The Journal of Maternal-Fetal Medicine 4:35-38 (1995)

Intracamniotic 15-Methyl Prostaglandin F,, Versus Intravaginal Prostaglandin E, for Second#Trimester

Labor Induction Berry A. Campbell, MD, Roger B. Newman, MD, Daniel P. Eller, MD, Susan M. Cox, MD,

Periclis Roussis, MD, E.J. Horn, MD, and Sue Stramm, RN

Charleston, South Carolina Lexington, Kentucky Maternal Fetal Medicine Division, Department of Obstetrics and Gynecology, Medical University of South Carolina,

University of Kentucky

Abstract Second-trimester labor induction is frequently complicated by significant morbidity. Al- though instrumental dilatation and evacuation is considered the safest method for second-trimester pregnancy termination, most younger physicians lack experience with this procedure. As a result, many physicians use vaginal prostaglandin suppositories for second trimester labor induction. Unfortunately, systemic side effects and in-complete abortion are common complications. We sought to compare the side effects and efficacy of intra-amniotic 15-methyl prostaglandin F,, (PGF,,) with intravaginal prostaglan- din E, (PGE,) for second-trimester labor induction. We compared outcomes in patients receiving intra- vaginal PGE, (group A, N = 24) with intra-amniotic 15-methyl prostaglandin F,, (group B, N = 25) for midtrimester labor induction. Group A patients received intravaginal PGE, 20 mg every 3-4 hr, and group B patients received intra-amniotic 15-methyl PGF,, 2.5 mg. Eighty-eight percent of patients in group A successfully delivered by 24 hr, and all did by 36 hr. Eight patients in group A required surgical interven- tion due to incomplete abortion. Likewise, 96% and 100% of group B patients delivered within 24 and 36 hr, respectively. Only 1 patient in group B had an incomplete abortion. Significant gastrointestinal side effects were noted more often in group A than in group B patients (P < 0.001). The efficacy of intra- amniotic 15-methyl PGF,, for second trimester labor induction is confirmed in this study with signifi- cantly fewer systemic side effects and fewer cases requiring surgical intervention. o 1995 WiIey-Liss, Inc.

Key Words: Labor induction, Abortion, Prostaglandins

IN T RO D U CTI 0 N Second-trimester abortions account for less than

10% of all abortions done in the United States. They are, however, associated with the majority of morbid- ity and mortality related to abortion [l]. Instrumental dilatation and evacuation is reported by many investi- gators to be the safest method of pregnancy termina- tion if performed by an experienced operator [2]. Many physicians, however, lack the experience neces- sary to perform this procedure safely.

The advent of prostaglandins as abortifacients has led to their common use for second trimester preg- nancy termination. Several prostaglandins can effec- tively induce uterine emptying in the second trimes- ter; unfortunately, serious side effects are associated with intravaginal prostaglandins, including fever, emesis, diarrhea, and incomplete abortion. The pur-

pose of this study was to investigate an alternative to intravaginal prostaglandins for medically indicated second-trimester labor induction.

MATERIALS AND METHODS The study consisted of 49 pregnancies in the second

trimester at 14-25 weeks gestation with medical indi- cations for labor induction. All patients were seen at the Medical University of South Carolina or at the University of Kentucky Medical Center. Patients in group A (N = 24) received intravaginal prostaglandin

Received February 21, 1994; revised August 25, 1994; accepted September 26, 1994.

Address reprint requests to Berry A. Campbell, M.D., Department of Obstetrics and Gynecology, 800 Rose Street, University of Kentucky, Lexington, KY 40536-0084.

0 1995 Wiley-Liss, Inc.

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36 CAMPBELL ET AL.

