Progestins for the prevention of spontaneous preterm birth review and implications of recent studies

Journal of Reproductive Medicine for the Obstetrician and Gynecologist

Volumn 54, Issue 2, 2009, Pages 73-87

  O'Brien, John M ^a,b   Lewis, David F ^a,b  

^a CENTRAL BAPTIST HOSPITAL   (United States)

^b UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

Author keywords

17 Hydroxyprogesterone caproate; Prematurity; Progesterone; Screening; Transvaginal ultrasound

Indexed keywords

GESTAGEN; HYDROXYPROGESTERONE CAPROATE; PROGESTERONE;

CLINICAL TRIAL; DRUG EFFICACY; DRUG INDICATION; DRUG SAFETY; FEMALE; HIGH RISK POPULATION; HUMAN; PATIENT SELECTION; PREGNANCY; PREMATURITY; PRIORITY JOURNAL; REVIEW; SCREENING;

DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; GESTONORONE CAPROATE; HUMANS; KAPLAN-MEIERS ESTIMATE; PREGNANCY; PREMATURE BIRTH; PROGESTERONE; PROGESTINS; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 62849098573     PISSN: 00247758     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (102)

1. Lopez AD, Mathers CD, Ezzati M, et al: Global and regional burden of disease and risk factors, 2001: Systematic analysis of population health data. Lancet 2006;367:1747-1757
2. Jamison DT, Shahid-Salles SA, Jamison J, et al: Incorporating deaths near the time of birth into estimates of the global burden of disease. In Global Burden of Disease and Risk Factors. Edited by AD Lopez, DS Mathers, M Ezzati, DT Jamison, CJL Murray. New York, Oxford University Press, 2006, pp 427-463
3. March of Dimes: United States: Infant mortality overview. http://www.marchofdimes.com/peristats/tlanding.aspx?reg=99&lev=0&top= 6&slev=1&dv=qf, accessed May 26, 2007
4. Goldenberg RL: Low birthweight in minority and high-risk women, patient outcomes research team (PORT) final report. AHCPR Publication no. 98-N005, Washington, DC Agency for Healthcare Compliance and Research, August 1998
5. Institute of Medicine: Preterm Birth: Causes, Consequences, and Prevention. Edited by RE Behrman, AS Butler. Washington DC, National Academies Press, 2006
6. Meis PJ, Klebanoff M, Thorn E, et al: Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Eng J Med 2003;348:2379-2385
7. Csapo AI, Pulkkinen MO, Ruttner B, et al: The significance of the human corpus luteum in pregnancy maintenance: I. Preliminary studies. Am J Obstet Gynecol 1972;112:1061-1067
8. Csapo A: The luteo-placental shift: The guardian of prenatal life. Postgrad Med J 1969;45:57-64
9. Csapo A: Progesterone block. Am J Anat 1956;98:273-291
10. Zakar T, Hertelendy F: Progesterone withdrawal: Key to parturition. Am J Obstet Gynecol 2007;196:289-296
11. Block BS, Liggins GC, Creasy RK: Preterm delivery is not predicted by serial plasma estradiol or progesterone concentration measurements. Am J Obstet Gynecol 1984;150: 716-722
12. Oh SY, Kim CJ, Park I, et al: Progesterone receptor isoform (A/B) ratio of human fetal membranes increases during term parturition. Am J Obstet Gynecol 2005;193:1156-1160
13. Karteris E, Zervou S, Pang Y, et al: Progesterone signaling in human myometrium through two novel membrane G protein coupled receptors: potential role in functional progesterone withdrawal at term. Mol Endocrinol 2006;20:1519-1534
14. Facchinetti F, Paganelli S, Comitini G, et al: Cervical length changes during preterm cervical ripening: Effects of 17-alpha-hydroxyprogesterone caproate. Am J Obstet Gynecol 2007;196:453.e1-e4
15. O'Brien JM, DeFranco EA, Adair D, et al: Progesterone reduces the rate of cervical shortening in women at risk for preterm birth: Secondary analysis from a randomized, double-blind, placebo controlled trial. Am J Obstet Gynecol (abstr) 2007;197:s7
16. Hegele-Hartung C, Chwalisz K, Beier HM, et al: Ripening of the uterine cervix of the guinea-pig after treatment with the progesterone antagonist onapristone (ZK 98.299): An electron microscopic study. Hum Reprod 1989;4:369-377
