Zusammenfassung
Wiederholte Spontanaborte (RSA: „recurrent spontaneous abortions“) sind als pathologische Entität zwar nicht häufig, für die betroffenen Frauen/Paare jedoch immer traumatisierend, unter anderem wegen der quälenden Ungewissheit des Wieso und Warum. Sehr ähnlich ist das beim wiederholten Implantationsversagen (RIF; „repetitive implantation failure“) im Rahmen von ART-Behandlungen. Und gar nicht so selten kommt es bei RIF-Patientinnen, wenn dann doch einmal eine Schwangerschaft eintritt, zu einem Abortgeschehen.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
Literatur
Agrawal D, Prakash S, Misra MK, Pahdke SR, Agrawal S (2015) Implication of HLA-G 5´upstream regulatory region polymorphisms in idiopathic recurrent abortions. ReprodBioMedOnline 30(1):82–91 https://doi.org/10.1016/j.rbmo.2014.09.015
Ahmadi M, Abdolmohammadi-Vahid S, Ghaebi M, Aghebati-Maleki L, Afkham A, Danaii S, Abdollahi-Fard S, Heidari L, Jadidi-Niaragh F, Younesi V, Nouri M, Yousefi M (2017) Effect of Intravenous immunoglobulin on Th1 and Th2 lymphocytes and improvement of pregnancy outcome in recurrent pregnancy loss (RPL). Biomed Pharmacother 92:1095–1102. https://doi.org/10.1016/j.biopha.2017.06.001
Akbari S, Ahmadi SAY, Shahsavar F (2018) The Relationship of Maternal KIR and Parental HLA-C Genes With Risk of Recurrent Spontaneous Abortion: A Regional Study in Lorestan Province, Iran. Crescent J Med Biol Sci 5(3):194–197
Alecsandru D, Garrido N, Vicario JL, Barrio A, Aparicio P, Requena A, García-Velasco JA (2014) Maternal KIR haplotype influences live birth rate after double embryo transfer in IVF cycles in patients with recurrent miscarriages and implantation failure. Hum Reprod 29(12):2637–2643. https://doi.org/10.1093/humrep/deu251
Aldrich CL, Stephenson MD, Karrison T, Odem RR, Branch DW, Scott JR, Schreiber JR, Ober C (2001) HLA-G genotypes and pregnancy outcome in couples with unexplained recurrent miscarriage. Mol Hum Reprod 7(12):1167–1172. https://doi.org/10.1093/molehr/7.12.1167
Alves R, Grimalt R (2018) A Review of Platelet-Rich Plasma: History, Biology, Mechanism of Action, and Classification. Skin Appendage Disord 4(1):18–24. https://doi.org/10.1159/000477353
Andronache A, Bi WG, Wie SQ (2020) Heparin and pregnancy outcomes: a systematic review and meta-analysis. Am J Obstet Gynecol 1(suppl.):S552–S553. https://doi.org/10.1016/j.ajog.2019.11.899
Aranda F, Udry S, Perés Wingeyer S, Amshoff LC, Bogdanova N, Wieacker P, Latino JO, Markoff A, de Larrañaga G (2018) Maternal carriers of the ANXA5 M2 haplotype are exposed to a greater risk for placenta-mediated pregnancy complications. J Assist Reprod Genet 35(5):921–928. https://doi.org/10.1007/s10815-018-1142-4
Armstrong S, Langlois A, Laparidou D et al (2017) Assessment of consent models as an ethical consideration in the conduct of prehospital ambulance randomised controlled clinical trials: a systematic review. BMC Med Res Methodol 17:142. https://doi.org/10.1186/s12874-017-0423-4
Aruna M, Nagaraja T, Bhaskar SA, Tarakeswari S, Reddy AG, Thangaraj K, Singh L, Reddy BM (2011) Novel alleles of HLA-DQ and -DR loci show association with recurrent miscarriages among South Indian women. Hum Reprod 26(44):765–774. https://doi.org/10.1093/humrep/der024
Aruna M, Sirisha PV, Andal Bhaskar S, Tarakeswari S, Thangaraj K, Reddy BM (2011) Role of 14-bp insertion/deletion polymorphism in HLA-G among Indian women with recurrent spontaneous abortions. Tissue Antigens 77(2):131–135. https://doi.org/10.1111/j.1399-0039.2010.01584.x
Atik RB, Christiansen OB, Elson J, Kolte AM, Lewis S, Middeldorp S, Nelen W, Peramo B, Quenby S, Vermeulen N, Goddijn M (2018) ESHRE guideline: recurrent pregnancy loss. Human Reproduction Open (Issue 2):hoy004. https://doi.org/10.1093/hropen/hoy004
Barnea ER, Hayrabedyan S, Todorova K, Almogi-Hazan O, Or R, Guingab J, McElhinney J, Fernandez N, Barder T (2016) PreImplantation factor (PIF*) regulates systemic immunity and targets protective regulatory and cytoskeleton proteins. Immunobiol 221(7):778–93. https://doi.org/10.1016/j.imbio.2016.02.004
Barnea ER, Kirk D, Paidas MJ (2012) Preimplantation factor (PIF) promoting role in embryo implantation: increases endometrial integrin-α2β3, amphiregulin and epiregulin while reducing betacellulin expression via MAPK in decidua. Reprod Biol Endocrinol 10(1):50. https://doi.org/10.1186/1477-7827-10-50
Barnea ER, Lahijani KI, Roussev R, Barnea JD, Coulam CB (1994) Use of lymphocyte platelet binding assay for detecting a preimplantation factor: a quantitative assay. Am J Reprod Immunol 32(3):133–138. https://doi.org/10.1111/j.1600-0897.1994.tb01103.x
Barton BM, Xu R, Wherry EJ, Porrett PM (2017) Pregnancy promotes tolerance to future offspring by programming selective dysfunction in long-lived maternal T cells. J Leukoc Biol 101(4):975–987. https://doi.org/10.1189/jlb.1A0316-135R
Bayry J, Mouthon L, Kaveri SV (2012) Intravenous immunoglobulin expands regulatory T cells in autoimmune rheumatic disease. J Rheumatol 39(2):450–451. https://doi.org/10.3899/jrheum.111123.Erratum.In:JRheumatol.2015Jan;42(1):141
Boldison J, Da Rosa LC, Davies J, Wen L, Wong FS (2020) Dendritic cells license regulatory B cells to produce IL-10 and mediate suppression of antigen-specific CD8 T cells. Cell Mol Immunol 17(8):843–855. https://doi.org/10.1038/s41423-019-0324-z
Bompeixe EP, Carvalho Santos PS, Vargas RG, von Linsingen R, Zeck SC, Wowk PF, Bicalho MG (2013) HLA class II polymorphisms and recurrent spontaneous abortion in a Southern Brazilian cohort. Int J Immunogenet 40(3):186–191. https://doi.org/10.1111/j.1744-313X.2012.01155.x
Boxer LA, Bolyard AA, Kelley ML, Marrero TM, Phan L, Bond JM, Newburger PE, Dale DC (2015 Jan) Use wiederholtenof granulocyte colony-stimulating factor during pregnancy in women with chronic neutropenia. Obstet Gynecol 125(1):197–203. https://doi.org/10.1097/AOG.0000000000000602
Boxkup K, Blanchard V, Castillo-Binder P, Alexander H, Engeland K, Schug S (2020) N- and O-glycosylation patterns and functional testing of CGB7 versus CGB3/5/8 variants of the human chorionic gonadotropin (hCG) beta subunit. Glycoconj J 37(5):599–610. https://doi.org/10.1007/s10719-020-09936-w
Branch DW, Peaceman AM, Druzin M, Silver RK, El-Sayed Y, Silver RM, Esplin MS, Spinnato J, Harger J (2000) A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. The Pregnancy Loss Study Group. Am J Obstet Gynecol 182(1 Pt 1):122–127. https://doi.org/10.1016/s0002-9378(00)70500-x
Cai J, Zhu Y, Pingyuan L, Guo CP, Hu XD, Tonghua W, Yin B, Li GG, Zeng Y (2012) Study on the HLA-DQA1 and HLA-DQB1 haplotypes in patients with recurrent miscarriage. J Reprod Immunol 94:122. https://doi.org/10.1016/j.jri.2012.03.472