TABLE 1. Demographic Data of Patients Receiving Intravaginal PGE, (Group A) and Patients Receiving

Intra-amniotic 15 Methvl-PGF,- (Grow B)

TABLE 2. Indications for Pregnancy Termination in the Intravaginal Prostaglandin E, (Group A) and Intra-amniotic

15-Methvl Prostaelandin F,- (GrouD B) Patients

Group A Group B (N = 24) (N = 25)

Age (mean) 23.6 yr 23.8 yr Nulliparous 13 14

Gestational age Multiparous 11 11

Mean 19.0 5 2.6 wk 18.0 f 2.5 wk Range 15-25 wk 14-24 wk

Previous cesarean section 3 2 Preeclampsia 1 1

Chromosomal aneuploidies Preterm rupture of membranes Fetal demise Anomalies

Renal agenesis Anencephaly Cystic hygroma

Severe pre-eclampsia Other (maternal illness. raue)

Group A Group B (N = 24) (N = 25)

2 10 5 0 3 5

5 0 3 3 3 4 1 1 2 2

E, (PGE,) 20 mg every 3-4 h until delivery. Group B (N = 25) received a single dose of intra-amniotic 15-methyl prostaglandin F,, (PGF,,) 2.5 mg using ultrasound guidance. After confirming intra-amniotic needle placement with easy return of amniotic fluid, 15-methyl PGF,, was injected. Patients refusing am- niocentesis or with oligohydramnios received intra- vaginal PGE,, while the remainder received intra- amniotic 15-methyl PGF,,. Laminaria were placed in all patients 6 h prior to labor induction and removed prior to prostaglandin administration. Continuous nursing supervision was provided, and vital signs were obtained hourly until the patient was stable postpar- tum. Uterine contractions were monitored with an external tocodynamometer.

The abortion was complete if the fetus and placenta were expelled spontaneously and incomplete if the fetus was expelled with a retained placenta after 2 h. Therapy was determined a failure if abortion had not been accomplished within 48 h of administration. Pa- tients were observed for 2 h after delivery of the fetus for expulsion of the placenta in the absence of exces- sive bleeding. If excessive bleeding was encountered or if placental expulsion had not occurred after 2 h, a sharp and/or suction curettage was performed. All pa- tients received premedication with acetaminophen, diphenoxylate hydrochloride with atropine sulfate, and promethazine hydrochloride. Patients were also offered epidural anesthesia or intravenous analgesics as needed. Statistical analysis was performed using chi- square analysis.

RESULTS Both groups were similar demographically with re-

spect to age, race, parity, gestational age, and previous cesarean section (Table 1). Indications for pregnancy

termination are shown in Table 2. Group A patients successfully delivered within 24 h in 88% of cases (21/24) and by 36 h in all patients. The mean induc- tion to delivery time was 16.0 k 5.1 h (range 9.8- 32.5 h). The mean delivery to placental expulsion time was 37.4 k 42.7 min (range 0 min to 2.0 h). Seven patients (29%) had a retained placenta requir- ing operative intervention.

All but one patient in group B delivered successfully within 24 h (96%) and the final patient delivered after 25 h. The mean induction to delivery time was 12.7 k 6.2 h (range 6.3-25.0 h). Delivery to placen- tal expulsion occurred in 15.9 k 3 1.9 min (range 0 min to 2 h). Nine patients delivered the placenta immediately following expulsion of the fetus, com- pared to only 2 in group A. Only one patient had an incomplete abortion requiring curettage. A compari- son of the efficiency of pregnancy termination for both groups is presented in Table 3.

Patients receiving intravaginal PGE, were signifi- cantly more likely to experience systemic side effects (Table 4).

DISCUSSION Second-trimester pregnancy termination accounts

for a small proportion of the abortions performed in the United States but disproportionately leads in abor- tion related morbidity and mortality [ 11. Dilatation and evacuation (D&E) in experienced hands is con- sidered the safest method of second- trimester preg- nancy termination available [2,3]. After 16 weeks ges- tation, however, the safety advantage over other medical interventions is not significant [4]. Despite the efficacy of this method, many physicians lack the expertise required to perform the procedure safely.