17. Stys SJ, Clewell WH, Meschia G: Changes in cervical compliance at parturition independent of uterine activity. Am J Obstet Gynecol 1978;130:414-418
18. Marx SG, Wentz MJ, Mackay LB, et al: Effects of progesterone on iNOS, COX-2, and collagen expression in the cervix. J Histochem Cytochem 200;5:623-639
19. Sato T, Michizu H, Hashizume K, et al: Hormonal regulation of PGE2 and COX-2 production in rabbit uterine cervical fibroblasts. J Appl Physiol 2001;90:1227-1231
20. Imada K, Ito A, Sato T, et al: Hormonal regulation of matrix metalloproteinase 9/gelatinase B gene expression in rabbit uterine cervical fibroblasts. Biol Reprod 1997;56:575-580
21. Sato T, Ito A, Mori Y, et al: Hormonal regulation of collagenolysis in uterine cervical fibroblasts: Modulation of synthesis of procollagenase, prostromelysin and tissue inhibitor of metalloproteinases (TIMP) by progesterone and oestradiol-17beta. Biochem J 1991;275:645-650
22. Xu H, Gonzales JM, Ofori E, et al: Preventing cervical ripening: primary mechanism by which progestational agents prevent preterm birth? Am J Obstet Gynecol 2008;198: 314.e1-314.e8.
23. Elovitz MA, Mrinalini C: Can medroxyprogesterone acetate alter Toll-like receptor expression in a mouse model of intrauterine inflammation? Am J Obstet Gynecol 2005;193: 1149-1155
24. Ito A, Imada K, Sato T, et al: Suppression of interleukin 8 production by progesterone in rabbit uterine cervix. Biochem J 1994;301:183-186
25. Hein M, Petersen AC, Helmig RB, et al: Immunoglobin levels and phagocytes in the cervical mucus plug at term of pregnancy. Act Obstet Gynecol Scand 2005;84:734-742
26. da Fonseca EB, Bittar RE, Carvalho MH, et al: Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: A randomized placebo-controlled double-blind study. Am J Obstet Gynecol 2003;188:419-424
27. Ruddock N, Shi SQ, Jain S, et al: Progesterone (P4), but not 17-alpha-hydroxylprogesterone caproate (ITP), inhibits human myometrial contractions. Am J Obstet Gynecol 2008;199:391.e1-7
28. Petrocelli T, Lye SJ: Regulation of transcripts encoding the myometrial gap junction protein, connexin-43, by estrogen and progesterone. Endocrinology 1993;133:284-290
29. Ou CW, Orsino A, Lye SJ: Expression of connexin-43 and connexin-26 in the rat myometrium during pregnancy and labor is regulated by mechanical and hormonal signals. Endocrinology 1997;138:5398-5407
30. Orsino A, Taylor CV, Lye SJ: Connexin-26 and connexin-43 are differently expressed and regulated in the rat myome-trium throughout late pregnancy and with the onset of labor. Endocrinology 1996;137:1545-1553
31. Sfakianaki AK, Norwitz ER: Mechanisms of progesterone action inhibiting prematurity. J Matern Fetal Neonatal Med 2006;19:763-772
32. Hardy DB, Janowski BA, Corey DR, et al: Progesterone receptor plays a major anti-inflammatory role in human myometrial cells by antagonism of nuclear factor kappaB activation of cyclooxygenase 2 expression. Mol Endocrinol 2006;20:2724-2733
33. Elovitz MA, Gonzalez J: Medroxyprogesterone acetate modulates the immune response in the uterus, cervix, and placenta in a mouse model. J Matern Fetal Neonatal Med 2008;21:223-230
34. Cakmak H, Schatz F, Huang ST, et al: Progestin suppresses thrombin- and interleukin-1beta-induced interleukin-11 production in term decidual cells: Implications for preterm delivery. J Clin Endocrinol Metab 2005;90:5279-5286
35. Norwitz ER, Snegovskikh V, Schatz F, et al: Progestin inhibits and thrombin stimulates the plasminogen activator/inhibitor system in term decidual stromal cells: Implications for parturition. Am J Obstet Gynecol 2007;196: 382.e1-382.e8
36. Goldman S, Weiss A, Shalev E: The effect of progesterone on gelatinase expression in the deciduas and fetal membranes before and after contractions. Am J Obstet Gynecol 2007;197:521.e1-521.e7
37. Oner C, Schatz F, Kizilay G, et al: Progestin-inflammatory cytokine interactions affect matrix metalloproteinase-1 and -3 expression in term decidual cells: Implications for treatment of chorioamnionitis-induced preterm delivery. J Clin Endocrinol Metab 2008;93:252-259
