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Intracervical administration of prostaglandin E2-gel prior to therapeutic abortion: a prospective randomized double-blind study
119
Int. J. Gynecol. Obstet., 1988,21: 119-122 International Federation of Gynecology&Obstetrics
Intracervical administration of prostaglandin E,-gel prior to therapeutic abortion: a prospective randomized double-blind study E. Shalev, A. Tsabari, S. Edelstein, E. Weiner and H. Zuckerman Department of Obstetrics and Gynecology, Central Emek Hospital, Afula (Israel) (Received January 5th, 1987) (Revised and accepted July 14th. 1987)
Abstract
Forty primigravid women due to undergo first trimster termination of pregnancy were randomly selected for intracervical application of 1 mg prostaglandin E, in gel or gel only as placebo. In the PGE,-gel group, a marked dilatation of the cervical canal was obtained, with post-gel treatment mean Hegar dilatation of Il.18 mm in that group, compared to 4.4 mm in the control group (P 0.001). Moreover, 16 (80%) patients in the PGE,-gel group had a complete abortion, one (5%) patient had an incomplete abortion and in the remaining three (15930)patients, fetal demise was observed. The mean inductionabortion interval in this group was 7.5 h. In the placebo group, none of the above effects were observed. The only side effect noted was vomiting, which occurred in five (25%) of the patients in the PGE,-gel group. Termination of pregnancy was found to be easier in the PGE,-gel group, compared to the placebo group. Key words: Prostaglandin
termination;
E,-gel; Pregnancy Therapeutic abortion.
Introduction
Cervical trauma
and uterine
perforation
0020-7292/88/$03.50 0 1988 International Federation of Gynecology&Obstetrics
caused by mechanical cervical dilatation and uterine curettage are well recognized complications of elective termination of pregnancy (TOP), particularly in primigravid women [5,18]. The incidence of subsequent cervical incompetence can be ten times as high as that which occurs in control groups [22]. In addition, incidence of premature rupture of membranes with a shorter duration of pregnancy has been documented [lo, 161. Various methods for ripening of the uterine cervix have been employed in an attempt to reduce these risks. Hydrophilic organic substances inserted in the cervical canal have been used as abortificants for more than a century, the best known being the seaweed digitata of Laminaria japonicum [4,8]. More recently, prostaglandins and their analogues have been successfully employed to induce softening and dilatation of the cervix prior to induction of labor [2,1 l] or termination of pregnancy in the first trimester [3,6,13,15]. When using the drug in effective doses, whether administered orally, intramuscularly, intravaginally or intracervically, systemic upset such as vomiting or diarrhea was a frequent side effect [3,9,12,17]. The same results but with fewer side effects were obtained using a reduced dose but with various vehicles such as suppositories, pessaries or gels applied locally [1,14,19,21]. Clinical and Clinical Research
120
Shatev et al.
