Dydrogesterone and the immunology of pregnancy

References

1. Mills JL, Simpson JL, Driscoll SG, Jovanic-Peterson L, Van Allen M, Aarons JH, Metzger B, Bieberf FR, Knopp RH, Holmes LB. Incidence of spontaneous abortion among normal women and insulin-dependent women whose pregnancies were identified within 21 days of conception. N Engl J Med 1988;319:1617–23.10.1056/NEJM198812223192501Search in Google Scholar

2. Brigham SA, Conlon C, Farquharson RG. A longitudinal study of pregnancy outcome following idiopathic recurrent miscarriage. Hum Reprod 1999;14:2868–77.10.1093/humrep/14.11.2868Search in Google Scholar

3. Nybo Andersen AM, Woglfahrt J, Christens P, Olsen J, Melbye, M. Maternal age and fetal loss: population based register linkage study. Br Med J 2000;320:1708–12.10.1136/bmj.320.7251.1708Search in Google Scholar

4. Tang AW, Alfirevic Z, Quenby S. Natural killer cells and pregnancy outcomes in women with recurrent miscarriage and infertility: a systematic review. Hum Reprod 2011;26:1971–80.10.1093/humrep/der164Search in Google Scholar

5. Tabiasco J, Rabot M, Aguerre-Girr M, El Costa H, Berrebi A, Parant O, Laskarin G, Juretic K, Bensussan A, Rukavina D, Le Bouteiller P. Human decidual NK cells: unique phenotype and functional properties – a review. Placenta 2006;27 Suppl A:S34–9.10.1016/j.placenta.2006.01.009Search in Google Scholar

6. 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;156:4027–34.10.4049/jimmunol.156.10.4027Search in Google Scholar

7. Yamamoto T, Takahasi Y, Kase N, Mori H. Role of decidual natural killer (NK) cells in patients with missed abortion: differences between cases with normal and abnormal chromosome. Clin Exp Immunol 1999;116:449–52.10.1046/j.1365-2249.1999.00820.xSearch in Google Scholar

8. Quack KC, Vassiliadou N, Pudney J, Anderson DJ, Hill JA. Leukocyte activation in the decidua of chromosomally normal and abnormal fetuses from women with recurrent abortion. Hum Reprod 2001;16:949–55.10.1093/humrep/16.5.949Search in Google Scholar

9. Mosmann TR, Kobie JJ, Lee FE, Quataert SA. T helper cytokine patterns: defined subsets, random expression, and external modulation. Immunol Res 2009;45:173–84.10.1007/s12026-009-8098-5Search in Google Scholar

10. Romagnani S. T cell subpopulations. Chem Immunol Aller 2014;100:155–64.10.1159/000358622Search in Google Scholar

11. Wegmann TG, Lin H, Guilbert L, Mosmann TR. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a Th2 phenomenon? Immunol Today 1993;14:353–6.10.1016/0167-5699(93)90235-DSearch in Google Scholar

12. Raghupathy R. Pregnancy: success and failure within the Th1/Th2/Th3 paradigm. Semin Immunol 2001;13:219–27.10.1006/smim.2001.0316Search in Google Scholar

13. Chaouat G, Menu E, Clark DA, Dy M, Minkowski M, Wegmann TG. Control of fetal survival in CBAxDBA/2 mice by lymphokine therapy. J Reprod Fertil 1990;89:447–57.10.1530/jrf.0.0890447Search in Google Scholar

14. Haimovici F, Hill JA, Anderson DJ. The effects of soluble products of activated lymphocytes and macrophages on blastocyst implantation events in vitro. Biol Reprod 1991;44:69–76.10.1095/biolreprod44.1.69Search in Google Scholar

15. Smith S, Francis R, Guilbert L, Baker PN. Growth factor rescue of cytokine mediated trophoblast apoptosis. Placenta 2002;23:322–30.10.1053/plac.2001.0783Search in Google Scholar

16. Tangri S, Wegmann TG, Lin H, Raghupathy R. Maternal anti-placental reactivity in natural, immunologically-mediated spontaneous fetal resorptions. J Immunol 1994;152:4903–11.10.4049/jimmunol.152.10.4903Search in Google Scholar