Canella PRBC, Barini R, Carvalho PDO, Razolli DS (2021) Lipid emulsion therapy in women with recurrent pregnancy loss and repeated implantation failure: The role of abnormal natural killer cell activity. J Cell Mol Med 25:2290–2296. https://doi.org/10.1111/jcmm.16257
Carbone J, Sarmiento E, Gallego A, Lanio N, Navarro J, García S, Fernandez-Cruz E (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
Cavalcante MB, Cavalcante C, Sarno M, da Silva ACB, Barini R (2020) Antinuclear antibodies and recurrent miscarriage: Systematic review and meta-analysis. Am J Reprod Immunol 83:e13215
Cavalcante MB, Sarno M, Araujo Júnior E, Da Silva CF, Barini R (2017) Lymphocyte immunotherapy in the treatment of recurrent miscarriage: systematic review and meta-analysis. Arch Gynecol Obstet 295(2):511–518. https://doi.org/10.1007/s00404-016-4270-z
Cavalcante MB, Sarno M, Niag M, Pimentel K, Luz I, Figueiredo B, Michelon T, Lima S, Machado IN, Araujo Júnior E, Barini R, Neumann J (2018) Lymphocyte immunotherapy for recurrent miscarriages: Predictors of therapeutic success. Am J Reprod Immunol 79(6):e12833. https://doi.org/10.1111/aji.12833
Chakravarty EF, Murray ER, Kelman A, Farmer P (2011) Pregnancy outcomes after maternal exposure to rituximab. Blood 117(5):1499–1506. https://doi.org/10.1182/blood-2010-07-295444
Chan RW, Schwab KE, Gargett CE (2004) Clonogenicity of human endometrial epithelial and stromal cells. Biol Reprod 70(6):1738–1750. https://doi.org/10.1095/biolreprod.103.024109
Chaouat G, Lédée-Bataille N, Zourbas S, Ostojic S, Dubanchet S, Martal J, Frydman R (2003) Cytokines, implantation and early abortion: re-examining the Th1/Th2 paradigm leads to question the single pathway, single therapy concept. Am J Reprod Immunol 50(3):177–186. https://doi.org/10.1034/j.1600-0897.2003.00080.x
Chen L, Hu R (2011) Thyroid autoimmunity and miscarriage: A meta-analysis. Clin Endocrinol (Oxf) 74:513–519
Chen S, Yang G, Wu P, Sun Y, Dai F, He Y, Qian H, Liu Y, Shi G (2020) Antinuclear antibodies positivity is a risk factor of recurrent pregnancy loss: A meta-analysis. Semin, Arthritis Rheum
Chen X, Liang PY, Li GG, Diao LH, Liu CC, Huang CY, Wu TH, Xu J, Zeng Y (2016) Association of HLA-DQ alleles with the presence of an anti-β2-glycoprotein I antibody in patients with recurrent miscarriage. HLA 87(1):19–24. https://doi.org/10.1111/tan.12713
Christiansen OB, Kolte AM, Krog MC, Nielsen HS, Egerup P (2019) Treatment with intravenous immunoglobulin in patients with recurrent pregnancy loss: An update. J Reprod Immunol 133:37–42. https://doi.org/10.1016/j.jri.2019.06.001
Christiansen OB, Larsen EC, Egerup P, Lunoee L, Egestad L, Nielsen HS (2015) Intravenous immunoglobulin treatment for secondary recurrent miscarriage: a randomised, double-blind, placebo-controlled trial. BJOG 122(4):500–508. https://doi.org/10.1111/1471-0528.13192
Christiansen OB, Pedersen B, Nielsen HS, Nybo Andersen AM (2004) Impact of the sex of first child on the prognosis in secondary recurrent miscarriage. Hum Reprod 19(12):2946–2951. https://doi.org/10.1093/humrep/deh516
Carkaci D, Afzal J, Jensen KS, Dannemann JL, Cinar B: The implication of HLA-F polymorphisms on the development of recurrent spontaneous abortions Bachelor Thesis, Rosklite University 2010
Clark MM, Chazara O, Sobel EM, Gjessing HK, Magnus P, Moffett A, Sinsheimer JS (2016) Human Birth Weight and Reproductive Immunology: Testing for Interactions between Maternal and Offspring KIR and HLA-C Genes. Hum Hered 81(4):181–193. https://doi.org/10.1159/000456033
Clay RA (2010) The pitfalls of randomized controlled trials. Monitor on Psychology 41(8). http://www.apa.org/monitor/2010/09/trials
Colucci F (2017) The role of KIR and HLA interactions in pregnancy complications. Immunogenetics 69(8–9):557–565. https://doi.org/10.1007/s00251-017-1003-9
Coulam CB (1994) Immunotherapy with intravenous immunoglobulin for treatment of recurrent pregnancy loss: American experience. Am J Reprod Immunol 32(4):286–289. https://doi.org/10.1111/j.1600-0897.1994.tb01127.x
Coulam CB (2021) Intralipid treatment for women with reproductive failures. Am J Reprod Immunol 85:e13290. https://doi.org/10.1111/aji.13290
Coulam CB, Roussev GR, Thomason EJ, Barnea ER (1995) Preimplantation Factor (PIF) Predicts Subsequent Pregnancy Loss. Am J Reprod Immunol 34(2):P88-92. https://doi.org/10.1111/j.1600-0897.1995.tb00923.x
Danaii S, Ghorbani F, Ahmadi M, Abbaszadeh H, Koushaeian L, Soltani-Zangbar MS, Mehdizadeh A, Hojjat-Farsangi M, Kafil HS, Aghebati-Maleki L, Yousefi M (2020) IL-10-producing B cells play important role in the pathogenesis of recurrent pregnancy loss. Int Immunopharmacol 87:106806. https://doi.org/10.1016/j.intimp.2020.106806
DeJong CS, Maurice NJ, McCartney SA, Prlic M (2020) Human Tissue-Resident Memory T Cells in the Maternal-Fetal Interface. Lost Soldiers or Special Forces? Cells 9(12):2699. https://doi.org/10.3390/cells9122699
De Sanctis JB, Blanca I, Bianco NE (1995) Expression of different lipoprotein receptors in natural killer cells and their effect on natural killer proliferative and cytotoxic activity. Immunology 86(3):399–407
D’Ippolito S, Gasbarrini A, Castellani R, Rocchetti S, Sisti LG, Scambia G, Di Simone N (2016) Human leukocyte antigen (HLA) DQ2/DQ8 prevalence in recurrent pregnancy loss women. Autoimmun Rev 15(7):638–643. https://doi.org/10.1016/j.autrev.2016.02.009
Di Simone N, Nicuolo F, Marana R, Castellani R, Ria F, Veglia M, Scambia G, Surbek D, Barnea E, Mueller M (2017) Synthetic PreImplantation Factor (PIF) prevents fetal loss by modulating LPS induced inflammatory response. PLOS ONE 12:e0180642. https://doi.org/10.1371/journal.pone.0180642
Du H, Naqvi H, Taylor HS (2012) Ischemia/reperfusion injury promotes and granulocyte-colony stimulating factor inhibits migration of bone marrow-derived stem cells to endometrium. Stem Cells Dev. 21(18):3324–3331. https://doi.org/10.1089/scd.2011.0193
Duzyj CM, Barnea ER, Li M, Huang SJ, Krikun G, Paidas MJ (2010) Am J Obstet Gynecol 203(4):402.e1–4. https://doi.org/10.1016/j.ajog.2010.06.060
Eapen A, Joing M, Kwon P, Tong J, Maneta E, De Santo C, Mussai F, Lissauer D, Carter D (2019) RESPONSE study group. Recombinant human granulocyte- colony stimulating factor in women with unexplained recurrent pregnancy losses: a randomized clinical trial. Hum Reprod 34(3):424–432. https://doi.org/10.1093/humrep/dey393
Elbaşı MO, Tulunay A, Karagözoğlu H, Kahraman S, Ekşioğlu-Demiralp E (2020) Maternal killer-cell immunoglobulin-like receptors and paternal human leukocyte antigen ligands in recurrent pregnancy loss cases in Turkey. Clin Exp Reprod Med 47(2):122–129. https://doi.org/10.5653/cerm.2019.03223
Ensom MH, Stephenson MD (2011) A two-center study on the pharmacokinetics of intravenous immunoglobulin before and during pregnancy in healthy women with poor obstetrical histories. Hum Reprod 26(9):2283–2288. https://doi.org/10.1093/humrep/der227
