Corticosteroid therapy in assisted reproduction - Immune suppression is a faulty premise

Human Reproduction

Volumn 31, Issue 10, 2016, Pages 2164-2173

  Robertson, Sarah A ^a   Jin, Min ^a,b   Yu, Danqing ^b   Moldenhauer, Lachlan M ^a   Davies, Michael J ^a   Hull, M Louise ^a   Norman, Robert J ^a,c  

^a UNIVERSITY OF ADELAIDE   (Australia)

^b ZHEJIANG UNIVERSITY   (China)

^c Fertility SA   (Australia)

Author keywords

corticosteroid; embryo implantation; endometrium; glucocorticoid; immune cells; immunology; inflammation; IVF failure; pregnancy; recurrent miscarriage

Indexed keywords

CORTICOSTEROID; PREDNISOLONE; IMMUNOSUPPRESSIVE AGENT;

ADVERSE DRUG REACTION; CONCEPTION; CONGENITAL MALFORMATION; CORTICOSTEROID THERAPY; DENDRITIC CELL; DRUG EFFICACY; ENDOMETRIUM; HUMAN; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; IMMUNOSUPPRESSIVE TREATMENT; INFERTILITY; INFERTILITY THERAPY; MACROPHAGE; NATURAL KILLER CELL; NIDATION; OUTCOME ASSESSMENT; PREGNANCY; PREMATURE LABOR; QUALITY CONTROL; REGULATORY T LYMPHOCYTE; REVIEW; FEMALE; IMMUNOLOGY; RECURRENT ABORTION;

ABORTION, HABITUAL; EMBRYO IMPLANTATION; ENDOMETRIUM; FEMALE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; PREDNISOLONE; PREGNANCY; REPRODUCTIVE TECHNIQUES, ASSISTED;

EID: 84992323007     PISSN: 02681161     EISSN: 14602350     Source Type: Journal    
DOI: 10.1093/humrep/dew186     Document Type: Review

References (93)

