Contraception
Volume 74, Issue 1 , Pages 66-86 , July 2006

Review of medical abortion using mifepristone in combination with a prostaglandin analogue

  • Christian Fiala

      Affiliations

    • Gynmed Clinic, Mariahilferguertel 37, A-1150 Vienna, Austria
    • Division for Obstetrics and Gynaecology, Department of Woman and Child Health, Karolinska Institutet, SE-17176 Stockholm, Sweden
    • Corresponding Author InformationCorresponding author. Gynmed Clinic, Vienna, Austria.
    • ,
  • Kristina-Gemzell Danielsson

      Affiliations

    • Division for Obstetrics and Gynaecology, Department of Woman and Child Health, Karolinska Institutet, SE-17176 Stockholm, Sweden

Received 10 March 2006 ,Revised 29 March 2006 ,Accepted 31 March 2006.

References 

  1. Lewin L. Fruchtabtreibung durch Gifte und andere Mittel (Abortion using poisons and other means), Berlin: Verlag von Georg Stilke; 1925;
  2. Riddle JM. Eve's herbes — a history of contraception and abortion. Cambridge (England): Harvard University Press; 1997;
  3. Bygdeman M, Wiqvist N. Induction of abortion by different prostaglandin analogues. Acta Obstet Gynecol Scand Suppl. 1974;37:67–72
  4. Lundström V, Bygdeman M, Fotiu S, Gréen K, Kinoshita K. Abortion in early pregnancy by vaginal administration of 16,16-dimethyl-PGE2 in comparison with vacuum aspiration. Contraception. 1977;16:167–173
  5. Ulmann A, Teutsch G, Philibert D. RU 486. Sci Am. 1990;262:42–48
  6. Herrman W, Wyss R, Riondel A, et al. Effect d'un steroid anti-progesteron chez la femme; interruption du cycle menstruel et de la grossess au debut (The effects of an antiprogesterone steroid in women: interruption of the menstrual cycle and of early pregnancy), C R Acad Sci (Paris). 1982;294:933–939
  7. Kovacs L, Sas M, Resch BA, et al. Termination of early pregnancy by RU 486 — an antiprogestational compound. Contraception. 1984;29:399–410
  8. Haspels AA. Interruption of early pregnancy by an anti-progestational compound, RU 486. Eur J Obstet Gynecol Reprod Biol. 1985;20:169–175
  9. Couzinet B, Le Strat N, Ulmann A, Baulieu EE, Schaison G. Termination of early pregnancy by the progesterone antagonist RU 486 (Mifepristone). N Engl J Med. 1986;315:1565–1570
  10. Birgerson L, Odlind V. Early pregnancy termination with antiprogestins: a comparative clinical study of RU 486 given in two dose regimens and Epostane. Fertil Steril. 1987;48:565–570
  11. Birgerson L, Odlind V. The antiprogestational agent RU 486 as an abortifacient in early human pregnancy: a comparison of three dose regimens. Contraception. 1988;38:391–400
  12. Cameron IT, Baird DT. Early pregnancy termination: a comparison between vacuum aspiration and medical abortion using prostaglandin (16,16 dimethyl-trans-delta 2-PGE1 methyl ester) or the antiprogestogen RU 486. Br J Obstet Gynaecol. 1988;95:271–276
  13. Van Look PFA, Bygdeman M. Antiprogestational steroids: a new dimension in human fertility regulation. In:  Mulligan SR editors. Oxford reviews of reproductive biology. England: Oxford; 1989;p. 1–60
  14. Bygdeman M, Swahn ML. Progesterone receptor blockage. Effect on uterine contractility and early pregnancy. Contraception. 1985;32:45–51
  15. Cameron IT, Michie AF, Baird DT. Therapeutic abortion in early pregnancy with antiprogestogen RU 486 alone or in combination with a prostaglandin analogue (gemeprost). Contraception. 1986;34:459–468
  16. Swahn ML, Bygdeman M. The effect of the antiprogestin RU 486 on uterine contractility and sensitivity to prostaglandin and oxytocin. Br J Obstet Gynaecol. 1988;95:126–134
  17. Ulmann A, Silvestre L, Chenama L, et al. Medical termination of early pregnancy with Mifepristone (RU 486) followed by a prostaglandin analogue. Acta Obstet Gynecol Scand. 1992;71:278–283
  18. UK Multicenter Trial . The efficacy and tolerance of mifepristone and prostaglandin in first trimester of pregnancy. Br J Obstet Gynaecol. 1990;97:480–486
  19. UK Multicenter study group. The efficacy and tolerance of mifepristone and prostaglandin in termination of pregnancy of less than 63 days gestation; UK multicenter study — final results. Contraception. 1997;55:1–5