ESHRE Guideline Group on RPL, Bender Atik R, Christiansen OB, Elson J, Kolte AM, Lewis S, Middeldorp S, Nelen W, Peramo B, Quenby S, Vermeulen N, Goddijn M (2018) ESHRE guideline: recurrent pregnancy loss. Hum Reprod Open 2018(2):hoy004 https://doi.org/10.1093/hropen/hoy004
Galeotti C, Karnam A, Dimitrov JD et al (2020) Anti-IgE IgG autoantibodies isolated from therapeutic normal IgG intravenous immunoglobulin induce basophil activation. Cell Mol Immunol 17:426–429. https://doi.org/10.1038/s41423-019-0334-x
Gargett CE, Chan RW, Schwab KE (2007) Endometrial stem cells. Curr Opin Obstet Gynecol 19(4):377–383. https://doi.org/10.1097/GCO.0b013e328235a5c6
Granato D, Blum S, Rossle C, Le Boucher J, Malnoe A, Dutot G (2000) Effects of parenteral lipid emulsions with different fatty acid composition on immune cell functions in vitro. Jpn. J. Parenter. Enter. Nutr. 24:113–118
Guerby P, Fillion A, O’Connor S, Bujold E (2021) Heparin for preventing adverse obstetrical outcomes in pregnant women with antiphospholipid syndrome, a systematic review and meta-analysis. J Gynecol Obstet Hum Reprod. 50(2):101974. https://doi.org/10.1016/j.jogoh.2020.101974
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(2):491–497. https://doi.org/10.1093/humrep/deq341
Faridi RM, Das V, Tripthi G, Talwar S, Parveen F, Agrawal S (2009) Influence of activating and inhibitory killer immunoglobulin-like receptors on predisposition to recurrent miscarriages. Human Reproduction 24:1758–1764. https://doi.org/10.1093/humrep/dep047
Fawzy M, Shokeir T, El-Tatongy M, Warda O, El-Refaiey AA, Mosbah A (2008) Treatment options and pregnancy outcome in women with idiopathic recurrent miscarriage: A randomized placebo-controlled study. Arch Gynecol Obstet 278:33–38
Fettke F, Schumacher A, Canellada A, Toledo N, Bekeredjian-Ding I, Bondt A, Wuhrer M, Costa SD, Zenclussen AC (2016) Maternal and Fetal Mechanisms of B Cell Regulation during Pregnancy: Human Chorionic Gonadotropin Stimulates B Cells to Produce IL-10 While Alpha-Fetoprotein Drives Them into Apoptosis. Front Immunol 8(7):495. https://doi.org/10.3389/fimmu.2016.00495
Feyaerts D, Joosten I, van der Molen RG (2020) A pregnancy to remember: trained immunity of the uterine mucosae. Mucosal Immunol. https://doi.org/10.1038/s41385-020-00362-7
Fotoohi M, Ghasemi N, Mirghanizadeh SA, Vakili M, Samadi M (2016) Association between HLA-E gene polymorphism and unexplained recurrent spontaneous abortion (RSA) in Iranian women. International Journal of Reproductive Biomedicine. 14(7):477–482
Gamliel M, Goldman-Wohl D, Isaacson B, Gur C, Stein N, Yamin R, Berger M, Grunewald M, Keshet E, Rais Y, Bornstein C, David E, Jelinski A, Eisenberg I, Greenfield C, Ben-David A, Imbar T, Gilad R, Haimov-Kochman R, Mankuta D, Elami-Suzin M, Amit I, Hanna JH, Yagel S, Mandelboim O (2018) Trained Memory of Human Uterine NK Cells Enhances Their Function in Subsequent Pregnancies. Immunity 48(5):951-962.e5. https://doi.org/10.1016/j.immuni.2018.03.030
Gao M, Jiang X, Li B, Li L, Duan M, Zhang X, Tian J, Qi K (2019) Intrauterine injection of human chorionic gonadotropin before embryo transfer can improve in vitro fertilization-embryo transfer outcomes: a meta-analysis of randomized controlled trials. Fertil Steril 112(1):89-97.e1. https://doi.org/10.1016/j.fertnstert.2019.02.027
Gharesi-Fard B, Askarinejad-Behbahani R, Behdin S (2014) The effect of HLA-DRB1 sharing between the couples with recurrent pregnancy loss on the pregnancy outcome after leukocyte therapy. Iran J Immunol 11(1):13–20
Gomaa MF, Elkholy AG, El-Said MM, Abdel-Salam NE (2014) Combined oral prednisolone and heparin versus heparin: The effect on peripheral nk cells and clinical outcome in patients with unexplained recurrent miscarriage. A double-blind placebo randomized controlled trial. Arch Gynecol Obstet 290:757–762
Goodale LF, Hayrabedyan S, Todorova K, Roussev R, Ramu S, Stamatkin C, Coulam CB, Barnea ER, Gilbert RO (2017) PreImplantation factor (PIF) protects cultured embryos against oxidative stress: relevance for recurrent pregnancy loss (RPL) therapy. Oncotarget 8(20):32419–32432. https://doi.org/10.18632/oncotarget.16028
Gupta R, Prakash S, Parveen F, Agrawal S (2012) Association of CTLA-4 and TNF-α polymorphism with recurrent miscarriage among North Indian women. Cytokine 60(2):456–462. https://doi.org/10.1016/j.cyto.2012.05.018. Epub 2012 Jun 22
Gur C, Diav-Citrin O, Shechtman S, Arnon J, Ornoy A (2004) Pregnancy outcome after first trimester exposure to corticosteroids: A prospective controlled study. Reprod Toxicol 18:93–101
Guzman-Genuino RM, Diener KR (2017) Regulatory B Cells in Pregnancy: Lessons from Autoimmunity, Graft Tolerance, and Cancer. Front Immunol 17(8):172. https://doi.org/10.3389/fimmu.2017.00172
Harrison RF (1985) Treatment of habitual abortion with human chorionic gonadotropin: results of open and placebo-controlled studies. Eur J Obstet Gynecol Reprod Biol 20(3):159–168. https://doi.org/10.1016/0028-2243(85)90015-2
Hayashi Y, Nishiyama T, Nakatochi M, Suzuki S, Takahashi S, Sugiura-Ogasawara M (2018) Association of genetic variants of PD1 with recurrent pregnancy loss. Reprod Med Biol. 17(2):195–202. https://doi.org/10.1002/rmb2.12093.PMID:29692678;PMCID:PMC5902459
He M, Kang B, Liao S, Yang K, Ding X, Wu D, Guo Q, Hou Q (2014) Association of polymorphisms of HLA-DRB1 gene with unexplained recurrent spontaneous abortion in ethnic Hans from Henan. Chinese J Med Genet. 31(4):504–507. https://doi.org/10.3760/cma.j.issn.1003-9406.2014.04.021
Hiby SE, Apps R, Chazara O, Farrell LE, Magnus P, Trogstad L, Gjessing HK, Carrington M, Moffett A (2014) Maternal KIR in combination with paternal HLA-C2 regulate human birth weight. J Immunol 192(11):5069–5073. https://doi.org/10.4049/jimmunol.1400577
Hiby SE, Regan L, Lo W, Farrell L, Carrington M, Moffett A (2008) Association of maternal killer-cell immunoglobulin-like receptors and parental HLA-C genotypes with recurrent miscarriage. Hum Reprod 23(4):972–976. https://doi.org/10.1093/humrep/den011
Hong KH, Forman EJ, Werner MD, Upham KM, Gumeny CL, Winslow AD, Kim TJ, Scott RT Jr (2014) Endometrial infusion of human chorionic gonadotropin at the time of blastocyst embryo transfer does not impact clinical outcomes: a randomized, double-blind, placebo-controlled trial. Fertil Steril 102(6):1591–5.e2. https://doi.org/10.1016/j.fertnstert.2014.08.006
Huang P, Yao C, Wei L, Lin Z (2020) The intrauterine perfusion of granulocyte-colony stimulating factor (G-CSF) before frozen-thawed embryo transfer in patients with two or more implantation failures. Hum Fertil (Camb) 31:1–5. https://doi.org/10.1080/14647273.2020.1811904
Hutton B, Sharma R, Fergusson D, Tinmouth A, Hebert P, Jamieson J, Walker M (2007) Use of intravenous immunoglobulin for treatment of recurrent miscarriage: a systematic review. BJOG: An International Journal of Obstetrics & Gynaecology 114:134–142. https://doi.org/10.1111/j.1471-0528.2006.01201.x
