Efectividad del tratamiento inmunomodulador con leucocitos alogénicos, en aborto involuntario recurrente. Revisión sistemática y metaanálisis


Autoria(s): Polaina Macías, Andrea Lorena; González Medina, Luz Elena
Contribuinte(s)

Ibáñez-Pinilla, Milcíades

Data(s)

12/02/2016

Resumo

Dentro del marco del aborto involuntario recurrente (AIR), se han propuesto causas autoinmunes y alogénicas, e implementación de terapias como la inmunización activa con leucocitos alogénicos de la pareja o de donantes. La evidencia disponible en cuanto a la efectividad de estos tratamientos es contradictoria, por lo que se desea realizar una revisión sistemática para evaluar la efectividad de la inmunización activa con leucocitos alogénicos de la pareja o de donantes para esta condición. Se realizó un estudio tipo revisión sistemática de la literatura, usando las siguientes bases de datos: Medline, Embase, Cochrane Library y Scielo. Se realizó una búsqueda a través del registro de ensayos clínicos del Instituto Nacional de Salud de los Estados Unidos (www.clinicaltrials.gov) y, una búsqueda manual a través de las referencias de los estudios seleccionados siguiendo la estrategia de bola de nieve. Se seleccionaron ensayos clínicos y estudios de cohorte analítica, en idioma inglés y español. Se realizó un análisis cuantitativo de la información por medio de un metaanálisis. El tratamiento inmunomodulador con linfocitos puede considerarse como una terapia efectiva para mantener la gestación y lograr recién nacido vivo según resultados estadísticos; sin embargo la calidad de los estudios incluidos es baja, por lo que no se aconseja para la práctica rutinaria. Se sugiere la realización de estudios con metodologías robustas y que apoyen los resultados presentados en esta investigación.

Involuntary recurrent abortion (IRA) is defined as the history of three or more abortions before 20 weeks of gestation. Within its etiology has been proposed and allogeneic or autoimmune causes, with the implementation of therapies that try to immunize women against "foreign" cells of a future pregnancy like the trophoblast membrane immunization, active immunization with allogeneic leukocytes partner or donor and the use of intravenous immunoglobulin (IVIG). The available evidence regarding their effectiveness is scarce and contradictory, which is why we want to conduct a systematic review to assess the effectiveness of this treatment, measured by the rate of live births in women with AIR, who were treted by immunomodulator, and the adverse events presented in the mother and child. Asystematic review of the literature will be conducted. First, a search will be make through the following databases: Medline, Embase, Cochrane Library and Scielo. Also a search made through the registration of clinical trials at the National Institute of Health in the United States (www.clinicaltrials. gov) and finally manual search will be made through the references of the selected studies following the snowball strategy. The following search terms will be used: Human, pregnancy, involuntary recurrent abortion, prevention, control, immunotherapy, immunization, allogeneic leukocytes, trophoblast, newborn, controlled clinical trials, cohort, in different combinations. If the studies allow a quantitative analysis of the information will be made. This systematic review will provide evidence about the effectiveness of immunomodulatory treatments to achieve pregnancy and live birth and assess gestational week at birth and complications in the newborn. The results will serve to discuss the use of inmunomodulator treatment in cases of IRA. It will serve as a starting point for the implementation of a treatment strategy that is beneficial to patients and complement existing clinical practice protocols.

Formato

application/pdf

Identificador

http://repository.urosario.edu.co/handle/10336/11848

Idioma(s)

spa

Publicador

Facultad de Medicina

Direitos

info:eu-repo/semantics/openAccess

Fonte

instname:Universidad del Rosario

reponame:Repositorio Institucional EdocUR

Toth B, Jeschke U, Rogenhofer N, Scholz C, Würfel W, Thaler CJ, et al. Recurrent miscarriage: current concepts in diagnosis and treatment. Journal of reproductive immunology. 2010;85(1):25-32.

Jauniaux E, Farquharson RG, Christiansen OB, Exalto N. Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage. Human reproduction. 2006;21(9):2216-22.

Shapira E, Ratzon R, Shoham-Vardi I, Serjienko R, Mazor M, Bashiri. Primary versus secondary recurrent pregnancy loss – epidemiological characteristics, etiology, and next pregnancy outcome. J Perinat Med 2012;40:389–96

Cavalcante MB, Costa FDS, Araujo Júnior E, Barini R. Risk factors associated with a new pregnancy loss and perinatal outcomes in cases of recurrent miscarriage treated with lymphocyte immunotherapy. The Journal of Maternal-Fetal & Neonatal Medicine. 2014(0):1-5

Porter TF, LaCoursiere Y, Scott JR: Immunotherapy for recurrent miscarriage. Cochrane Database Syst Rev. 2006, 2:CD000112.

