- Email: [email protected]
Second trimester abortion using prostaglandin E2 suppositories with or without intracervical Laminaria japonica: a randomized study
Second Trimester Abortion Using Prostaglandin E2 Suppositories With or Without Intracervical Laminaria japonica: A Randomized Study ROBERT O. ATLAS, MD, JULIO LEMUS, MD, JAMES REED, III, PhD, DOROTHY ATKINS, RN, AND LINDSAY S. ALGER, MD Objective: To compare the abortifacient efficacy of vaginal prostaglandin (PG) E2 suppositories with and without pretreatment with intracervical PGE2 gel and Laminaria japonica. Methods: One hundred seventy-five women between 16 and 20 weeks’ gestation requesting abortion were divided randomly into three groups. Forty-one received PGE2 vaginal suppositories alone to induce abortion, 72 had Laminaria placed 24 hours before vaginal PGE2, and 62 were given intracervical 0.5 mg PGE2 gel plus Laminaria 24 hours before vaginal PGE2. Maternal demographic characteristics, induction to delivery time, number of suppositories required, and complications were analyzed. Results: The mean maternal age, gravidity, parity, race, and gestational age were similar among groups. Ninety-five percent of all women delivered within 24 hours. The induction to delivery time was significantly longer in the PGE2only women (mean 6 standard deviation 689 6 319 minutes) compared with that of those receiving PGE2 plus Laminaria (487 6 321 minutes) and PGE2 plus Laminaria plus gel (547 6 374 minutes, P 5 .01). There was a statistically significant difference in the number of suppositories needed to complete the abortion process. The PGE2-only group required more suppositories (median three, range 1– 8) compared with PGE2 plus Laminaria (median 3, range 1–3) and PGE2 plus Laminaria plus gel (median 2.5, range 1–9; P 5 .001). Patients in the PGE2 plus Laminaria plus gel group reported more pain associated with placement (median pain score 4, range 0 –10) compared with PGE2 plus Laminaria (median 2, range 0 –9; P 5 .003). There was a lower incidence of febrile episodes in the PGE2-only group (29%) compared with PGE2 plus Laminaria (68%) and PGE2 plus Laminaria plus gel (54%, P 5 .002). Conclusion: Placement of Laminaria japonica 24 hours before PGE2 vaginal suppository-induced abortion resulted in a significantly shorter induction-to-delivery time, and pretreatment with Laminaria japonica decreased the number of suppositories required to complete abortion. Pretreatment From the University of Maryland Medical Systems, Baltimore, Maryland, and Lehigh Valley Hospital, Allentown, Pennsylvania.
398 0029-7844/98/$19.00 PII S0029-7844(98)00194-X
with intracervical PGE2 gel increased pain associated with Laminaria placement and did not improve the efficacy of the procedure. (Obstet Gynecol 1998;92:398 – 402. © 1998 by The American College of Obstetricians and Gynecologists.)
Prostaglandin (PG) E2 vaginal suppositories, used as abortifacients in the United States since 1978, are a simple, effective, and safe means of effecting second trimester abortions.1–3 They have been shown to be superior to other methods including intramniotic PGE2a and intramuscular 15-methyl PGF2a.4 –7 Prostaglandin E1 has been shown to be at least as effective as PGE2 abortions,8 however, only two thirds of the patients treated with PGE1 vaginal tablets aborted within 24 hours of initial treatment.9 Laminaria japonica has been used in a variety of first and second trimester abortion techniques to dilate the cervix.4,10 In previous studies,3,4,9 –13 researchers have examined the use of different abortifacients with and without Laminaria japonica. Of these studies, only two10,11 demonstrated benefit of Laminaria japonica in decreasing the interval from induction to delivery. The purpose of this investigation was to determine if pretreatment with intracervical Laminaria tents with or without the concurrent treatment of intracervical PGE2 gel improves the efficiency of PGE2 suppositoryinduced second trimester abortion.