  20. Wu S. Medical abortion in China. J Am Med Womens Assoc 2000;55(3 Suppl):197–9, 204.
  21. WHO . Model list of essential medicines. 14th ed.. Geneva: WHO; 2005;Available at http://mednet3.who.int/EMLib/
  22. Grimes DA. Medical abortion in early pregnancy: a review of the evidence. Obstet Gynecol. 1997;89:790–796
  23. Teutsch G. Analogues of RU 486 for the mapping of the progestin receptor: synthetic and structural aspects. In:  Balieu EE,  Segal SJ editor. The antiprogestin steroid RU 486 and human fertility control. New York: Plenum Press; 1985;p. 27–47
  24. Benhamou B, Garcia T, Lerouge T, et al. A single amino acid that determines the sensitivity of progesterone receptors to RU 486. Science. 1992;255:206–209
  25. Baulieu EE. Contragestion and other clinical applications of RU 486, an antiprogesterone at the receptor. Science. 1989;245:1351–1357
  26. Moguilewsky M, Philibert D. Biochemical profile of RU 486. In:  Balieu EE,  Segal SJ editor. The antiprogestin steroid RU 486 and human fertility control. New York: Plenum Press; 1985;p. 87–97
  27. Lähteenmäki P, Heikinheimo O, Croxatto H, et al. Pharmacokinetics and metabolism of RU 486. J Steroid Biochem. 1987;27:859–863
  28. Gravanis A, Schaison G, George M, et al. Endometrial and pituitary responses to the steroidal antiprogestin RU 486 in postmenopausal women. J Clin Endocrinol Metab. 1985;60:156–163
  29. Terakawa N, Shimizu I, Tanizawa O, Matsumoto K. RU 486, a progestin antagonist, binds to progesterone receptors in a human endometrial cancer cell line and reverses the growth inhibition by progestins. J Steroid Biochem. 1988;31:161–166
  30. Baulieu EE. RU 486, an antisteroid molecule: cellular mechanism and clinical use. In:  Harddy MA,  Kinne RKH,  Karger B editor. Biology and medicine into the 21st century. Issues Biomed. vol. 15:Basel, Switzerland: Karger; 1991;p. 127–157
  31. Spitz IM, Bardin CW. Clinical pharmacology of RU 486 — an antiprogestin and antiglucocorticoid. Contraception. 1993;48:403–444
  32. Gao Y, Cheng L, Liu Y. Failure of mifepristone induced interruption of pregnancy: point mutation at genetic codon 722 in human progesterone receptor gene. Zhonghua Fu Chan Ke Za Zhi. 1998;33:549–552
  33. Sitruk-Ware R, Spitz I. Pharmacological properties of mifepristone: toxicology and safety in animal and human studies. Contraception. 2003;68:409–420
  34. Heikinheimo O, Kontula K, Croxatto H, Spitz I, Luukkainen T, Lahteenmaki P. Plasma concentrations and receptor binding of RU 486 and its metabolites in humans. J Steroid Biochem. 1987;26:279–284
  35. Heikinheimo O, Kekkonen R, Lahteenmaki P. The pharmacokinetics of mifepristone in humans reveal insights into differential mechanisms of antiprogestin action. Contraception. 2003;68:421–426
  36. Csapo AI, Pulkkinen MO, Wiest WG. Effects of luteectomy and progesterone replacement therapy in early pregnant patients. Am J Obstet Gynecol. 1973;115:759–765
  37. Csapo AI. Prostaglandin impact? For menstrual induction. Popul Rep G. 1974;4:33–40
  38. Garfield RE, Blennerhasset MG, Miller SM. Control of myometrial contractility: role and regulation of gap junctions. Oxf Rev Reprod Biol. 1988;10:436–490
  39. Norman JE, Kelly RW, Baird DT. Uterine activity and decidual prostaglandin production in women in early pregnancy in response to mifepristone with or without indomethacin in vivo. Hum Reprod. 1991;6:740–744
  40. Gemzell K, Swahn ML, Bygdeman M. Regulation of non-pregnant human uterine contractility. Effect of antihormones. Contraception. 1990;42:323–335
  41. Gemzell Danielsson K, Swahn ML, Bygdeman M. Effect of antiprogestin, hCG and a prostaglandin analogue on human uterine contractility. Contraception. 1993;47:295–301
  42. Ben-Chetrit A, Eldar-Geva T, Lindenberg T, et al. Mifepristone does not induce cervical softening in non-pregnant women. Hum Reprod. 2004;19:2372–2376
  43. Heikinheimo O, Ylikorkala O, Turpeinen U, Lahteenmaki P. Pharmacokinetics of the antiprogesterone RU 486: no correlation to clinical performance of RU 486. Acta Endocrinol (Copenh). 1990;123:298–304
  44. Exelgyn . Summary of product characteristics (SmPC). In: Paris: Exelgyn; 1998;
  45. Heikinheimo O, Croxatto H, Salvatierra AM, Chang CC, Luukkainen T, Lahteenmaki P. Intravaginal administration of RU 486 in humans and rats: inadequate absorption in humans. Hum Reprod. 1987;2:645–648
  46. Deraedt R, Bonnat C, Busigny M, et al. Pharmacokinetics of RU 486. In:  Baulieu E-E,  Segal SJ editor. The antiprogestin steroid RU 486 and human fertility control. New York: Plenum Press; 1985;p. 103–122
  47. Heikinheimo O, Lähteemäki PLA, Koivunen E, et al. Metabolism and serum binding of RU 486 in women after various single doses. Hum Reprod. 1987;2:379–385