Ford HB, Schust DJ. Recurrent pregnancy loss: etiology, diagnosis, and therapy. Reviews in Obstetrics and Gynecology. 2009;2(2):76.

Branch DW, Gibson M, Silver RM. Recurrent miscarriage. New England Journal of Medicine. 2010;363(18):1740-7.

Schwab I, Nimmerjahn F. Intravenous immunoglobulin therapy: how does IgG modulate the immune system? Nature Reviews Immunology. 2013;13(3):176-89

Pandey MK, Agrawal S. Induction of MLR-Bf and protection of fetal loss: a current double blind randomized trial of paternal lymphocyte immunization for women with recurrent spontaneous abortion. International immunopharmacology. 2004;4(2):289-98.

Pandey MK, Saxena V, Agrawal S. Characterization of mixed lymphocyte reaction blocking antibodies (MLR-Bf) in human pregnancy. BMC pregnancy and childbirth. 2003;3(1):2.

Kling C, Schmutzler A, Wilke G, Hedderich J, Kabelitz D. Two-year outcome after recurrent implantation failure: prognostic factors and additional interventions. Archives of gynecology and obstetrics. 2008;278(2):135-42

Egerup P, Lindschou J, Gluud C, Christiansen OB, ImmuRe MIPDSG. The Effects of Intravenous Immunoglobulins in Women with Recurrent Miscarriages: A Systematic Review of Randomised Trials with Meta-Analyses and Trial Sequential Analyses Including Individual Patient Data. PloS one. 2015;10(10):e0141588

Pandey MK, Rani R, Agrawal S. An update in recurrent spontaneous abortion. Archives of gynecology and obstetrics. 2005;272(2):95-108.

Costa CM, Mattos CA, Cuce MR. Estrategia pico para la construcción de la pregunta de investigación y la búsqueda de evidencias. Rev Latino-am Enfermagem. 2007;15(3). .

Khonina N, Broitman E, Shevela E, Pasman N, Chernykh E. Mixed lymphocyte reaction blocking factors (MLR-Bf) as potential biomarker for indication and efficacy of paternal lymphocyte immunization in recurrent spontaneous abortion. Archives of gynecology and obstetrics. 2013;288(4):933-7

Wong LF, Porter TF, Scott JR. Immunotherapy for recurrent miscarriage. The Cochrane Library. 2014

Daya S, Gunby J. The effectiveness of allogeneic leukocyte immunization in unexplained primary recurrent spontaneous abortion. American Journal of Reproductive Immunology. 1994;32(4):294-302

Branch W, Gibson M, silver M. Recurrent Miscarriage. N engl J Med. 2010 28;363(18):1740-7

American college of Obstetricians and Gynecologists. 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 Gynaecol Obstet. 2002 aug;78(2):179-90.

Rai R, Regan L. Recurrent miscarriage. The Lancet. 2006;368(9535):601-11.

Sugiura-Ogasawara M, Ozaki Y, Kitaori T, Kumagai K, Suzuki S. Midline uterine defect size is correlated with miscarriage of euploid embryos in recurrent cases. Fertility and sterility. 2010;93(6):1983-8.

Sugiura-Ogasawara M, Ozaki Y, Sato T, Suzumori N, Suzumori K. Poor prognosis of recurrent aborters with either maternal or paternal reciprocal translocations. Fertility and sterility. 2004;81(2):367-73

Sugiura‐Ogasawara M, Ozaki Y, Suzumori N. Management of recurrent miscarriage. Journal of Obstetrics and Gynaecology Research. 2014;40(5):1174-9

Erlebacher A. Immunology of the maternal-fetal interface. Annual review of immunology. 2013;31:387-411.

Salamonsen LA, Evans J, Nguyen H, Edgell TA. The Microenvironment of Human Implantation: Determinant of Reproductive Success. American Journal of Reproductive Immunology. 2015

Sugiura-Ogasawara M, Ozaki Y, Katano K, Suzumori N, Kitaori T, Mizutani E. Abnormal embryonic karyotype is the most frequent cause of recurrent miscarriage. Human reproduction. 2012;27(8):2297-303.

Golos TG, Bondarenko GI, Dambaeva SV, Breburda EE, Durning M. On the role of placental Major Histocompatibility Complex and decidual leukocytes in implantation and pregnancy success using non-human primate models. The International journal of developmental biology. 2010;54(2-3):431.

Moffett-King A. Natural killer cells and pregnancy. Nature Reviews Immunology. 2002;2(9):656-63.

Tilburgs T, Scherjon SA, van der Mast BJ, Haasnoot GW, Voort-Maarschalk MV-v, Roelen DL, et al. Fetal–maternal HLA-C mismatch is associated with decidual T cell activation and induction of functional T regulatory cells. Journal of reproductive immunology. 2009;82(2):148-57.