Methods From December 1990 to December 1991, women requesting elective abortion of pregnancy at 16 –20 weeks’ gestation gave informed consent for participation in this study, which had been approved by the Internal Review Board of the University of Maryland Medical Systems. Exclusion criteria included histories of asthma,
Obstetrics & Gynecology
chronic pulmonary disease, active genital infection, or cervical malignancy. Each participant had an ultrasonographic examination to confirm gestational age, estimated by measuring the fetal biparietal diameter and correlating the measurement with a standard table described by Shepard et al.14 A random number table was used to assign women to one of three groups. The first received PGE2 20 mg (Prostin E2; UpJohn Co., Kalamazoo, MI) vaginal suppositories alone. The second group received pretreatment with Laminaria japonica (Dilateria; Milex Products Inc., Chicago, IL) followed by 20 mg PGE2 vaginal suppositories. The third group received pretreatment with intracervical 0.5 mg PGE2 gel plus Laminaria japonica followed by 20 mg PGE2 vaginal suppositories. The PGE2 gel was prepared by the hospital pharmacy using a standard protocol to produce 0.5 mg of PGE2 in 2.5 mL of gel, similar to the method described by Gauger.15 Prostaglandin E2– only patients were admitted the day of procedure. Prostaglandin E2 plus laminaria patients were seen in the clinic 1 day prior to treatment with PGE2 suppositories. These patients were pretreated with insertion of as many thin and medium Laminaria tents as the endocervical canal could accommodate and secured in place by one saline-moistened and one dry gauze pad. Prostaglandin E2 plus Laminaria plus gel patients were pretreated with 0.5 mg of intracervical PGE2 gel followed by Laminaria insertion as in the PGE2 plus Laminaria group. Upon admission to the hospital the next day, patients in the latter two groups were asked to rate pain severity between placement of Laminaria and admission on a scale from 1 to 10 with 10 the most severe. After the procedures, all patients were asked to evaluate pain severity during abortion using the same pain score. Once hospitalized, all patients were treated using a standard protocol of care: soap suds enema; intravenous 5% dextrose Ringer’s lactate solution at 150 mL/hour; 10 mg intramuscular prochlorperazine given prior to the procedure and every 6 hours afterward to treat nausea and vomiting; 2.5 mg diphenoxylate plus 0.025 mg atropine, initially two tablets orally, then every 4 hours to treat diarrhea; initially 1 g acetaminophen orally followed by 650 mg per rectum every 6 hours as needed to treat fever (temperature above 38C); and 50 mg meperidine with 50 mg intramuscular hydroxyzine hydrochloride to treat any pain with the procedure. One 20-mg PGE2 suppository was placed intravaginally every 3 hours in the posterior vaginal fornix. Patients with Laminaria had the gauze removed before abortion; however, the Laminaria tents remained in situ for the abortion. After expulsion of the fetus, the Lami-
VOL. 92, NO. 3, SEPTEMBER 1998
naria tents were counted to ensure all were recovered, and subjects were started on an intravenous infusion of oxytocin administered as 40 units in 1 L of 5% dextrose Ringer’s lactate solution. If the placenta was not delivered within 2 hours, it was removed during manual examination. Placentas were examined, and if not complete, a curettage of the uterus was performed. A complete abortion was defined as one in which curettage was not required. Subjects who required more than 24 hours to abort were deemed failures. All patients were discharged to home with a standard course of tetracycline 500 mg orally every 6 hours for 7 days and methylergonovine maleate 0.2 mg every 4 hours for 24 hours. Variables analyzed included age, gravidity, parity, gestational age, race, interval since last pregnancy, number of vaginal suppositories, completion of abortion, pain during Laminaria placement and abortion, and complications. All variables were compared within each group and between groups. The main outcome variable of this investigation was the induction-to-delivery interval, defined as the time between placement of the first vaginal PGE2 suppository to delivery of fetus. Statistical analysis used x2 for categoric data, analysis of variance for interval data, and Kruskal-Wallis test for ordinal data with a standard statistical program (SPSS Inc., Raleigh, NC). A mid-study analysis revealed a statistically significant difference between PGE2-only patients and the other women; therefore, no subjects were assigned to PGE2-only after the 41st patient. The study was continued comparing only the latter two groups and due to the mid-study analysis, the threshold for statistical significance was established at P , .01.
Results One hundred eighty-one pregnant women with gestational ages of 16 –20 weeks were enrolled from December 1990 to December 1991. After enrollment, six patients decided against abortion and were excluded from analysis. The mean maternal age, gravidity, parity, race, and gestational age were similar between groups (Table 1). As noted in Table 2, PGE2-only patients had the longest mean interval between induction and delivery (689 6 319 minutes, P 5 .01). In a separate analysis, PGE2 plus Laminaria and PGE2 plus Laminaria and gel were compared, and no difference was found in induction-to-delivery time. Thirty-eight (52.8%) and 32 (51.6%) of patients in PGE2 plus Laminaria and PGE2 plus Laminaria and gel groups, respectively, delivered within 6.5 hours compared with only 5 (12.2%) in PGE2-only (P 5 ,0.001). Analysis of the time from induction to completion of abortion revealed that the
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Table 1. Demographic Data Treatment group
PGE2
PGE2 1 Laminaria
PGE2 1 Laminaria 1 gel
n Maternal age (y) Gestational age (wk) Gravida Race Asian Black White Parity Nulliparous Multiparous Interval since last pregnancy (mo)
41 22.6 6 4.4 16.9 6 2.0 4.0 (1–7)
72 22.6 6 4.8 17.0 6 2.0 3.5 (1–13)
62 23.0 6 5.6 17.0 6 2.0 3.5 (1–12)
0.0% 90.2% 9.8%
0.0% 97.2% 2.8%
1.6% 93.6% 4.8%
7.3% 92.7% 21.8 6 17.1
9.7% 90.3% 19.0 6 15.1
12.9% 87.1% 21.5 6 19.9
PGE2 5 prostaglandin E2. Data are presented as n, mean 6 standard deviation, median (range), or percent.