17. Kwak-Kim J, Bao S, Lee SK, Kim JW, Gilman-Sachs A. Immunological modes of pregnancy loss: inflammation, immune effectors, and stress. Am J Reprod Immunol 2014;72:129–40.10.1111/aji.12234Search in Google Scholar

18. Polgar K, Hill JA. Identification of the white blood cell populations responsible for Th1 immunity to trophoblast and the timing of the response in women with recurrent pregnancy loss. Gynecol Obstet Invest 2002;53:59–64.10.1159/000049413Search in Google Scholar

19. Raghupathy R, Makhseed M, Azizieh F, Omu A, Gupta M, Farhat R. Cytokine production by maternal lymphocytes during normal human pregnancy and in unexplained recurrent spontaneous abortion. Hum Reprod 2000;15:713–8.10.1093/humrep/15.3.713Search in Google Scholar

20. Makhseed M, Raghupathy R, Azizieh F, Al-Azemi MMK, Hassan NA, Bandar A. Mitogen-induced cytokine responses of maternal peripheral blood lymphocytes indicate a differential Th-type bias in normal pregnancy and pregnancy failure. Am J Reprod Immunol 1999;42:273–81.10.1111/j.1600-0897.1999.tb00101.xSearch in Google Scholar

21. Raghupathy R, Makhseed M, Azizieh F, Hassan N, Al-Azemi M, Al-Shamali E. Maternal Th1- and Th2-type reactivity to placental antigens in normal human pregnancy and unexplained recurrent spontaneous abortions. Cell Immunol 1999;196:122–30.10.1006/cimm.1999.1532Search in Google Scholar

22. Piccinni M-P, Scaletti C, Vultaggio A, Maggi E, Romagnani S. Defective production of LIF, M-CSF and Th2-type cytokines by T cells at fetomaternal interface is associated with pregnancy loss. J Reprod Immunol 2001;52:35–43.10.1016/S0165-0378(01)00111-5Search in Google Scholar

23. Marzi M, Vigano A, Trabattoni D, Villa ML, Salvaggio A, Clerici F, Clerici M. Characterization of type 1 and type 2 cytokine production profile in physiologic and pathologic human pregnancy. Clin Exp Immunol 1996;106:127–33.10.1046/j.1365-2249.1996.d01-809.xSearch in Google Scholar

24. Jenkins C, Roberts J, Wilson R, MacLean MA, Shilito J, Walker JJ. Evidence of a Th1 type response associated with recurrent miscarriage. Fertil Steril 2000;73:1206–8.10.1016/S0015-0282(00)00517-3Search in Google Scholar

25. Lee SK, Na BJ, Kim JY, Hur SE, Lee M, Gilman-Sachs A, Kwak-Kim J. Determination of clinical cellular immune markers in women with recurrent pregnancy loss. Am J Reprod Immunol 2013;70:398–411.10.1111/aji.12137Search in Google Scholar

26. Banerjee P, Ghosh S, Dutta M, Subramani E, Khalpada J, RoyChoudhury S, Chakravarty B, Chaudhury K. Identification of key contributory factors responsible for vascular dysfunction in idiopathic recurrent spontaneous miscarriage. PloS One 2013;8:e80940.10.1371/journal.pone.0080940Search in Google Scholar

27. Calleja-Agius J, Muttukrishna S, Pizzey AR, Jauniaux E. Pro- and antiinflammatory cytokines in threatened miscarriages. Am J Obstet Gynecol 2011;83:8–16.10.1016/j.ajog.2011.02.051Search in Google Scholar

28. Stites DP, Pavia CS, Clemens LE, Kuhn RW, Siiteri PK. Immunologic regulation in pregnancy. Arthritis Rheum 1979;22:1300–7.10.1002/art.1780221119Search in Google Scholar

29. Moriyama I., Sugawa T. Progesterone facilitates implantation of xenogeneic cultured cells in hamster uterus. Nature New Biol 1972;236:150–2.10.1038/newbio236150a0Search in Google Scholar

30. Zhang J, Dunk C, Croy AB, Lye SJ. To serve and to protect: the role of decidual innate immune cells on human pregnancy. Cell Tissue Res 2015; PMID: 26572540.10.1007/s00441-015-2315-4Search in Google Scholar