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INTRA-AMNIOTIC 15-METHYL PCF,, VERSUS INTRAVACINAL PCE,

TABLE 3. Comparison of Patients Receiving Intravaginal PGE, (Group A) and Patients Receiving Intra-amniotic 15-Methyl PGF,, (Group B)

Group A Group B (N = 24) (N = 25) P

Induction to delivery (h) 16.0 +- 5.1 12.7 ? 6.2 NS Delivery to placenta (min) 37.4 2 42.7 15.9 2 31.9 <0.01 Incomplete abortion 7124 (29%) 1/25 (4%) CO.01 Estimated blood loss (ml) 230 120 NS

37

TABLE 4. Side Effects in Patients Receiving Intravaginal PGE, (Group A) and Patients Receiving Intra-amniotic

15-Methyl PGF,, (Group B)

Side Group A Group B effects (N = 24) (N = 25) P Emesis 11 (46%) 3 (12%) <0.01 Diarrhea 15 (63%) 1 (4%) <0.001 Pain 24 (100%) 25 (100%) NS Fever 8 (33%) 0 <0.01

For many years, intra-amniotic instillation of hyper- tonic solutions was the only alternative to D&E. While these agents were effective, they were associ- ated with frequent complications and longer induc- tion-to-delivery intervals. The advent of prostaglan- din abortifacients has added significantly to our medical armamentarium. PGF,, was initially used in- traamniotically but was associated with significant sys- temic side effects and the frequent need for repeated intraamniotic injection. The synthetic derivative, 15- methyl PGF,,, has been shown to be efficacious when administered intramuscularly [5]. The frequency of in- tramuscular dosing necessary to attain the desired ef- fect renders this method least desirable. PGE, admin- istered by vaginal suppositories is also proven to be effective for second trimester abortion but is also asso- ciated with a high rate of systemic side effects.

Dingfelder et al. [6] found a 95% success rate 36 h following placement of intra-amniotic 15-methyl PGF,,, 2.5 mg. More than one-half of patients had significant gastrointestinal symptoms, and 45% had incomplete abortion requiring curettage. Cervical rip- ening with laminaria was not performed.

A multicenter study undertaken by the World Health Organization (WHO) compared intra-amni- otic 15 methyl-PGF,, with intra-amniotic PGF,, [7]. In this investigation, a significantly higher success rate with 15-methyl PGF,, (95.6% vs. 81.7% at 48 hr)

was noted; however, only 55% of abortions were com- plete. The gastrointestinal side effects appeared to be more common with 15-methyl PGF,,, but they oc- curred frequently in both groups. Cervical rupture was seen in 2.9% of patients. Again, cervical ripening was not performed in this study population. Similarly, other studies have confirmed the efficacy of intra- amniotic 15 -methyl PGF,,, but gastrointestinal side effects and incomplete abortion are recurrent prob- lems [&lo].

The literature also supports the use of vaginal PGE, for pregnancy termination. Surrago et al. [ I l l used PGE, 20 mg vaginally every 3 hr, with 90% of patients successfully aborting by 24 hr. The mean time from induction to abortion was 13.4 hr. Although only 15% were incomplete abortions, side effects were re- ported in 53% of patients. Other studies using vaginal PGE, have shown varying results with induction to abortion intervals ranging from 11.9 to 17.5 hr. In- complete abortion occurred in 1 5 2 7 % of cases. Gas- trointestinal side effects and pyrexia were seen in 50- 81% [12,13].

Because of the paucity of data directly comparing vag- inal PGE, and intra-amniotic 15-methyl PGF,,, we chose to evaluate these modes of administration. While our data suggest a shorter induction to delivery time in the intra-amniotic group, this was not statistically signif- icant. The frequency of incomplete abortion and the interval from fetal expulsion to placental delivery were significantly less in the intra-amniotic group. This is in sharp contrast to other studies in the literature [&lo]. Cervical trauma was not seen in either of our groups, which we attribute to the cervical ripening employed prior to labor induction with laminaria.

A surprising finding in our study is the paucity of gastrointestinal side effects in the intra-amniotic group. While all patients received premedication, only the patients receiving the vaginal suppositories developed significant side effects. Although systemic

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38 CAMPBELL ET AL.

absorption of intra-amniotic prostaglandin is known to occur, it would appear that its main action is ex- erted locally on the uterus and is released more slowly into the systemic circulation.

