checola MG, Cittadini E, Margaglione M (2001) Inherited thrombophilia and in vitro fertilization implantation failure. Fertil Steril 76:201–202

    Article  CAS  PubMed  Google Scholar 

  • Hoogenhuijze NE van, Torrance HL, Mol F, Laven JSE, Scheenjes E, Traas MAF, Janssen C, Cohlen B, Teklenburg G, de Bruin JP, van Oppenraaij R, Maas JWM, Moll E, Fleischer K, van Hooff MH, de Koning C, Cantineau A, Lambalk CB, Verberg M, Nijs M, Manger AP, van Rumste M, van der Voet LF, Preys-Bosman A, Visser J, Brinkhuis E, den Hartog JE, Sluijmer A, Jansen FW, Hermes W, Bandell ML, Pelinck MJ, van Disseldorp J, van Wely M, Smeenk J, Pieterse QD, Boxmeer JC, Groenewoud ER, Eijkemans MJC, Kasius JC, Broekmans FJM (2017) Endometrial scratching in women with implantation failure after a first IVF/ICSI cycle; does it lead to a higher live birth rate? The SCRaTCH study: a randomized controlled trial (NTR 5342). BMC Womens Health 17:47

    Google Scholar 

  • Jacobson TZ, Duffy JM, Barlow D, Farquhar C, Koninckx PR, Olive D (2010) Laparoscopic surgery for subfertility associated with endometriosis. Cochrane Database Syst Rev (1):CD001398

    Google Scholar 

  • Johnson N, van Voorst S, Sowter MC, Strandell A, Mol BW (2010) Surgical treatment for tubal disease in women due to undergo in vitro fertilisation. Cochrane Database Syst Rev (1):CD002125

    Google Scholar 

  • Johnston-MacAnanny EB, Hartnett J, Engmann LL, Nulsen JC, Sanders MM, Benadiva CA (2010) Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization. Fertil Steril 93:437–441

    Article  PubMed  Google Scholar 

  • Kitaya K, Matsubayashi H, Yamaguchi K, Nishiyama R, Takaya Y, Ishikawa T, Yasuo T, Yamada H (2016) Chronic endometritis: potential cause of infertility and obstetric and neonatal complications. Am J Reprod Immunol 75:13–22

    Article  PubMed  Google Scholar 

  • Kitaya K, Matsubayashi H, Takaya Y, Nishiyama R, Yamaguchi K, Takeuchi T, Ishikawa T (2017) Live birth rate following oral antibiotic treatment for chronic endometritis in infertile women with repeated implantation failure. Am J Reprod Immunol 2017 Nov; 78(5). https://doi.org/10.1111/aji.12719. Epub 2017 Jun 13

    Article  CAS  Google Scholar 

  • Kohn TP, Kohn JR, Darilek S, Ramasamy R, Lipshultz L (2016) Genetic counseling for men with recurrent pregnancy loss or recurrent implantation failure due to abnormal sperm chromosomal aneuploidy. J Assist Reprod Genet 33:571–576

    Article  PubMed  PubMed Central  Google Scholar 

  • Lessey BA, Kim JJ (2017) Endometrial receptivity in the eutopic endometrium of women with endometriosis: it is affected, and let me show you why. Fertil Steril 108:19–27

    Article  PubMed  PubMed Central  Google Scholar 

  • Macklon N (2017) Recurrent implantation failure is a pathology with a specific transcriptomic signature. Fertil Steril 108:9–14

    Article  PubMed  Google Scholar 

  • Magdi Y, El-Damen A, Fathi AM, Abdelaziz AM, Abd-Elfatah Youssef M, Abd-Allah AA, Ahmed Elawady M, Ahmed Ibrahim M, Edris Y (2017) Revisiting the management of recurrent implantation failure through freeze-all policy. Fertil Steril 108:72–77

    Article  PubMed  Google Scholar 

  • Mollo A, De Franciscis P, Colacurci N, Cobellis L, Perino A, Venezia R, Alviggi C, De Placido G (2009) Hysteroscopic resection of the septum improves the pregnancy rate of women with unexplained infertility: a prospective controlled trial. Fertil Steril 91:2628–2631

