Clinical and Experimental Reproductive Medicine

  • 제48권4호
  • /
  • Pages.295-302
  • /
  • 2021
  • /
  • 2233-8233(pISSN)
  • /
  • 2233-8241(eISSN)
대한생식의학회 (The Korean Society for Reproductive Medicine)
권호 표지
DOI QR코드

DOI QR Code

Glucocorticoid therapy in assisted reproduction

  • Kim, Yong Jin (Department of Obstetrics and Gynecology, Korea University College of Medicine)
  • 투고 : 2021.07.01
  • 심사 : 2021.08.02
  • 발행 : 2021.12.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

As glucocorticoids are well-known as important regulators of stress and the immune system, their function and clinical use have elicited substantial interest in the field of reproduction. In particular, the effect of glucocorticoid therapy on endometrial receptivity during assisted reproduction, including in vitro fertilization (IVF) cycles, has led to a great deal of interest and controversy. However, previous studies have not been able to provide consistent and reliable evidence due to their small, non-controlled designs and use of different criteria. Considering the potential risk of exposure to glucocorticoids for mothers and fetuses in early pregnancy, the use of glucocorticoids in IVF cycles should be carefully evaluated, including the balance between risk and benefit. To date, there is no conclusive evidence that the use of glucocorticoids improves the pregnancy rate in IVF cycles with unselected subjects, and a further investigation should be considered with a proper study design.

키워드

참고문헌

  1. Kolibianakis EM, Kalogeropoulou L, Griesinger G, Papanikolaou EG, Papadimas J, Bontis J, et al. Among patients treated with FSH and GnRH analogues for in vitro fertilization, is the addition of recombinant LH associated with the probability of live birth?: a systematic review and meta-analysis. Hum Reprod Update 2007;13:445-52. https://doi.org/10.1093/humupd/dmm008
  2. Benaglia L, Busnelli A, Biancardi R, Vegetti W, Reschini M, Vercellini P, et al. Oocyte retrieval difficulties in women with ovarian endometriomas. Reprod Biomed Online 2018;37:77-84. https://doi.org/10.1016/j.rbmo.2018.03.020
  3. Zheng D, Zeng L, Yang R, Lian Y, Zhu YM, Liang X, et al. Intracytoplasmic sperm injection (ICSI) versus conventional in vitro fertilisation (IVF) in couples with non-severe male infertility (NSMI-ICSI): protocol for a multicentre randomised controlled trial. BMJ Open 2019;9:e030366. https://doi.org/10.1136/bmjopen-2019-030366
  4. Chronopoulou E, Harper JC. IVF culture media: past, present and future. Hum Reprod Update 2015;21:39-55. https://doi.org/10.1093/humupd/dmu040
  5. Bashiri A, Halper KI, Orvieto R. Recurrent implantation failure: update overview on etiology, diagnosis, treatment and future directions. Reprod Biol Endocrinol 2018;16:121. https://doi.org/10.1186/s12958-018-0414-2
  6. Edwards RG. Human implantation: the last barrier in assisted reproduction technologies? Reprod Biomed Online 2006;13:887-904. https://doi.org/10.1016/S1472-6483(10)61039-5
  7. Lessey BA, Young SL. Structure, function, and evaluation of the female reproductive tract. In: Strauss JF, Barbieri RL. editors. Yen and Jaffe's reproductive endocrinology. Philadelphia: Elsevier; 2019. p. 206-47.