median times in the PGE2 plus Laminaria (390 minutes) and PGE2 plus Laminaria plus gel (390 minutes) were significantly shorter than the median time in the PGE2only group (595 minutes, P 5 .001) (Figure 1). Ninetyfive percent of patients delivered within 24 hours. All patients had successful abortions with PGE2 without additional modalities. Patients receiving PGE2 only with a median of 3 (range 1– 8) required more suppositories than in either patients receiving PGE2 plus Laminaria (median 3, range 1–13) or PGE2 plus Laminaria and gel (median, 2.5, range 1–9, P 5 .001). When PGE2 plus Laminaria and PGE2 plus Laminaria and gel were compared, there were no significant differences in number of suppositories (P 5 .8). These comparisons are illustrated in Figure 2. The median number of laminaria placed in both PGE2 plus Laminaria and PGE2 plus Laminaria and gel groups was 5 with no significant differences within the two groups (P 5 .63). The pain scores were ranked in patients who received Laminaria. There was a significantly higher incidence of pain experienced in patients receiving Laminaria and gel with a median score of 4
Figure 1. Cumulative abortion rate. *Prostaglandin (PG) E2 alone versus PGE2 1 Laminaria (P 5 .001), PGE2 alone versus PGE2 1 Laminaria 1 gel (P 5 .001), PGE2 1 Laminaria versus PGE2 1 Laminaria 1 gel (P 5 .9).
(range 0 –10) compared with Laminaria alone (median 2, range 0 –9, P 5 .003). Pain during the placement of PGE2 vaginal suppositories was similar in all groups (P 5 .1). The overall complication profile was not different among the groups with the exception of a higher incidence of fever in PGE2 plus Laminaria and PGE2 plus Laminaria and gel groups compared with PGE2-only (P 5 .002) (Table 3). A power analysis was conducted post hoc with respect to the variable of induction to delivery time. Assuming a standard a 5 .05, the calculated power of this investigation was .88.
Discussion The safest form of second trimester abortion is dilatation and evacuation.16 Unfortunately, there is a problem with availability of providers for abortion services.17 Only a small percentage of residency training programs in obstetrics and gynecology routinely include abortion training, most making it optional.18,19 Forms of medical abortion include PGF2a, PGE2, and more recently PGE1
Table 2. Time, Suppositories Required, and Rate of Complete Abortion Treatment group
PGE2
PGE2 1 Laminaria
PGE2 1 Laminaria 1 gel
P
n Mean induction to delivery (6SD) Suppositories (no.) Median (range) #2 #3 Complete abortion
41 689 6 319 3 (1– 8)
72 487 6 321 3 (1–13)
62 547 6 374 2.5 (1–9)
.01* .001*
22.0% 56.1% 33 (80.5%)
48.6% 84.7% 48 (67.0%)
48.4% 67.7% 46 (74.2%)
.01* .003* .06†
PGE2 5 prostaglandin E2; SD 5 standard deviation. Categoric data expressed as a percentage. * PGE2 1 Laminaria and PGE2 1 Laminaria 1 gel are significantly different from PGE2 alone. † No significant difference noted among groups.
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Obstetrics & Gynecology
Figure 2. A comparative histogram illustrating number of PGE2 suppositories required for each group to complete abortion. *Prostaglandin (PG) E2 alone versus PGE2 1 Laminaria (P 5 .001), PGE2 alone versus PGE2 1 Laminaria 1 gel (P 5 .001), PGE2 1 Laminaria versus PGE2 1 Laminaria 1 gel (P 5 .8).
analogues, and our study compared three different medical protocols. Our results show that the addition of Laminaria to vaginal PGE2 suppositories is effective for abortion in the second trimester of pregnancy. The addition of intracervical PGE2 gel as a preinduction cervical ripening agent was not found to decrease the abortion-to-delivery interval. Pretreatment with intracervical PGE2 gel also was shown to increase pain associated with placement of Laminaria. Our results do not support the addition of intracervical PGE2 gel as a preinduction agent at this dose. Robins and Surrago4 showed an overall initiation-toabortion time shorter when using PGE2 with or without Laminaria than when using hypertonic saline, PGE2a, or intramuscular 15(s) 15-methyl PGE2a. Prostaglandin E2 with Laminaria yielded significantly shorter times than PGE2-only between 13 and 15 weeks in nulliparous patients. However, between 16 and 19 weeks, PGE2 alone and PGE2 plus Laminaria did not differ significantly.4 In a follow-up study, Robins and Surrago3 com-
Table 3. Pain and Fever
Treatment group
PGE2
n Pain score for Laminaria placement Pain score for abortion Fever
41
7 (1–10) 29%
PGE2 1 Laminaria
PGE2 1 Laminaria 1 gel
P
72 2 (0 –9)
62 4 (0 –10)
.003
8 (2–10) 68%
8 (1–10) 54%
.1* .002†
PGE2 5 prostaglandin E2. Ordinal data expressed in median (range). Categoric data expressed as a percentage. * No significant difference noted among groups. † PGE2 1 Laminaria and PGE2 1 Laminaria 1 gel are significantly different from PGE2 alone.