Most of the previously published studies lack randomization and are not prospective. The aim of this study is to evaluate in a randomized double-blind fashion the use of 1 mg PGE, in viscous gel methylcellulose 3% for ripening and dilatation of the uterine cervix prior to TOP using sharp curettage technique. Materials and methods During a 9-month period from March until November 1985, a randomized prospective double-blind study was performed. Forty primigravid women aged 16-25 years due to undergo therapeutic abortion with gestational age between 7 and 12 weeks participated in the study. The women were randomly selected for intracervical application of 1 mg prostaglandin E, in viscous gel methylcellulose 3% (PGE,gel) or gel only (placebo). Two groups of 20 patients each, similar in regard to their ages, gestational age and cervical dilatation prior to treatment, were selected. They were admitted in the evening prior to the operation, generally two patients at a time. The study design was explained and they gave their consent to participate in the study. All the patients were hospitalized. After a medical history was taken and a physical examination completed, application of PGE,-gel or placebo was performed at 2200 h under aseptic conditions while the patients were in the lithotomy position. The patients were asked to remain recumbent for 1 h. To prepare the gel, 3 g of methylcellulose 4000 (B.P. 73) powder was mixed with 100 ml of distilled water in a vial, the mixture was then shaken thoroughly without delay to prevent lump formation, and was stored in a refrigerator for 24 h. Sealed vials were autoclaved at 120°C for 20 min. Cooling was allowed to occur with little disturbance of the vials. Only vials containing an even smooth emulsion were retained, the others were rejected. The sterilized gel can be stored at room temperature or in the refrigerator for almost unlimited periods. One hour before clinical use, the gel was Int J Gynecol Obstet 27
activated by the addition of 1 mg (0.1 ml) of PGE, (Prostin E, 10 mg/ml, Upjohn Co.) Thorough mixing by vigorous shaking for 15 min is imperative. For the purpose of the study, the gel of PGE, 1 mg gel was transferred into 10 ml syringes, separated and coded. The codes were broken only after the study was completed. The cervix was grasped by a single tenaculum in the upper lip. The cervical canal diameter, through the internal OS, was measured according to the largest Hegar which could pass through it without resistance. The drug was inserted via a plastic cannula (Venflon IV Cannula 17G/14mm “VIGGO”) into the cervix to a depth of 2.5 cm. Dolestin 75 mg and Phenergan 25 mg were administered intramuscularly on the patient’s request. The cervical dilatation was planned to be evaluated by Hegar at 0800 h, using the same technique of pretreatment measurement. If needed, further dilatation by Hegar was performed. The difficulty of operation was scored from 1 to 4 with score 1 for the more difficult operations. Vital signs including temperature, blood pressure and heart rate, and symptoms such as vomiting, diarrhea, chills and pain were registered at the time of hospitalization and 4 weeks later. The results were analyzed using SPSS software on an IBM-PC microcomputer. Student’s t-test was used for testing statistical significance. Results No statistical difference between the PGE,gel and the control groups regarding the patient’s age, gestational age and the pretreatment cervical dilatation (Hegar 1) was noted. There is a significant statistical difference between the two groups in the cervical dilatation after treatment (Hegar II) and DeltaHegar (A), as shown in Table I. Abortions occurred in 17 (85070)patients of the PGE,-gel group: 16 (80%) complete abortions and one (5%) incomplete abortion. Fetal demise occurred in the remaining three patients (15%) and curettage was performed on all
Prostaglandin E,-gel prior to pregnancy termination Table I. Cervical dilatation, pretreatment (Hegar I), post-treatment gel and placebo gel control groups.
Hegar I Hegar II A Hegar
pre-operative (Hegar II) and Delta-Hegar (A Hegar) in PGE,-
Treated group
Control group
121
mean + S.D.
Range
mean k SD.
Range
3.15 f 0.71 4.4 f 0.73 1.25 -c 0.40
2.0 -5 3.5 -6 0.25-1.5
3.3 f 0.91 11.18 f 1.70 7.88 f 2.0
2- 5 7-13 5-10.5
t-test
P-value
0.54 15.97 14.16
NS” 0.001 0.001
‘NS = not significant.
patients to confirm diagnosis. Further dilatation before curettage was required in only one patient of this group. All the spontaneous abortions occurred in the morning, with a mean induction-abortion interval of 7.5 h (range 6-9.5 h). Thus dilatation was determined before the planned time. In the placebo-gel control group no spontaneous abortion occurred, and all of the patients needed cervical dilatation before curettage. In the treated group, patients complained of pain from 5 to 45 min (mean 17 min) after the application of the drug. All the patients (20) in this group needed analgesia (Pethidin 1 mg/kg). In the placebo group no patients complained of pain. Vomiting in 4 (20%) patients was noted in the treated group. The difficulty of operation scored from ldifficult, to Ceasy, is presented in Table 11. In the treated group the total scoring was 76 with a mean of 3.8. In the control group, the operation was difficult in all patients (20), with a total scoring of 20 and mean score 1 (P < 0.001). Table II.