  8. Hernandez-Vargas P, Munoz M, Dominguez F. Identifying biomarkers for predicting successful embryo implantation: applying single to multi-OMICs to improve reproductive outcomes. Hum Reprod Update 2020;26:264-301. https://doi.org/10.1093/humupd/dmz042
  9. Drakopoulos P, Racca A, Errazuriz J, De Vos M, Tournaye H, Blockeel C, et al. The role of progesterone elevation in IVF. Reprod Biol 2019;19:1-5. https://doi.org/10.1016/j.repbio.2019.02.003
  10. Olesen MS, Hauge B, Ohrt L, Olesen TN, Roskaer J, Baek V, et al. Therapeutic endometrial scratching and implantation after in vitro fertilization: a multicenter randomized controlled trial. Fertil Steril 2019;112:1015-21. https://doi.org/10.1016/j.fertnstert.2019.08.010
  11. Kim H, Shin JE, Koo HS, Kwon H, Choi DH, Kim JH. Effect of autologous platelet-rich plasma treatment on refractory thin endometrium during the frozen embryo transfer cycle: a pilot study. Front Endocrinol (Lausanne) 2019;10:61. https://doi.org/10.3389/fendo.2019.00061
  12. Zhang T, Chen X, Wang CC, Li TC, Kwak-Kim J. Intrauterine infusion of human chorionic gonadotropin before embryo transfer in IVF/ET cycle: the critical review. Am J Reprod Immunol 2019;81:e13077. https://doi.org/10.1111/aji.13077
  13. Bourdon M, Maignien C, Pocate-Cheriet K, Plu Bureau G, Marcellin L, Patrat C, et al. The freeze-all strategy after IVF: which indications? Reprod Biomed Online 2021;42:529-45. https://doi.org/10.1016/j.rbmo.2020.11.013
  14. 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. https://doi.org/10.1189/jlb.0708395
  15. Redman CW, Sargent IL. Immunology of pre-eclampsia. Am J Reprod Immunol 2010;63:534-43. https://doi.org/10.1111/j.1600-0897.2010.00831.x
  16. Robertson SA, Jin M, Yu D, Moldenhauer LM, Davies MJ, Hull ML, et al. Corticosteroid therapy in assisted reproduction: immune suppression is a faulty premise. Hum Reprod 2016;31:2164-73. https://doi.org/10.1093/humrep/dew186
  17. Hasegawa I, Yamanoto Y, Suzuki M, Murakawa H, Kurabayashi T, Takakuwa K, et al. Prednisolone plus low-dose aspirin improves the implantation rate in women with autoimmune conditions who are undergoing in vitro fertilization. Fertil Steril 1998;70:1044-8. https://doi.org/10.1016/S0015-0282(98)00343-4
  18. Krigstein M, Sacks G. Prednisolone for repeated implantation failure associated with high natural killer cell levels. J Obstet Gynaecol 2012;32:518-9. https://doi.org/10.3109/01443615.2012.693988
  19. Whirledge S, Cidlowski JA. Glucocorticoids and reproduction: traffic control on the road to reproduction. Trends Endocrinol Metab 2017;28:399-415. https://doi.org/10.1016/j.tem.2017.02.005
  20. Aguilera G. Regulation of pituitary ACTH secretion during chronic stress. Front Neuroendocrinol 1994;15:321-50. https://doi.org/10.1006/frne.1994.1013
  21. Edwards CR, Benediktsson R, Lindsay RS, Seckl JR. 11 beta-Hydroxysteroid dehydrogenases: key enzymes in determining tissue-specific glucocorticoid effects. Steroids 1996;61:263-9. https://doi.org/10.1016/0039-128X(96)00033-5
  22. Lu NZ, Collins JB, Grissom SF, Cidlowski JA. Selective regulation of bone cell apoptosis by translational isoforms of the glucocorticoid receptor. Mol Cell Biol 2007;27:7143-60. https://doi.org/10.1128/MCB.00253-07
  23. Nehme A, Lobenhofer EK, Stamer WD, Edelman JL. Glucocorticoids with different chemical structures but similar glucocorticoid receptor potency regulate subsets of common and unique genes in human trabecular meshwork cells. BMC Med Genomics 2009;2:58. https://doi.org/10.1186/1755-8794-2-58