VOL. 92, NO. 3, SEPTEMBER 1998
pared three different groups of patients (PGE2 alone, PGE2 with intracervical Laminaria, and PGE2 with Laminaria and continuous intravenous oxytocin). They found no significant difference with the addition of Laminaria. However, Laminaria were placed concurrently with the first PGE2 suppository.3 From these two studies, vaginal PGE2 alone had been noted as an effective abortifacient. No benefit was noted with addition of Laminaria between 16 and 19 weeks in either study.3,4 More recently, prostaglandin E1 analogues have been used with and without Laminaria as an abortifacient. No significant improvement in the abortifacient effect of vaginal prostaglandin E1 analogues with Laminaria tents inserted concurrently with the first dose was seen.9 Previous studies3,10,12,13 produced mixed results on the benefit of pretreatment with intracervical Laminaria. In the studies showing no improvement in the initiation-to-abortion interval, two studies used one Laminaria concurrently with the first dose of abortifacient.3,13 In contrast, Duenhoelter et al13 showed improvement in induction-to-abortion time with concurrent use of Laminaria. This benefit was limited to nulliparous patients. Placement of Laminaria at the time of first dose of abortifacient may not give the Laminaria optimal time to be effective. The maximum dilation and softening effect of Laminaria japonica occurs within 12 hours after placement.13 Our study demonstrated the benefit of using multiple Laminaria tents placed the day prior to the procedure in preparation for second trimester abortion with intravaginal PGE2. These findings are in agreement with Stubblefield et al,11 who pretreated with multiple intracervical Laminaria tents 1 day prior to initiation of second trimester abortion. Approximately 90% of women in our investigation were multiparous; therefore, no valid comparison between nulliparous patients could be performed on this population. The addition of Laminaria tents did not appear to significantly alter pain associated with the procedure. As with all prior studies on abortion using PGE2 suppositories, concerns about side effects of the medication have been raised. Our data showed a statistically significant increase in febrile morbidity with use of Laminaria. However, the percentage of febrile morbidity is similar to that described in the literature.1– 4,7,8,11,12 In addition, this increase in febrile morbidity did not appear to be of clinical significance with spontaneous resolution after the procedure and no increased risk of infection in patients undergoing PGE2 abortion. Our results show patients undergoing second trimester abortion, between 16 and 20 weeks, should consider placement of as many Laminaria tents as possible in the endocervical canal the day before abortion to improve induction-to-delivery time. A mean induction-to-
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delivery time of 8 hours would allow for same-day discharge and potentially decrease procedure cost.
References 1. Lauersen NH, Secher NJ, Wilson KH. Midtrimester abortion induced by intravaginal administration of prostaglandin E2 suppositories. Am J Obstet Gynecol 1975;122:947–52. 2. Rakhshani R, Grimes DA. Prostaglandin E2 suppositories as a second trimester abortifacient. J Reprod Med 1988;33:817–20. 3. Surrago EJ, Robins J. Midtrimester pregnancy termination by intravaginal administration of prostaglandin E2. Contraception 1982;26:285–94. 4. Robins J, Surrago EJ. Alternatives in midtrimester abortion induction. Obstet Gynecol 1980;56:716 –22. 5. Karim SM, Sharma SD. Therapeutic abortion and induction of labour by the intravaginal administration of prostaglandins E2 and F2a. J Obstet Gynaecol Br Commonw 1971;78:294 –300. 6. Sorensen SS, Heisterberg L, Wolf P. Midtrimester abortion by intracervical prostaglandin E2. Eur J Obstet Gynecol Reprod Biol 1986;21:165–71. 7. Borgida AF, Rodis JF, Hanlon W, Craffey A, Ciarleglio L, Campbell WA. Second trimester abortion by intramuscular 15-methylprostaglandin F2a or intravaginal prostaglandin E2 suppositories: A randomized trial. Obstet Gynecol 1996;85:697–700. 8. Jain JK, Mishell DR. A comparison of intravaginal misoprostol with prostaglandin E2 for termination of second trimester pregnancy. N Engl J Med 1994;331:290 –3. 9. Jain JK, Mishell DR. A comparison of misoprostol with and without laminaria tents for induction of second trimester abortion. Am J Obstet Gynecol 1996;175:173–7. 10. Herczeg J, Sas M, Szabo J, Vajda G. Pre-evacuation dilatation of the pregnant uterine cervix by Laminaria japonica. Acta Med Hung 1986;43:145–54. 11. Stubblefield PG, Naftolin F, Lee EY, Frigoletto FD, Ryan KJ. Combination therapy for midtrimester abortion: Laminaria and analogues of prostaglandins. Contraception 1976;13:723–9.
