Medical methods for mid-trimester termination of pregnancy.
BACKGROUND
With the improvement of ultrasound technology, the likelihood of detection of major fetal structural anomalies in mid-pregnancy has increased considerably. Upon the detection of serious anomalies, women typically are offered the option of pregnancy termination. Additionally, there are still many reasons other than fetal anomalies why women seek abortion in the mid-trimester.


OBJECTIVE
To compare different methods of second trimester medical termination of pregnancy for their efficacy and side-effects.


METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, Popline and reference lists of retrieved papers and other sources.


METHODS
All randomised controlled trials (RCTs) examining medical regimens for termination of pregnancy of a singleton living fetus between 12-28 weeks' gestation were analysed. The outcome measures were the induction to abortion interval, abortion rate within 24 hours, need for surgical evacuation, blood loss, uterine rupture, pain, and side-effects.Trials including >20% fetal death, multiple pregnancies, previous uterine scars and regimens which involved cervical preparation were excluded.


METHODS
Two authors selected the trials and three authors extracted data.


RESULTS
Fourty RCTs were included, addressing various agents for pregnancy termination and methods of administration. When used alone, misoprostol was an effective inductive agent, though it appeared to be more effective in combination with mifepristone. However, the evidence from RCTs is limited.Misoprostol was preferably administered vaginally, although among multiparous women sublingual administration appeared equally effective. A range of doses of vaginally administered misoprostol has been used. No randomised trials comparing doses of misoprostol were identified; however low doses of misoprostol appear to be associated with fewer side-effects while moderate doses appear to be more efficient in completing abortion. Four RCTs showed that the induction to abortion interval with 3-hourly vaginal administration of prostaglandins is shorter than 6-hourly administration without an increase in side-effects.Many studies reported the need for surgical evacuation. Indications for surgical evacuation include retained products of the placenta and heavy vaginal bleeding. Fewer women required surgical evacuation when misoprostol was administrated vaginally compared with women receiving intra-amniotical PGF(2a) . Mild, self-limiting diarrhoea was more common among women who received misoprostol compared to other agents.