  48. Swahn ML, Wang G, Aedo AR, Cekan SZ, Bygdeman M. Plasma levels of antiprogestin RU 486 following oral administration to non-pregnant and early pregnant women. Contraception. 1986;34:469–481
  49. Shi E, Ye Z, He C, et al. Pharmacokinetic study of RU 486 and its metabolites after oral administration of single doses to pregnant and non-pregnant women. Contraception. 1993;48:133–149
  50. Sitruk-Ware R. Medical recommendations for the safe use of mifepristone. In:  Coutinho EM,  Spinola P editor. Reproductive medicine — a millennium review. New York: The Parthenon Publishing Group; 1999;p. 288–299
  51. Blanchard K, Clark S, Winikoff B, Gaines G, Kabani G, Shannon C. Misoprostol for women's health: a review. Obstet Gynecol. 2002;99:316–332
  52. Ngai SW, Tang OS, Chan YM, Ho PC. Vaginal misoprostol alone for medical abortion up to 9 weeks of gestation: efficacy and acceptability. Hum Reprod. 2000;15:1159–1162
  53. Odlind V. Induced abortion — a global health problem. Acta Obstet Gynecol Scand Suppl. 1997;164:43–45
  54. WHO . Global and regional estimates of the incidence of unsafe abortion and associated mortality in 2000. In: 4th ed.. Geneva: WHO; 2004;[Available at] http://www.who.int/reproductive-health/publications/unsafe_abortion_estimates_04/estimates.pdf
  55. Sang GW, Weng LJ, Shao QX, et al. Termination of early pregnancy by two regimens of mifepristone with misoprostol and mifepristone with PG05 — a multicenter randomized clinical trial in China. Contraception. 1994;50:501–510
  56. WHO task force on post-ovulatory methods for fertility regulation . Pregnancy termination with mifepristone and gemeprost: a multicenter comparison between repeated doses and a single dose of mifepristone. Fertil Steril. 1991;56:32–40
  57. Thong KJ, Baird DT. Induction of abortion with mifepristone and misoprostol in early pregnancy. Br J Obstet Gynaecol. 1992;99:1004–1007
  58. McKinley C, Thong KJ, Baird DT. The effect of dose of mifepristone and gestation on the efficacy of medical abortion with mifepristone and misoprostol. Hum Reprod. 1993;8:1502–1505
  59. el-Refaey H, Templeton A. Early abortion induction by a combination of mifepristone and oral misoprostol: a comparison between two dose regimens of misoprostol and their effect on blood pressure. Br J Obstet Gynaecol. 1994;101:792–796
  60. Penny GC, McKessok L, Rispin R, et al. An effective, low cost regimen for early medical abortion. Br J Fam Plann. 1995;21:5–6
  61. von Hertzen H. Research on regimens for early medical abortion. J Am Med Womens Assoc 2000;55(3 Suppl):133–6,150.
  62. WHO Task Force on Post-Ovulatory Methods for Fertility Regulation . Termination of pregnancy with reduced doses of mifepristone. Br Med J. 1993;307:532–537
  63. WHO Task Force on Post-Ovulatory Methods for Fertility Regulation . Lowering the doses of mifepristone and gemeprost for early abortion: a randomised controlled trial. BJOG. 2001;108:738–742
  64. Bartley J, Brown A, Elton R, Baird DT. A double blind randomized control trial between vaginal gemeprost and misoprostol in combination with mifepristone for induction of abortion in early pregnancy. Hum Reprod. 2001;16:2098–2102
  65. Ashok PW, Penney GC, Flett GM, Templeton A. An effective regimen for early medical abortion: a report of 2000 consecutive cases. Hum Reprod. 1998;13:2962–2965
  66. Schaff EA, Fielding SL, Eisinger SH, Stadalius LS, Fuller L. Low-dose mifepristone followed by vaginal misoprostol at 48 hours for abortion up to 63 days. Contraception. 2000;61:41–46
  67. Schaff E, Fielding SL, Westhoff C, et al. Vaginal misoprostol administered 1, 2, or 3 days after mifepristone for early medical abortion. A randomized trial. JAMA. 2000;18(284):1948–1953
  68. Ashok PW, Templeton A, Wagaarachchi PT, Flett GM. Factors affecting the outcome of early medical abortion: a review of 4132 consecutive cases. BJOG. 2002;109:1281–1289
  69. von Hertzen H, Honkanen H, Piaggio G, et al. WHO multinational study of three misoprostol regimens after mifepristone for early medical abortion. I: efficacy. BJOG. 2003;110:808–818
  70. WHO . Safe abortion: technical and policy guidance for health systems. In: Geneva: WHO; 2003;
  71. Royal College of Obstetricians and Gynaecologists (RCOG) . The care of women requesting induced abortion evidence-based clinical guideline no. 7. 2004;[London]
  72. NAF . Early medical abortion with mifepristone and other agents: overview and protocol recommendations. Washington (DC): National Abortion Federation; 2002;
  73. WHO Task Force on Post-Ovulatory Methods for Fertility Regulation . Comparison of two doses of mifepristone in combination with misoprostol for early medical abortion: a randomised trial. BJOG. 2000;107:524–530