  24. Gross KL, Oakley RH, Scoltock AB, Jewell CM, Cidlowski JA. Glucocorticoid receptor alpha isoform-selective regulation of antiapoptotic genes in osteosarcoma cells: a new mechanism for glucocorticoid resistance. Mol Endocrinol 2011;25:1087-99. https://doi.org/10.1210/me.2010-0051
  25. Joseph DN, Whirledge S. Stress and the HPA axis: balancing homeostasis and fertility. Int J Mol Sci 2017;18:2224. https://doi.org/10.3390/ijms18102224
  26. Kadmiel M, Cidlowski JA. Glucocorticoid receptor signaling in health and disease. Trends Pharmacol Sci 2013;34:518-30. https://doi.org/10.1016/j.tips.2013.07.003
  27. Whirledge S, Cidlowski JA. A role for glucocorticoids in stress-impaired reproduction: beyond the hypothalamus and pituitary. Endocrinology 2013;154:4450-68. https://doi.org/10.1210/en.2013-1652
  28. Takumi K, Iijima N, Higo S, Ozawa H. Immunohistochemical analysis of the colocalization of corticotropin-releasing hormone receptor and glucocorticoid receptor in kisspeptin neurons in the hypothalamus of female rats. Neurosci Lett 2012;531:40-5. https://doi.org/10.1016/j.neulet.2012.10.010
  29. Luo E, Stephens SB, Chaing S, Munaganuru N, Kauffman AS, Breen KM. Corticosterone blocks ovarian cyclicity and the LH surge via decreased kisspeptin neuron activation in female mice. Endocrinology 2016;157:1187-99. https://doi.org/10.1210/en.2015-1711
  30. Clarke IJ, Bartolini D, Conductier G, Henry BA. Stress increases gonadotropin inhibitory hormone cell activity and input to GnRH cells in ewes. Endocrinology 2016;157:4339-50. https://doi.org/10.1210/en.2016-1513
  31. Kirby ED, Geraghty AC, Ubuka T, Bentley GE, Kaufer D. Stress increases putative gonadotropin inhibitory hormone and decreases luteinizing hormone in male rats. Proc Natl Acad Sci U S A 2009;106:11324-9. https://doi.org/10.1073/pnas.0901176106
  32. Yuan XH, Yang BQ, Hu Y, Fan YY, Zhang LX, Zhou JC, et al. Dexamethasone altered steroidogenesis and changed redox status of granulosa cells. Endocrine 2014;47:639-47. https://doi.org/10.1007/s12020-014-0250-x
  33. Yuan HJ, Han X, He N, Wang GL, Gong S, Lin J, et al. Glucocorticoids impair oocyte developmental potential by triggering apoptosis of ovarian cells via activating the Fas system. Sci Rep 2016;6:24036. https://doi.org/10.1038/srep24036
  34. Huang TJ, Shirley Li P. Dexamethasone inhibits luteinizing hormone-induced synthesis of steroidogenic acute regulatory protein in cultured rat preovulatory follicles. Biol Reprod 2001;64:163-70. https://doi.org/10.1095/biolreprod64.1.163
  35. Michael AE, Pester LA, Curtis P, Shaw RW, Edwards CR, Cooke BA. Direct inhibition of ovarian steroidogenesis by cortisol and the modulatory role of 11 beta-hydroxysteroid dehydrogenase. Clin Endocrinol (Oxf) 1993;38:641-4. https://doi.org/10.1111/j.1365-2265.1993.tb02147.x
  36. Rhen T, Grissom S, Afshari C, Cidlowski JA. Dexamethasone blocks the rapid biological effects of 17beta-estradiol in the rat uterus without antagonizing its global genomic actions. FASEB J 2003;17:1849-70. https://doi.org/10.1096/fj.02-1099com
  37. Johnson DC, Dey SK. Role of histamine in implantation: dexamethasone inhibits estradiol-induced implantation in the rat. Biol Reprod 1980;22:1136-41. https://doi.org/10.1093/biolreprod/22.5.1136
  38. Henderson TA, Saunders PT, Moffett-King A, Groome NP, Critchley HO. Steroid receptor expression in uterine natural killer cells. J Clin Endocrinol Metab 2003;88:440-9. https://doi.org/10.1210/jc.2002-021174