Hviid TV, Hylenius S, Hoegh AM, Kruse C, Christiansen OB (2002) HLA-G polymorphisms in couples with recurrent spontaneous abortions. Tissue Antigens 60(2):122–132. https://doi.org/10.1034/j.1399-0039.2002.600202.x
Inada K, Shima T, Nakashima A, Aoki K, Ito M, Saito S (2013) Characterization of regulatory T cells in decidua of miscarriage cases with abnormal or normal fetal chromosomal content. J Reprod Immunol 97(1):104–111. https://doi.org/10.1016/j.jri.2012.12.001
Jablonowska B, Selbing A, Palfi M, Ernerudh J, Kjellberg S, Lindton B (1999) Prevention of recurrent spontaneous abortion by intravenous immunoglobulin: a double-blind placebo-controlled study. Hum Reprod 14(3):838–841. https://doi.org/10.1093/humrep/14.3.838
Jin LP, Fan DX, Zhang T, Guo PF, Li DJ (2011) The costimulatory signal upregulation is associated with Th1 bias at the maternal-fetal interface in human miscarriage. Am J Reprod Immunol 66(4):270–278. https://doi.org/10.1111/j.1600-0897.2011.00997.x
Jolles S, Sewell WA, Misbah SA (2005) Clinical uses of intravenous immunoglobulin. Clin Exp Immunol 142(1):1–11. https://doi.org/10.1111/j.1365-2249.2005.02834.x
Kelemu T, Erlandsson L, Seifu D, Hansson E, Abebe M, Teklu S, Girma S, Traherne JA, Moffett A, Hansson SR (2020) Polymorphism in killer cell immunoglobulin-like receptors and human leukocyte antigen-c and predisposition to preeclampsia in Ethiopian pregnant women population. J Reprod Immunol 141:103169. https://doi.org/10.1016/j.jri.2020.103169
Keller CC, Eikmans M, van der Hoorn MP, Lashley LEELO (2020) Recurrent miscarriages and the association with regulatory T cells; A systematic review. J Reprod Immunol 139:103105. https://doi.org/10.1016/j.jri.2020.103105
Kessel A, Ammuri H, Peri R, Pavlotzky ER, Blank M, Shoenfeld Y, Toubi E (2007) Intravenous Immunoglobulin Therapy Affects T Regulatory Cells by Increasing Their Suppressive Function. J Immunol 179(8):5571–5575. https://doi.org/10.4049/jimmunol.179.8.5571
Kheshtchin N, Gharagozloo M, Andalib A, Ghahiri A, Maracy MR, Rezaei A (2010) The Expression of Th1- and Th2-Related Chemokine Receptors in Women with Recurrent Miscarriage: the Impact of Lymphocyte Immunotherapy. Am J Reprod Immunol 64:104–112. https://doi.org/10.1111/j.1600-0897.2010.00829.x
Kieffer TEC, Laskewitz A, Scherjon SA, Faas MM, Prins JR (2019) Memory T Cells in Pregnancy. Front Immunol 10:625. Published 2019 Apr 2 https://doi.org/10.3389/fimmu.2019.00625
Kimura F, Takebayashi A, Ishida M, Nakamura A, Kitazawa J, Morimune A, Hirata K, Takahashi A, Tsuji S, Takashima A, Amano T, Tsuji S, Ono T, Kaku S, Kasahara K, Moritani S, Kushima R, Murakami T (2019) Review: Chronic endometritis and its effect on reproduction. J Obstet Gynaecol Res 45(5):951–960. https://doi.org/10.1111/jog.13937
Kinder JM, Jiang TT, Clark DR, Chaturvedi V, Xin L, Ertelt JM, Way SS (2014) Pregnancy-induced maternal regulatory T cells, bona fide memory or maintenance by antigenic reminder from fetal cell microchimerism? Chimerism 5(1):16–9. https://doi.org/10.4161/chim.28241
Kolben TM, Rogatsch E, Hester A, Kuhn C, Schmoeckel E, Czogalla B, Mahner S, Jeschke U, Kolben T (2019) Involvement of ILR4α and TLR4 in miscarriages. J Reprod Immunol 131:36–43. https://doi.org/10.1016/j.jri.2018.12.001
Kolte AM, Steffensen R, Nielsen HS, Hviid TV, Christiansen OB (2010) Study of the structure and impact of human leukocyte antigen (HLA)-G-A, HLA-G-B, and HLA-G-DRB1 haplotypes in families with recurrent miscarriage. Hum Immunol 71(5):482–488. https://doi.org/10.1016/j.humimm.2010.02.001
Kruse C, Steffensen R, Varming K, Christiansen OB (2004) A study of HLA-DR and -DQ alleles in 588 patients and 562 controls confirms that HLA-DRB1*03 is associated with recurrent miscarriage. Hum Reprod 19(5):1215–1221. https://doi.org/10.1093/humrep/deh200
Kumari S, Rani A, Diwan A, Srivastava A, Mehta V, Suri R (2016) Morphological and morphometric evaluation of placenta in hypothyroid mothers. Astrocyte 2:19–23
Kurosaki T, Kometani K, Ise W (2015) Memory B cells. Nat Rev Immunol 15(3):149–159. https://doi.org/10.1038/nri3802. Epub 2015 Feb 13 PMID: 25677494
Kusumi M, Ihana T, Kurosawa T, Ohashi Y, Tsutsumi O (2020) Intrauterine administration of platelet-rich plasma improves embryo implantation by increasing the endometrial thickness in women with repeated implantation failure: A single-arm self-controlled trial. Reprod Med Biol. 19:350–356. https://doi.org/10.1002/rmb2.12334
Kwiatek M, Gęca T, Krzyżanowski A, Malec A, Kwaśniewska A (2015) Peripheral Dendritic Cells and CD4+CD25+Foxp3+ Regulatory T Cells in the First Trimester of Normal Pregnancy and in Women with Recurrent Miscarriage. PLoS ONE 10(5):e0124747. https://doi.org/10.1371/journal.pone.0124747
Laokirkkiat P, Thanaboonyawat I, Boonsuk S, Petyim S, Prechapanich J, Choavaratana R (2019) Increased implantation rate after intrauterine infusion of a small volume of human chorionic gonadotropin at the time of embryo transfer: a randomized, double-blind controlled study. Arch Gynecol Obstet 299(1):267–275. https://doi.org/10.1007/s00404-018-4962-7
Li G, Lu C, Gao J, Wang X, Wu H, Lee C, Xing B, Zhang Q (2015) Association between PD-1/PD-L1 and T regulate cells in early recurrent miscarriage. Int J Clin Exp Pathol 8(6):6512–6518
Li J, Mo S, Chen Y (2017) The effect of G-CSF on infertile women undergoing IVF treatment: A meta-analysis. Syst Biol Reprod Med. 63(4):239–247. https://doi.org/10.1080/19396368.2017.1287225
Liang P, Mo M, Li G-G, Yin B, Cai J, Wu T, He X, Zhang X, Zeng Y (2012) Comprehensive analysis of peripheral blood lymphocytes in 76 women with recurrent miscarriage before and after lymphocyte immunotherapy. Am J Reprod Immunol 2012
Liu S, Wei H, Li Y, Diao L, Lian R, Zhang X, Zeng Y (2019) Characterization of dendritic cell (DC)-10 in recurrent miscarriage and recurrent implantation failure. Reproduction 158(3):247–255. https://doi.org/10.1530/REP-19-0172
Liu S, Wei H, Li Y, Huang C, Lian R, Xu J, Chen L, Zeng Y (2018) Downregulation of ILT4+ dendritic cells in recurrent miscarriage and recurrent implantation failure. Am J Reprod Immunol 80(4):e12998. https://doi.org/10.1111/aji.12998. Epub 2018 Jun 14
Liu Z, Xu H, Kang X, Wang T, He L, Zhao A (2016) Allogenic lymphocyte immunotherapy for unexplained recurrent spontaneous abortion: a meta-analysis. Am J Reprod Immunol 76:443–453
Long W, Shi Z, Fan S, Liu L, Lu Y, Guo X, Rong C, Cui X, Ding H (2015) Association of maternal KIR and fetal HLA-C genes with the risk of preeclampsia in the Chinese Han population. Placenta 36(4):433–437. https://doi.org/10.1016/j.placenta.2014.05.008
Makhseed M, Raghupathy R, Azizieh F, Omu A, Al-Shamali E, Ashkanani L (2001) Th1 and Th2 cytokine profiles in recurrent aborters with successful pregnancy and with subsequent abortions. Hum Reprod 16(10):2219–2226. https://doi.org/10.1093/humrep/16.10.2219
