Cochrane Update

Abstracts from Cochrane Reviews that relate to the practice of obstetrics and gynecology

Medical Methods for Mid-TrimesterTermination of PregnancyCOCHRANE ABSTRACTBACKGROUND: With the improvement of ultrasoundtechnology, the likelihood of detection of major fetal struc-tural anomalies in mid-pregnancy has increased consider-ably. Upon the detection of serious anomalies, womentypically are offered the option of pregnancy termination.Additionally, there are still many reasons other than fetalanomalies why women seek abortion in the mid-trimester.

OBJECTIVES: To compare different methods of secondtrimester medical termination of pregnancy for their effi-cacy and side-effects.

SEARCH STRATEGY: We searched the Cochrane CentralRegister of Controlled Trials (CENTRAL) (The CochraneLibrary), MEDLINE, Popline and reference lists of retrievedpapers and other sources.

SELECTION CRITERIA: All randomized controlled trials(RCTs) examining medical regimens for termination ofpregnancy of a singleton living fetus between 12–28 weeksof gestation were analyzed. The outcome measures werethe induction to abortion interval, abortion rate within24 hours, need for surgical evacuation, blood loss,uterine rupture, pain, and side-effects. Trials including>20% fetal death, multiple pregnancies, previous uter-ine scars and regimens which involved cervical prepa-ration were excluded.

DATA COLLECTION AND ANALYSIS: Two authors se-lected the trials and three authors extracted data.

MAIN RESULTS: Forty RCTs were included, addressingvarious agents for pregnancy termination and methods ofadministration. When used alone, misoprostol was an

effective inductive agent, although it appeared to bemore effective in combination with mifepristone. How-ever, the evidence from RCTs is limited.

Misoprostol was preferably administered vaginally,although among multiparous women sublingualadministration appeared equally effective. A range ofdoses of vaginally administered misoprostol has beenused. No randomized trials comparing doses of miso-prostol were identified; however low doses of miso-prostol appear to be associated with fewer side-effectswhile moderate doses appear to be more efficientin completing abortion. Four RCTs showed that theinduction to abortion interval with 3-hourly vaginaladministration of prostaglandins is shorter than6-hourly administration without an increase in side-effects.

Many studies reported the need for surgical evac-uation. Indications for surgical evacuation include re-tained products of the placenta and heavy vaginalbleeding. Fewer women required surgical evacuationwhen misoprostol was administrated vaginally comparedwith women receiving intra-amniotical PGF2a. Mild, self-limiting diarrhea was more common among women whoreceived misoprostol compared to other agents.

AUTHORS’ CONCLUSION: Medical abortion in the sec-ond trimester using the combination of mifepristone andmisoprostol appeared to have the highest efficacy andshortest abortion time interval. Where mifepristone is notavailable, misoprostol alone is a reasonable alternative.The optimal route for administering misoprostol isvaginally, preferably using tablets at 3-hourly intervals.Apart from pain, the side-effects of vaginal misoprostolare usually mild and self limiting. Conclusions from thisreview are limited by the gestational age ranges andvariable medical regimens, including dosing, adminis-trative routes and intervals of medication, of the in-cluded trials.

Wildschut J, Both MI, Medema S, Thomee E, Wildhagen MF,Kapp N. Medical methods for mid-trimester termination of preg-nancy. Cochrane Database of Systematic Reviews 2011, Issue 1. Art.No.: CD005216. DOI: 10.1002/14651858.CD005216.pub2. Copy-right The Cochrane Collaboration, reproduced with permission.

Address correspondence to: Melissa L. Gilliam, MD, MPH, University of Chicago,Department of Obstetrics and Gynecology, 5841 South Maryland Avenue, MC2050, Chicago, IL 60637; e-mail: mgilliam@babies.bsd.uchicago.edu.

Cochrane Reviews are regularly updated as new evidence emerges and in responseto feedback, and the Cochrane Library (http://www.thecochranelibrary.com)should be consulted for the most recent version of the review.