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12. Wiley TL, Poole CP, Gookin KS, Wiser WL, Morrison, JC. Prostaglandin E2 induction of abortion and fetal demise. Int Fed Gynecol Obstet 1989;28:171–5. 13. Duenhoelter JH, Gant NF, Jiminez JM. Concurrent use of prostaglandin F2a and laminaria tents for induction of midtrimester abortion. Obstet Gynecol 1976;47:469 –72. 14. Shepard MJ, Richards VA, Berkowitz RL, Warsof SL, Hobbins JC. An evaluation of two equations for predicting fetal weight by ultrasound. Am J Obstet Gynecol 1982;142:47–54. 15. Gauger LJ. Extemporaneous preparation of a dinoprostone gel for cervical ripening. Am J Hosp Pharm 1983;40:2195– 6. 16. Grimes DA, Cates W. Complications from legally-induced abortion: A review. Obstet Gynecol Surv 1979;34:177–91. 17. Rosenfield A. The difficult issue of second trimester abortion [editorial]. N Engl J Med 1994;331:324 –5. 18. Westhoff C, Marks F, Rosenfield A. Residency training in contraception, sterilization, and abortion. Obstet Gynecol 1993;81:311– 4. 19. Grimes DA. Clinicians who provide abortion: The thinning ranks. Obstet Gynecol 1992;80:719 –23.
Address reprint requests to:
Robert O. Atlas, MD Lehigh Valley Hospital PO Box 7107 Allentown, PA 18105–7017 E-mail: [email protected]
Received December 30, 1997. Received in revised form March 31, 1998. Accepted April 10, 1998.
Copyright © 1998 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.
Obstetrics & Gynecology
398 0029-7844/98/$19.00 PII S0029-7844(98)00194-X
with intracervical PGE2 gel increased pain associated with Laminaria placement and did not improve the efficacy of the procedure. (Obstet Gynecol 1998;92:398 – 402. © 1998 by The American College of Obstetricians and Gynecologists.)
Prostaglandin (PG) E2 vaginal suppositories, used as abortifacients in the United States since 1978, are a simple, effective, and safe means of effecting second trimester abortions.1–3 They have been shown to be superior to other methods including intramniotic PGE2a and intramuscular 15-methyl PGF2a.4 –7 Prostaglandin E1 has been shown to be at least as effective as PGE2 abortions,8 however, only two thirds of the patients treated with PGE1 vaginal tablets aborted within 24 hours of initial treatment.9 Laminaria japonica has been used in a variety of first and second trimester abortion techniques to dilate the cervix.4,10 In previous studies,3,4,9 –13 researchers have examined the use of different abortifacients with and without Laminaria japonica. Of these studies, only two10,11 demonstrated benefit of Laminaria japonica in decreasing the interval from induction to delivery. The purpose of this investigation was to determine if pretreatment with intracervical Laminaria tents with or without the concurrent treatment of intracervical PGE2 gel improves the efficiency of PGE2 suppositoryinduced second trimester abortion.
Methods From December 1990 to December 1991, women requesting elective abortion of pregnancy at 16 –20 weeks’ gestation gave informed consent for participation in this study, which had been approved by the Internal Review Board of the University of Maryland Medical Systems. Exclusion criteria included histories of asthma,
Obstetrics & Gynecology
chronic pulmonary disease, active genital infection, or cervical malignancy. Each participant had an ultrasonographic examination to confirm gestational age, estimated by measuring the fetal biparietal diameter and correlating the measurement with a standard table described by Shepard et al.14 A random number table was used to assign women to one of three groups. The first received PGE2 20 mg (Prostin E2; UpJohn Co., Kalamazoo, MI) vaginal suppositories alone. The second group received pretreatment with Laminaria japonica (Dilateria; Milex Products Inc., Chicago, IL) followed by 20 mg PGE2 vaginal suppositories. The third group received pretreatment with intracervical 0.5 mg PGE2 gel plus Laminaria japonica followed by 20 mg PGE2 vaginal suppositories. The PGE2 gel was prepared by the hospital pharmacy using a standard protocol to produce 0.5 mg of PGE2 in 2.5 mL of gel, similar to the method described by Gauger.15 Prostaglandin E2– only patients were admitted the day of procedure. Prostaglandin E2 plus laminaria patients were seen in the clinic 1 day prior to treatment with PGE2 suppositories. These patients were pretreated with insertion of as many thin and medium Laminaria tents as the endocervical canal could accommodate and secured in place by one saline-moistened and one dry gauze pad. Prostaglandin E2 plus Laminaria plus gel patients were pretreated with 0.5 mg of intracervical PGE2 gel followed by Laminaria insertion as in the PGE2 plus Laminaria group. Upon admission to the hospital the next day, patients in the latter two groups were asked to rate pain severity between placement of Laminaria and admission on a scale from 1 to 10 with 10 the most severe. After the procedures, all patients were asked to evaluate pain severity during abortion using the same pain score. Once hospitalized, all patients were treated using a standard protocol of care: soap suds enema; intravenous 5% dextrose Ringer’s lactate solution at 150 mL/hour; 10 mg intramuscular prochlorperazine given prior to the procedure and every 6 hours afterward to treat nausea and vomiting; 2.5 mg diphenoxylate plus 0.025 mg atropine, initially two tablets orally, then every 4 hours to treat diarrhea; initially 1 g acetaminophen orally followed by 650 mg per rectum every 6 hours as needed to treat fever (temperature above 38C); and 50 mg meperidine with 50 mg intramuscular hydroxyzine hydrochloride to treat any pain with the procedure. One 20-mg PGE2 suppository was placed intravaginally every 3 hours in the posterior vaginal fornix. Patients with Laminaria had the gauze removed before abortion; however, the Laminaria tents remained in situ for the abortion. After expulsion of the fetus, the Lami-