Porter TF, Scott JR, editors. Alloimmune causes of recurrent pregnancy loss. Seminars in reproductive medicine; 2000.

Radović-Janošević D, Lilić V, Bašić H, Tubić-Pavlović A, Stefanović M, Milošević J. Decidual natural killer cells in recurrent spontaneous abortions. Vojnosanitetski pregled. 2011;68(1):41-5

Wu L, Luo L-H, Zhang Y-X, Li Q, Xu B, Zhou G-X, et al. Alteration of Th17 and Treg cells in patients with unexplained recurrent spontaneous abortion before and after lymphocyte immunization therapy. Reprod Biol Endocrinol. 2014;12(74):10.1186.

Khonina NA, Broitman EV, Shevela EY, Pasman NM, Chernykh ER. Mixed lymphocyte reaction blocking factors (MLR-Bf) as potential biomarker for indication and efficacy of paternal lymphocyte immunization in recurrent spontaneous abortion. Archives of gynecology and obstetrics. 2013;288(4):933-7.

Pandey MK, Thakur S, Agrawal S. Lymphocyte immunotherapy and its probable mechanism in the maintenance of pregnancy in women with recurrent spontaneous abortion. Archives of gynecology and obstetrics. 2004;269(3):161-72

Nonaka T, Takakuwa K, Ooki I, Akashi M, Yokoo T, Kikuchi A, et al. Results of Immunotherapy for Patients with Unexplained Primary Recurrent Abortions–Prospective Non‐Randomized Cohort Study. American Journal of Reproductive Immunology. 2007;58(6):530-6

ICH-Guideline for Good Clinical Practice. [Internet]; 2002. [fecha de consulta 5 de Agosto de 2015]. Disponible en: [http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002874.pdf%5D.

OCEBM Levels of Evidence Working Group. The oxford levels of evidence 2. [Internet]; 2009 [fecha de consulta 6 de Agosto de 2015]. Disponible en: http://www.cebm.net/index.aspx?o=5653

Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions: Wiley Online Library; 2008

Wells GA, Shea B, O’connell D, Peterson JEA, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2000.

Borenstein M, Hedges L, Higgins J, Rothstein H. Publication Bias. En Borenstein M, Hedges L, Higgins J, Rothstein H. Introduction to meta-analysis Londres. London: Wiley; 2009.

Gharesi‐Fard B, Zolghadri J, Kamali‐Sarvestani E. Effect of Leukocyte Therapy on Tumor Necrosis Factor‐Alpha and Interferon‐Gamma Production in Patients with Recurrent Spontaneous Abortion. American Journal of Reproductive Immunology. 2008;59(3):242-50

Gharesi-Fard B, Zolghadri J, Foroughinia L, Tavazoo F, Samsami Dehaghani A. Effectiveness of leukocyte immunotherapy in primary recurrent spontaneous abortion (RSA). Iran J Immunol. 2007;4(3):173-8.

Katano K, Ogasawara M, Aoyama T, Ozaki Y, Kajiura S, Aoki K. Clinical trial of immunostimulation with a biological response modifier in unexplained recurrent spontaneous abortion patients. Journal of clinical immunology. 1997;17(6):472-7.

Illeni MT, Marelli G, Parazzini F, Acaia B, Bocciolone L, Bontempelli M, et al. Immunology: Immunotherapy and recurrent abortion: a randomized clinical trial. Human Reproduction. 1994;9(7):1247-9.

Christiansen OB, Mathiesen O, Husth M, Lauritsen JG, Grunnet N. Placebo-controlled trial of active immunization with third party leukocytes in recurrent miscarriage. Acta obstetricia et gynecologica Scandinavica. 1994;73(3):261-8

Gatenby PA, Cameron K, Adelstein S, Simes R, Bennett MJ, Jansen RP, et al. Treatment of recurrent spontaneous abortion by immunization with paternal lymphocytes: results of a controlled trial. American Journal of Reproductive Immunology. 1993;29(2):88-94

Kilpatrick DC. Soluble interleukin-2 receptors in recurrent miscarriage and the effect of leukocyte immunotherapy. Immunology letters. 1992;34(3):201-6

TEME

Palavras-Chave #618.2 #Embarazo #Aborto espontáneo #Inmunoterapia #Inmunización #Trofoblastos #Recién nacido #Human #Pregnancy #Recurrent miscarriage #Prevention #Control #Immunotherapy #Immunization #Allogeneic leukocytes #Trophoblast #Newborn #Controlled clinical trials #Cohort
Tipo

info:eu-repo/semantics/bachelorThesis

info:eu-repo/semantics/acceptedVersion