31. Sargent IL, Borzychowski AM, Redman CW. Immunoregulation in normal pregnancy and pre-eclampsia: an overview. Reprod Biomed Online 2006;13:680–6.10.1016/S1472-6483(10)60659-1Search in Google Scholar

32. Hanna J, Goldman-Wohl D, Hamani Y, Avraham I, Greenfield C, Nathanson-Yaron S, Prus D, Cohen-Daniel L, Arnon TI, Manaster I, Gazit R, Yutkin V, Beaharroch D, Porgador A, Keshet E, Yagel S, Mandelboim O. Decidual NK cells regulate key developmental processes at the human fetal-maternal interface Nat Med 2006;12:1065–74.10.1038/nm1452Search in Google Scholar PubMed

33. Milne SA, Henderson TA, Kelly RW, Saunders PT, Baird DT, Critchley HO. Leukocyte populations and steroid receptor expression in human first-trimester decidua; regulation by antiprogestin and prostaglandin E analog. J Clin Endocrinol Metabol 2005;90:4315–21.10.1210/jc.2004-2338Search in Google Scholar PubMed

34. Van den Heuvel MJ, Chantakru S, Xumei X, Evans EE, Tekpetey F, Mote PA, Clarke CL, Croy BA. Trafficking of circulating pro-NK cells to the decidualizing uterus: regulatory mechanisms in the mouse and human. Immunol Invest 2005;34:273–93.10.1081/IMM-200064488Search in Google Scholar PubMed PubMed Central

35. Campbell JJ, Qin S, Unutmaz D, Soler D, Murphy KE, Hodge MR, Wu L, Butcher EC. Unique subpopulations of CD56+ NK and NK-T peripheral blood lymphocytes identified by chemokine receptor expression repertoire. J Immunol 2001;166:6477–82.10.4049/jimmunol.166.11.6477Search in Google Scholar PubMed

36. Kalkunte S, Chichester CO, Gotsch F, Sentman CL, Romero R, Sharma S. Evolution of non-cytotoxic uterine natural killer cells. Am J Reprod Immunol. 2008;59:425–32.10.1111/j.1600-0897.2008.00595.xSearch in Google Scholar PubMed PubMed Central

37. Yao MW, Lim H, Schust DJ, Choe SE, Farago A, Ding Y, Michaud S, Church GM, Maas RL. Gene expression profiling reveals progesterone-mediated cell cycle and immunoregulatory roles of Hoxa-10 in the preimplantation uterus. Molec Endocrinol 2003;17:610–27.10.1210/me.2002-0290Search in Google Scholar PubMed

38. Rahman MA, Li M, Li P, Wang H, Dey SK, Da SK Hoxa-10 deficiency alters region-specific gene expression and perturbs differentiation of natural killer cells during decidualization. Dev Biol 2006;290:105–17.10.1016/j.ydbio.2005.11.016Search in Google Scholar PubMed PubMed Central

39. Crncic TB, Laskarin G, Frankovic KJ, Tokmadzic VS, Strobo N, Bedenicki I, Le Bouteiller P, Tabiasco J, Rukavina D. Early pregnancy decidual lymphocytes beside perforin use Fas ligand (FasL) mediated cytotoxicity. J Reprod Immunol 2007;73:108–17.10.1016/j.jri.2006.07.001Search in Google Scholar PubMed

40. McMaster MT, Librach CL, Zhou Y, Lim KH, Janatpour MJ, DeMars R, Kovats S, Damsky C, Fisher SJ. Human placental HLA-G expression is restricted to differentiated cytotrophoblasts. J Immunol 1995;154:3771–8.10.4049/jimmunol.154.8.3771Search in Google Scholar

41. Hedley ML, Drake BL, Head JR, Tucker W, Forman J. Differential expression of class I MHC genes in the embryo and placenta during midgestational development in the mouse. J Immunol 1989;142:4046–53.10.4049/jimmunol.142.11.4046Search in Google Scholar

42. Billington WD. The nature and possible functions of MHC antigens on the surface of human trophoblast. In: Gupta SK, editor. New Delhi, India: Narosa Publishing House, 1999:71–8.10.1007/978-94-011-4197-0_7Search in Google Scholar

