title: Medical methods for first trimester abortion.
abstract: BACKGROUND
  Surgical abortion by vacuum aspiration or dilatation and curettage has been the method of choice for early pregnancy termination since the 1960s. Medical abortion became an alternative method of first trimester pregnancy termination with the availability of prostaglandins in the early 1970s and anti-progesterones in the 1980s. The most widely researched drugs are prostaglandins (PGs) alone, mifepristone alone, methotrexate alone, mifepristone with prostaglandins and methotrexate with prostaglandins.
  
  
  OBJECTIVE
  To compare different medical methods for first trimester abortion.
  
  
  METHODS
  The Cochrane Controlled Trials Register, MEDLINE and Popline were systematically searched. Reference lists of retrieved papers were also searched. Experts in WHO/HRP were contacted.
  
  
  METHODS
  Types of studies Randomised controlled trials comparing different medical methods for abortion during first trimester (e.g. single drug, combination) were considered. Trials were assessed and included if they had adequate concealment of allocation, randomisation procedure and follow-up. Women, pregnant during the first trimester, undergoing medical abortion were the participants. The outcomes were mortality, failure to achieve complete abortion, surgical evacuation, ongoing pregnancy at follow-up, time until passing of conceptus, blood transfusion, side effects and women's dissatisfaction with the procedure.
  
  
  METHODS
  Two reviewers independently selected trials for inclusion from the results of the search strategy described previously.The selection of trials for inclusion in the review was performed independently by two reviewers after employing the search strategy described previously. Trials under consideration were evaluated for appropriateness for inclusion and methodological quality without consideration of their results. Data were processed using Revman software.
  
  
  RESULTS
  Fifty-eight trials were included in the review. The effectiveness outcomes below refer to 'failure to achieve complete abortion' with the intended method unless otherwise stated. 1) Combined regimen mifepristone/prostaglandin: Mifepristone 600 mg compared to 200 mg shows similar effectiveness in achieving complete abortion (4 trials, RR 1.07, 95% CI 0.87 to 1.32). Misoprostol administered orally is less effective (more failures) than the vaginal route (RR 3.00, 95% CI 1.44 to 6.24) and may be associated with more frequent side effects such as nausea and diarrhoea. Sublingual and buccal routes were similarly effective compared to the vaginal route, but had higher rates of side effects. 2) Mifepristone alone is less effective when compared to the combined regimen mifepristone/prostaglandin (RR 3.76 95% CI 2.30 to 6.15). 3) Five trials compared prostaglandin alone to the combined regimen (mifepristone/prostaglandin). All but one reported higher effectiveness with the combined regimen. The results of these studies could not be combined but the RR of failure with prostaglandin alone is reportedly between 1.4 to 3.75 with the 95% confidence intervals indicating statistical significance. 4) In one trial comparing gemeprost 0.5 mg with misoprostol 800 mcg, misoprostol was more effective (failure with gemeprost: RR 2.86, 95% CI 1.14 to 7.18). 5) There was no difference in effectiveness with use of a divided dose compared to a single dose of prostaglandin. 6) Combined regimen methotrexate/prostaglandin demonstrates similar rates of failure to complete abortion when comparing intramuscular to oral methotrexate administration (RR 2.04, 95% CI 0.51 to 8.07). Similarly, day 3 vs. day 5 administration of prostaglandin following methotrexate administration showed no significant differences (RR 0.72, 95% CI 0.36 to 1.43). One trial compared the effect of tamoxifen vs. methotrexate and no statistically significant differences were observed in effectiveness between the groups.
  