1. Abrahams VM, Kim YM, Straszewski SL, Romero R, Mor G. Macrophages and apoptotic cell clearance during pregnancy. Am J Reprod Immunol 2004;51:275-282.
2. Aluvihare VR, Kallikourdis M, Betz AG. Regulatory T cells mediate maternal tolerance to the fetus. Nat Immunol. 2004;5:266-271.
3. Andre S, Tough DF, Lacroix-Desmazes S, Lacroix-Desmazes S, Kaveri SV, Bayry J. Surveillance of antigen-presenting cells by CD4+ CD25+ regulatory T cells in autoimmunity: immunopathogenesis and therapeutic implications. Am J Pathol 2009;174:1575-1587.
4. Azab NA, Bassyouni IH, Emad Y, Abd El-Wahab GA, Hamdy G, Mashahit MA. CD4+ CD25+ regulatory T cells (TREG) in systemic lupus erythematosus (SLE) patients: The possible influence of treatment with corticosteroids. Clin Immunol 2008;127:151-157.
5. Bamberger AM, Milde-Langosch K, Loning T, Bamberger CM. The glucocorticoid receptor is specifically expressed in the stromal compartment of the human endometrium. J Clin Endocrinol Metab 2001; 86:5071-5074.
6. Blois SM, Kammerer U, Alba Soto C, Tometten MC, Shaikly V, Barrientos G, Jurd R, Rukavina D, Thomson AW, Klapp BF et al. Dendritic cells: key to fetal tolerance Biol Reprod 2007;77:590-598.
7. Blois SM, Klapp BF, Barrientos G. Decidualization and angiogenesis in early pregnancy: unravelling the functions of DC and NK cells. J Reprod Immunol 2011;88:86-92.
8. Boomsma CM, Keay SD, Macklon NS. Peri-implantation glucocorticoid administration for assisted reproductive technology cycles. Cochrane Database Syst Rev 2012;6:CD005996.
9. Boumpas DT, Chrousos GP, Wilder RL, Cupps TR, Balow JE. Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Ann Intern Med 1993;119:1198-1208.
10. Brosens I, Pijnenborg R, Vercruysse L, Romero R. The 'Great Obstetrical Syndromes' are associated with disorders of deep placentation. Am J Obstet Gynecol 2011;204:193-201.
11. Care AS, Diener KR, Jasper MJ, Brown HM, Ingman WV, Robertson SA. Macrophages regulate corpus luteum development during embryo implantation in mice. J Clin Invest 2013;123:3472-3487.
12. Carmichael SL, Shaw GM. Maternal corticosteroid use and risk of selected congenital anomalies. Am J Med Genet 1999;86:242-244.
13. Chen X, Oppenheim JJ, Winkler-Pickett RT, Ortaldo JR, Howard OM. Glucocorticoid amplifies IL-2-dependent expansion of functional FoxP3(+) CD4(+)CD25(+) T regulatory cells in vivo and enhances their capacity to suppress EAE. Eur J Immunol 2006;36:2139-2149.
14. Dekel N, Gnainsky Y, Granot I, Racicot K, Mor G. The role of inflammation for a successful implantation. Am J Reprod Immunol 2014;72:141-147.
15. Duvan CI, Ozmen B, Satiroglu H, Atabekoglu CS, Berker B. Does addition of low-dose aspirin and/or steroid as a standard treatment in nonselected intracytoplasmic sperm injection cycles improve in vitro fertilization success A randomized, prospective, placebo-controlled study. J Assist Reprod Genet 2006;23:15-21.
16. Fowden AL, Forhead AJ. Glucocorticoids as regulatory signals during intrauterine development. Exp Physiol 2015;100:1477-1487.
17. Fox C, Morin S, Jeong JW, Scott RT Jr, Lessey BA. Local and systemic factors and implantation: what is the evidence Fertil Steril 2016; 105:873-884.
18. Franchimont D. Overview of the actions of glucocorticoids on the immune response: A good model to characterize new pathways of immunosuppression for new treatment strategies. Ann NY Acad Sci 2004;1024: 124-137.
19. Fukui A, Fujii S, Yamaguchi E, Kimura H, Sato S, Saito Y. Natural killer cell subpopulations and cytotoxicity for infertile patients undergoing in vitro fertilization. Am J Reprod Immunol 1999;41:413-422.