  39. Logie JJ, Ali S, Marshall KM, Heck MM, Walker BR, Hadoke PW. Glucocorticoid-mediated inhibition of angiogenic changes in human endothelial cells is not caused by reductions in cell proliferation or migration. PLoS One 2010;5:e14476. https://doi.org/10.1371/journal.pone.0014476
  40. McDonald SE, Henderson TA, Gomez-Sanchez CE, Critchley HO, Mason JI. 11Beta-hydroxysteroid dehydrogenases in human endometrium. Mol Cell Endocrinol 2006;248:72-8. https://doi.org/10.1016/j.mce.2005.12.010
  41. Rae M, Mohamad A, Price D, Hadoke PW, Walker BR, Mason JI, et al. Cortisol inactivation by 11beta-hydroxysteroid dehydrogenase-2 may enhance endometrial angiogenesis via reduced thrombospondin-1 in heavy menstruation. J Clin Endocrinol Metab 2009;94:1443-50. https://doi.org/10.1210/jc.2008-1879
  42. Figueiredo AS, Schumacher A. The T helper type 17/regulatory T cell paradigm in pregnancy. Immunology 2016;148:13-21. https://doi.org/10.1111/imm.12595
  43. Madeja Z, Yadi H, Apps R, Boulenouar S, Roper SJ, Gardner L, et al. Paternal MHC expression on mouse trophoblast affects uterine vascularization and fetal growth. Proc Natl Acad Sci U S A 2011;108:4012-7. https://doi.org/10.1073/pnas.1005342108
  44. Lima PD, Zhang J, Dunk C, Lye SJ, Croy BA. Leukocyte driven-decidual angiogenesis in early pregnancy. Cell Mol Immunol 2014;11:522-37. https://doi.org/10.1038/cmi.2014.63
  45. Moffett A, Colucci F. Uterine NK cells: active regulators at the maternal-fetal interface. J Clin Invest 2014;124:1872-9. https://doi.org/10.1172/JCI68107
  46. Blois SM, Kammerer U, Alba Soto C, Tometten MC, Shaikly V, Barrientos G, et al. Dendritic cells: key to fetal tolerance? Biol Reprod 2007;77:590-8. https://doi.org/10.1095/biolreprod.107.060632
  47. 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;182:8080-93. https://doi.org/10.4049/jimmunol.0804018
  48. Plaks V, Birnberg T, Berkutzki T, Sela S, BenYashar A, Kalchenko V, et al. Uterine DCs are crucial for decidua formation during embryo implantation in mice. J Clin Invest 2008;118:3954-65. https://doi.org/10.1172/JCI36682
  49. Pollard JW. Trophic macrophages in development and disease. Nat Rev Immunol 2009;9:259-70. https://doi.org/10.1038/nri2528
  50. 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;123:3472-87. https://doi.org/10.1172/JCI60561
  51. Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol 2010;11:889-96. https://doi.org/10.1038/ni.1937
  52. Van Ginderachter JA, Movahedi K, Hassanzadeh Ghassabeh G, Meerschaut S, Beschin A, Raes G, et al. Classical and alternative activation of mononuclear phagocytes: picking the best of both worlds for tumor promotion. Immunobiology 2006;211:487-501. https://doi.org/10.1016/j.imbio.2006.06.002
  53. 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. https://doi.org/10.1095/biolreprod.110.088591
  54. 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. https://doi.org/10.1016/j.jri.2010.11.002
  55. 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;67:434-42. https://doi.org/10.1111/j.1600-0897.2012.01105.x
  56. Hsu P, Santner-Nanan B, Dahlstrom JE, Fadia M, Chandra A, Peek M, et al. Altered decidual DC-SIGN+ antigen-presenting cells and impaired regulatory T-cell induction in preeclampsia. Am J Pathol 2012;181:2149-60. https://doi.org/10.1016/j.ajpath.2012.08.032
  57. Gnainsky Y, Granot I, Aldo PB, Barash A, Or Y, Schechtman E, et al. Local injury of the endometrium induces an inflammatory response that promotes successful implantation. Fertil Steril 2010;94:2030-6. https://doi.org/10.1016/j.fertnstert.2010.02.022