  74. Schaff EA, Fielding SL, Westhoff C. Randomized trial of oral versus vaginal misoprostol 2 days after mifepristone 200 mg for abortion up to 63 days of pregnancy. Contraception. 2002;66:247–250
  75. Shannon CS, Winikoff B, Hausknecht R, et al. Multicenter trial of a simplified mifepristone medical abortion regimen. Obstet Gynecol. 2005;105:345–351
  76. Aubeny E, Bureau A, Gabeaud P, et al. [Clinical trial of pregnancy terminations in 353 patients where amenorrhea was present for less than 49 days by 600 mg of RU 486 (administered orally) and 500 mg of sulprostone (Nalador) administered intramuscularly]. Contracept Fertil Sex. 1989;17:307–314
  77. Peyron R, Aubeny E, Targosz V, et al. Early pregnancy interruption with RU 486 (mifepristone) and misoprostol, an orally active prostaglandin analogue. N Engl J Med. 1993;328:1509–1513
  78. Anonymous . A death associated with mifepristone/sulprostone. Lancet. 1991;337:969–970
  79. Fliers E, Duren DR, van Zwieten PA. A prostaglandin analogue as a probable cause of myocardial infarction in a young woman. BMJ. 1991;302:416
  80. Aubeny E, Baulieu EE. Contraceptive activity of RU486 and oral active prostaglandin combination (Activité contragestive de l'association au RU 486 d'une prostaglandine active par voie orale), C R Acad Sci III. 1991;312:539–545
  81. Norman JE, Thong KJ, Baird DT. Uterine contractility and induction of abortion in early pregnancy by misoprostol and mifepristone. Lancet. 1991;338:1233–1236
  82. Goldberg AB, Greenberg MB, Darney PD. Misoprostol and pregnancy. N Engl J Med. 2001;344:38–47
  83. Weeks AD, Fiala C, Safar P. Misoprostol and the debate over off-label drug use. BJOG. 2000;112:269–272
  84. FDA registration of mifepristone 2000. Available www.fda.gov/cder/foi/label/2000/20687lbl.htm[Accessed July 2005]
  85. FDA-ACOG Committee Opinion No. 283. New US Food and Drug administration labelling on Cytotec (misoprostol) use in pregnancy. Obstet Gynecol. 2003;101:1049–1050
  86. ANAES (Agence nationale d'accréditation et d'évaluation en santé) . Induced abortion up to 14 weeks (Prise en charge de l'interruption volontaire de grossesse jusqu'à 14 semaines), In: Paris: ANAES; 2001;
  87. British National Formulary (BNF) 47 . London: British Medical Association Joint Formulary Committee; 2004;
  88. Foote EF, Lee DR, Karim A, Keane WF, Halstenson CE. Disposition of misoprostol and its active metabolite in patients with normal and impaired renal function. J Clin Pharmacol. 1995;35:384–389
  89. Zieman M, Fong SK, Benowitz NL, Banskter D, Darney PD. Absorption kinetics of misoprostol with oral or vaginal administration. Obstet Gynecol. 1997;90:88–92
  90. Tang OS, Schweer H, Seyberth HW, Lee SW, Ho PC. Pharmacokinetics of different routes of administration of misoprostol. Hum Reprod. 2002;17:332–336
  91. Gemzell Danielsson K, Marions L, Rodriguez A, Spur BW, Wong PY, Bygdeman M. Comparison between oral and vaginal administration of misoprostol on uterine contractility. Obstet Gynecol. 1999;93:275–280
  92. Khan RU, El-Refaey H, Sharma S, Sooranna D, Stafford M. Oral, rectal, and vaginal pharmacokinetics of misoprostol. Obstet Gynecol. 2004;103:866–870
  93. Schaff EA, DiCenzo R, Fielding SL. Comparison of misoprostol plasma concentrations following buccal and sublingual administration. Contraception. 2005;71:22–25
  94. Winikoff B. Acceptability of medical abortion in early pregnancy. Fam Plann Perspect. 1995;185:142–148
  95. Ho PC, Ngai SW, Liu KL, Wong GC, Lee SW. Vaginal misoprostol compared with oral misoprostol in termination of second trimester pregnancy. Obstet Gynecol. 1997;90:735–738
  96. Arvidsson C, Hellborg M, Gemzell-Danielsson K. Preference and acceptability of oral versus vaginal administration of misoprostol in medical abortion with mifepristone. Eur J Obstet Gynecol Reprod Biol. 2005;123:87–91
  97. Bygdeman M, Christensen NJ, Dimov V, Green K. Termination of pregnancy by a slow release device containing 16,16-dimethyl-trans-delta 2 PGE1 methyl ester. Asia Oceania J Obstet Gynaecol. 1984;10:359–365
  98. Cameron IT, Baird DT. A controlled release form of 16,16-dimethyl-trans-delta 2-PGE1, methyl ester for early abortion. Contraception. 1986;33:121–125
  99. Chen D, Tsay R-J, Lin H-I, Chen H, Chao SC, Ku H. Stabilization and sustained-release effect of misoprostol with metharylate copolymer. Int J Pharm. 2000;203:141–148
  100. Fiala C, Aronsson A, Granath F, et al. Pharmacokinetics of a novel oral slow-release form of misoprostol. Hum Reprod. 2005;20:3414–3418
  101. Fiala C, Aronsson A, Stephansson O, Gemzell-Danielsson K. Effects of slow release misoprostol on uterine contractility in early pregnancy. Hum Reprod. 2005;20:2648–2652
  102. Costa SH, Vessey MP. Misoprostol and illegal abortion in Rio de Janeiro, Brazil. Lancet. 1993;341:1258–1261