Mansour R, Tawab N, Kamal O, El-Faissal Y, Serour A, Aboulghar M, Serour G (2011) Intrauterine injection of human chorionic gonadotropin before embryo transfer significantly improves the implantation and pregnancy rates in in vitro fertilization/intracytoplasmic sperm injection: a prospective randomized study. Fertil Steril 96(6):1370-1374.e1. https://doi.org/10.1016/j.fertnstert.2011.09.044
Martini AE, Jasulaitis S, Fogg LF, Uhler ML, Hirshfeld-Cytron JE (2018) Evaluating the Utility of Intralipid Infusion to Improve Live Birth Rates in Patients with Recurrent Pregnancy Loss or Recurrent Implantation Failure. J Hum Reprod Scien 11(3):261–268. https://doi.org/10.4103/jhrs.jhrs_28_18
Meng L, Lin J, Chen L, Wang Z, Liu M, Liu Y, Chen X, Zhu L, Chen H, Zhang J (2016) Effectiveness and potential mechanisms of intralipid in treating unexplained recurrent spontaneous abortion. Arch Gynecol Obstet 294(1):29–39. https://doi.org/10.1007/s00404-015-3922-8
Mengling T, Hernandez-Frederick CJ, Fandel D, Sauter J, Schetelig J, Schmidt AH, Ehninger G (2015) Long-Term HSC Donor Follow-up: Malignancy Incidences after Donation Are Identical Compared to a Matched Control Sample of Registered Donors, but Different to Expected General Population Rates. Blood 126(23):269. https://doi.org/10.1182/blood.V126.23.269.269
Mestman JH (2004) Hyperthyroidism in pregnancy. Best Pract Res Clin Endocrinol Metab 18(2):267–268. https://doi.org/10.1016/j.beem.2004.03.005
Metcalf D (1985) The granulocyte-macrophage colony-stimulating factors. Science 229(4708):16–22. https://doi.org/10.1126/science.2990035
Meuleman T, Lashley LE, Dekkers OM, van Lith JM, Claas FH, Bloemenkamp KW (2015) HLA associations and HLA sharing in recurrent miscarriage: A systematic review and meta-analysis. Hum Immunol 76(5):362–373. https://doi.org/10.1016/j.humimm.2015.02.004. Epub 2015 Feb 17
Meuleman T, van Beelen E, Kaaja RJ, van Lith JM, Claas FH, Bloemenkamp KW (2016) HLA-C antibodies in women with recurrent miscarriage suggests that antibody mediated rejection is one of the mechanisms leading to recurrent miscarriage. J Reprod Immunol 116:28–34. https://doi.org/10.1016/j.jri.2016.03.003
Miko E, Meggyes M, Doba K, Barakonyi A, Szereday L (2019) Immune Checkpoint Molecules in Reproductive Immunology. Front Immunol 18(10):846. https://doi.org/10.3389/fimmu.2019.00846.PMID:31057559;PMCID:PMC6482223
Miwa N, Hayakawa S, Miyazaki S, Myojo S, Sasaki Y, Sakai M, Takikawa O, Saito S (2005) IDO expression on decidual and peripheral blood dendritic cells and monocytes/macrophages after treatment with CTLA-4 or interferon-gamma increase in normal pregnancy but decrease in spontaneous abortion. Mol Hum Reprod 11(12):865–870. https://doi.org/10.1093/molehr/gah246
Moindjie H, Santos ED, Gouesse RJ, Swierkowski-Blanchard N, Serazin V, Barnea ER, Vialard F, Dieudonné MN (2016) Cell Death Dis 7(12):e2504. https://doi.org/10.1038/cddis.2016.382
Moraru M, Carbone J, Alecsandru D, Castillo-Rama M, García-Segovia A, Gil J, Alonso B, Aguarón A, Ramos-Medina R, Martínez de María J, Oliver-Miñarro D, Rodríguez-Mahou M, Ortega V, Caballero P, Meliá E, Vidal J, Cianchetta-Sivori M, Esteban C, Vargas-Henny L, Dale J, Ortiz-Quintana L, Fernández-Cruz E, Sánchez-Ramón S (2012) Intravenous immunoglobulin treatment increased live birth rate in a Spanish cohort of women with recurrent reproductive failure and expanded CD56(+) cells. Am J Reprod Immunol 68(1):75–84. https://doi.org/10.1111/j.1600-0897.2012.01135.x
Mosaad YM, Abdel-Dayem Y, El-Deek BS, El-Sherbini SM (2011) Association between HLA-E *0101 homozygosity and recurrent miscarriage in Egyptian women. Scand J Immunol 74(2):205–209. https://doi.org/10.1111/j.1365-3083.2011.02559.x
Mueller-Eckhardt G (1994) Alternative Treatment to Lymphocyte Immunization for Treatment of Recurrent Spontaneous Abortion: Immunotherapy With Intravenous Immunoglobulin for Prevention of Recurrent Pregnancy Loss: European Experience. Am J Reprod Immunol 32:281–285. https://doi.org/10.1111/j.1600-0897.1994.tb01126.x
Muzzio D, Zenclussen AC, Jensen F (2013) The Role of B Cells in Pregnancy: the Good and the Bad. Am J Reprod Immunol 69:408–412
Nazari L, Salehpour S, Hosseini MS, Hashemi MP (2020) The effects of autologous platelet-rich plasma in repeated implantation failure: a randomized controlled trial. Hum Fertil (Camb) 23(3):209–213. https://doi.org/10.1080/14647273.2019.1569268
Nielsen HS, Andersen AM, Kolte AM, Christiansen OB (2008) A firstborn boy is suggestive of a strong prognostic factor in secondary recurrent miscarriage: a confirmatory study. Fertil Steril 89(4):907–911. https://doi.org/10.1016/j.fertnstert.2007.04.029
Nielsen HS, Wu F, Aghai Z, Steffensen R, van Halteren AG, Spierings E, Christiansen OB, Miklos D, Goulmy E (2010) H-Y antibody titers are increased in unexplained secondary recurrent miscarriage patients and associated with low male: female ratio in subsequent live births. Hum Reprod 25(11):2745–2752. https://doi.org/10.1093/humrep/deq242. Epub 2010 Sep 7
Nowak I, Malinowski A, Tchórzewski H, Barcz E, Wilczyński JR, Banasik M, Gryboś M, Kurpisz M, Luszczek W, Majorczyk E, Wiśniewski A, Senitzer D, Sun JY, Kuśnierczyk P (2011) HLA-C C1C2 heterozygosity may protect women bearing the killer immunoglobulin-like receptor AA genotype from spontaneous abortion. J Reprod Immunol 88(1):32–37. https://doi.org/10.1016/j.jri.2010.11.001
Nowak I, Wilczyńska K, Radwan P, Wiśniewski A, Krasiński R, Radwan M, Wilczyński JR, Malinowski A, Kuśnierczyk P (2020) Association of Soluble HLA-G Plasma Level and HLA-G Genetic Polymorphism With Pregnancy Outcome of Patients Undergoing in vitro Fertilization Embryo Transfer. Front Immunol 14(10):2982. https://doi.org/10.3389/fimmu.2019.02982
Olivito B, Taddio A, Simonini G, Massai C, Ciullini S, Gambineri E, de Martino M, Azzari C, Cimaz R (2010) Defective FOXP3 expression in patients with acute Kawasaki disease and restoration by intravenous immunoglobulin therapy. Clin Exp Rheumatol 28(1 Suppl 57):93–7
Olmos-Ortiz A, Flores-Espinosa P, Mancilla-Herrera I, Vega-Sánchez R, Díaz L, Zaga-Clavellina V (2019) Innate Immune Cells and Toll-like Receptor-Dependent Responses at the Maternal-Fetal Interface. Int J Mol Sci 20(15):3654. https://doi.org/10.3390/ijms20153654
Ozturk OG, Sahın G, Karacor ED, Kucukgoz U (2012) Evaluation of KIR genes in recurrent miscarriage. J Assist Reprod Genet 29(9):933–938. https://doi.org/10.1007/s10815-012-9811-1
Palmsten K, Bandoli G, Vazquez-Benitez G, Xi M, Johnson DL, Xu R, Chambers CD (2020) Oral corticosteroid use during pregnancy and risk of preterm birth. Rheumatology (Oxf. Engl.) 59:1262–1271
Pepe PE, Aufderheide TP (2017) EBM vs. EBM: combining evidence-based and experienced-based medicine in resuscitation research. Curr Opin Crit Care 23(3):199–203. https://doi.org/10.1097/MCC.0000000000000413