VOL. 92, NO. 3, SEPTEMBER 1998
naria tents were counted to ensure all were recovered, and subjects were started on an intravenous infusion of oxytocin administered as 40 units in 1 L of 5% dextrose Ringer’s lactate solution. If the placenta was not delivered within 2 hours, it was removed during manual examination. Placentas were examined, and if not complete, a curettage of the uterus was performed. A complete abortion was defined as one in which curettage was not required. Subjects who required more than 24 hours to abort were deemed failures. All patients were discharged to home with a standard course of tetracycline 500 mg orally every 6 hours for 7 days and methylergonovine maleate 0.2 mg every 4 hours for 24 hours. Variables analyzed included age, gravidity, parity, gestational age, race, interval since last pregnancy, number of vaginal suppositories, completion of abortion, pain during Laminaria placement and abortion, and complications. All variables were compared within each group and between groups. The main outcome variable of this investigation was the induction-to-delivery interval, defined as the time between placement of the first vaginal PGE2 suppository to delivery of fetus. Statistical analysis used x2 for categoric data, analysis of variance for interval data, and Kruskal-Wallis test for ordinal data with a standard statistical program (SPSS Inc., Raleigh, NC). A mid-study analysis revealed a statistically significant difference between PGE2-only patients and the other women; therefore, no subjects were assigned to PGE2-only after the 41st patient. The study was continued comparing only the latter two groups and due to the mid-study analysis, the threshold for statistical significance was established at P , .01.
Results One hundred eighty-one pregnant women with gestational ages of 16 –20 weeks were enrolled from December 1990 to December 1991. After enrollment, six patients decided against abortion and were excluded from analysis. The mean maternal age, gravidity, parity, race, and gestational age were similar between groups (Table 1). As noted in Table 2, PGE2-only patients had the longest mean interval between induction and delivery (689 6 319 minutes, P 5 .01). In a separate analysis, PGE2 plus Laminaria and PGE2 plus Laminaria and gel were compared, and no difference was found in induction-to-delivery time. Thirty-eight (52.8%) and 32 (51.6%) of patients in PGE2 plus Laminaria and PGE2 plus Laminaria and gel groups, respectively, delivered within 6.5 hours compared with only 5 (12.2%) in PGE2-only (P 5 ,0.001). Analysis of the time from induction to completion of abortion revealed that the
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Table 1. Demographic Data Treatment group
PGE2
PGE2 1 Laminaria
PGE2 1 Laminaria 1 gel
n Maternal age (y) Gestational age (wk) Gravida Race Asian Black White Parity Nulliparous Multiparous Interval since last pregnancy (mo)
41 22.6 6 4.4 16.9 6 2.0 4.0 (1–7)
72 22.6 6 4.8 17.0 6 2.0 3.5 (1–13)
62 23.0 6 5.6 17.0 6 2.0 3.5 (1–12)
0.0% 90.2% 9.8%
0.0% 97.2% 2.8%
1.6% 93.6% 4.8%
7.3% 92.7% 21.8 6 17.1
9.7% 90.3% 19.0 6 15.1
12.9% 87.1% 21.5 6 19.9
PGE2 5 prostaglandin E2. Data are presented as n, mean 6 standard deviation, median (range), or percent.
median times in the PGE2 plus Laminaria (390 minutes) and PGE2 plus Laminaria plus gel (390 minutes) were significantly shorter than the median time in the PGE2only group (595 minutes, P 5 .001) (Figure 1). Ninetyfive percent of patients delivered within 24 hours. All patients had successful abortions with PGE2 without additional modalities. Patients receiving PGE2 only with a median of 3 (range 1– 8) required more suppositories than in either patients receiving PGE2 plus Laminaria (median 3, range 1–13) or PGE2 plus Laminaria and gel (median, 2.5, range 1–9, P 5 .001). When PGE2 plus Laminaria and PGE2 plus Laminaria and gel were compared, there were no significant differences in number of suppositories (P 5 .8). These comparisons are illustrated in Figure 2. The median number of laminaria placed in both PGE2 plus Laminaria and PGE2 plus Laminaria and gel groups was 5 with no significant differences within the two groups (P 5 .63). The pain scores were ranked in patients who received Laminaria. There was a significantly higher incidence of pain experienced in patients receiving Laminaria and gel with a median score of 4
Figure 1. Cumulative abortion rate. *Prostaglandin (PG) E2 alone versus PGE2 1 Laminaria (P 5 .001), PGE2 alone versus PGE2 1 Laminaria 1 gel (P 5 .001), PGE2 1 Laminaria versus PGE2 1 Laminaria 1 gel (P 5 .9).
