Medical methods for mid-trimester termination of pregnancy: Cochrane systematic review


Assessed as up to date: 2009/12/31


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.


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

Search strategy

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

Selection criteria

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.

Data collection and analysis

Two authors selected the trials and three authors extracted data.

Main 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 PGF2a. Mild, self-limiting diarrhoea was more common among women who received misoprostol compared to other agents.

Authors' 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.


Wildschut Hajo, Both Marieke I, Medema Suzanne, Thomee Eeke, Wildhagen Mark F, Kapp Nathalie


Planned abortion after three months of pregnancy can be done using several medicines. This review looked at which medical procedure is the best.

There are many medical methods for planned termination of pregnancy in the second trimester of pregnancy (abortion after three months). We did a search of the scientific literature to find out which is the best method. We identified 38 studies and came to the conclusion that misoprostol is the drug of choice for medical pregnancy termination, preferably in combination with mifepristone which facilitates the effectiveness of misoprostol. Misoprostol works best when it is administered into the vagina. Women who had previously given birth could take misoprostol by mouth (under the tongue). Irrespective of the medication used for second trimester termination there is a considerable risk of surgical intervention because of vaginal bleeding or incomplete abortion.

Reviewer's Conclusions

Implications for practice

The results of this review suggest that the most efficient regimen for medical abortion in the second trimester is the combination of mifepristone and misoprostol. If mifepristone is not available, misoprostol alone is a reasonable alternative. The available data suggest that vaginal administration is the most efficient route of administration, and 3-hourly intervals of administration are more effective than 6-hourly intervals. Meta-analysis of the various randomised controlled trials on misoprostol was hampered by the heterogeneity in medical regimens used among the included trials. Included studies indicate that adverse effects of misoprostol are usually mild and dose dependant. Apart from pain resulting from uterine contractions, diarrhoea is the most common side-effect that has been reported consistently with misoprostol. There are considerable differences in practices regarding the management of the placenta following the expulsion of the fetus.

Implications for research

This review highlights the importance of developing a standardised medical method for women requesting mid-trimester abortion. Further research is needed to evaluate the gestational-age-specific dosage of misoprostol for mid-trimester abortion. In addition, more data are needed to guide medical and/or surgical strategies for women with a uterine scar resulting from prior hysterotomy (see ) and for those who failed to abort within 24 hours or five doses of misoprostol. Finally, more research is needed to evaluate the additional value, optimal dose and timing of mifepristone when used in combination with misoprostol.

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