  
  CONCLUSIONS
  Safe and effective medical abortion methods are available. Combined regimens are more effective than single agents. In the combined regimen, the dose of mifepristone can be lowered to 200 mg without significantly decreasing the method effectiveness. Vaginal misoprostol is more effective than oral administration, and has less side effects than sublingual or buccal. Some results are limited by the small numbers of participants on which they are based. Almost all trials were conducted in settings with good access to emergency services, which may limit the generalizability of these results.
authors.affiliation: World Health Organization, , Geneva, Switzerland. regina.kulier@bluewin.ch
authors.forename: Regina
authors.initials: R
authors.lastname: Kulier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Kapp
authors.forename: A Metin
authors.initials: AM
authors.lastname: Gülmezoglu
authors.forename: G Justus
authors.initials: GJ
authors.lastname: Hofmeyr
authors.forename: Linan
authors.initials: L
authors.lastname: Cheng
authors.forename: Aldo
authors.initials: A
authors.lastname: Campana
mesh_terms: D000019:Abortifacient Agents / Q000008:administration & dosage; D000027:Abortion, Incomplete / Q000139:chemically induced; D000028:Abortion, Induced / Q000009:adverse effects / Q000379:methods*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D015735:Mifepristone / Q000008:administration & dosage; D016595:Misoprostol / Q000008:administration & dosage; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011453:Prostaglandins / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D013629:Tamoxifen / Q000008:administration & dosage
chemical_list: D000019:Abortifacient Agents; D011453:Prostaglandins; D013629:Tamoxifen; D016595:Misoprostol; D015735:Mifepristone; D008727:Methotrexate
references.citation: Obstet Gynecol. 2007 Apr;109(4):885-94
references.pmid: 17400850
references.citation: Hum Reprod. 1995 Jun;10(6):1521-7
references.pmid: 7593528
references.citation: Int J Gynaecol Obstet. 1998 Dec;63 Suppl 1:S131-9
references.pmid: 10075223
references.citation: Hum Reprod. 1999 Mar;14(3):722-5
references.pmid: 10221703
references.citation: Contraception. 2004 Dec;70(6):463-6
references.pmid: 15541407
references.citation: Contraception. 1998 Aug;58(2):99-103
references.pmid: 9773264
references.citation: Br J Obstet Gynaecol. 1992 Jul;99(7):601-6
references.pmid: 1525104
references.citation: BJOG. 2000 Apr;107(4):524-30
references.pmid: 10759273
references.citation: Obstet Gynecol. 1999 Jun;93(6):904-9
references.pmid: 10362152
references.citation: Contraception. 2002 Jun;65(6):419-23
references.pmid: 12127641
references.citation: Am J Obstet Gynecol. 1999 Jul;181(1):149-52
references.pmid: 10411811
references.citation: Acta Obstet Gynecol Scand. 1999 Oct;78(9):806-9
references.pmid: 10535346
references.citation: Acta Obstet Gynecol Scand. 2001 May;80(5):447-51
references.pmid: 11328223
references.citation: J Reprod Med. 2001 Feb;46(2):125-9
references.pmid: 11255811
references.citation: BJOG. 2007 Feb;114(2):207-15
references.pmid: 17305893
references.citation: Obstet Gynecol. 2001 Sep;98(3):434-9
references.pmid: 11530125
references.citation: Hum Reprod. 1989 Aug;4(6):718-25
references.pmid: 2778058
references.citation: Am J Obstet Gynecol. 1995 Nov;173(5):1578-84
references.pmid: 7503204
references.citation: Obstet Gynecol. 2008 Dec;112(6):1303-1310
references.pmid: 19037040
references.citation: BJOG. 2003 Sep;110(9):808-18
references.pmid: 14511962
references.citation: Contraception. 1999 Apr;59(4):209-17
references.pmid: 10457864
references.citation: BJOG. 2006 Jun;113(6):621-8
references.pmid: 16709204
references.citation: Contraception. 1989 May;39(5):497-502
references.pmid: 2656087
references.citation: Zhonghua Fu Chan Ke Za Zhi. 2000 Sep;35(9):554-7
references.pmid: 11775949
references.citation: Contraception. 1994 Dec;50(6):501-10
references.pmid: 7705093
references.citation: Eur J Obstet Gynecol Reprod Biol. 2004 Oct 15;116(2):211-6
references.pmid: 15358467
references.citation: Contraception. 1998 Feb;57(2):83-8
references.pmid: 9589833
references.citation: Hum Reprod. 1994 Jan;9(1):57-63
references.pmid: 8195352
references.citation: Contraception. 1999 Apr;59(4):265-70
references.pmid: 10457872
references.citation: JAMA. 1994 Oct 19;272(15):1190-5
references.pmid: 7523739
references.citation: Hum Reprod. 2001 Oct;16(10):2098-102
references.pmid: 11574498
references.citation: BJOG. 2001 Jul;108(7):738-42
references.pmid: 11467701