(range 0 –10) compared with Laminaria alone (median 2, range 0 –9, P 5 .003). Pain during the placement of PGE2 vaginal suppositories was similar in all groups (P 5 .1). The overall complication profile was not different among the groups with the exception of a higher incidence of fever in PGE2 plus Laminaria and PGE2 plus Laminaria and gel groups compared with PGE2-only (P 5 .002) (Table 3). A power analysis was conducted post hoc with respect to the variable of induction to delivery time. Assuming a standard a 5 .05, the calculated power of this investigation was .88.
Discussion The safest form of second trimester abortion is dilatation and evacuation.16 Unfortunately, there is a problem with availability of providers for abortion services.17 Only a small percentage of residency training programs in obstetrics and gynecology routinely include abortion training, most making it optional.18,19 Forms of medical abortion include PGF2a, PGE2, and more recently PGE1
Table 2. Time, Suppositories Required, and Rate of Complete Abortion Treatment group
PGE2
PGE2 1 Laminaria
PGE2 1 Laminaria 1 gel
P
n Mean induction to delivery (6SD) Suppositories (no.) Median (range) #2 #3 Complete abortion
41 689 6 319 3 (1– 8)
72 487 6 321 3 (1–13)
62 547 6 374 2.5 (1–9)
.01* .001*
22.0% 56.1% 33 (80.5%)
48.6% 84.7% 48 (67.0%)
48.4% 67.7% 46 (74.2%)
.01* .003* .06†
PGE2 5 prostaglandin E2; SD 5 standard deviation. Categoric data expressed as a percentage. * PGE2 1 Laminaria and PGE2 1 Laminaria 1 gel are significantly different from PGE2 alone. † No significant difference noted among groups.
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Figure 2. A comparative histogram illustrating number of PGE2 suppositories required for each group to complete abortion. *Prostaglandin (PG) E2 alone versus PGE2 1 Laminaria (P 5 .001), PGE2 alone versus PGE2 1 Laminaria 1 gel (P 5 .001), PGE2 1 Laminaria versus PGE2 1 Laminaria 1 gel (P 5 .8).
analogues, and our study compared three different medical protocols. Our results show that the addition of Laminaria to vaginal PGE2 suppositories is effective for abortion in the second trimester of pregnancy. The addition of intracervical PGE2 gel as a preinduction cervical ripening agent was not found to decrease the abortion-to-delivery interval. Pretreatment with intracervical PGE2 gel also was shown to increase pain associated with placement of Laminaria. Our results do not support the addition of intracervical PGE2 gel as a preinduction agent at this dose. Robins and Surrago4 showed an overall initiation-toabortion time shorter when using PGE2 with or without Laminaria than when using hypertonic saline, PGE2a, or intramuscular 15(s) 15-methyl PGE2a. Prostaglandin E2 with Laminaria yielded significantly shorter times than PGE2-only between 13 and 15 weeks in nulliparous patients. However, between 16 and 19 weeks, PGE2 alone and PGE2 plus Laminaria did not differ significantly.4 In a follow-up study, Robins and Surrago3 com-
Table 3. Pain and Fever
Treatment group
PGE2
n Pain score for Laminaria placement Pain score for abortion Fever
41
7 (1–10) 29%
PGE2 1 Laminaria
PGE2 1 Laminaria 1 gel
P
72 2 (0 –9)
62 4 (0 –10)
.003
8 (2–10) 68%
8 (1–10) 54%
.1* .002†
PGE2 5 prostaglandin E2. Ordinal data expressed in median (range). Categoric data expressed as a percentage. * No significant difference noted among groups. † PGE2 1 Laminaria and PGE2 1 Laminaria 1 gel are significantly different from PGE2 alone.
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pared three different groups of patients (PGE2 alone, PGE2 with intracervical Laminaria, and PGE2 with Laminaria and continuous intravenous oxytocin). They found no significant difference with the addition of Laminaria. However, Laminaria were placed concurrently with the first PGE2 suppository.3 From these two studies, vaginal PGE2 alone had been noted as an effective abortifacient. No benefit was noted with addition of Laminaria between 16 and 19 weeks in either study.3,4 More recently, prostaglandin E1 analogues have been used with and without Laminaria as an abortifacient. No significant improvement in the abortifacient effect of vaginal prostaglandin E1 analogues with Laminaria tents inserted concurrently with the first dose was seen.9 Previous studies3,10,12,13 produced mixed results on the benefit of pretreatment with intracervical Laminaria. In the studies showing no improvement in the initiation-to-abortion interval, two studies used one Laminaria concurrently with the first dose of abortifacient.3,13 In contrast, Duenhoelter et al13 showed improvement in induction-to-abortion time with concurrent use of Laminaria. This benefit was limited to nulliparous patients. Placement of Laminaria at the time of first dose of abortifacient may not give the Laminaria optimal time to be effective. The maximum dilation and softening effect of Laminaria japonica occurs within 12 hours after placement.13 Our study demonstrated the benefit of using multiple Laminaria tents placed the day prior to the procedure in preparation for second trimester abortion with intravaginal PGE2. These findings are in agreement with Stubblefield et al,11 who pretreated with multiple intracervical Laminaria tents 1 day prior to initiation of second trimester abortion. Approximately 90% of women in our investigation were multiparous; therefore, no valid comparison between nulliparous patients could be performed on this population. The addition of Laminaria tents did not appear to significantly alter pain associated with the procedure. As with all prior studies on abortion using PGE2 suppositories, concerns about side effects of the medication have been raised. Our data showed a statistically significant increase in febrile morbidity with use of Laminaria. However, the percentage of febrile morbidity is similar to that described in the literature.1– 4,7,8,11,12 In addition, this increase in febrile morbidity did not appear to be of clinical significance with spontaneous resolution after the procedure and no increased risk of infection in patients undergoing PGE2 abortion. Our results show patients undergoing second trimester abortion, between 16 and 20 weeks, should consider placement of as many Laminaria tents as possible in the endocervical canal the day before abortion to improve induction-to-delivery time. A mean induction-to-
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delivery time of 8 hours would allow for same-day discharge and potentially decrease procedure cost.