43. Blaschitz A, Juch H, Volz A, Hutter H, Dohr G. Soluble HLA-G, the discussion is going on! Molec Hum Reprod 2005;11:723–7.10.1093/molehr/gah238Search in Google Scholar PubMed

44. Le Bouteiller P. HLA-G in human early pregnancy: control of uterine immune cell activation and likely vascular remodeling. Biomed J 2015;38:32–8.10.4103/2319-4170.131376Search in Google Scholar PubMed

45. Rabot M, Tabiasco J, Polgar B, Aguerre-Girr M, Berrebi A, Bensussan A, Strbo N, Rukavina D, Le Bouteiller P. HLA class I/NK cell receptor interaction in early human decidua basalis: possible functional consequences. Chem Immunol Aller 2005;89:72–83.10.1159/000087914Search in Google Scholar PubMed

46. Vacca P, Moretta L, Moretta A, Mingari MC. Origin, phenotype and function of human natural killer cells in pregnancy. Trends Immunol 2011;32:517–23.10.1016/j.it.2011.06.013Search in Google Scholar

47. Lee N, Llano M, Carretero M, Ishitani A, Navarro F, López-Botet M, Geraghty D. HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A. Proc Natl Acad Sci USA 1998;95:5199–204.10.1073/pnas.95.9.5199Search in Google Scholar

48. Llano M, Lee N, Navarro F, Garcia P, Alber JP, Geraghty DE, Lopez-Botet M. HLA-E-bound peptides influence recognition by inhibitory and triggering CD94/NKG2 receptors: preferential response to an HLA-G-derived nonamer. Eur J Immunol 1998;28:2854–63.10.1002/(SICI)1521-4141(199809)28:09<2854::AID-IMMU2854>3.0.CO;2-WSearch in Google Scholar

49. LeMaoult J, Caumartin J, Daouya M, Favier B, Le Rond S, Gonzalez A, Carosella ED. Immune regulation by pretenders: cell-to-cell transfers of HLA-G make effector T cells act as regulatory cells. Blood 2007;109:2040–8.10.1182/blood-2006-05-024547Search in Google Scholar

50. Hunt JA, Petroff MG, McIntire RH, Ober C. HLA-G and immune tolerance in pregnancy, FASEB J 2005;19:681–93.10.1096/fj.04-2078revSearch in Google Scholar

51. Fons P, Chabot S, Cartwright JE, Lenfant F, L’Faqihi F, Giustiniani J, Herault JP, Gueguen G, Bono F, Savi P, Aguerre-Girr M, Fournel S, Malecaze F, Bensussan A, Plouet J, Le Bouteiller P. Soluble HLA-G1 inhibits angiogenesis through an apoptotic pathway and by direct binding to CD160 receptor expressed by endothelial cells. Blood 2006;108:2608–15.10.1182/blood-2005-12-019919Search in Google Scholar

52. Yie SM, Xiao R, Librach CL. Progesterone regulates HLA-G gene expression through a novel progesterone response element. Hum Reprod 2006;21:2538–44.10.1093/humrep/del126Search in Google Scholar

53. Blois SM, Ilarregui JM, Tometten M, Garcia M, Orsal AS, Cordo-Russo R, Toscano MA, Bianco GA, Kobelt P, Handjiski B, Tirado I, Markert UR, Klapp BF, Poirier F, Szekeres-Bartho J, Rabinovich GA, Arck PC. A pivotal role for galectin-1 in fetomaternal tolerance. Nat Med 2007;12:1450–7.10.1038/nm1680Search in Google Scholar

54. Kruse C, Varming K, Christiansen OB. Prospective, serial investigations of in-vitro lymphocyte cytokine production, CD62L expression and proliferative response to microbial antigens in women with recurrent miscarriage. Hum Reprod 2003;18:2465–72.10.1093/humrep/deg469Search in Google Scholar

55. Szekeres-Bartho J, Reznikoff-Etievant MF, Varga P, Pichon MF, Varga Z, Chaouat G. Lymphocytic progesterone receptors in normal and pathological human pregnancy. J Reprod Immunol 1989;16:239–47.10.1016/0165-0378(89)90053-3Search in Google Scholar