CONCLUSIONS
Medical abortion in the second trimester using the combination of mifepristone and misoprostol appeared to have the highest efficacy and shortest abortion time interval. Where mifepristone is not available, misoprostol alone is a reasonable alternative. The optimal route for administering misoprostol is vaginally, preferably using tablets at 3-hourly intervals. Apart from pain, the side-effects of vaginal misoprostol are usually mild and self limiting. Conclusions from this review are limited by the gestational age ranges and variable medical regimens, including dosing, administrative routes and intervals of medication, of the included trials.
Department of Obstetrics and Gynaecology, Erasmus Medical Center, PO Box 2040, Rotterdam, Netherlands, 3000 CA.
Hajo
H
Wildschut
Marieke I
MI
Both
Suzanne
S
Medema
Eeke
E
Thomee
Mark F
MF
Wildhagen
Nathalie
N
Kapp
D000019:Abortifacient Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000028:Abortion, Induced / Q000379:methods*; D000282:Administration, Intravaginal; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015735:Mifepristone / Q000008:administration & dosage*; D016595:Misoprostol / Q000008:administration & dosage* / Q000009:adverse effects; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011454:Prostaglandins A / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic
D000019:Abortifacient Agents; D011454:Prostaglandins A; D016595:Misoprostol; D015735:Mifepristone
Obstet Gynecol. 2003 Jun;101(6):1294-9
12798539
Int J Gynaecol Obstet. 2006 Mar;92(3):270-1
16430901
Aust N Z J Obstet Gynaecol. 1996 Aug;36(3):296-9
8883754
Obstet Gynecol. 1997 Jul;90(1):88-92
9207820
Br J Obstet Gynaecol. 1992 Jul;99(7):601-6
1525104
Contraception. 1981 Aug;24(2):151-7
7297067
Reprod Health Matters. 2008 May;16(31 Suppl):196-204
18772101
Contraception. 1993 Feb;47(2):123-9
8449013
BJOG. 2008 May;115(6):689-96
18410651
Contraception. 1981 Jun;23(6):621-8
6793303
Ultrasound Obstet Gynecol. 1999 Feb;13(2):117-26
10079491
Contraception. 1998 Oct;58(4):207-10
9866000
Br J Obstet Gynaecol. 1993 Aug;100(8):758-61
8399016
Acta Obstet Gynecol Scand. 1992 May;71(4):278-83
1322621
Acta Obstet Gynecol Scand. 1979;58(1):121-2
419946
Int J Gynaecol Obstet. 1991 Aug;35(4):337-40
1682182
Steroids. 1981 Apr;37(4):361-82
7245285
Acta Obstet Gynecol Scand Suppl. 1974;37:57-60
4533699
Contraception. 2007 Dec;76(6):461-6
18061705
Contraception. 1996 May;53(5):281-3
8724617
Arch Gynecol Obstet. 2007 Nov;276(5):511-6
17453221
Reprod Health Matters. 2008 May;16(31 Suppl):18-29
18772080
BJOG. 2005 Sep;112(9):1297-301
16101611
N Engl J Med. 2001 Jan 4;344(1):38-47
11136959
Trop Doct. 2001 Jul;31(3):157-61
11444340
J Obstet Gynaecol Res. 2008 Apr;34(2):199-203
18412782
Hum Reprod. 2005 Nov;20(11):3062-6
16037110
BJOG. 2005 Mar;112(3):266-8
15713137
Acta Obstet Gynecol Scand. 1997 Aug;76(7):680-3
9292644
Acta Obstet Gynecol Scand. 1998 Apr;77(4):429-32
9598952
Hum Reprod. 2005 Aug;20(8):2348-54
15878927
J Matern Fetal Med. 1998 May-Jun;7(3):115-9
9642607
S Afr Med J. 1993 Oct;83(10):737-8
8191328
Obstet Gynecol. 1997 Nov;90(5):735-8
9351755
J Indian Med Assoc. 1982 Jul;79(1-2):7-9
7142727
J Indian Med Assoc. 1984 Dec;82(12):432-4
6535811
Hum Reprod. 1988 Oct;3(7):915-21
2846630
Int J Gynaecol Obstet. 1976;14(5):393-6
15903
Contraception. 1992 Jul;46(1):11-7
1424619
Hum Reprod. 2002 Feb;17(2):332-6
11821273
Contraception. 2008 Jan;77(1):50-5
18082667
Contraception. 1985 Jul;32(1):45-51
4053605
N Engl J Med. 2001 Jan 4;344(1):61
11187113
Cochrane Database Syst Rev. 2008 Jan 23;(1):CD006714
18254113
Eur J Obstet Gynecol Reprod Biol. 1986 Mar;21(3):165-71