Patient assignments were based on patient preference and/or the presence of oligohydramnios. Fourteen pa- tients in the intravaginal group refused amniocentesis, and 10 patients had absolute oligo-hydramnios. In the absence of amniotic fluid, intra-amniotic injection of 15-methyl PGF,, is much more difficult, and potentially hazardous, if maternal intravascular injection should oc- cur. For these reasons, intravaginal prostaglandin induc- tion was performed in these patient+ These inequalities in patient groups could potentially lead to selection bias. However, if the 10 patients with oligohydramnios were excluded, there was no change in demographic data or in the results listed in Tables 3 and 4. A further randomized trial excluding the patients with oligohydramnios may be warranted to remove this potential selection bias.

There are few data available on the safety of pros- taglandins for second trimester labor induction in pa- tients with severe preeclampsia or previous cesarean sections. Three patients in group A and two patients in group B had a previous cesarean section. One pa- tient in each group had severe pre-eclampsia. These abortions were completed without complication. Care must be taken to avoid intravascular injection of the potent 15-methyl derivative of PGF,, by scrupulous ultrasound visualization of the amniocentesis needle during injection.

Intra-amniotic 15-methyl PGF,, appears to be more effective for second trimester pregnancy termi- nation and is associated with fewer systemic side ef- fects.

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REFERENCES

Centers for Disease Control: Abortion Surveillance 1979-80. C W , Atlanta, 1983. Grimes DA, Schulz KF, Cates W Jr, Tyler CW: Midtrimester abortion by dilatation and evacuation: A safe and practical alternative. N Engl J Med 296:1141-1145, 1977. Grimes DA, Schulz KF: Morbidity and mortality from second trimes- ter abortions. J Reprod Med 30505-514, 1985. Kafrissen ME, Schulz KE, Grimes DA, Cates W Jr: A comparison of intraamniotic instillation of hyperosmolar urea and prostaglandin F,, vs. dilatation and evacuation for midtrimester abortion. JAMA 251: 916919, 1984. World Health Organization Task Force on the Use of Prostaglandins for Fertility Regulation: Termination of second trimester pregnancy with laminaria and intramuscular 15 methyl PGF,, or 16 phenoxy-W- 17, 18, 19, 20-tetranor PGE, methylsulfonylamide. A randomized multicenter study. Int J Gynecol Obstet 26:129-135, 1988. Dingfelder JR, Black J , Brenner WE, Staurovsky LG, Gruber W: lntraamniotic administration of 15 (S)-15-methyl prostaglandin F,, for the induction of midtrimester abortion. Am J Obstet Gynecol 125:821-826, 1976. World Health Organization Task Force on the Use of Prostaglandins for the Regulation of Fertility: Comparison of single intraamniotic injections of 15 methyl prostaglandin F,, and prostaglandin F,, for termination of second trimester pregnancy: An international multi- center study. Am J Obstet Gynecol 129:601-606, 1978. Karim SMM: Termination of second trimester pregnancy with intra- amniotic 15 (s) 15 methyl prostaglandin F,,-A two dose schedule study. Prostaglandins 9:487494, 1975. Krishna U, Ganguli AV, Mandlekar AV, Purandare VN: Administra- tion of prostaglandins by various routes for induction of abortion. Prostaglandins 15:685493, 1978. Bergquist C , Nyberg R: Intraamniotic and Intra-muscular Administra- tion of 15 methyl prostaglandin F,, for midtrimester abortion. Acta Obstet Gynecol Scand 66:19-26, 1977.

11. Surrago EJ, Robins J: Midtrimester pregnancy termination by intra- vaginal administration of prostaglandin E,. Prostaglandins 26:285- 294, 1982.

12. Lauersen NH, Secher NJ, Wilson KH: Midtrimester abortion induced by intravaginal administration of prostaglandin E, suppositories. Am J Obstet Gynecol 122:947-954, 1975.

13. Hochman M, Laufe LE: Midtrimester pregnancy termination with pros- taglandin E, vaginal suppositories. J Reprcd Med 16:263-268, 1976.

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