© 2011 by The American College of Obstetricians and Gynecologists. Publishedby Lippincott Williams & Wilkins.ISSN: 0029-7844/11DOI: 10.1097/AOG.0b013e3182178ffb

VOL. 117, NO. 5, MAY 2011 OBSTETRICS & GYNECOLOGY 1223

COMMENTARY

Approximately 10% of abortions occur after 14weeks. The majority of women will undergo dilata-

tion and evacuation for second-trimester pregnancytermination, although the frequency of labor induc-tion increases at greater gestational ages and for fetalanomalies.1 Misoprostol has become the agent ofchoice for this procedure because it is low-cost, heat-stable, and safe. Yet there is great variation in howmisoprostol is used; specifically, the optimal dose,frequency of administration, and route of administra-tion vary in clinical practice. In addition, misoprostolhas been used in conjunction with mechanical dilatorsand other pharmacologic agents. Wildschut and col-leagues review 40 studies of 24 regimens and clarifysecond-trimester abortion procedures.

The optimal regimen for second-trimester abor-tion is misoprostol with the addition of mifepristone;this regimen is the fastest and most efficacious. Mife-pristone is given 24 to 48 hours in advance ofmisoprostol. This combination results in 95% comple-tion within 24 hours.2 Yet mifepristone may be un-available or cost-prohibitive in some centers, in whichcase misoprostol alone is also effective. Misoprostolshould be given at 3-hour intervals because longerintervals are less effective. The optimal dose is notknown, but lower doses (eg, 300 micrograms) havefewer side effects. Oral dosing should not be used,although sublingual dosing may be as effective asvaginal dosing in multiparous women.3 Misoprostol

does not increase the risk of retained placenta or needfor surgical follow-up. This review includes gesta-tional ages from 12 to 28 weeks and cannot addresswhether different doses of mifepristone are needed atdifferent gestational ages. The results of this revieware consistent with a recent guideline from the Societyof Family Planning, further supporting this approachto second-trimester abortion (Borgatta L, Kapp N;Society of Family Planning. Labor induction abortionin second trimester. Contraception 2011; 83. In press.).

There is still a need for additional research onquestions such as the optimal dose of misoprostol, theoptimal use of mifepristone in combination withmisoprostol, and changes in dose according to gesta-tional age. Yet the results of this review consistentlyshow that mifepristone at low doses in 3-hour inter-vals is an effective and well-tolerated approach toinduction abortion at all gestational ages in the secondtrimester. Future studies should focus on fine-tuningthis regimen.

REFERENCES1. Strauss LT, Gamble SB, Parker WY, Cook DA, Zane SB,

Hamdan S. Abortion surveillance–United States, 2004.MMWR Surveill Summ 2007;56:1–33.

2. Kapp N, Borgatta L, Stubblefield PG, Vragovic O, Moreno N.Mifepristone in midtrimester medical abortion: a randomizedcontrolled trial. Obstet Gynecol 2007;110:1304–10.

3. von Hertzen H, Piaagio G, Wojdyla D, Nguyen TM, MarionsL, Okoev G, et al. Comparison of vaginal and sublingualmisoprostol for second trimester abortion: randomized con-trolled equivalence trial. Human Reproduction. 24:106–12.

VISIT THE COCHRANE COLLABORATION WEB SITE FOR THE FULL TEXT OF THISMONTH’S FEATURED REVIEW:

http://www.cochrane.org/reviews/index.htmOther recent reviews of interest to obstetricians and gynecologists from the CochraneLibrary:• Gøtzsche PC, Nielsen M. Screening for breast cancer with mammography. Cochrane

Database of Systematic Reviews 2011, Issue 1. Art. No.: CD001877. DOI: 10.1002/14651858.CD001877.pub4.

• Taylor F, Ward K, Moore THM, Burke M, Davey Smith G, Casas J-P, Ebrahim S. Statins for theprimary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews2011, Issue 1. Art. No.: CD004816. DOI: 10.1002/14651858.CD004816.pub4.

• Abdel-Aleem H, Abdel-Aleem MA, Shaaban OM. Tocolysis for management of retainedplacenta. Cochrane Database of Systematic Reviews 2011, Issue 1. Art. No.: CD007708. DOI:10.1002/14651858.CD007708.pub2.

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