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Rectal misoprostol vs 15-methyl prostaglandin F 2for retained placenta after second-trimester deliverySubha Sundaram, MD; John P. Diaz, MD; Vctor Hugo Gonzlez-Quintero, MD, MPH; Usha Verma, MD

OBJECTIVE: The purpose of this study was to compare rectal miso-prostol (RM) with 15-methyl prostaglandin F2 (PGF2 ) for the man-agement of retained placenta after second-trimester deliveries.

STUDY DESIGN: A retrospective study of all second-trimester deliver-ies between the years 2000 and 2005 was performed. Women weredivided into 2 groups, depending on whether they received RM orPGF2 after the delivery.

RESULTS: Three hundred three second-trimester deliveries were ana-lyzed. The time from the administration of medications to the placental

delivery was signicantly shorter in women who received PGF2 , com-pared with the RM group (49.5 vs 89 minutes; P .01). Women whoreceived PGF2 had lower rates of retained placenta (4.9% vs 12.4%;P .02).

CONCLUSION: The use of PGF2 after second-trimester deliveries re-sults in shorter third stage of labor and lower rates of retained placencompared with RM.

Key words: misoprostol, prostaglandin F2 , retained placenta,second-trimester delivery

R etained placenta is a signicantcause of maternal morbidity aftersecond-trimester deliveries. Tradition-ally, this complicationhas been managedby instrumental removal and curettagewith general anesthesia, which may beassociated with hemorrhage, infection,and uterine perforation. Medical man-agement to facilitate the delivery of theretained placenta is a safe alternative thatavoids surgical intervention.

Prostaglandins and prostaglandin an-alogues (PGs) in various routes havebeen investigatedfor usein thecontrolof postpartum hemorrhage. However,most literature that involves PGs in the

third stage o f labor have focused on termpregnancies. 1,2

Only a limited number of studies havedescribed the use of PGs after second-trimester deliveries. 3-5

The purpose of our study was to com-pare the efcacy of RM and 15-methylprostaglandin F 2 (PGF2 ) in the man-agement of retained placenta after thedelivery of the fetus in women with sec-ond-trimester deliveries.

M ATERIALS AND M ETHODS

This retrospective study was done atJackson Memorial Hospital/University of Miami and was approved by our in-stitutional review board. All womenbetween 13 and 28 weeks of gestationwho had been admitted betweenJanuary 2000 and January 2006 wereidentied and included women inspontaneous labor, preterm premature

rupture of membranes, fetal death, se-rious fetal anomaly, and advanced cer-vical dilation. Maternal demographicparameters, gestational age at the timeof induction, parity, indication andmode of induction, and duration of in-duction were abstracted. Labor for allwomen was induced with 200 gofmi-soprostol every 6 hours for 24 hours,which was repeated if delivery had notoccurred to a maximum period of 48hours.

After the fetus was delivered, spon-taneous expulsion of the placenta was

awaited for 30 minutes. At the attend-ing physicians discretion, if the pla-centa did not deliver within 30 min-utes, either 800 g of misoprostol wasplaced rectally or 250 g of PGF2 wasgiven intramuscularly. In patients whoreceived PGF2 , if placenta did not de-liver spontaneously within the next 20minutes after the rst injection, themedication was repeated up to 2 moreinjections at 20-minute intervals. TheRM was not repeated in any of the pa-tients. If the placenta was undeliveredup to 2 hours after the delivery of thefetus, the retained placenta was diag-nosed, and instrumented removal orcurettage with anesthesia was per-formed. Women were divided into 2groups, depending on whether they re-ceived rectal misoprostol (RM) orPGF 2 .

The primary outcomes that were mea-

sured included the time from the deliv-ery of the fetus to the administration of medication, the duration of third stageof labor, and the rates of retained pla-centa that required intervention. Theduration of induction was dened as thetime from the administration of the mi-soprostol to the delivery of the fetus. Thethird stage of labor was dened as thetime from the delivery of the fetus to thetime of placental delivery, either sponta-neously or by instrumental removal. In-

strumental removal was denedas the re-moval of the placenta with a ring forceps

From theDepartment of Obstetrics andGynecology, University of Miami, MillerSchool of Medicine, Miami,FL.Presented at the 55th Annual Clinical Meetingof The American College of Obstetricians andGynecologists, San Diego, CA, May 5-9, 2007.

Received July 6, 2008; revised Sept. 19, 2008;accepted Sept. 26, 2008.

Reprints: Usha Verma, MD, Department of Obstetrics and Gynecology, University of Miami, Miller School of Medicine, PO Box016960, Miami, FL 33136.uverma@med.miami.edu .

Authorship and contribution to the article islimited to the 4 authors indicated. There wasno outside funding or technical assistance withthe production of this article.

0002-9378/free 2009 Mosby, Inc. All rights reserved.

doi: 10.1016/j.ajog.2008.09.868

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or curettage with general or regionalanesthesia.