Major complications such as tear of the cervix or perforation of the uterus were not recorded in the two groups. On examination of the patients 4 weeks later, none of them showed any signs of pelvic inflammatory disease, but one patient in the placebo group complained of irregular bleeding and needed recurettage. Discussion
Various methods of application with different doses of prostaglandins have been reported as being used for ripening of the cervix prior to therapeutic abortion [1,3,6,9,12,15,17,19,20]. The best effect with the fewest side effects was obtained with the local application of PGE, .using viscous gel as a vehicle [17,20,21], in comparison to the administration of the drug intramuscularly [5] or by the oral route [14]. Incidence of systemic side effects using PGE, in gel were found to be dose-related with a high rate of side effects using 3 mg of PGE, [ 151.
Score of difficulty from score 1 (difficult) to score 4 (easy) in both groups. Control group
Treated group
No. of patients
Total score (mean)
No. of patients
Total score (mean)
Score 1 Score 2
20 -
20 -
-
-
Score 3 Score 4
-
-
1 2 17
2 6 68
Total
20
20 (1)
20
76 (3.8) -Clinical and Clinical Research
122
Shalev et al.
Although cervical dilatation was obtained using a low dose of PGE, in viscous gel (0.25 mg and 0.75 mg), the abortion rate was still low [7,20,21]. Using a low dose, the rate of uterine perforation [22] and cervical tear due to further dilatation was high [7,21]. In the present study with the application of 1 mg of PGE, in viscous gel, significant dilatation was obtained in the treated group in comparison with the placebo, and, furthermore, complete abortion occurred in a high percentage (80%) of the case in the first group; side effects were minimal. We highly advocate the use of 1 mg intracervical PGE; gel in primigravid patients prior to TOP. In the present study, patients were hospitalized because of the study, but the procedure can be adapted to an out-patient setting with application of the drug in the early morning and termination by afternoon. References Djahanbaknch 0, Bassom TS, Marshall DE, Gardner NH: Single extra-amniotic injection of prostaglandin E, in tylose gel to induce first trimester abortion in young nullipara. Acta Obstet Gynecol Stand 61: 445, 1982. Ekman G, Perssen PH. Ulmsten U, Wingerup L: The impact on labour induction of intracervically applied PGE,-gel, related to gestational age in patients with an unripe cervix. Acta Obstet Gynecol Stand Suppl M3: 173, 1983. Fehrman H, Praetorious B: The cervix-ripening effect of prostaglandin E analogue sulprostone, before vacuum aspiration in first trimester pregnancy. Acta Obstet Gyneco1 Stand Suppl M3: 141,1983. Golditch IM, Glasser MH: The use of laminario-tents for cervical dilatation prior to vacuum aspiration abortion. Am J Obstet Gynecol 119: 481, 1973. Grimes DA, Cates W: Complication from legally-induced abortion: A review. Obstet Gynecol Survey 34: 177, 1979. Heinz1 S, Andor J: Pre-operation administration of prostaglandin to avoid dilatation induced damage in first trimester pregnancy termination. Gynecol Obstet Invest 12: 296, 1981. Iversen T, Skjeldestad FE: Intracervical administration of prostaglandin E, Prior to vacuum aspiration a prospective double-blind randomized study. Int J Gynecol Obstet 23: 95, 1985. Killick SR, Vaughan W, Elstein M: A comparison of prostaglandin E, pessaries and laminaria tents for ripening the cervix before termination of pregnancy. Br J Obstet GynecolY2: 518, 1985. Int JGynecol
Obstet 27
9
10
11
12
13
14
15
16 17
18
19
20
21
22