  58. 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;66:320-8. https://doi.org/10.1111/j.1600-0897.2011.00992.x
  59. 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 U S A 2015;112:15166-71. https://doi.org/10.1073/pnas.1508056112
  60. Chen Y, Wang Y, Zhuang Y, Zhou F, Huang L. Mifepristone increases the cytotoxicity of uterine natural killer cells by acting as a glucocorticoid antagonist via ERK activation. PLoS One 2012;7:e36413. https://doi.org/10.1371/journal.pone.0036413
  61. 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;84:980-4. https://doi.org/10.1016/j.fertnstert.2005.05.012
  62. Andre S, Tough DF, 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;174:1575-87. https://doi.org/10.2353/ajpath.2009.080987
  63. 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 N Y Acad Sci 2004;1024:124-37. https://doi.org/10.1196/annals.1321.009
  64. 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;36:2139-49. https://doi.org/10.1002/eji.200635873
  65. Cheloufi M, Kazhalawi A, Pinton A, Rahmati M, Chevrier L, Prat-Ellenberg L, et al. The endometrial immune profiling may positively affect the management of recurrent pregnancy loss. Front Immunol 2021;12:656701. https://doi.org/10.3389/fimmu.2021.656701
  66. Hviid Saxtorph M, Persson G, Hallager T, Birch Petersen K, Eriksen JO, Larsen LG, et al. Are different markers of endometrial receptivity telling us different things about endometrial function? Am J Reprod Immunol 2020;84:e13323. https://doi.org/10.1111/aji.13323
  67. Smith MP, Mathur RS, Keay SD, Hall L, Hull MG, Jenkins JM. Periovulatory human oocytes, cumulus cells, and ovarian leukocytes express type 1 but not type 2 11beta-hydroxysteroid dehydrogenase RNA. Fertil Steril 2000;73:825-30. https://doi.org/10.1016/S0015-0282(99)00607-X
  68. Casanueva FF, Burguera B, Muruais C, Dieguez C. Acute administration of corticoids: a new and peculiar stimulus of growth hormone secretion in man. J Clin Endocrinol Metab 1990;70:234-7. https://doi.org/10.1210/jcem-70-1-234
  69. Miell JP, Taylor AM, Jones J, Holly JM, Gaillard RC, Pralong FP, et al. The effects of dexamethasone treatment on immunoreactive and bioactive insulin-like growth factors (IGFs) and IGF-binding proteins in normal male volunteers. J Endocrinol 1993;136:525-33. https://doi.org/10.1677/joe.0.1360525
  70. Michael AE. Life after liquorice: the link between cortisol and conception. Reprod Biomed Online 2003;7:683-90. https://doi.org/10.1016/S1472-6483(10)62091-3
  71. Kemeter P, Feichtinger W. Prednisolone supplementation to Clomid and/or gonadotrophin stimulation for in-vitro fertilization: a prospective randomized trial. Hum Reprod 1986;1:441-4. https://doi.org/10.1093/oxfordjournals.humrep.a136451
  72. Keay SD, Lenton EA, Cooke ID, Hull MG, Jenkins JM. Low-dose dexamethasone augments the ovarian response to exogenous gonadotrophins leading to a reduction in cycle cancellation rate in a standard IVF programme. Hum Reprod 2001;16:1861-5. https://doi.org/10.1093/humrep/16.9.1861
  73. Liu S, Shi L, Wang T, Shi J. Effect of low-dose dexamethasone on patients with elevated early follicular phase progesterone level and pregnancy outcomes in IVF-ET treatment: a randomized controlled clinical trial. Clin Endocrinol (Oxf) 2018;89:771-8. https://doi.org/10.1111/cen.13824
  74. Boomsma CM, Keay SD, Macklon NS. Peri-implantation glucocorticoid administration for assisted reproductive technology cycles. Cochrane Database Syst Rev 2012;(6):CD005996.