Perino A, Vassiliadis A, Vucetich A, Colacurci N, Menato G, Cignitti M, Semprini AE (1997) Short-term therapy for recurrent abortion using intravenous immunoglobulins: results of a double-blind placebo-controlled Italian study. Hum Reprod 12(11):2388–2392. https://doi.org/10.1093/humrep/12.11.2388
Perricone R, De Carolis C, Kröegler B, Greco E, Giacomelli R, Cipriani P, Fontana L, Perricone C (2008) Intravenous immunoglobulin therapy in pregnant patients affected with systemic lupus erythematosus and recurrent spontaneous abortion. Rheumatology (Oxford) 47(5):646–651. https://doi.org/10.1093/rheumatology/ken046
Plaçais L, Kolanska K, Kraiem YB, Cohen J, Suner L, Bornes M, Sedille L, Rosefort A, D’Argent EM, Selleret L, Abisror N, Johanet C, Buffet NC, Darai E, Antoine JM, Fain O, Kayem G, Mekinian A (2020) Intralipid therapy for unexplained recurrent miscarriage and implantation failure: Case-series and literature review. Eur J Obstet Gynecol Reprod Biol 252:100–104. https://doi.org/10.1016/j.ejogrb.2020.06.017
Practice Committee of the American Society for Reproductive Medicine (2012) Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril 98(5):1103–11. https://doi.org/10.1016/j.fertnstert.2012.06.048
Puchner A, Gröchenig HP, Sautner J, Helmy-Bader Y, Juch H, Reinisch S, Ch, Högenauer, Koch R, Hermann J, Studnicka-Benke A, Weger W, Puchner R, Dejaco C (2019) Immunosuppressives and biologics during pregnancy and lactation. Wien Klin Wochenschr 131:29–44. https://doi.org/10.1007/s00508-019-1448-y
Qian ZD, Huang LL, Zhu XM (2015) An immunohistochemical study of CD83- and CD1a-positive dendritic cells in the decidua of women with recurrent spontaneous abortion. Eur J Med Res 20(1):2. https://doi.org/10.1186/s40001-014-0076-2
Rabi S, Jacob TM, Lionel J, Indrasingh I (2014) Different subsets of Langerhans cells in human uterine tubes and uterus. J Obstet Gynaecol Res 40(7):1833–1839. https://doi.org/10.1111/jog.12446
Raghupathy R, Al-Mutawa E, Al-Azemi M, Makhseed M, Azizieh F, Szekeres-Bartho J (2009) Progesterone-induced blocking factor (PIBF) modulates cytokine production by lymphocytes from women with recurrent miscarriage or preterm delivery. J Reprod Immunol 80(1–2):91–99. https://doi.org/10.1016/j.jri.2009.01.004
Rahmati M, Petitbarat M, Dubanchet S, Bensussan A, Chaouat G, Ledee N (2014) Granulocyte-colony stimulating factor related pathways tested on an endometrial ex-vivo model. PLoS ONE 9:e102286. https://doi.org/10.1371/journal.pone.0102286
Rajgopal S, Raghupathy R (2021) Using the Immune System to Manage Immunologically-Mediated Pregnancy Loss. Annals Nat Acad MedSciences (India) 57(01):08–15. https://doi.org/10.1055/s-0040-1718234
Rogenhofer N, Engels L, Bogdanova N, Tüttelmann F, Thaler CJ, Markoff A (2014) Lower incidence of M2/ANXA5 carriage in recurrent pregnancy loss patients with elevated lipoprotein(a) levels. Clin Appl Thromb Hemost 20(7):706–709. https://doi.org/10.1177/1076029613516189
Rogenhofer N, Ochsenkühn R, von Schönfeldt V, Assef RB, Thaler CJ (2012) Antitrophoblast antibodies are associated with recurrent miscarriages. Fertil Steril 97(2):361–366. https://doi.org/10.1016/j.fertnstert.2011.11.014
Rossetti M, Gregori S, Roncarolo MG (2010) Granulocyte-colony stimulating factor drives the in vitro differentiation of human dendritic cells that induce anergy in naïve T cells. Eur J Immunol 40(11):3097–3106. https://doi.org/10.1002/eji.201040659
Roussev RG, Acacio B, Ng SC, Coulam CB (2008) Duration of intralipid’s suppressive effect on NK cell’s functional activity. Am J Reprod Immunol 60(3):258–263. https://doi.org/10.1111/j.1600-0897.2008.00621.x
Roussev RG, Dons’koi BV, Stamatkin C, Ramu S, Chernyshov VP, Coulam CB, Barnea ER (2013) Preimplantation factor inhibits circulating natural killer cell cytotoxicity and reduces CD69 expression: implications for recurrent pregnancy loss therapy. Reprod Biomed Online 26(1):79–87. https://doi.org/10.1016/j.rbmo.2012.09.017
Rushworth FH, Backos M, Rai R, Chilcott IT, Baxter N, Regan L (2000) Prospective pregnancy outcome in untreated recurrent miscarriers with thyroid autoantibodies. Hum Reprod (Oxf. Engl.) 15:1637–1639
Rutella S, Zavala F, Danese S, Kared H, Leone G (2005) Granulocyte colony-stimulating factor: a novel mediator of T cell tolerance. J Immunol 175:7085–7091. https://doi.org/10.4049/jimmunol.175.11.7085
Saito S, Nakashima A, Shima T, Ito M (2010) Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol 63(6):601–610. https://doi.org/10.1111/j.1600-0897.2010.00852.x
Sanson-Fisher RW, Bonevski B, Green LW, D’Este C (2007) Limitations of the randomized controlled trial in evaluating population-based health interventions. Am J Prev Med 33(2):155–161. https://doi.org/10.1016/j.amepre.2007.04.007
Santamaria X, Mas A, Cervelló I, Taylor H, Simon C (2018) Uterine stem cells: from basic research to advanced cell therapies. Human Reproduction Update 24(Issue 6):673–693. https://doi.org/10.1093/humupd/dmy028
Santjohanser C, Knieper C, Franz C, Hirv K, Meri O, Schleyer M, Würfel W, Toth B (2013) Granulocyte-Colony Stimulating Factor as treatment option in patients with recurrent miscarriage. Arch Immunol Ther Exp 61:159–164. https://doi.org/10.1007/s00005-012-0212-z
Santjohanser C, Wagner A, Hirv K (2020) G-CSF and repeated spontaneous abortions: comparability of inclusion and exclusion criteria in existing RCT-studies. Hum Reprod 35(6):1470. https://doi.org/10.1093/humrep/deaa079
Sarno M, Cavalcante MB, Niag M, Pimentel K, Luz I, Figueiredo B, Michelon T, Neumann J, Lima S, Machado IN, Araujo Júnior E, Barini R (2019) Gestational and perinatal outcomes in recurrent miscarriages couples treated with lymphocyte immunotherapy. Eur J Obstet Gynecol Reprod Biol X 7(3):100036. https://doi.org/10.1016/j.eurox.2019.100036
Sasaki Y, Sakai M, Miyazaki S, Higuma S, Shiozaki A, Saito S (2004) Decidual and peripheral blood CD4+CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases. Mol Hum Reprod 10(5):347–353. https://doi.org/10.1093/molehr/gah044
Sbracia M, Scarpellini F, Stamenov G (2020) G-CSFin RPL: what’s new? Hum Reprod 35(6):1469–1474. https://doi.org/10.1093/humrep/deaa078. PMID: 32426799
Scarpellini F, Klinger FG, Rossi G, Sbracia M (2019) Immunohistochemical Study on the Expression of G-CSF, G-CSFR, VEGF, VEGFR-1, Foxp3 in First Trimester Trophoblast of Recurrent Pregnancy Loss in Pregnancies Treated with G-CSF and Controls. Int J Mol Sci 21(1):285. https://doi.org/10.3390/ijms21010285
Scarpellini F, Sbracia M (2009) Use of granulocyte colony-stimulating factor for the treatment of unexplained recurrent miscarriage: a randomised controlled trial. Hum Reprod 24(11):2703–2708. https://doi.org/10.1093/humrep/dep240