20. Geva E, Amit A, Lerner-Geva L, Yaron Y, Daniel Y, Schwartz T, Azem F, Yovel I, Lessing JB. Prednisone and aspirin improve pregnancy rate in patients with reproductive failure and autoimmune antibodies: A prospective study. Am J Reprod Immunol 2000;43:36-40.
21. Gnainsky Y, Granot I, Aldo PB, Barash A, Or Y, Schechtman E, Mor G, Dekel N. Local injury of the endometrium induces an inflammatory response that promotes successful implantation. Fertil Steril 2010;94: 2030-2036.
22. Guerin LR, Moldenhauer LM, Prins JR, Bromfield JJ, Hayball JD, Robertson SA. Seminal fluid regulates accumulation of FOXP3+ regulatory T cells in the preimplantation mouse uterus through expanding the FOXP3+ cell pool and CCL19-mediated recruitment. Biol Reprod 2011; 85:397-408.
23. Guerin LR, Prins JR, Robertson SA. Regulatory T-cells and immune tolerance in pregnancy: A new target for infertility treatment Hum Reprod Update 2009;15:517-535.
24. Gur C, Diav-Citrin O, Shechtman S, Arnon J, Ornoy A. Pregnancy outcome after first trimester exposure to corticosteroids: A prospective controlled study. Reprod Toxicol 2004;18:93-101.
25. Hanson RG, Peters MG, Hoofnagle JH. Effects of immunosuppressive therapy with prednisolone on B and T lymphocyte function in patients with chronic type B hepatitis. Hepatology 1986;6:173-179.
26. Hasegawa I, Yamanoto Y, Suzuki M, Murakawa H, Kurabayashi T, Takakuwa K, Tanaka K. Prednisolone plus low-dose aspirin improves the implantation rate in women with autoimmune conditions who are undergoing in vitro fertilization. Fertil Steril 1998;70:1044-1048.
27. Henderson TA, Saunders PT, Moffett-King A, Groome NP, Critchley HO. Steroid receptor expression in uterine natural killer cells. J Clin Endocrinol Metab 2003;88:440-449.
28. Hsu P, Santner-Nanan B, Dahlstrom JE, Fadia M, Chandra A, Peek M, Nanan R. Altered decidual DC-SIGN+ antigen-presenting cells and impaired regulatory T-cell induction in preeclampsia. Am J Pathol 2012;181:2149-2160.
29. Huppertz B. Placental origins of preeclampsia: challenging the current hypothesis. Hypertension 2008;51:970-975.
30. Jasper MJ, Tremellen KP, Robertson SA. Primary unexplained infertility is associated with reduced expression of the T-regulatory cell transcription factor Foxp3 in endometrial tissue. Mol Hum Reprod 2006;12:301-308.
31. Krigstein M, Sacks G. Prednisolone for repeated implantation failure associated with high natural killer cell levels. J Obstet Gynaecol 2012;32: 518-519.
32. Kuroda K, Venkatakrishnan R, James S, Šucurovic S, Mulac-Jericevic B, Lucas ES, Takeda S, Shmygol A, Brosens JJ, Quenby S. Elevated periimplantation uterine natural killer cell density in human endometrium is associated with impaired corticosteroid signaling in decidualizing stromal cells. J Clin Endocrinol Metab 2013;98:4429-4437.
33. Kuroda K, Venkatakrishnan R, Salker MS, Lucas ES, Shaheen F, Kuroda M, Blanks A, Christian M, Quenby S, Brosens JJ. Induction of 11beta-HSD 1 and activation of distinct mineralocorticoid receptor-and glucocorticoid receptor-dependent gene networks in decidualizing human endometrial stromal cells. Mol Endocrinol 2013;27:192-202.
34. Lachapelle MH, Miron P, Hemmings R, Roy DC. Endometrial T, B, and NK cells in patients with recurrent spontaneous abortion. Altered profile and pregnancy outcome. J Immunol 1996;156:4027-4034.
35. Lainas T, Petsas G, Stavropoulou G, Alexopoulou E, Iliadis G, Minaretzis D. Administration of methylprednisolone to prevent severe ovarian hyperstimulation syndrome in patients undergoing in vitro fertilization. Fertil Steril 2002;78:529-533.
36. Lash GE, Bulmer JN, Innes BA, Drury JA, Robson SC, Quenby S. Prednisolone treatment reduces endometrial spiral artery development in women with recurrent miscarriage. Angiogenesis 2011;14:523-532.