56. Szekeres-Bartho J, Szekeres G, Debre P, Autran B, Chaouat G. Reactivity of lymphocytes to a progesterone receptor-specific monoclonal antibody. Cell Immunol 1990;125:273–83.10.1016/0008-8749(90)90083-4Search in Google Scholar

57. Piccinni M-P. T cells in pregnancy. Chem Immunol Aller 2005;89:3–9.10.1159/000087904Search in Google Scholar

58. Chiu L, Nishimura M, Ishi Y, Nieda M, Maeshima M, Takedani Y, Tadokoro K, Juji T. Enhancement of the expression of progesterone receptor on progesterone-treated lymphocytes after immunotherapy in unexplained recurrent spontaneous abortion. Am J Reprod Immunol 1996;35:552–7.10.1111/j.1600-0897.1996.tb00056.xSearch in Google Scholar

59. Van den Heuvel M, McBey B-A, Hahnel AC, Croy BA. An analysis of the uterine lymphocyte-derived hybridoma cell line GWM 1–2 for expression of receptors for estrogen, progesterone and interleukin 2. J Reprod Immunol 1996;31:37–50.10.1016/0165-0378(96)00966-7Search in Google Scholar

60. Roussev RG, Higgins NG, McIntyre JA. Phenotypic characterization of normal human placental mononuclear cells. J Reprod Immunol 1993;25:15–29.10.1016/0165-0378(93)90039-KSearch in Google Scholar

61. De León-Nava MA, Nava K, Soldevila G, López-Griego L, Chávez-Ríos JR, Vargas-Villavicencio JA, Morales-Montor J. Immune sexual dimorphism: effect of gonadal steroids on the expression of cytokines, sex steroid receptors, and lymphocyte proliferation. J Steroid Biochem Mol Biol 2009;113:57–64.10.1016/j.jsbmb.2008.11.003Search in Google Scholar PubMed

62. Butts CL, Shukair SA, Duncan KM, Bowers E, Horn C, Belyavskaya E, Tonelli L, Sternberg EM. Progesterone inhibits mature rat dendritic cells in a receptor-mediated fashion. Int Immunol 2007;19:287–96.10.1093/intimm/dxl145Search in Google Scholar PubMed

63. Szekeres-Bartho J, Kilar F, Falkay G, Csernus V, Torok A, Pacsa AS. Progesterone-treated lymphocytes of healthy pregnant women release a factor inhibiting cytotoxicity and prostaglandin synthesis. Am J Reprod Immunol Microbiol 1985;9:15–8.10.1111/j.1600-0897.1985.tb00334.xSearch in Google Scholar PubMed

64. Polgar B, Kispal Gy, Lachmann M, Paar C, Nagy E, Csere P, Miko E, Szereday L, Varga P, Szekeres-Bartho J. Molecular cloning and immunological characterization of a novel cDNA coding for PIBF. J Immunol 2003;171:5956–63.10.4049/jimmunol.171.11.5956Search in Google Scholar PubMed

65. Lachmann M, Gelbmann D, Kálmán E, Polgár B, Buschle M, von Gabain A, Szekeres-Barthó J, Nagy E. PIBF (Progesterone Induced Blocking Factor) is overexpressed in highly proliferating cells and associated with the centrosome. Int J Cancer 2004;112:51–60.10.1002/ijc.20326Search in Google Scholar PubMed

66. Kozma N, Halasz M, Polgar B, Poehlmann TG, Markert UR, Palkovics T, Keszei M, Kiss K, Szeberenyi J, Par G, Grama L, Szekeres-Bartho J. PIBF activates STAT6 via binding to a novel IL-4 receptor. J Immunol 2006;176:819–26.10.4049/jimmunol.176.2.819Search in Google Scholar

67. Szekeres-Bartho J, Wegmann TG. A progesterone-dependent immunomodulatory protein alters the Th1/Th2 balance. J Reprod Immunol 1996;31:81–95.10.1016/0165-0378(96)00964-3Search in Google Scholar

68. Raghupathy R., Al Mutawa E., Al-Azemi M., Makhseed M., Azizieh F. and Szekeres-Bartho F. The progesterone-induced blocking factor (PIBF) modulates cytokine production by lymphocytes from women with recurrent miscarriage. J Reprod Immunol 2009;80:91–9.10.1016/j.jri.2009.01.004Search in Google Scholar PubMed