Schumacher A, Zenclussen A (2020) Human Chorionic Gonadotropin acts as a central regulator of adaptive immune responses during early pregnancy safeguarding fetal survival. J Immunol 204 (1 Supplement):235.17
Schust DJ, Bonney EA, Sugimoto J, Ezashi T, Roberts RM, Choi S, Zhou J (2021) The Immunology of Syncytialized Trophoblast. Int J Mol Sci 22(4):1767. https://doi.org/10.3390/ijms22041767.PMID:33578919;PMCID:PMC7916661
Sha J, Liu F, Zhai J, Liu X, Zhang Q, Zhang B (2017) Alteration of Th17 and Foxp3+ regulatory T cells in patients with unexplained recurrent spontaneous abortion before and after the therapy of hCG combined with immunoglobulin. Exp Ther Med 14:1114–1118
Sharief M, Mohammed R, Shani SW (2014) The role of Th1 and Th2 cytokines among women with recurrent spontaneous miscarriage. Scientific Journal of Medical Science 3(7):345–351
Shaughnessy PJ, Bachier C, Lemaistre CF, Akay C, Pollock BH, Gazitt Y (2006) Granulocyte colony-stimulating factor mobilizes more dendritic cell subsets than granulocyte-macrophage colony-stimulating factor with no polarization of dendritic cell subsets in normal donors. Stem Cells 24(7):1789–1797. https://doi.org/10.1634/stemcells
Shen Y, Wang C, Hong D, Zeng B, Fang C, Yuan C, Fan L, Lv H, Zhu M (2013) The relationship between polymorphisms in the promoter region of Tim-3 and unexplained recurrent spontaneous abortion in Han Chinese women. Reprod Biol Endocrinol 11(11):104. https://doi.org/10.1186/1477-7827-11-104
Sipak O, Rył A, Grzywacz A, Laszczyńska M, Szymański S, Karakiewicz B, Rotter I, Cybulski C (2019) Molecular Analysis of HLA-G in Women with High-Risk Pregnancy and Their Partners with Regard to Possible Complications. Int J Environ Res Public Health 16(6):982. https://doi.org/10.3390/ijerph16060982
Somerset DA, Zheng Y, Kilby MD, Sansom DM, Drayson MT (2004) Normal human pregnancy is associated with an elevation in the immune suppressive CD25+ CD4+ regulatory T-cell subset. Immunology 112(1):38–43. https://doi.org/10.1111/j.1365-2567.2004.01869.x
Southcombe JH, Mounce G, McGee K, et al. (2017) An altered endometrial CD8 tissue resident memory T cell population in recurrent miscarriage. Sci Rep 7:41335. Published 2017 Jan 23. https://doi.org/10.1038/srep41335
Stamatkin CW, Roussev RG, Stout M, Absalon-Medina V, Ramu S, Goodman C, Coulam CB, Gilbert RO, Godke RA, Barnea ER (2011) Reprod Biol Endocrinol 9(1):63. https://doi.org/10.1186/1477-7827-9-63
Steck T, Becker W, Albert P, Pruteanu A, Börner W, Würfel W (1989) Erste Erfahrungen mit der Hysterosalpingoszintigraphie (HSS) bei normaler und pathologischer Tubenpassage. Geburtsh Frauenheilk. 49:889–893. https://doi.org/10.1055/s-2008-1036105
Steck T, van der Ven K, Kwak J, Beer A, Ober C (1995) HLA-DQA1 and HLA-DQB1 haplotypes in aborted fetuses and couples with recurrent spontaneous abortion. J Reprod Immunol 29(2):95–104. https://doi.org/10.1016/0165-0378(95)00937-g
Steffensen R, Christiansen OB, Bennett EP, Jersild C (1998) HLA-E polymorphism in patients with recurrent spontaneous abortion. Tissue Antigens 52(6):569–572. https://doi.org/10.1111/j.1399-0039.1998.tb03088.x
Stepanova EO, Nikolaeva MA, Golubeva EL et al (2016) Detection of Antileukocytic Antibodies in Blood Serum using Lymphocytes and Latex Microspheres Carrying HLA-Antigens upon Alloimmunization of Women with Recurrent Pregnancy Loss. Bull Exp Biol Med 160:722–726. https://doi.org/10.1007/s10517-016-3260-2
Stephenson MD, Dreher K, Houlihan E, Wu V (1998) Prevention of Unexplained Recurrent Spontaneous Abortion Using Intravenous Immunoglobulin: A Prospective, Randomized, Double-Blinded, Placebo-Controlled Trial. Am J Reprod Immunol 39:82–88. https://doi.org/10.1111/j.1600-0897.1998.tb00339.x
Stricker RB, Winger EE (2005) Update on Treatment of Immunologic Abortion with Low-dose Intravenous Immunoglobulin. Am J Reprod Immunol 54:390–396. https://doi.org/10.1111/j.1600-0897.2005.00335.x
Su N, Wang H, Zhang B, Kang Y, Guo Q, Xiao H, Yang H, Liao S (2018) Maternal natural killer cell immunoglobulin receptor genes and human leukocyte antigen-C ligands influence recurrent spontaneous abortion in the Han Chinese population. Exp Ther Med 15:327–337
Su YC, Li SC, Hsu CK, Yu CC, Lin TJ, Lee CY, Liao HF (2012) G-CSF downregulates natural killer cell-mediated cytotoxicity in donors for hematopoietic SCT. Bone Marrow Transplant 47:73–81. https://doi.org/10.1038/bmt.2011.22
Sun J, Yang M, Ban Y, Gao W, Song B, Wang Y, Zhang Y, Shao Q, Kong B, Qu X (2016) Tim-3 Is Upregulated in NK Cells during Early Pregnancy and Inhibits NK Cytotoxicity toward Trophoblast in Galectin-9 Dependent Pathway. PLoS ONE 11(1):e0147186. https://doi.org/10.1371/journal.pone.0147186
Sung N, Byeon HJ, Garcia MDS, Skariah A, Wu L, Dambaeva S, Beaman K, Gilman-Sachs A, Kwak-Kim J (2016) Deficiency in memory B cell compartment in a patient with infertility and recurrent pregnancy losses. J Reprod Immunol 118:70–75. https://doi.org/10.1016/j.jri.2016.09.003
Szekeres-Bartho J (2018) The Role of Progesterone in Feto-Maternal Immunological Cross Talk. Med Princ Pract 27(4):301–307. https://doi.org/10.1159/000491576. Epub 2018 Jun 27
Tarbell KV, Yamazaki S, Steinman RM (2006) The interactions of dendritic cells with antigen-specific, regulatory T cells that suppress autoimmunity. Semin Immunol 18(2):93–102. https://doi.org/10.1016/j.smim.2006.01.009
Terpylyak O, Sosnina K, Zastavna D, Helner N, Mikula M (2013) The distribution of allelic variants of genes HLA-DRB1, HLA-DQA1, HLA-DQB1 and HlA-G among women with idiopathic recurrent pregnancy loss. Biopolym Cell 29:413–417. https://doi.org/10.7124/bc.000832
Thangaratinam S, Tan A, Knox E, Kilby MD, Franklyn J, Coomarasamy A (2011) Association between thyroid autoantibodies and miscarriage and preterm birth: Meta-analysis of evidence. BMJ 342:d2616
Thomsen CK, Steffensen R, Nielsen HS, Kolte AM, Krog MC, Egerup P, Larsen EC, Hviid TV, Christiansen OB (2021) HLA-DRB1 polymorphism in recurrent pregnancy loss: New evidence for an association to HLA-DRB1*07. J Reprod Immunol 145:103308. https://doi.org/10.1016/j.jri.2021.103308
Ticconi C, Pietropolli A, Di Simone N, Piccione E, Fazleabas A (2019) Endometrial Immune Dysfunction in Recurrent Pregnancy Loss. Int J Mol Sci 20(21):5332. https://doi.org/10.3390/ijms20215332
Toth D, Tempfer C (2023) Diagnostik und Therapie wiederholter Spontanaborte gemäß S2K-Leitlinie. Die Gynäkologie 56, 115–126
Toth B, Würfel W, Bohlmann M, Zschocke J, Rudnik-Schöneborn S, Nawroth F, Schleußner E, Rogenhofer N, Wischmann T, von Wolff M, Hancke K, von Otte S, Kuon R, Feil K, Tempfer C (2018) Recurrent Miscarriage: Diagnostic and Therapeutic Procedures. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry Number 015/050). Geburtshilfe Frauenheilkd 78(4):364–381. https://doi.org/10.1055/a-0586-4568
Tripathi P, Naik S, Agrawal S (2006) HLA-E and immunobiology of pregnancy. Tissue Antigens 67(3):207–213. https://doi.org/10.1111/j.1399-0039.2005.00550.x