37. Laskin CA, Bombardier C, Hannah ME, Mandel FP, Ritchie JW, Farewell V, Farine D, Spitzer K, Fielding L, Soloninka CA et al. Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss. N Engl J Med 1997;337:148-153.
38. Lee KA, Koo JJ, Yoon TK, Do BR, Ko JJ, Cha KY. Immunosuppression by corticosteroid has no effect on the pregnancy rate in routine in-vitro fertilization/ embryo transfer patients. Hum Reprod 1994;9:1832-1835.
39. Lessey BA. Assessment of endometrial receptivity. Fertil Steril 2011;96: 522-529.
40. Lima PD, Zhang J, Dunk C, Lye SJ, Croy BA. Leukocyte driven-decidual angiogenesis in early pregnancy. Cell Mol Immunol 2014;11:522-537.
41. Luther C, Adamopoulou E, Stoeckle C, Brucklacher-Waldert V, Rosenkranz D, Stoltze L, Lauer S, Poeschel S, Melms A, Tolosa E. Prednisolone treatment induces tolerogenic dendritic cells and a regulatory milieu in myasthenia gravis patients. J Immunol 2009;183:841-848.
42. Macklon NS, Brosens JJ. The human endometrium as a sensor of embryo quality. Biol Reprod 2014;91:98.
43. Madeja Z, Yadi H, Apps R, Boulenouar S, Roper SJ, Gardner L, Moffett A, Colucci F, Hemberger M. Paternal MHC expression on mouse trophoblast affects uterine vascularization and fetal growth. Proc Natl Acad Sci USA 2011;108:4012-4017.
44. Matteo MG, Greco P, Rosenberg P, Mestice A, Baldini D, Falagario T, Martino V, Santodirocco M, Massenzio F, Castellana L et al. Normal percentage of CD56bright natural killer cells in young patients with a history of repeated unexplained implantation failure after in vitro fertilization cycles. Fertil Steril 2007;88:990-993.
45. Michael AE, Papageorghiou AT. Potential significance of physiological and pharmacological glucocorticoids in early pregnancy. Hum Reprod Update 2008;14:497-517.
46. Mjosberg J, Svensson J, Johansson E, Hellström L, Casas R, Jenmalm MC, Boij R, Matthiesen L, Jönsson JI, Berg G et al. Systemic reduction of functionally suppressive CD4dimCD25highFoxp3+ Tregs in human second trimester pregnancy is induced by progesterone and 17beta-estradiol. J Immunol 2009;183:759-769.
47. Moffett A, Colucci F. Uterine NK cells: Active regulators at the maternalfetal interface. J Clin Invest 2014;124:1872-1879.
48. Moffett A, Shreeve N. First do no harm: uterine natural killer (NK) cells in assisted reproduction. Hum Reprod 2015;30:1519-1525.
49. Moffitt D, Queenan JT Jr, Veeck LL, Schoolcraft W, Miller CE, Muasher SJ. Low-dose glucocorticoids after in vitro fertilization and embryo transfer have no significant effect on pregnancy rate. Fertil Steril 1995;63: 571-577.
50. Moldenhauer LM, Diener KR, Thring DM, Brown MP, Hayball JD, Robertson SA. Cross-presentation of male seminal fluid antigens elicits T cell activation to initiate the female immune response to pregnancy. J Immunol 2009;182:8080-8093.
51. Mor G, Cardenas I, Abrahams V, Guller S. Inflammation and pregnancy: The role of the immune system at the implantation site. Ann NY Acad Sci 2011;1221:80-87.
52. Motteram C, Vollenhoven B, Hope N, Osianlis T, Rombauts LJ. Live birth rates after combined adjuvant therapy in IVF-ICSI cycles: A matched case-control study. Reprod Biomed Online 2015;30:340-348.
53. Nagamatsu T, Schust DJ. The contribution of macrophages to normal and pathological pregnancies. Am J Reprod Immunol 2010;63:460-471.
54. Nakamura H, Jasper MJ, Hull ML, Aplin JD, Robertson SA. Macrophages regulate expression of alpha1, 2-fucosyltransferase genes in human endometrial epithelial cells. Mol Hum Reprod 2012;18:204-215.
55. Ogasawara M, Aoki K. Successful uterine steroid therapy in a case with a history of ten miscarriages. Am J Reprod Immunol 2000;44:253-255.