  103. Blanchard K, Winikoff B, Coyaji K, Nguyen TN. Misoprostol alone — a new method of medical abortion?. J Am Med Womens Assoc. 2000;55(3 Suppl):189–190
  104. Aubeny E, Peyron R, Turpin CL, et al. Termination of early pregnancy (up to 63 days of amenorrhea) with mifepristone and increasing doses of misoprostol. Int J Fertil Menopausal Stud. 1995;40(Suppl 2):85–91
  105. Spitz IM, Bardin CW, Benton L, Robbins A. Early termination of pregnancy with mifepristone (RU 486) and the orally active prostaglandin misoprostol. N Engl J Med. 1998;21:1509–1513
  106. el-Refaey H, Rajasekar D, Abdalla M, Calder L, Templeton A. Induction of abortion with mifepristone (RU 486) and oral or vaginal misoprostol. N Engl J Med. 1995;332:983–987
  107. Schaff EA, Stadalius LS, Eisinger SH, Franks P. Vaginal misoprostol administered at home after mifepristone (RU486) for abortion. J Fam Pract. 1997;44:353–360
  108. Schaff EA, Fielding SL, Westhoff C. Randomized trial of oral versus vaginal misoprostol at one day after mifepristone for early medical abortion. Contraception. 2001;64:81–85
  109. Honkanen H, Piaggio G, Hertzen H, et al. WHO Research Group on Post-Ovulatory Methods for Fertility Regulation WHO multinational study of three misoprostol regimens after mifepristone for early medical abortion-side effects. BJOG. 2004;111:715–725
  110. Caldeyro-Barcia R, Poserro JJ. Oxytocin and contractility of the human pregnant uterus. Ann N Y Acad Sci. 1959;75:813–830
  111. Tang OS, Ho PC. Pilot study on the use of sublingual misoprostol for medical abortion. Contraception. 2001;64:315–317
  112. Aronsson A, Bygdeman M, Gemzell-Danielsson K. Effects of misoprostol on uterine contractility following different routes of administration. Hum Reprod. 2004;19:81–84
  113. Aronsson A, Helstrom L, Gemzell-Danielsson K. Sublingual compared with oral misoprostol for cervical dilatation prior to vacuum aspiration: a randomized comparison. Contraception. 2004;69:165–169
  114. Hamoda H, Ashok PW, Dow J, Flett GM, Templeton A. A pilot study of mifepristone in combination with sublingual or vaginal misoprostol for medical termination of pregnancy up to 63 days gestation. Contraception. 2003;68:335–338
  115. Schaff EA, DiCenzo R, Fielding SL. Comparison of misoprostol plasma concentrations following buccal and sublingual administration. Contraception. 2005;71:22–25
  116. Middleton T, Schaff E, Fielding SL, et al. Randomized trial of mifepristone and buccal or vaginal misoprostol for abortion through 56 days of last menstrual period. Contraception. 2005;72:328–332
  117. Ashok PW, Templeton A. Nonsurgical mid-trimester termination of pregnancy: a review of 500 consecutive cases. Br J Obstet Gynaecol. 1999;106:706–710
  118. Ngai SW, Tang OS, Ho PC. Randomized comparison of vaginal (200 microg every 3 h) and oral (400 microg every 3 h) misoprostol when combined with mifepristone in termination of second trimester pregnancy. Hum Reprod. 2000;15:2205–2208
  119. Spitz IM, Bardin CW, Benton L, Robbins A. Early pregnancy termination with mifepristone and misoprostol in the United States. N Engl J Med. 1993;338:1241–1247
  120. Aubeny E. A two-stage increase in the dose of misoprostol improves the efficacy of medical abortion with mifepristone and prostaglandins. Eur J Contracept Reprod Health Care. 2001;6:54–55
  121. Tang OS, Lee SW, Ho PC. A prospective randomized study on the measured blood loss in medical termination of early pregnancy by three different misoprostol regimens after pretreatment with mifepristone. Hum Reprod. 2002;17:2865–2868
  122. Creinin MD, Fox MC, Teal S, Chen A, Schaff EA, Meyn LA. A randomized comparison of misoprostol 6 to 8 hours versus 24 hours after mifepristone for abortion. Obstet Gynecol. 2004;103:851–859
  123. Aubeny E. Trends since 1989, in France, of induced abortions by mifepristone (RU486) combined with a prostaglandin analogue (Evolution depuis 1989, en France, des interruptions volontaire de grossesse par mifépristone (RU 486) associée à un analogue de prostaglandine), Contracept Fertil Sex. 1997;25:777–781
  124. Guengant JP, Bangou J, Elul B, Ellertson C. Mifepristone-misoprostol medical abortion: home administration of misoprostol in Guadeloupe. Contraception. 1999;60:167–172
  125. Elul B, Pearlman E, Sorhaindo A, Simonds W, Westhoff C. In-depth interviews with medical abortion clients: thoughts on the method and home administration of misoprostol. J Am Med Womens Assoc. 2000;55(3 Suppl):169–172
  126. Harper C, Ellertson C, Winikoff B. Could American women use mifepristone–misoprostol pills safely with less medical supervision?. Contraception. 2002;65:133–142
  127. Fiala C, Winikoff B, Helstrom L, Hellborg M, Gemzell-Danielsson K. Acceptability of home-use of misoprostol in medical abortion. Contraception. 2004;70:387–392