Tugcu AU, Ince DA, Esin S, Turan O, Erdogan I, Ecevit A (2020) Complete Fetal Atrioventricular Block Associated with Maternal Autoinflammatory Diseases: Case Report and Literature Review. Acta Cardiologica Sinica 36(1):72–75. https://doi.org/10.6515/ACS.202001_36(1).20190711A
Varla-Leftherioti M (2004) Role of a KIR/HLA-C allorecognition system in pregnancy. J Reprod Immunol 62(1–2):19–27. https://doi.org/10.1016/j.jri.2003.09.002
Vomstein K, Feil K, Strobel L, Aulitzky A, Hofer-Tollinger S, Kuon R-J, Toth B (2021) Immunological Risk Factors in Recurrent Pregnancy Loss: Guidelines Versus Current State of the Art. J Clin Med 10(4):869. https://doi.org/10.3390/jcm10040869
Wang L, Jiang P, Zhao S et al (2021) The dynamic profile and potential function of B-cell subsets during pregnancy. Cell Mol Immunol 18:1082–1084. https://doi.org/10.1038/s41423-020-00535-1
Wang S, Cao C, Piao H, Li Y, Tao Y, Zhang X, Zhang D, Sun C, Zhu R, Wang Y, Yuan M, Li D, Du M (2015) Tim-3 protects decidual stromal cells from toll-like receptor-mediated apoptosis and inflammatory reactions and promotes Th2 bias at the maternal-fetal interface. Sci Rep 11(5):9013. https://doi.org/10.1038/srep09013
Wang W, Sung N, Gilman-Sachs A, Kwak-Kim J (2020) T Helper (Th) Cell Profiles in Pregnancy and Recurrent Pregnancy Losses: Th1/Th2/Th9/Th17/Th22/Tfh Cells. Front Immunol 18(11):2025. https://doi.org/10.3389/fimmu.2020.02025
Wilczyńska K, Wiśniewski A, Malinowski A, Barcz E, Wilczyński JR, Kuśnierczyk P, Nowak I (2019) ERAP, KIR and HLA-C gene interaction in susceptibility to recurrent spontaneous abortion in the Polish population. Hum Immunol 80(5):344–348. https://doi.org/10.1016/j.humimm.2019.02.010
WO/2019/207039 (2019) HLA-J Medical and diagnostic uses thereof
WO/2021/005001 (2020) HLA-H in medicine and diagnostics
Wong LF, Porter TF, Scott JR (2014) Immunotherapy for recurrent miscarriage. Cochrane Database of Systematic Reviews (Issue 10) Art. No.:CD000112. https://doi.org/10.1002/14651858.CD000112.pub3
Worsham C, Jena AB (2019) The art of evidence-based medicine. Harvard Business Rev
Wu W (2018) Study on the protective effect of G-CSF on RIF and RA patients with low HCG level in early pregnancy. Fertil Steril 110(4) suppl.:E257–E258. DOI:https://doi.org/10.1016/j.fertnstert.2018.07.734
Würfel W (2016) Heparin and related substances: physiology and pathophysiology in general and in human reproduction – Part 1. J Reproduktionsmed Endokrinol Online 13(2):38–48
Würfel W (2015) Treatment with granulocyte colony-stimulating factor in patients with repetitive implantation failures and/or recurrent spontaneous abortions. J Reprod Immunol 108:123–135. https://doi.org/10.1016/j.jri.2015.01.010
Wuerfel F, Huebner HH, Strich R, Fasching P, Beckmann M, Wuerfel W, Ruebner M (2016) Does differential HLA-E and -F expression cause an aberrant immune tolerance in preeclampsia and HELLP? J Reprod Immunol 115:75. https://doi.org/10.1016/j.jri.2016.04.233
Würfel W, Santjohanser CG (2020) CSF and repeated spontaneous abortions: deficiency is an indication, previous live births and ‘unexplained’ situations are not. Human Reproduction 35(6):147. https://doi.org/10.1093/humrep/deaa080
Yamada H, Morikawa M, Furuta I, Kato EH, Shimada S, Iwabuchi K, Minakami H (2003) Intravenous Immunoglobulin Treatment in Women with Recurrent Abortions: Increased Cytokine Levels and Reduced Th1/Th2 Lymphocyte Ratio in Peripheral Blood. Am J Reprod Immunol 49:84–89. https://doi.org/10.1034/j.1600-0897.2003.01184.x
Yan WH, Lin A, Chen XJ, Dai MZ, Gan LH, Zhou MY, Zhu M, Shi WW, Liu JM (2006) Association of the maternal 14-bp insertion polymorphism in the HLA-G gene in women with recurrent spontaneous abortions. Tissue Antigens 68(6):521–523. https://doi.org/10.1111/j.1399-0039.2006.00723.x
Yang X, Meng T (2020) Is there a Role of Intravenous Immunoglobulin in Immunologic Recurrent Pregnancy Loss? J Immunol Res 27(2020):6672865. https://doi.org/10.1155/2020/6672865
Zafardoust S, Akhondi MM, Sadeghi MR, Mohammadzadeh A, Karimi A, Jouhari S, Ansaripour S (2017) Efficacy of Intrauterine Injection of Granulocyte Colony Stimulating Factor (G-CSF) on Treatment of Unexplained Recurrent Miscarriage: A Pilot RCT Study. J Reprod Infertil 18(4):379–385
Zamaniyan M, Peyvandi S, Heidaryan Gorji H, Moradi S, Jamal J, Yahya Poor Aghmashhadi F, Hossein Mohammadi M (2021) Effect of platelet-rich plasma on pregnancy outcomes in infertile women with recurrent implantation failure: a randomized controlled trial. Gynecol Endocrinol 37(2):141–145. https://doi.org/10.1080/09513590.2020.1756247
Zenclussen AC, Fest S, Busse P, Joachim R, Klapp BF, Arck PC (2002) Questioning the Th1/Th2 paradigm in reproduction: peripheral levels of IL-12 are down-regulated in miscarriage patients. Am J Reprod Immunol 48(4):245–251. https://doi.org/10.1034/j.1600-0897.2002.01136.x
Zeng M, Wen P, Duan J (2019) Association of antinuclear antibody with clinical outcome of patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment: A meta-analysis. Am J Reprod Immunol 82:e1
Zeng W, Qin S, Wang R et al (2020) PDL1 blockage increases fetal resorption and Tfr cells but does not affect Tfh/Tfr ratio and B-cell maturation during allogeneic pregnancy. Cell Death Dis 11:119. https://doi.org/10.1038/s41419-020-2313-7
Zhang L, Xu WH, Fu XH, Huang QX, Guo XY, Zhang L, Li SS, Zhu J, Shu J (2018) Therapeutic role of granulocyte colony-stimulating factor (G-CSF) for infertile women under in vitro fertilization and embryo transfer (IVF-ET) treatment: a meta-analysis. Arch Gynecol Obstet 298(5):861–871. https://doi.org/10.1007/s00404-018-4892-4
Zheng J, Zhang H, Xu X, Ma W, Li J, Xia S, Wang H, Shen X (2016) Analysis of the association of human leukocyte antigen DQ gene polymorphisms with unexplained recurrent spontaneous abortion among ethnic Han Chinese from Wenzhou region. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 33(1):81–84. https://doi.org/10.3760/cma.j.issn.1003-9406.2016.01.020
Zhu Y, Huo Z, Lai J, Li S, Jiao H, Dang J, Jin C (2010) Case-control study of a HLA-G 14-bp insertion-deletion polymorphism in women with recurrent miscarriages. Scand J Immunol 71(1):52–54. https://doi.org/10.1111/j.1365-3083.2009.02348.x
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 Der/die Autor(en), exklusiv lizenziert an Springer-Verlag GmbH, DE, ein Teil von Springer Nature
About this chapter
Cite this chapter
Würfel, W. (2023). Wiederholte Spontanaborte. In: Würfel, W. (eds) Reproduktionsimmunologie. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-63907-8_13
Download citation
DOI: https://doi.org/10.1007/978-3-662-63907-8_13
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-662-63906-1
Online ISBN: 978-3-662-63907-8
eBook Packages: Medicine (German Language)