56. Park-Wyllie L, Mazzotta P, Pastuszak A, Moretti ME, Beique L, Hunnisett L, Friesen MH, Jacobson S, Kasapinovic S, Chang D et al. Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology 2000;62:385-392.
57. Piccinni MP, Beloni L, Livi C, Maggi E, Scarselli G, Romagnani S. Defective production of both leukemia inhibitory factor and type 2 T-helper cytokines by decidual T cells in unexplained recurrent abortions. Nat Med 1998;4:1020-1024.
58. Pijnenborg R, Vercruysse L, Hanssens M. Fetal-maternal conflict, trophoblast invasion, preeclampsia, and the red queen. Hypertens Pregnancy 2008;27:183-196.
59. Pinsky L, Digeorge AM. Cleft palate in the mouse: A teratogenic index of glucocorticoid potency. Science 1965;147:402-403.
60. Plaks V, Birnberg T, Berkutzki T, Sela S, BenYashar A, Kalchenko V, Mor G, Keshet E, Dekel N, Neeman M et al. Uterine DCs are crucial for decidua formation during embryo implantation in mice. J Clin Invest 2008; 118:3954-3965.
61. Polak de Fried E, Blanco L, Lancuba S, Asch RH. Improvement of clinical pregnancy rate and implantation rate of in-vitro fertilization-embryo transfer patients by using methylprednisone. Hum Reprod 1993;8: 393-395.
62. Pollard JW. Trophic macrophages in development and disease. Nat Rev Immunol 2009;9:259-270.
63. Quenby S, Bates M, Doig T, Brewster J, Lewis-Jones DI, Johnson PM, Vince G. Pre-implantation endometrial leukocytes in women with recurrent miscarriage. Hum Reprod 1999;14:2386-2391.
64. Quenby S, Farquharson R, Young M, Vince G. Successful pregnancy outcome following 19 consecutive miscarriages: case report. Hum Reprod 2003;18:2562-2564.
65. Quenby S, Kalumbi C, Bates M, Farquharson R, Vince G. Prednisolone reduces preconceptual endometrial natural killer cells in women with recurrent miscarriage. Fertil Steril 2005;84:980-984.
66. Quenby S, Nik H, Innes B, Lash G, Turner M, Drury J, Bulmer J. Uterine natural killer cells and angiogenesis in recurrent reproductive failure. Hum Reprod 2009;24:45-54.
67. Rae M, Mohamad A, Price D, Hadoke PW, Walker BR, Mason JI, Hillier SG, Critchley HO. Cortisol inactivation by 11beta-hydroxysteroid dehydrogenase-2 may enhance endometrial angiogenesis via reduced thrombospondin-1 in heavy menstruation. J Clin Endocrinol Metab 2009;94:1443-1450.
68. Redman CW, Sargent IL. Immunology of pre-eclampsia. Am J Reprod Immunol 2010;63:534-543.
69. Revelli A, Casano S, Piane LD, Grassi G, Gennarelli G, Guidetti D, Massobrio M. A retrospective study on IVF outcome in euthyroid patients with anti-thyroid antibodies: effects of levothyroxine, acetyl-salicylic acid and prednisolone adjuvant treatments. Reprod Biol Endocrinol 2009;7:137.
70. Revelli A, Dolfin E, Gennarelli G, Ghaemmaghami P, Räikkönen K. Lowdose acetylsalicylic acid plus prednisolone as an adjuvant treatment in IVF: A prospective, randomized study. Fertil Steril 2008;90:1685-1691.
71. Reynolds RM, Labad J, Buss C, Ghaemmaghami P, Räikkönen K. Transmitting biological effects of stress in utero: implications for mother and offspring. Psychoneuroendocrinology 2013;38:1843-1849.
72. Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids-new mechanisms for old drugs. N Engl J Med 2005;353:1711-1723.
73. Robertson SA. Immune regulation of conception and embryo implantation-all about quality control J Reprod Immunol 2010;85:51-57.
74. Robertson SA, Petroff M, Hunt JS. Chapter 41: The Immunology of Pregnancy. In: Plant TM, Zeleznik A (eds). Knobil and Neill's Physiology of Reproduction, 4th edn. Ireland: Elsevier, 2014;1835-1874.
75. Russell P, Sacks G, Tremellen K, Gee A. The distribution of immune cells and macrophages in the endometrium of women with recurrent reproductive failure. III: Further observations and reference ranges. Pathology 2013;45:393-401.