  75. Dan S, Wei W, Yichao S, Hongbo C, Shenmin Y, Jiaxiong W, et al. Effect of prednisolone administration on patients with unexplained recurrent miscarriage and in routine intracytoplasmic sperm injection: a meta-analysis. Am J Reprod Immunol 2015;74:89-97. https://doi.org/10.1111/aji.12373
  76. Kalampokas T, Pandian Z, Keay SD, Bhattacharya S. Glucocorticoid supplementation during ovarian stimulation for IVF or ICSI. Cochrane Database Syst Rev 2017;3:CD004752.
  77. Achilli C, Duran-Retamal M, Saab W, Serhal P, Seshadri S. The role of immunotherapy in in vitro fertilization and recurrent pregnancy loss: a systematic review and meta-analysis. Fertil Steril 2018;110:1089-100. https://doi.org/10.1016/j.fertnstert.2018.07.004
  78. Zhou G, Zhou M, Duan X, Li W. Glucocorticoid supplementation improves reproductive outcomes in infertile women with antithyroid autoimmunity undergoing ART: a meta-analysis. Medicine (Baltimore) 2021;100:e25554. https://doi.org/10.1097/MD.0000000000025554
  79. Geva E, Amit A, Lerner-Geva L, Yaron Y, Daniel Y, Schwartz T, et al. 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. https://doi.org/10.1111/j.8755-8920.2000.430107.x
  80. Revelli A, Casano S, Piane LD, Grassi G, Gennarelli G, Guidetti D, et al. 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. https://doi.org/10.1186/1477-7827-7-137
  81. 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;8:393-5. https://doi.org/10.1093/oxfordjournals.humrep.a138058
  82. Ogasawara M, Aoki K. Successful uterine steroid therapy in a case with a history of ten miscarriages. Am J Reprod Immunol 2000;44:253-5. https://doi.org/10.1111/j.8755-8920.2000.440411.x
  83. Quenby S, Farquharson R, Young M, Vince G. Successful pregnancy outcome following 19 consecutive miscarriages: case report. Hum Reprod 2003;18:2562-4. https://doi.org/10.1093/humrep/deg502
  84. 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;9:1832-5. https://doi.org/10.1093/oxfordjournals.humrep.a138343
  85. 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;63:571-7. https://doi.org/10.1016/S0015-0282(16)57428-7
  86. Ubaldi F, Rienzi L, Ferrero S, Anniballo R, Iacobelli M, Cobellis L, et al. Low dose prednisolone administration in routine ICSI patients does not improve pregnancy and implantation rates. Hum Reprod 2002;17:1544-7. https://doi.org/10.1093/humrep/17.6.1544
  87. 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. https://doi.org/10.1007/s10815-005-9003-3
  88. 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;30:340-8. https://doi.org/10.1016/j.rbmo.2014.12.004
  89. Seckl JR, Meaney MJ. Glucocorticoid programming. Ann N Y Acad Sci 2004;1032:63-84. https://doi.org/10.1196/annals.1314.006
  90. Pinsky L, Digeorge AM. Cleft palate in the mouse: a teratogenic index of glucocorticoid potency. Science 1965;147:402-3. https://doi.org/10.1126/science.147.3656.402
  91. 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. https://doi.org/10.1016/j.reprotox.2003.10.007
  92. Laskin CA, Bombardier C, Hannah ME, Mandel FP, Ritchie JW, Farewell V, et al. Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss. N Engl J Med 1997;337:148-53. https://doi.org/10.1056/NEJM199707173370302
  93. Carmichael SL, Shaw GM. Maternal corticosteroid use and risk of selected congenital anomalies. Am J Med Genet 1999;86:242-4. https://doi.org/10.1002/(SICI)1096-8628(19990917)86:3<242::AID-AJMG9>3.0.CO;2-U
  94. Park-Wyllie L, Mazzotta P, Pastuszak A, Moretti ME, Beique L, Hunnisett L, et al. Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology 2000;62:385-92. https://doi.org/10.1002/1096-9926(200012)62:6<385::AID-TERA5>3.0.CO;2-Z