    Article  PubMed  Google Scholar 

  • Nastri CO, Lensen SF, Gibreel A, Raine-Fenning N, Ferriani RA, Bhattacharya S, Martins WP (2015) Endometrial injury in women undergoing assisted reproductive techniques. Cochrane Database Syst Rev (3):CD009517

    Google Scholar 

  • Nawroth F, Frahm SO (2017) Die chronische Endometritis bei wiederholten Aborten und Implantationsversagen. Frauenarzt 59:649–651

    Google Scholar 

  • Nawroth F, von Wolff M (2018) Seminal plasma activity to improve implantation in In vitro fertilisation – how can it be used in daily practice? Front Endocrinol (Lausanne) 9:208.

    Article  Google Scholar 

  • Pabuçcu R, Gomel V (2004) Reproductive outcome after hysteroscopic metroplasty in women with septate uterus and otherwise unexplained infertility. Fertil Steril 81:1675–1678

    Article  PubMed  Google Scholar 

  • Panagiotopoulou N, Karavolos S, Choudhary M (2015) Endometrial injury prior to assisted reproductive techniques for recurrent implantation failure: a systematic literature review. Eur J Obstet Gynecol Reprod Biol 193:27–33

    Article  PubMed  Google Scholar 

  • Papanikolaou EG, Bourgain C, Kolibianakis E, Tournaye H, Devroey P (2005) Steroid receptor expression in late follicular phase endometrium in GnRH antagonist IVF cycles is already altered, indicating initiation of early luteal phase transformation in the absence of secretory changes. Hum Reprod 20:1541–1547

    Article  CAS  PubMed  Google Scholar 

  • Polanski LT, Baumgarten MN, Quenby S, Brosens J, Campbell BK, Raine-Fenning NJ (2014) What exactly do we mean by ‚recurrent implantation failure‘? A systematic review and opinion. Reprod Biomed Online 28:409–423

    Article  PubMed  Google Scholar 

  • Potdar N, Gelbaya TA, Konje JC, Nardo LG (2013) Adjunct low-molecular-weight heparin to improve live birth rate after recurrent implantation failure: a systematic review and meta-analysis. Hum Reprod Update 19:674–684

    Article  CAS  PubMed  Google Scholar 

  • Rackow BW, Taylor HS (2010) Submucosal uterine leiomyomas have a global effect on molecular determinants of endometrial receptivity. Fertil Steril 93:2027–2034

    Article  CAS  PubMed  Google Scholar 

  • Robertson SA, Jin M, Yu D, Moldenhauer LM, Davies MJ, Hull ML, Norman RJ (2016) Corticosteroid therapy in assisted reproduction – immune suppression is a faulty premise. Hum Reprod 31:2164–2173

    Article  PubMed  Google Scholar 

  • Ruiz-Alonso M, Blesa D, Díaz-Gimeno P, Gómez E, Fernández-Sánchez M, Carranza F, Carrera J, Vilella F, Pellicer A, Simón C (2013) The endometrial receptivity array for diagnosis and personalized embryo transfer as a treatment for patients with repeated implantation failure. Fertil Steril 100:818–824

    Article  PubMed  Google Scholar 

  • Saccone G, Di Spiezio Sardo A, Ciardulli A, Caissutti C, Spinelli M, Surbek D, von Wolff M (2017) Effectiveness of seminal plasma in IVF treatment: a systematic review and meta-analysis. BJOG [Epub vor Druck]

    Google Scholar 

  • Shapiro BS, Garner FC (2017) Recurrent implantation failure is another indication for the freeze-all strategy. Fertil Steril 108:44

    Article  PubMed  Google Scholar 

  • Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S (2011a) Evidence of impaired endometrial receptivity after ovarian stimulation for in vitro fertilization: a prospective randomized trial comparing fresh and frozen-thawed embryo transfer in normal responders. Fertil Steril 96:344–348