References 1. Lauersen NH, Secher NJ, Wilson KH. Midtrimester abortion induced by intravaginal administration of prostaglandin E2 suppositories. Am J Obstet Gynecol 1975;122:947–52. 2. Rakhshani R, Grimes DA. Prostaglandin E2 suppositories as a second trimester abortifacient. J Reprod Med 1988;33:817–20. 3. Surrago EJ, Robins J. Midtrimester pregnancy termination by intravaginal administration of prostaglandin E2. Contraception 1982;26:285–94. 4. Robins J, Surrago EJ. Alternatives in midtrimester abortion induction. Obstet Gynecol 1980;56:716 –22. 5. Karim SM, Sharma SD. Therapeutic abortion and induction of labour by the intravaginal administration of prostaglandins E2 and F2a. J Obstet Gynaecol Br Commonw 1971;78:294 –300. 6. Sorensen SS, Heisterberg L, Wolf P. Midtrimester abortion by intracervical prostaglandin E2. Eur J Obstet Gynecol Reprod Biol 1986;21:165–71. 7. Borgida AF, Rodis JF, Hanlon W, Craffey A, Ciarleglio L, Campbell WA. Second trimester abortion by intramuscular 15-methylprostaglandin F2a or intravaginal prostaglandin E2 suppositories: A randomized trial. Obstet Gynecol 1996;85:697–700. 8. Jain JK, Mishell DR. A comparison of intravaginal misoprostol with prostaglandin E2 for termination of second trimester pregnancy. N Engl J Med 1994;331:290 –3. 9. Jain JK, Mishell DR. A comparison of misoprostol with and without laminaria tents for induction of second trimester abortion. Am J Obstet Gynecol 1996;175:173–7. 10. Herczeg J, Sas M, Szabo J, Vajda G. Pre-evacuation dilatation of the pregnant uterine cervix by Laminaria japonica. Acta Med Hung 1986;43:145–54. 11. Stubblefield PG, Naftolin F, Lee EY, Frigoletto FD, Ryan KJ. Combination therapy for midtrimester abortion: Laminaria and analogues of prostaglandins. Contraception 1976;13:723–9.
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12. Wiley TL, Poole CP, Gookin KS, Wiser WL, Morrison, JC. Prostaglandin E2 induction of abortion and fetal demise. Int Fed Gynecol Obstet 1989;28:171–5. 13. Duenhoelter JH, Gant NF, Jiminez JM. Concurrent use of prostaglandin F2a and laminaria tents for induction of midtrimester abortion. Obstet Gynecol 1976;47:469 –72. 14. Shepard MJ, Richards VA, Berkowitz RL, Warsof SL, Hobbins JC. An evaluation of two equations for predicting fetal weight by ultrasound. Am J Obstet Gynecol 1982;142:47–54. 15. Gauger LJ. Extemporaneous preparation of a dinoprostone gel for cervical ripening. Am J Hosp Pharm 1983;40:2195– 6. 16. Grimes DA, Cates W. Complications from legally-induced abortion: A review. Obstet Gynecol Surv 1979;34:177–91. 17. Rosenfield A. The difficult issue of second trimester abortion [editorial]. N Engl J Med 1994;331:324 –5. 18. Westhoff C, Marks F, Rosenfield A. Residency training in contraception, sterilization, and abortion. Obstet Gynecol 1993;81:311– 4. 19. Grimes DA. Clinicians who provide abortion: The thinning ranks. Obstet Gynecol 1992;80:719 –23.
Address reprint requests to:
Robert O. Atlas, MD Lehigh Valley Hospital PO Box 7107 Allentown, PA 18105–7017 E-mail: [email protected]
Received December 30, 1997. Received in revised form March 31, 1998. Accepted April 10, 1998.
Copyright © 1998 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.
Obstetrics & Gynecology