69. Kalinka J, Szekeres-Bartho J. The impact of dydrogesterone supplementation on hormonal profile and progesterone-induced blocking factor concentrations in women with threatened abortion. Am J Reprod Immunol 2005;53:166–71.10.1111/j.1600-0897.2005.00261.xSearch in Google Scholar PubMed

70. Lje SJ, Porter DG. Demonstration that progesterone blocks uterine activity in the ewe in vivo by a direct action on the myometrium. J Reprod Fertil 1978;52:87–94.10.1530/jrf.0.0520087Search in Google Scholar PubMed

71. Par G, Geli J, Kozma N, Varga P, Szekeres-Bartho J: Progesterone regulates IL12 expression in pregnancy lymphocytes by inhibiting phospholipase A2. Am J Reprod Immunol 2003;49:1–5.10.1034/j.1600-0897.2003.01149.xSearch in Google Scholar PubMed

72. Laskarin G, Tokmadzić VS, Strbo N, Bogović T, Szekeres-Bartho J, Randić L, Podack ER, Rukavina D. Progesterone induced blocking factor (PIBF) mediates progesterone induced suppression of decidual lymphocyte cytotoxicity. Am J Reprod Immunol 2002;48:201–9.10.1034/j.1600-0897.2002.01133.xSearch in Google Scholar PubMed

73. Faust Z, Laskarin G, Rukavina D, Szekeres-Bartho J. Progesterone-induced blocking factor inhibits degranulation of natural killer cells. Amer J Reprod Immunol 1999;42:71–5.10.1111/j.1600-0897.1999.tb00468.xSearch in Google Scholar

74. Kinsky R, Delage G, Rosin N, Thang MN, Hoffmann M, Chaouat G. A murine model of NK cell mediated resorption. Am J Reprod Immunol 1990;23:73–7.10.1111/j.1600-0897.1990.tb00675.xSearch in Google Scholar PubMed

75. Szekeres-Bartho J, Kinsky R, Chaouat G. The effect of a progesterone induced immunologic blocking factor on NK-mediated resorption. Am J Reprod Immunol 1990;24:105–7.10.1111/j.1600-0897.1990.tb01047.xSearch in Google Scholar PubMed

76. Szekeres-Bartho J, Par G, Dombay Gy, Smart Y C, Volgyi Z. The anti-abortive effect of PIBF in mice is manifested by modulating NK activity. Cell Immunol 1997;177:194–9.10.1006/cimm.1997.1090Search in Google Scholar PubMed

77. Szekeres-Bartho J, Kinsky R, Chaouat G. A progesterone-induced immunologic blocking factor corrects high resorption rate in mice treated with antiprogesterone. Am J Ob Gyn 1990;163:1320–2.10.1016/0002-9378(90)90713-HSearch in Google Scholar

78. Szekeres-Bartho J, Par G, Szereday L, Smart CY, Achacz I. Progesterone and non-specific immunological mechanisms in pregnancy. Am J Reprod Immunol 1997;38:176–82.10.1111/j.1600-0897.1997.tb00295.xSearch in Google Scholar

79. Polgár B, Nagy E, Mikó É, Varga P, Szekeres-Barthó J. Urinary PIBF (Progesterone Induced Blocking Factor) concentration is related to pregnancy outcome. Biol Reprod 2004;71:1699–705.10.1095/biolreprod.104.030437Search in Google Scholar

80. Check JH, Levin E, Bollendorf A, Locuniak J. Miscarriage in the first trimester according to the presence or absence of the progesterone-induced blocking factor at three to five weeks from conception in progesterone supplemented women. Clin Exp Obstet Gynecol 2005;32:13–4.Search in Google Scholar

81. Check JH, Arwitz M, Gross J, Szekeres-Bartho J, Wu CH. Evidence that the expression of progesterone-induced blocking factor by maternal T-lymphocytes is positively correlated with conception. Am J Reprod Immunol 1997;38:6–8.10.1111/j.1600-0897.1997.tb00269.xSearch in Google Scholar