38. Gotkin JL, Celver J, McNutt P, et al: Progesterone reduces lipopolysaccharide induced interleukin-6 secretion in fetoplacental chorionic arteries, fractionated cord blood, and maternal mononuclear cells. Am J Obstet Gynecol 2006;195: 1015-1019
39. Zicari A, Ticconi C, Realacci M, et al: Hormonal regulation of cytokine release by human fetal membranes at term gestation: effects of oxytocin, hydrocortisone and progesterone on tumour necrosis factor-alpha and transforming growth factor-beta 1 output. J Reprod Immunol 2002;56:123-136
40. Loudon JA, Elliott CL, Hills F, et al: Progesterone represses interleukin-8 and cyclo-oxygenase-2 in human lower segment fibroblast cells and amnion epithelial cells. Biol Reprod 2003;69:331-337
41. Allport VC, Pieber D, Slater DM, et al: Human labour is associated with nuclear factor-kappaB activity which mediates cyclo-oxygenase-2 expression and is involved with the 'functional progesterone withdrawal'. Mol Human Reprod 2001;7:581-586
42. Challis JRG, Sloboda DM, Alfaidy N, et al: Prostaglandins and mechanisms of preterm birth. Reproduction 2002;124: 1-17
43. Challis JRG, Matthews SG, Gibb W, et al: Endocrine and paracrine regulation of birth at term and preterm. Endocr Rev 2000;21:514-550
44. Karalis K, Goodwin G, Majzoub JA: Cortisol blockade of progesterone: a possible molecular mechanism involved in the initiation of human labor. Nat Med 1996;2:556-560
45. Murtha AP, Feng L, Yonish B, et al: Progesterone protects fetal chorion and maternal deciduas cells from calcium-induced death. Am J Obstet Gynecol 2007;196:257.e1-257.e5
46. Mazor M, Hershkovitz R, Chaim W, et al: Human preterm birth is associated with systematic and local changes in progesterone/17 beta-estradiol ratios. Am J Obstet Gynecol 1994;171:231-236
47. Norwitz ER, Robinson JN, Challis JR: The control of labor. N Engl J Med 1999;341:660-666
48. Romero R, Espinoza J, Kusanovic JP, et al: The preterm parturition syndrome. BJOG (suppl) 2006;113:17-42
49. Green NS, Damus K, Simpson JL, et al: Research agenda for preterm birth: Recommendations from the March of Dimes. Am J Obstet Gynecol 2005;193:626-635
50. Honest H, Bachmann LM, Sundaram R, et al: The accuracy of risk scores in predicting preterm birth: A systematic review. J Obstet Gynaecol 2004;24:343-359
51. Mercer BM, Goldenberg RL, Moawad AH, et al: The preterm prediction study: Effect of gestational age and cause of preterm birth on subsequent obstetric outcome. Am J Obstet Gynecol 1999;181:1216-1221
52. Adams MM, Elam-Evans LD, Wilson HG, et al: Rates of and factors associated with recurrence of preterm delivery. JAMA 2000;283:1591-1596
53. Carr-Hill RA, Hall MH: The repetition of spontaneous preterm labour. Br J Obstet Gynaecol 1985;92:921-928
54. To MS, Palaniappan V, Skentou CA, et al: Elective cerclage vs. ultrasound-indicated cerclage in high-risk pregnancies. Ultrasound Obstet Gynecol 2002;19:475-477
55. Iams JD, Goldenberg RL, Meis PJ, et al: The length of the cervix and the risk of spontaneous premature delivery. N Engl J Med 1996;334:567-572
56. Gomez R, Galasso M, Romero R, et al: Ultrasonographic examination of the uterine cervix is better than cervical digital examination as a predictor of the likelihood of premature delivery in patients with preterm labor and intact membranes. Am J Obstet Gynecol 1994;171:956-964
57. To MS, Skentou CA, Royston P, et al: Prediction of patient-specific risk of early preterm delivery using maternal history and sonographic measurement of cervical length: A population-based prospective study. Ultrasound Obstet Gynecol 2006;27:362-367
58. Owen J, Yost N, Berghella V, et al: Can shortened midtrimester cervical length predict very early spontaneous preterm birth? Am J Obstet Gynecol 2004;191:298-303