3456942
BJOG. 2005 Mar;112(3):269-72
15713138
Aust N Z J Obstet Gynaecol. 1989 Aug;29(3 Pt 2):299-302
2515847
J Matern Fetal Med. 1999 Mar-Apr;8(2):48-50
10090490
Acta Obstet Gynecol Scand. 2006;85(7):825-9
16817081
J Obstet Gynaecol. 2006 Aug;26(6):546-9
17000504
Int J Gynaecol Obstet. 2007 Dec;99 Suppl 2:S160-7
17963768
Int J Gynaecol Obstet. 2005 Jun;89(3):276-7
15919397
Acta Obstet Gynecol Scand. 1983;62(4):303-6
6416016
Am J Obstet Gynecol. 2004 Mar;190(3):755-62
15042010
Am J Obstet Gynecol. 2002 Mar;186(3):470-4
11904609
Contraception. 1996 Jul;54(1):23-5
8804804
J Matern Fetal Neonatal Med. 2008 Nov;21(11):847-51
18979392
Aust N Z J Obstet Gynaecol. 2008 Apr;48(2):165-71
18366490
Hum Reprod. 1988 Aug;3(6):803-6
3065355
Int J Gynaecol Obstet. 1980 Jan-Feb;17(4):368-71
6102059
Am J Public Health. 1999 Nov;89(11):1649-57
10553384
Gynecol Obstet Invest. 1999;48(2):113-8
10461002
J Indian Med Assoc. 1992 Sep;90(9):237-9
1460314
BJOG. 2009 Aug;116(9):1151-7
19438490
Hum Reprod. 2000 Mar;15(3):709-12
10686224
Hum Reprod. 2002 Jun;17(6):1483-9
12042266
N Engl J Med. 2000 Mar 30;342(13):946-56
10738054
Obstet Gynecol. 1999 Apr;93(4):571-5
10214835
Clin Exp Obstet Gynecol. 2009;36(4):245-7
20101858
Reprod Fertil Dev. 1990;2(5):495-8
2075246
Obstet Gynecol. 1995 May;85(5 Pt 1):697-700
7724098
Contraception. 1984 Feb;29(2):171-9
6586395
Aust N Z J Obstet Gynaecol. 2001 Nov;41(4):407-10
11787914
Hum Reprod. 1993 Oct;8(10):1744-6
8300840
Obstet Gynecol. 1996 Jul;88(1):110-3
8684741
JAMA. 1998 Aug 26;280(8):747-50
9728652
J Reprod Med. 2005 Mar;50(3):173-80
15841929
Obstet Gynecol. 2006 Jan;107(1):128-35
16394050
Am J Obstet Gynecol. 2002 Oct;187(4):853-7
12388963
Ultrasound Obstet Gynecol. 2006 Dec;28(7):925-33
17121414
Br Med J. 1976 Jun 5;1(6022):1373-6
1276696
Int J Gynaecol Obstet. 1980 Jul-Aug;18(1):40-3
6106599
J Obstet Gynaecol Res. 2001 Jun;27(3):125-8
11561827
N Engl J Med. 1994 Aug 4;331(5):290-3
8022438
Ultrasound Obstet Gynecol. 1998 Apr;11(4):246-53
9618846
Eur J Contracept Reprod Health Care. 2009 Feb;14(1):55-60
19241302
Contraception. 1996 Aug;54(2):97-100
8842586
Zentralbl Gynakol. 1998;120(6):293-300
9659700
BJOG. 2004 Sep;111(9):1001-5
15327617
Int J Gynaecol Obstet. 2007 Dec;99 Suppl 2:S178-81
17961566
Am J Obstet Gynecol. 2005 Oct;193(4):1410-4
16202734
J Obstet Gynaecol India. 1975 Apr;25(2):165-75
1100457
Eur J Obstet Gynecol Reprod Biol. 2010 Aug;151(2):149-53
20434827
Am J Obstet Gynecol. 2005 Sep;193(3 Pt 2):1065-70
16157113
Am J Bioeth. 2009 Aug;9(8):48-56
19998163
Am J Obstet Gynecol. 1999 Nov;181(5 Pt 1):1057-61
10561618
BJOG. 2002 Nov;109(11):1290-4
12452468
Eur J Obstet Gynecol Reprod Biol. 1996 Nov;69(2):97-102
8902440
Br J Obstet Gynaecol. 1996 Jul;103(7):706-9
8688400
Hum Reprod. 2009 Jan;24(1):106-12
18794161
Prenat Diagn. 2007 May;27(5):457-62
17335106
Obstet Gynecol. 2007 Dec;110(6):1304-10
18055725
Am J Obstet Gynecol. 2003 Sep;189(3):710-3
14526299
Fetal Diagn Ther. 2005 Nov-Dec;20(6):544-8
16260893
Eur J Obstet Gynecol Reprod Biol. 1979 Dec;9(6):385-9
299462
Hum Reprod. 2000 Oct;15(10):2205-8
11006200
J Obstet Gynaecol. 2003 Jul;23(4):407-11
12881083
Hum Reprod. 2009 Feb;24(2):320-4
19049993
J Reprod Med. 2009 Aug;54(8):511-6
19769198
Gynecol Obstet Invest. 1988;26(3):177-80
3240887
Acta Obstet Gynecol Scand. 1978;57(4):333-6
358728
J Gynecol Obstet Biol Reprod (Paris). 2001 Sep;30(5):439-43
11598557
Obstet Gynecol. 2004 Jul;104(1):138-45
15229013
Hum Reprod. 1995 Feb;10(2):475-8
7769082
Obstet Gynecol. 1997 Dec;90(6):896-900
9397098
Pak J Biol Sci. 2008 Nov 1;11(21):2505-8
19205272
BMJ. 2003 Sep 6;327(7414):557-60
12958120