82. Salomon LJ, Rozenberg P, Szekeres-Bartho J, Malagrida L, Giudicelli Y, Ville Y. Changes in progesterone-induced-blocking-factor expression rates following mifepristone administration in termination of pregnancy at 5 to 8 weeks. J Matern Fetal Neonatal Med 2005;17:353–6.10.1080/14767050500140370Search in Google Scholar

83. Stites DP, Bugbee S, Siiteri PK. Differential actions of progesterone and cortisol on lymphocyte and monocyte interaction during lymphocyte activation – relevance to immunosuppression in pregnancy. J Reprod Immunol 1993;5:215–28.10.1016/0165-0378(83)90237-1Search in Google Scholar

84. Peltier RM. Immunology of term and preterm labour. Reprod Biol Endocrinol 2003;2:122–9.10.1186/1477-7827-1-122Search in Google Scholar PubMed PubMed Central

85. Raghupathy R, Al Mutawa E, Szekeres-Bartho J. Modulation of cytokine production by dydrogesterone in lymphocytes from women with recurrent abortion. Brit J Ob Gyn 2005;112:1096–101.10.1111/j.1471-0528.2005.00633.xSearch in Google Scholar PubMed

86. Raghupathy R, Al-Azemi M. Modulation of cytokine production by the dydrogesterone metabolite dihydrodydrogesterone Am J Reprod Immunol 2015;74:419–26.10.1111/aji.12418Search in Google Scholar PubMed

87. Haas DM, Ramsey PS. Progestogen for preventing miscarriage. Cochrane Database Syst Rev 2013; doi: 10.1002/14651858.CD003511.pub3.Search in Google Scholar PubMed

88. Wahabi HA, Fayed AA, Esmaeil SA, Al Zeidan RA. Progestogen for treating threatened miscarriage. Cochrane Database Syst Rev 2011; doi: 10.1002/14651858.CD005943.pub4.10.1002/14651858.CD005943.pub4Search in Google Scholar

89. Szekeres-Bartho J, Balasch T. Progestagen therapy for recurrent miscarriage. Hum Reprod Update 2008;14:27–35.10.1093/humupd/dmm035Search in Google Scholar

90. Choi BC, Polgar K, Xiao L, Hill JA. Progesterone inhibits in vitro embryotoxic Th1 cytokine production to trophoblast in women with recurrent pregnancy loss. Hum Reprod 2000;15 Suppl 1:46–59.10.1093/humrep/15.suppl_1.46Search in Google Scholar

91. Sitruk-Ware R. New progestogens: a review of their effects in perimenopausal and postmenopausal women. Drug Aging 2004;21:865–83.10.2165/00002512-200421130-00004Search in Google Scholar

92. de Lignihes B. Oral micronized progesterone. Clin Ther 1999;1:41–60.10.1016/S0149-2918(00)88267-3Search in Google Scholar

93. McAuley JW, Kroboth FJ, Kroboth PD. Oral administration of micronized progesterone: a review and more experience. Pharmacotherapy 1996;16:453–7.10.1002/j.1875-9114.1996.tb02977.xSearch in Google Scholar

94. El-Zibdeh MY. Dydrogesterone in the reduction of recurrent spontaneous abortion. J Steroid Biochem Mol Biol 2005;97:431–4.10.1016/j.jsbmb.2005.08.007Search in Google Scholar PubMed

95. Omar MH, Mashita MK, Lim PS, Jamil MA. Dydrogesterone in threatened abortion: pregnancy outcome. J Steroid Bochem Mol Bol 2005;95:421–5.10.1016/j.jsbmb.2005.08.013Search in Google Scholar PubMed

96. Kumar A, Begum N, Prasad S, Aggarwal S, Sharma S. Oral dydrogesterone treatment during early pregnancy to prevent recurrent pregnancy loss and its role in modulation of cytokine production: a double-blind, randomized, parallel, placebo-controlled trial. Fertil Steril 2014;102:1357–63.e3.10.1016/j.fertnstert.2014.07.1251Search in Google Scholar PubMed

97. Carp H. A systematic review of dydrogesterone for the treatment of threatened miscarriage. Gynecol Endocrinol 2012;28:983–90.10.3109/09513590.2012.702875Search in Google Scholar PubMed PubMed Central