Lauersen NH, Den T, Iliescu C, Wilson KH, Graves ZR: Cervical ripening prior to dilatation and evacuation: A comparison of methods. Am J Obstet Gynecol 144: 890, 1982. Lin DTY, Melville HAH, Martin T: subsequent gestational morbidity after various types of abortion. Lancet 2: 431, 1972. MacKenzie IZ, Embrey MP: Cervical ripening with intravaginal prostaglandin E gel. Br J Obstet Gynecol 88: 1033, 1981. MacKenzie IZ, Embrey MP: Single extra-amniotic injection of prostaglandins in various gel to induce abortion. Br J Obstet Gynecol83: 505, 1976. MacKenzie IZ, Fry A: Prostaglandin E, pessaries to facilitate first trimester aspiration termination. Br J Obstet Gynecol88: 1033.1981. Moberg PJ, Bygdeman M, Carnsjo LG, Frankman 0, Green K: Pre-abortion treatment with a single vaginal suppository containing Y-deoxo-16, Ii-dimethyline PGE, in late first and early second trimester pregnancies. Acta Obstet Gynecol Stand SupplIl3: 137,1983. Nilson S, Johnell H, Langhoff-Roos J, Nyberg R, Green K: Vaginal administration of 15-methyl-PGE,-methylester prior to vacuum aspiration. cell and postoperative complication. Acta Obstet Gynecol Stand 62: 599, 1983. Richardson, JA, Dixon G: Effects of legal termination of subsequent pregnancy. Br Med J 1: 1303,1976. Some11C, Oland A, Kindahl H, Larsson B: Dilatation of the cervix by oral PGE, before first trimester termination of pregnancy. Acta Obstet Gynecol Stand 63: 625,1984. Stallworthy JA, Moolgacker AS, Walsh JJ: Legal abortion: A critical assessment of its risks. Lancet 2: 1245, 1971. Welch C, Elder MC: Cervical dilatation with 16, 16dimethyl-trans PGE, methyl ester vaginal pessaries before surgical termination of first trimster pregnancies. Br J Obstet Gynecol89: 849, 1982. Wingerup L, Ekman G, Ulmsten U: Local application of prostaglandin E, in gel. A new technique to ripen the cervix during pregnancy. Acta Obstet Gynecol Stand SuppI M3: 131,1983. Wingerup L, Imsten U, Andersson KE: Ripening of the cervix by intracetvical application of PGE,-gel before termination of pregnancy with dilatation and evacuation. ActaObstetGynecolScandSuppl84: 15,197Y. Wright CSW, Campbell S, Beazley J: Second trimester abortion after vaginal termination of pregnancy. Lancet 1: 1278, 1972.
Address for reprints: E. Sbnlev. MD Department of Obstetrics and Gynecology Central Emek Hospital Afuln 18 101 Israel
Int. J. Gynecol. Obstet., 1988,21: 119-122 International Federation of Gynecology&Obstetrics
Intracervical administration of prostaglandin E,-gel prior to therapeutic abortion: a prospective randomized double-blind study E. Shalev, A. Tsabari, S. Edelstein, E. Weiner and H. Zuckerman Department of Obstetrics and Gynecology, Central Emek Hospital, Afula (Israel) (Received January 5th, 1987) (Revised and accepted July 14th. 1987)
Abstract
Forty primigravid women due to undergo first trimster termination of pregnancy were randomly selected for intracervical application of 1 mg prostaglandin E, in gel or gel only as placebo. In the PGE,-gel group, a marked dilatation of the cervical canal was obtained, with post-gel treatment mean Hegar dilatation of Il.18 mm in that group, compared to 4.4 mm in the control group (P 0.001). Moreover, 16 (80%) patients in the PGE,-gel group had a complete abortion, one (5%) patient had an incomplete abortion and in the remaining three (15930)patients, fetal demise was observed. The mean inductionabortion interval in this group was 7.5 h. In the placebo group, none of the above effects were observed. The only side effect noted was vomiting, which occurred in five (25%) of the patients in the PGE,-gel group. Termination of pregnancy was found to be easier in the PGE,-gel group, compared to the placebo group. Key words: Prostaglandin
termination;
E,-gel; Pregnancy Therapeutic abortion.