59. Owen J, Yost N, Berghella V, et al: Mid-trimester endovaginal sonography in women at high risk for spontaneous preterm birth. JAMA 2001;286:1340-1348
60. Kusanovic JP, Espinoza J, Romero R, et al: Clinical significance of the presence of amniotic fluid 'sludge' in asymptomatic patients at high risk for spontaneous preterm labor. Ultrasound Obstet Gynecol 2007;30:706-714
61. Goldenberg RL, Goepfert AR, Ramsey PS: Biochemical markers for the prediction of preterm birth. Am J Obstet Gynecol 2005;192:S36-S46
62. Romero R, Espinoza J, Gotsch F, et al: The use of high-dimensional biology (genomics, transcriptomics, proteomics, and metabolomics) to understand the preterm parturition syndrome. BJOG 2006;113:118-135
63. Hassan SS, Romero R, Tarca AL, et al: Signature pathways identified from gene expression profiles in the human uterine cervix before and after spontaneous term parturition. Am J Obstet Gynecol 2007;197:250.e1-250.e7
64. Papiernik-Berkauer E: Double blind study of an agent to prevent pre-term delivery among women at increased risk. Edition Schering 1970;4:65-68
65. Johnson JWC, Austin KL, Jones GS, et al: Efficacy of 17alpha- hydroxyprogesterone caproate in the prevention of premature labor. N Engl J Med 1975;293:675-680
66. Hartikanainen-Sorri AL, Kauppila A, Táimala R: Inefficacy of 17 alpha-hydroxyprogesterone caproate in the prevention of prematurity in twin pregnancy. Obstet Gynecol 1980;56:692-695
67. Hauth JC, Gilstrap LC, Brekken AL, et al: The effect of 17 alpha-hydroxyprogesterone caproate on pregnancy outcome in an active-duty military population. Am J Obstet Gynecol 1983;146:187-190
68. Yemini M, Borenstein R, Dreazen I, et al: Prevention of premature labor by 17 alpha-hydroxyprogesterone caproate. Am J Obstet Gynecol 1985;151:574-577
69. Rouse DJ, Caritis SN, Peaceman AM, et al: A trial of 17 alpha-hydroxyprogesterone caproate to prevent prematurity in twins. N Engl J Med 2007;357:454-461
70. Fonseca EB, Celik E, Parra M, et al: Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med 2007;357:462-169
71. O'Brien JM, Adair CD, Lewis DF, et al: Progesterone vaginal gel for the reduction of recurrent preterm birth: Primary results from a randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol 2007;30:687-696
72. DeFranco EA, O'Brien JM, Adair CD, et al: Vaginal progesterone is associated with a decreased risk of early preterm birth and improved neonatal outcome in women with a short cervix. Ultrasound Obstet Gynecol 2007;30:697-705
73. Borna S, Sahabi N: Progesterone for maintenance tocolytic therapy after threatened preterm labour: A randomized controlled trial. Aust N Z J Obstet Gynaecol 2008:48:58-63
74. Goldstein P, Berrier J, Rosen S, et al: A meta-analysis of randomized control trials of progestational agents in pregnancy. Br J Obstet Gynaecol 1989;96:265-274
75. Kierse MJ: Progestogen administration in pregnancy may prevent preterm delivery. Br J Obstet Gynaecol 1990;97: 149-154
76. Sanchez-Ramos L, Kaunitz AM. Delke I: Progestational agents to prevent preterm birth: A meta-analysis of randomized controlled trials. Obstet Gynecol 2005;105:273-279
77. Dodd JM, Flenady V, Cincotta R, et al: Prenatal administration of progesterone for preventing preterm birth. Cochrane Database Syst Rev 2006;1:CD004947
78. Mackenzie R, Walker M, Armson A, et al: Progesterone for the prevention of preterm birth among women at increased risk: A systematic review and meta-analysis of randomized controlled trials. Am J Obstet Gynecol 2006;194:1234-1242
79. Clarke MJ, Stewart LA: Systematic reviews of randomized controlled trials: The need for complete data. J Eval Clin Pract 1995;1:119-126
80. Food and Drug Administration: 17α-hydroxyprogesterone caproate for prevention of preterm birth: Overview of PDA background document, http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4227B1-02-01-FDA-Back ground.pdf, accessed July 13, 2007