  128. Faucher P, Baunot N, Madelenat P. The efficacy and acceptability of mifepristone medical abortion with home administration misoprostol provided by private providers linked with the hospital: a prospective study of 433 patients. [Article in French] Gynecol Obstet Fertil. 2005;33:220–227
  129. Hamoda H, Critchley HO, Paterson K, Guthrie K, Rodger M, Penney GC. The acceptability of home medical abortion to women in UK settings. BJOG. 2005;112:781–785
  130. Bygdeman M, Danielsson KG. Options for early therapeutic abortion. A comparative review. Drugs. 2002;62:2459–2470
  131. Holmgren K. Women's evaluation of three early abortion methods. Acta Obstet Gynecol Scand. 1992;71:616–623
  132. Henshaw RC, Naji SA, Russell IT, Templeton AA. Comparison of medical abortion with surgical vacuum aspiration: women's preferences and acceptability of treatment. BMJ. 1993;307:714–717
  133. Safar P, Fiala C. Abortion with mifepristone and misoprostol in Austria — first experiences (Schwangerschaftsabbruch mit Mifepriston und Misoprostol in Österreich-erste Erfahrungen), Frauenarzt. 2000;41:325–330
  134. Fielding SL, Edmunds E, Schaff EA. Having an abortion using mifepristone and home misoprostol: a qualitative analysis of women's experiences. Perspect Sex Reprod Health. 2002;34:34–40
  135. Winikoff B, Ellertson C, Elul B, Sivin I. Acceptability and feasibility of early pregnancy termination by mifepristone–misoprostol. Results of a large multicenter trial in the United States. Mifepristone Clinical Trials Group. Arch Fam Med. 1998;7:360–366
  136. Henshaw R, Naji S, Russell I, Templeton A. Psychological responses following medical abortion (using mifepristone and gemeprost) and surgical vacuum aspiration. A patient-centered, partially randomised prospective study. Acta Obstet Gynecol Scand. 1994;73:812–818
  137. Urquhart DR, Templeton AA. Psychiatric morbidity and acceptability following medical and surgical methods of induced abortion. BJOG. 1991;98:396–399
  138. Howie FL, Henshaw RC, Naji SA, Russell IT, Templeton AA. Medical abortion or vacuum aspiration? Two year follow up of a patient preference trial. BJOG. 1997;104:829–833
  139. Slade P, Heke S, Fletcher J, Stewart P. A comparison of medical and surgical termination of pregnancy: choice, emotional impact and satisfaction with care. BJOG. 1998;105:1288–1295
  140. Ashok PW, Flett GM, Templeton A. Mifepristone versus vaginally administered misoprostol for cervical priming before first-trimester termination of pregnancy: a randomized, controlled study. Am J Obstet Gynecol. 2000;183:998–1002
  141. Heikinheimo O, Suhonen S, Haukkamaa M. One- and 2-day mifepristone–misoprostol intervals are both effective in medical termination of second-trimester pregnancy. Reprod Biomed Online. 2004;8:236–239
  142. Sandstrom O, Brooks L, Schantz A, et al. Interruption of early pregnancy with mifepristone in combination with gemeprost. Acta Obstet Gynecol Scand. 1999;78:806–809
  143. Basu R, Gundlach T, Tasker M. Mifepristone and misoprostol for medical termination of pregnancy: the effectiveness of a flexible regimen. J Fam Plann Reprod Health Care. 2003;29:139–141
  144. Pymar HC, Creinin MD, Schwartz JL. Mifepristone followed on the same day by vaginal misoprostol for early abortion. Contraception. 2001;64:87–92
  145. Creinin MD, Schwartz JL, Pymar HC, Fink W. Efficacy of mifepristone followed on the same day by misoprostol for early termination of pregnancy: report of a randomised trial. BJOG. 2001;108:469–473
  146. Murthy AS, Creinin MD, Harwood B, Schreiber C. A pilot study of mifepristone and misoprostol administered at the same time for abortion up to 49 days gestation. Contraception. 2005;71:333–336
  147. Schreiber CA, Creinin MD, Harwood B, Murthy AS. A pilot study of mifepristone and misoprostol administered at the same time for abortion in women with gestation from 50 to 63 days. Contraception. 2005;71:447–450
  148. Creinin MD, Schwartz JL, Pymar HC, Fink W. Efficacy of mifepristone followed on the same day by misoprostol for early termination of pregnancy: report of a randomised trial. BJOG. 2001;108:469–473
  149. Trussell J, Ellertson C. Estimating the efficacy of medical abortion. Contraception. 1999;60:119–135
  150. Thonneau P, Fougeyrollas B, Spira A. Analysis of 369 abortions conducted by mifepristone (RU486) associated with sulprostone in a French family planning center. Fertil Steril. 1994;61:627–631
  151. Paul M, Schaff E, Nichols M. The roles of clinical assessment, human chorionic gonadotropin assays, and ultrasonography in medical abortion practice. Am J Obstet Gynecol. 2000;183(2 Suppl):S34–S43
  152. Bygdeman M, (Gemzell) Danielsson KG, Marions L. Medical termination of early pregnancy: the Swedish experience. J Am Med Womens Assoc 2000;55:195–6,204.