76. Sacks G, Yang Y, Gowen E, Smith S, Fay L, Chapman M. Detailed analysis of peripheral blood natural killer cells in women with repeated IVF failure. Am J Reprod Immunol 2012;67:434-442.
77. Sargent IL, Borzychowski AM, Redman CW. NK cells and human pregnancy-an inflammatory view. Trends Immunol 2006;27:399-404.
78. Sasaki Y, Sakai M, Miyazaki S, Higuma S, Shiozaki A, Saito S. Decidual and peripheral blood CD4+ CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases. Mol Hum Reprod 2004;10:347-353.
79. Sbiera S, Dexneit T, Reichardt SD, Michel KD, van den Brandt J, Schmull S, Kraus L, Beyer M, Mlynski R, Wortmann S et al. Influence of short-term glucocorticoid therapy on regulatory T cells in vivo. PLoS One 2011;6: e24345.
80. Seckl JR, Meaney MJ. Glucocorticoid programming. Ann NY Acad Sci 2004;1032:63-84.
81. Segerer SE, Muller N, van den Brandt J, Kapp M, Dietl J, Reichardt HM, Rieger L, Kämmerer U. Impact of female sex hormones on the maturation and function of human dendritic cells. Am J Reprod Immunol 2009;62:165-173.
82. Seshadri S, Sunkara SK. Natural killer cells in female infertility and recurrent miscarriage: A systematic review and meta-analysis. Hum Reprod Update 2014;20:429-438.
83. Sharkey DJ, Tremellen KP, Jasper MJ, Gemzell-Danielsson K, Robertson SA. Seminal fluid induces leukocyte recruitment and cytokine and chemokine mRNA expression in the human cervix after coitus. J Immunol 2012;188:2445-2454.
84. Suarez A, Lopez P, Gomez J, Gutiérrez C. Enrichment of CD4+ CD25 high T cell population in patients with systemic lupus erythematosus treated with glucocorticoids. Ann Rheum Dis 2006;65:1512-1517.
85. Tang AW, Alfirevic Z, Turner MA, Drury JA, Small R, Quenby S. A feasibility trial of screening women with idiopathic recurrent miscarriage for high uterine natural killer cell density and randomizing to prednisolone or placebo when pregnant. Hum Reprod 2013;28:1743-1752.
86. Thiruchelvam U, Maybin JA, Armstrong GM, Greaves E, Saunders PT, Critchley HO. Cortisol regulates the paracrine action of macrophages by inducing vasoactive gene expression in endometrial cells. J Leukoc Biol 2016;99:1165-1171.
87. Thum MY, Bhaskaran S, Abdalla HI, Ford B, Sumar N, Shehata H, Bansal AS. An increase in the absolute count of CD56dimCD16+CD69+ NK cells in the peripheral blood is associated with a poorer IVF treatment and pregnancy outcome. Hum Reprod 2004;19:2395-2400.
88. Tilburgs T, Scherjon SA, van der Mast BJ, Haasnoot GW, Versteeg VD, Voort-Maarschalk M, Roelen DL, van Rood JJ, Claas FH. Fetalmaternal HLA-C mismatch is associated with decidual T cell activation and induction of functional T regulatory cells. J Reprod Immunol 2009;82:148-157.
89. Ubaldi F, Rienzi L, Ferrero S, Anniballo R, Iacobelli M, Cobellis L, Greco E. Low dose prednisolone administration in routine ICSI patients does not improve pregnancy and implantation rates. Hum Reprod 2002;17:1544-1547.
90. van Mourik MS, Macklon NS, Heijnen CJ. Embryonic implantation: cytokines, adhesion molecules, and immune cells in establishing an implantation environment. J Leukoc Biol 2009;85:4-19.
91. Vassiliadou N, Searle RF, Bulmer JN. Elevated expression of activation molecules by decidual lymphocytes in women suffering spontaneous early pregnancy loss. Hum Reprod 1999;14:1194-1200.
92. Whirledge SD, Oakley RH, Myers PH, Lydon JP, DeMayo F, Cidlowski JA. Uterine glucocorticoid receptors are critical for fertility in mice through control of embryo implantation and decidualization. Proc Natl Acad Sci USA 2015;112:15166-71.
93. Winger EE, Reed JL. Low circulating CD4(+) CD25(+) Foxp3(+) T regulatory cell levels predict miscarriage risk in newly pregnant women with a history of failure. Am J Reprod Immunol 2011;66:320-328.