81. Yost NP, Owen J, Berghella V, et al: Number and gestational age of prior preterm births does not modify the predictive value of a short cervix. Am J Obstet Gynecol 2004;191: 241-246
82. Lyall F, Lye S, Teoh T, et al: Expression of Gsalpha, connexin-43, connexin-26, and EP1, 3, and 4 receptors in myometrium of prelabor singleton versus multiple gestations and effects of mechanical stretch and steroids on Gsalpha. J Soc Gynecol Investig 2002;9:299-307
83. Yan R, Fokina V, Hankins GDV, et al: The effect of esterases on 17α-hydroxyprogesterone caproate. Am J Obstet Gynecol 2008;198:229.e1-229. e5
84. Dudas I, Gidai J, Czeizel AE: Population-based case-control teratogenic study of hydroxyprogesterone treatment during pregnancy. Congenit Anom 2006;46:194-198
85. Katz Z, Lancet M, Skornik J, et al: Teratogenicity of progestogens given during the first trimester of pregnancy. Obstet Gynecol 1985;65:775-780
86. Attardi B, Zeleznik A, Simhan H, et al: Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone, 17-alpha hydroxyprogesterone caproate, and related progestins. Am J Obstet Gynecol 2007;197:599.e1-599.e7
87. Gonzalez-Quintero VH, Smarkusky L, Carter J, et al: 17 Alpha-hydroxyprogesterone caproate: Perinatal mortality and pregnancy outcomes. Obstet Gynecol 2007;109:1S-2S
88. Food and Drug Administration: Summary minutes of the Advisory Committee for Reproductive Health Drugs, http://www.fda.gov/ohrms/dockets/ac/06/minutes/ 2006-4227M1.pdf. Accessed July 13, 2007
89. Christian MS, Brent RL, Calda P: Embryo-fetal toxicity signals for 17alpha-hydroxyprogesterone caproate in highrisk pregnancies: A review of the non-clinical literature for embryo-fetal toxicity with progestins. J Matern Fetal Neonatal Med 2007;20:89-112
90. Hendrickx AG, Korte R, Leuschner F, et al: Embryotoxicity of sex steroidal hormones in nonhuman primates: II. Hydroxyprogesterone caproate, estradiol valerate. Teratology 1987;5:129-136
91. Rebarber A, Istwan N, Russo-Stieglitz K, et al: Increased incidence of gestational diabetes in women receiving prophylactic 17 alpha- hydroxyprogesterone caproate for prevention of recurrent preterm delivery. Diabetes Care 2007;30: 2277-2280
92. Elovitz MA, Mrinalini C: The use of progestational agents for preterm birth: Lessons from a mouse model. Am J Obstet Gynecol 2006;195:1004-1010
93. Miles RA, Paulson RJ, Obo RA, et al: Pharmacokinetics and endometrial tissue levels of progesterone after administration by intramuscular and vaginal routes. Fertil Steril 1994; 62:485-490
94. Toner JP: The luteal phase: Luteal phase support protocols. In Textbook of Assisted Reproductive Techniques. Edited by DK Gardner, A Weissman, CM Howles, Z Shoham. London, Martin Dunitz Ltd, 2004, pp 639-650
95. To MS, Skentou C, Cicero S, et al: Cervical assessment at the routine 23-weeks' scan: Problems with transabdominal sonography. Ultrasound Obstet Gynecol 2000;15:292-296
96. Fuchs F, Stakemann G: Treatment of threatened premature labor with large doses of progesterone. Am J Obstet Gynecol 1960;79:172-176
97. Erny R, PigneA, Prouvost C, et al: The effects of oral administration of progesterone from premature labor. Am J Obstet Gynecol 1986;154:525-529
98. Northen AT, Norman GS, Anderson K, et al: Follow-up of children exposed in utero to 17α-hydroxyprogesterone caproate. Obstet Gynecol 2007;110:865-872
99. Romero R: Prevention of spontaneous preterm birth: The role of sonographic cervical length in identifying patients who may benefit from progesterone. Ultrasound Obstet Gynecol 2007;30:675-686
100. Nicolaides KH: Some thoughts on the true value of ultrasound. Ultrasound Obstet Gynecol 2007;30:671-674
101. Althuisius SM, Dekker GA, Hummel P, et al: Cervical incompetence prevention randomized cerclage trial: Emergency cerclage with bed rest versus bed rest alone. Am J Obstet Gynecol 2003;189:907-910
102. Daskalakis G, Papantoniou N, Mesogitis S, et al: Management of cervical insufficiency and bulging fetal membranes. Obstet Gynecol 2006;107:221-226