  153. Walker K, Schaff E, Fielding S, Fuller L. Monitoring serum chorionic gonadotropin levels after mifepristone abortion. Contraception. 2001;64:271–273
  154. Honkanen H, Ranta S, Ylikorkala O, Heikinheimo O. The kinetics of serum hCG and progesterone in response to oral and vaginal administration of misoprostol during medical termination of early pregnancy. Hum Reprod. 2002;17:2315–2319
  155. Acharya G, Haugen M, Brathen A, Nilsen I, Maltau JM. Role of routine ultrasonography in monitoring the outcome of medical abortion in a clinical setting. Acta Obstet Gynecol Scand. 2004;83:390–394
  156. Fiala C, Safar P, Bygdeman M, Gemzell-Danielsson K. Verifying the effectiveness of medical abortion; ultrasound versus hCG testing. Eur J Obstet Gynecol Reprod Biol. 2003;109:190–195
  157. Gemzell-Danielsson H, Helström Abort PM. Guideline for SESAM. Stockholm (Sweden): Karolinska University Hospital; 2005;
  158. Jourdan MC, van den Bossche MC. Usefulness of β-hCG in medical abortion (Intert des beta hCG dans l'IVG medicamenteuse), In: ANCIC 9th congress, France. 1991;www.ancic.asso.fr
  159. Legarth J, Peen UB, Michelsen JW. Mifepristone or vacuum aspiration in termination of early pregnancy. Eur J Obstet Gynecol Reprod Biol. 1991;41:91–96
  160. Grunberg SM, Weiss MH, Spitz IM, et al. Treatment of unresectable meningiomas with the antiprogesterone agent mifepristone. J Neurosurg. 1991;74:861–866
  161. Perrault D, Eisenhauer EA, Pritchard KI, et al. Phase II study of the progesterone antagonist mifepristone in patients with untreated metastatic breast carcinoma: a National Cancer Institute of Canada Clinical Trials Group study. J Clin Oncol. 1996;14:2709–2712
  162. Kettel LM, Murphy AA, Morales AJ, Ulmann A, Baulieu EE, Yen SS. Treatment of endometriosis with the antiprogesterone mifepristone (RU486). Fertil Steril. 1996;65:23–28
  163. Murphy AA, Morales AJ, Kettel LM, Yen SS. Regression of uterine leiomyomata to the antiprogesterone RU486: dose-response effect. Fertil Steril. 1995;64:187–190
  164. Spitz IM, Grunberg SM, Chabbert-Buffet N, Lindenberg T, Gelber H, Sitruk-Ware R. Management of patients receiving long-term treatment with mifepristone. Fertil Steril. 2005;84:1719–1726
  165. Sitruk-Ware R, Davey A, Sakiz E. Fetal malformation and failed medical termination of pregnancy. Lancet. 1998;352:323
  166. The Population Council . Misoprostol and teratogenicity: reviewing the evidence. New York: The Population Council; 2003;
  167. Zhou W, Nielsen GL, Moller M, Olsen J. Short-term complications after surgically induced abortions: a register-based study of 56 117 abortions. Acta Obstet Gynecol Scand. 2002;81:331–336
  168. Shannon C, Brothers LP, Philip NM, Winikoff B. Infection after medical abortion: a review of the literature. Contraception. 2004;70:183–190
  169. Wiebe E, Guilbert E, Jacot F, Shannon C, Winikoff B. A fatal case of Clostridium sordellii septic shock syndrome associated with medical abortion. Obstet Gynecol. 2004;104:1142–1144
  170. Centers for Disease Control and Prevention (CDC) . Clostridium sordellii toxic shock syndrome after medical abortion with mifepristone and intravaginal misoprostol — United States and Canada, 2001-2005. MMWR Morb Mortal Wkly Rep. 2005;54:724
  171. Fischer M, Bhatnagar J, Guarner J, et al. Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion. N Engl J Med. 2005;353:2352–2360
  172. Abdulla A, Yee L. The clinical spectrum of Clostridium sordellii bacteraemia: two case reports and a review of the literature. J Clin Pathol. 2000;53:709–712
  173. FDA . Public Health Advisory. Sepsis and medical abortion update. 2006;www.fda.gov/cder/drug/advisory/mifeprex200603.htm
  174. Wiebe ER. Pain control in medical abortion. Int J Gynecol Obstet. 2001;74:275–280
  175. Jain JK, Harwood B, Meckstroth KR, Mishell DR. Early pregnancy termination with vaginal misoprostol and acetaminophen prophylaxis. Contraception. 2001;63:217–221
  176. Ölund A. The effect of indomethacin on the instillation–abortion interval in rivanol-induced mid-trimester abortion. Acta Obstet Gynecol Scand. 1979;58:121–122
  177. Lundström V, Green K, Wiqvist N. Prostaglandins, indomethacin and dysmenorrhea. Prostaglandins. 1976;11:893–907
  178. Smith RP. The dynamics of nonsteroidal anti-inflammatory therapy for primary dysmenorrhoea. Obstet Gynecol. 1987;70:785–788
  179. Rådestad A, Bygdeman M. Cervical softening with mifepristone (RU 486) after pretreatment with naproxen. A double-blind randomized study. Contraception. 1992;45:221–227
  180. Li CFI, Wong CYG, Chan CPB, Ho PC. A study of co-treatment of nonsteroidal anti-inflammatory drugs (NSAIDs) with misoprostol for cervical priming before suction termination of first trimester pregnancy. Contraception. 2003;67:101–105