    Article  PubMed  Google Scholar 

  • Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C, Thomas S (2011b) Evidence of impaired endometrial receptivity after ovarian stimulation for in vitro fertilization: a prospective randomized trial comparing fresh and frozen-thawed embryo transfers in high responders. Fertil Steril 96:516–518

    Article  PubMed  Google Scholar 

  • Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C (2014) Freeze-all can be a superior therapy to another fresh cycle in patients with prior fresh blastocyst implantation failure. Reprod Biomed Online 29:286–290

    Article  PubMed  Google Scholar 

  • Song D, Feng X, Zhang Q, Xia E, Xiao Y, Xie W, Li TC (2018) Prevalence and confounders of chronic endometritis in premenopausal women with abnormal bleeding or reproductive failure. Reprod Biomed Online 36:78–83

    Article  PubMed  Google Scholar 

  • Sugiura-Ogasawara M, Ozaki Y, Kitaori T, Kumagai K, Suzuki S (2010) Midline uterine defect size is correlated with miscarriage of euploid embryos in recurrent cases. Fertil Steril 93:1983–1988

    Article  PubMed  Google Scholar 

  • Tan BK, Vandekerckhove P, Kennedy R, Keay SD (2005) Investigation and current management of recurrent IVF treatment failure in the UK. BJOG 112:773–780

    Article  PubMed  Google Scholar 

  • Taylor HS, Bagot C, Kardana A, Olive D, Arici A (1999) HOX gene expression is altered in the endometrium of women with endometriosis. Hum Reprod 14:1328–1331

    Article  CAS  PubMed  Google Scholar 

  • Teh WT, McBain J, Rogers P (2016) What is the contribution of embryo-endometrial asynchrony to implantation failure? J Assist Reprod Genet 33:1419–1430

    Article  PubMed  PubMed Central  Google Scholar 

  • Toth B, Würfel W, Germeyer A, Hirv K, Makrigiannakis A, Strowitzki T (2011) Disorders of implantation – are there diagnostic and therapeutic options? J Reprod Immunol 90:117–123

    Article  CAS  PubMed  Google Scholar 

  • Valbuena D, Valdes CT, Simon C (2017) Introduction: Endometrial function: facts, urban legends, and an eye to the future. Fertil Steril 108:4–8

    Article  PubMed  Google Scholar 

  • Valdes CT, Schutt A, Simon C (2017) Implantation failure of endometrial origin: it is not pathology, but our failure to synchronize the developing embryo with a receptive endometrium. Fertil Steril 108:15–18

    Article  PubMed  Google Scholar 

  • Vicetti Miguel RD, Chivukula M, Krishnamurti U, Amortegui AJ, Kant JA, Sweet RL, Wiesenfeld HC, Phillips JM, Cherpes TL (2011) Limitations of the criteria used to diagnose histologic endometritis in epidemiologic pelvic inflammatory disease research. Pathol Res Pract 207:680–685

    Article  PubMed  PubMed Central  Google Scholar 

  • Vitagliano A, Saccardi C, Noventa M, Di Spiezio Sardo A, Saccone G, Cicinelli E, Pizzi S, Andrisani A, Litta PS (2018) Effects of chronic endometritis therapy on in vitro fertilization outcome in women with repeated implantation failure: a systematic review and meta-analysis. Fertil Steril [Epub vor Druck].

    Article  PubMed  Google Scholar 

  • Wolff M von, Rösner S, Thöne C, Pinheiro RM, Jauckus J, Bruckner T, Biolchi V, Alia A, Strowitzki T (2009) Intravaginal and intracervical application of seminal plasma in in vitro fertilization or intracytoplasmic sperm injection treatment cycles – a double-blind, placebo-controlled, randomized pilot study. Fertil Steril 91:167–172

    Google Scholar 

  • Wong KM, van Wely M, Mol F, Repping S, Mastenbroek S (2017) Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database Syst Rev (3):CD011184

    Google Scholar 

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Nawroth, F., Ludwig, M. (2018). Wiederholtes Implantationsversagen – diagnostische und therapeutische Ansätze. In: Diedrich, K., Ludwig, M., Griesinger, G. (eds) Reproduktionsmedizin. Springer Reference Medizin. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-55601-6_41-1

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