Descriptive statisticswereobtainedfor

all variables. Continuous variables wereanalyzed with the Students t -test. Cate-goric variables were analyzed with the 2

test. Statistical analysis was done by means of the Statistical Packages for theSocial Sciences (SPSS-PC, version 13.0;SPSS Inc, Chicago, IL). A probability value of .05 was considered to be sta-tistically signicant.

R ESULTS

A total of 335 second-trimester deliv-

eries were available for study: 161women received RM, and 142 womenreceived PGF2 in the third stage.Thirty-two women were excludedfrom analysis for the following rea-sons: failed induction, delivery of thefetus and placenta together, delivery of the placenta 30 minutes within expul-sion of the fetus, and missing data.Twelve of the 32 women had delivered

the placenta within 30 minutes of thedelivery of the fetus and were not eligi-ble for treatment.

Table 1 shows the demographic fea-tures of the study population. Therewere no signicant differences betweenthe RM and PGF 2 groups, respectively,in indications for delivery: fetal death(59% vs 61%), fetal anomaly (26% vs24%), preterm premature rupture of membranes at 24 weeks of gestation(10% vs 11%), advanced cervical dila-tion (4% vs 3%), and maternal indica-tion (1% vs 1%). All of the pregnancies

between 24 and 28 weeks of gestationwere terminations of pregnancy for fetaldeaths.

Table 2 shows the outcome measures.Although the duration of induction andthe time from delivery of the fetus tomedication were similar, women in thePGF2 group had a shorter third stage of labor and lower rates of instrumental re-moval of placenta.

C OMMENT

Our study found that the PGF 2 groupdelivered, on average, 14 minutes afterthe drug was administered; the RMgroup required, on average,54 minutesuntil the delivery of the placenta. Car-

lan et al4

reported a reduction in thethird stage of labor with PGF 2 com-pared with placebo. Leader et al 5 re-ported that serial oral misoprostol of 200 g every hour for a maximum of 2doses did not reduce the time to spon-taneous placental delivery. Li and Yin 3

reported 100% success with the use of 800 g of RM in the delivery of theplacenta. However, their study in-volved only 8 women who underwentmedical termination of pregnancy in

their second trimester.In our study, we noted a signicant re-

duction in the number of women whorequired instrumental removal of pla-centa in the PGF 2 group. Although theexact mechanismof the superior efcacy of PGF2 over RM is not clear exactly, wespeculate that it may be related to phar-macokinetics of rectal administration.Meckstroth et al, 6 in their study on drugabsorption of misoprostol that was ad-ministered by various routes found that,after rectal administration, the serumlevels peakedearlier, then dropped moreabruptly, and that the peak tone andpeak uterine activity were lower thanother routes. Also, our rates of retainedplacenta after second-trimester deliver-ies were lower (4% in the PGF 2 groupand 12% in the RM group), comparedwith the rates quoted by other authors.Leader et al5 had reported a higher inci-dence (26%) of curettage in their study.

There is no consensus about the op-timal time for instrumental removal ina woman with retained placenta whodoes not experience bleeding compli-cations.Kirz andHang 7 have suggestedthat expectant management of thethird stage of labor beyond 30 minutesmay produce increased complicationrates, such as hemorrhage. However,we did not notice an increase in com-plications with expectant managementup to 2 hours.

In summary, we conclude that use of PGF2 for retained placenta after second-

TABLE 1Maternal demographics

Variable RM (n 161)15-methyl PGF 2(n 142) P value

Age (y)a 29.8 4.5 29.0 5.3 .189..............................................................................................................................................................................................................................................

Gestational age (wk)a

19.6 2.8 19.0 3.2 .104..............................................................................................................................................................................................................................................Nulliparity (%) 74 72 .867..............................................................................................................................................................................................................................................

Previous cesarean delivery (%) 5.2 4.6 .816..............................................................................................................................................................................................................................................

Twins (%) 2.4 3.1 .702..............................................................................................................................................................................................................................................a Data are presented as mean SD.Sundaram.RM vs 15-methylPGF 2 for retained placenta after 2nd trimesterdelivery. Am J Obstet Gynecol 2009.

TABLE 2Outcome measures

Variable RM (n 161)15-methyl PGF 2(n 142) P value

Duration of induction (h)a 16.1 3.2 16.5 3.5 .629..............................................................................................................................................................................................................................................

Time from delivery of fetus tomedication (min)a

34.5 4.3 35 4.1 .533

..............................................................................................................................................................................................................................................

Time from initiation of medication toplacental delivery (min)a

89.1 17.8 49.5 17.4 .01

..............................................................................................................................................................................................................................................

Retained placenta at 2 hr that requiredinstrumental removal (%)

12.4 4.9 .02

..............................................................................................................................................................................................................................................a Data are presented as mean SD.Sundaram.RM vs 15-methylPGF 2 for retained placenta after 2nd trimesterdelivery. Am J Obstet Gynecol 2009.

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trimester deliveries results in shorter thirdstage of labor and reduced rates of instru-mented removal, compared with RM. f

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