  181. Creinin MD, Shulman T. Effect of nonsteroidal anti-inflammatory drugs on the action of misoprostol in a regimen for early abortion. Contraception. 1997;56:165–168
  182. Fiala C, Swahn ML, Stephansson O, Gemzell-Danielsson K. The effect of non-steroidal anti-inflammatory drugs on medical abortion with mifepristone and misoprostol at 13–22 weeks gestation. Hum Reprod. 2005;20:3072–3077
  183. Chan YF, Ho PC, Ma HK. Blood loss in termination of early pregnancy by vacuum aspiration and by combination of mifepristone and gemeprost. Contraception. 1993;47:85–95
  184. Prasad RN, Choolani M, Roy A, Ratnam SS. Blood loss in termination of early pregnancy with mifepristone and gemeprost. Aust N Z J Obstet Gynaecol. 1995;35:329–331
  185. Harper C, Winikoff B, Ellertson C, Coyaji K. Blood loss with mifepristone–misoprostol abortion: measures from a trial in China, Cuba and India. Int J Gynaecol Obstet. 1998;63:39–49
  186. Martin CW, Brown AH, Baird DT. A pilot study of the effect of methotrexate or combined oral contraceptive on bleeding patterns after induction of abortion with mifepristone and a prostaglandin pessary. Contraception. 1998;58:99–103
  187. Tang OS, Gao PP, Cheng L, Lee SW, Ho PC. A randomized double-blind placebo-controlled study to assess the effect of oral contraceptive pills on the outcome of medical abortion with mifepristone and misoprostol. Hum Reprod. 1999;14:722–725
  188. Tang OS, Xu J, Cheng L, Lee SW, Ho PC. The effect of contraceptive pills on the measured blood loss in medical termination of pregnancy by mifepristone and misoprostol: a randomized placebo controlled trial. Hum Reprod. 2002;17:99–102
  189. Bygdeman M, Gemzell K, Gottlieb C, Swahn ML. Uterine contractility and interaction between prostaglandins and antiprogestins. Clinical implications. Ann N Y Acad Sci. 1991;626:561–567
  190. Baulieu EE, Ulmann A. Steroidal antihormones: the antiprogesterone activity of RU486 and its contragestive and other applications. Bull Acad Natl Med. 1985;169:1191–1200
  191. Haspels AA. Interruption of early pregnancy by an anti-progestational compound, RU 486. Eur J Obstet Gynecol Reprod Biol. 1985;20:169–175
  192. Cameron IT, Michie AF, Baird DT. Therapeutic abortion in early pregnancy with antiprogestogen RU 486 alone or in combination with a prostaglandin analogue (gemeprost). Contraception. 1986;34:459–468
  193. Rodger MW, Baird DT. Induction of therapeutic abortion in early pregnancy with mifepristone in combination with prostaglandin pessary. Lancet. 1987;2:1415–1418
  194. Hill NC, Selinger M, Ferguson J, Lopez Bernal A, Mackenzie IZ. The physiological and clinical effects of progesterone inhibition with mifepristone (RU 486) in the second trimester. Br J Obstet Gynaecol. 1990;97:487–492
  195. Rodger MW, Baird DT. Pretreatment with mifepristone (RU 486) reduces interval between prostaglandin administration and expulsion in second trimester abortion. BJOG. 1990;97:41–45
  196. Urquhart DR, Templeton AA. The use of mifepristone prior to prostaglandin-induced mid-trimester abortion. Hum Reprod. 1990;5:883–886
  197. Ashok PW, Kidd A, Flett GM, Fitzmaurice A, Graham W, Templeton A. A randomized comparison of medical abortion and surgical vacuum aspiration at 10–13 weeks gestation. Hum Reprod. 2002;17:92–98
  198. Hamoda H, Ashok PW, Flett GM, Templeton A. Medical abortion at 9–13 weeks' gestation: a review of 1076 consecutive cases. Contraception. 2005;71:327–332
  199. el-Refaey H, Hinshaw K, Templeton A. The abortifacient effect of misoprostol in the second trimester. A randomized comparison with gemeprost in patients pre-treated with mifepristone (RU 486). Hum Reprod. 1993;8:1744–1746
  200. Gemzell-Danielsson K, Ostlund E. Termination of second trimester pregnancy with mifepristone and gemeprost. The clinical experience of 197 consecutive cases. Acta Obstet Gynecol Scand. 2000;79:702–706
  201. Thong KJ, Norman JE, Baird DT. Changes in the concentration of α-fetoprotein and placental hormones following two methods of medical abortion in early pregnancy. BJOG. 1993;100:1111–1114
  202. Jabara S, Barnhart K. Is Rh immune globulin needed in early first-trimester abortion? A review. Am J Obstet Gynecol. 2003;188:623–627
  203. Fiala C, Fux M, Gemzell Danielsson K. Rh-prophylaxis in early abortion. Acta Obstet Gynecol Scand. 2003;82:892–903
  204. Jones ML, Wray J, Wight J, et al. A review of the clinical effectiveness of routine antenatal anti-D prophylaxis for rhesus-negative women who are pregnant. BJOG. 2004;111:892–902

PII: S0010-7824(06)00116-8

doi: 10.1016/j.contraception.2006.03.018

Contraception
Volume 74, Issue 1 , Pages 66-86 , July 2006

Article Tools

* Image Usage & Resolution