references.citation: Fertil Steril. 1991 Jul;56(1):32-40
references.pmid: 1712323
references.citation: Contraception. 1986 Nov;34(5):459-68
references.pmid: 3816230
references.citation: Drugs. 2002;62(17):2459-70
references.pmid: 12421103
references.citation: Hum Reprod. 1989 Jan;4(1):21-8
references.pmid: 2651472
references.citation: Obstet Gynecol. 2004 May;103(5 Pt 1):851-9
references.pmid: 15121556
references.citation: Int Fam Plan Perspect. 2007 Sep;33(3):106-16
references.pmid: 17938093
references.citation: Hum Reprod. 1994 Nov;9(11):2167-72
references.pmid: 7868693
references.citation: Br J Obstet Gynaecol. 1994 Sep;101(9):792-6
references.pmid: 7947529
references.citation: Ann N Y Acad Sci. 1997 Sep 26;828:47-58
references.pmid: 9329823
references.citation: Acta Obstet Gynecol Scand Suppl. 1989;149:19-23
references.pmid: 2694737
references.citation: Contraception. 1985 Jul;32(1):45-51
references.pmid: 4053605
references.citation: Contraception. 1996 Jul;54(1):19-22
references.pmid: 8804803
references.citation: JAMA. 2000 Oct 18;284(15):1948-53
references.pmid: 11035891
references.citation: BJOG. 2004 Jul;111(7):715-25
references.pmid: 15198763
references.citation: Contraception. 2009 Feb;79(2):84-90
references.pmid: 19135563
references.citation: Contraception. 2005 Aug;72(2):91-7
references.pmid: 16022846
references.citation: Eur J Obstet Gynecol Reprod Biol. 2005 Nov 1;123(1):87-91
references.pmid: 16260342
references.citation: Contraception. 1996 Apr;53(4):244-6
references.pmid: 8706443
references.citation: Hum Reprod. 2000 May;15(5):1159-62
references.pmid: 10783370
references.citation: Acta Obstet Gynecol Scand. 1990;69(2):135-8
references.pmid: 2117332
references.citation: Contraception. 1992 Jun;45(6):547-59
references.pmid: 1617964
references.citation: Contraception. 1996 Apr;53(4):238-42
references.pmid: 8706442
references.citation: Hum Reprod. 1993 Sep;8(9):1502-5
references.pmid: 8253942
references.citation: Contraception. 1997 Mar;55(3):165-8
references.pmid: 9115005
references.citation: N Engl J Med. 1995 Apr 13;332(15):983-7
references.pmid: 7885426
references.citation: Obstet Gynecol. 1997 May;89(5 Pt 1):790-6
references.pmid: 9166323
references.citation: Contraception. 1997 Jan;55(1):1-5
references.pmid: 9013053
references.citation: Am J Obstet Gynecol. 1997 Dec;177(6):1444-9
references.pmid: 9423749
references.citation: Cochrane Database Syst Rev. 2002;(4):CD003037
references.pmid: 12519584
references.citation: Contraception. 1988 Oct;38(4):391-400
references.pmid: 3208513
references.citation: Hum Reprod. 2002 Nov;17(11):2865-8
references.pmid: 12407040
references.citation: Br J Obstet Gynaecol. 1990 Jun;97(6):480-6
references.pmid: 2198917
references.citation: Contraception. 1996 Jul;54(1):15-8
references.pmid: 8804802
references.citation: Zhonghua Fu Chan Ke Za Zhi. 1999 May;34(5):268-71
references.pmid: 11326930
references.citation: Contraception. 1999 Dec;60(6):353-6
references.pmid: 10715370
references.citation: Contraception. 1993 Oct;48(4):339-48
references.pmid: 8222661
references.citation: Contraception. 1999 Jun;59(6):389-94
references.pmid: 10518234
references.citation: Am J Obstet Gynecol. 1997 Feb;176(2):431-7
references.pmid: 9065194
references.citation: BJOG. 2002 Nov;109(11):1281-9
references.pmid: 12452467
references.citation: Contraception. 2000 Dec;62(6):305-9
references.pmid: 11239617
references.citation: Hum Reprod. 2002 Jun;17(6):1477-82
references.pmid: 12042265
references.citation: Lancet. 2007 Jun 9;369(9577):1938-46
references.pmid: 17560446
references.citation: BJOG. 2005 Aug;112(8):1102-8
references.pmid: 16045525
references.citation: Int J Gynaecol Obstet. 2006 Dec;95(3):286-7
references.pmid: 16997301
references.citation: BJOG. 2001 May;108(5):469-73
references.pmid: 11368131
references.citation: Eur J Contracept Reprod Health Care. 2000 Sep;5(3):171-6
references.pmid: 11131781
references.citation: Contraception. 2001 Aug;64(2):81-5
references.pmid: 11704083
references.citation: BMJ. 1993 Aug 28;307(6903):532-7
references.pmid: 8400972
references.citation: Hum Reprod. 2003 Nov;18(11):2315-8
references.pmid: 14585880
references.citation: Contraception. 2000 Sep;62(3):125-30
references.pmid: 11124359
references.citation: BJOG. 2007 Mar;114(3):271-8
references.pmid: 17217359
references.citation: BJOG. 2009 Feb;116(3):381-9
references.pmid: 19187370
references.citation: Contraception. 2005 Nov;72(5):328-32
references.pmid: 16246656
references.citation: Contraception. 1997 Sep;56(3):169-74
references.pmid: 9347208