Introduction
Cervical trauma
and uterine
perforation
0020-7292/88/$03.50 0 1988 International Federation of Gynecology&Obstetrics
caused by mechanical cervical dilatation and uterine curettage are well recognized complications of elective termination of pregnancy (TOP), particularly in primigravid women [5,18]. The incidence of subsequent cervical incompetence can be ten times as high as that which occurs in control groups [22]. In addition, incidence of premature rupture of membranes with a shorter duration of pregnancy has been documented [lo, 161. Various methods for ripening of the uterine cervix have been employed in an attempt to reduce these risks. Hydrophilic organic substances inserted in the cervical canal have been used as abortificants for more than a century, the best known being the seaweed digitata of Laminaria japonicum [4,8]. More recently, prostaglandins and their analogues have been successfully employed to induce softening and dilatation of the cervix prior to induction of labor [2,1 l] or termination of pregnancy in the first trimester [3,6,13,15]. When using the drug in effective doses, whether administered orally, intramuscularly, intravaginally or intracervically, systemic upset such as vomiting or diarrhea was a frequent side effect [3,9,12,17]. The same results but with fewer side effects were obtained using a reduced dose but with various vehicles such as suppositories, pessaries or gels applied locally [1,14,19,21]. Clinical and Clinical Research
120
Shatev et al.
Most of the previously published studies lack randomization and are not prospective. The aim of this study is to evaluate in a randomized double-blind fashion the use of 1 mg PGE, in viscous gel methylcellulose 3% for ripening and dilatation of the uterine cervix prior to TOP using sharp curettage technique. Materials and methods During a 9-month period from March until November 1985, a randomized prospective double-blind study was performed. Forty primigravid women aged 16-25 years due to undergo therapeutic abortion with gestational age between 7 and 12 weeks participated in the study. The women were randomly selected for intracervical application of 1 mg prostaglandin E, in viscous gel methylcellulose 3% (PGE,gel) or gel only (placebo). Two groups of 20 patients each, similar in regard to their ages, gestational age and cervical dilatation prior to treatment, were selected. They were admitted in the evening prior to the operation, generally two patients at a time. The study design was explained and they gave their consent to participate in the study. All the patients were hospitalized. After a medical history was taken and a physical examination completed, application of PGE,-gel or placebo was performed at 2200 h under aseptic conditions while the patients were in the lithotomy position. The patients were asked to remain recumbent for 1 h. To prepare the gel, 3 g of methylcellulose 4000 (B.P. 73) powder was mixed with 100 ml of distilled water in a vial, the mixture was then shaken thoroughly without delay to prevent lump formation, and was stored in a refrigerator for 24 h. Sealed vials were autoclaved at 120°C for 20 min. Cooling was allowed to occur with little disturbance of the vials. Only vials containing an even smooth emulsion were retained, the others were rejected. The sterilized gel can be stored at room temperature or in the refrigerator for almost unlimited periods. One hour before clinical use, the gel was Int J Gynecol Obstet 27
activated by the addition of 1 mg (0.1 ml) of PGE, (Prostin E, 10 mg/ml, Upjohn Co.) Thorough mixing by vigorous shaking for 15 min is imperative. For the purpose of the study, the gel of PGE, 1 mg gel was transferred into 10 ml syringes, separated and coded. The codes were broken only after the study was completed. The cervix was grasped by a single tenaculum in the upper lip. The cervical canal diameter, through the internal OS, was measured according to the largest Hegar which could pass through it without resistance. The drug was inserted via a plastic cannula (Venflon IV Cannula 17G/14mm “VIGGO”) into the cervix to a depth of 2.5 cm. Dolestin 75 mg and Phenergan 25 mg were administered intramuscularly on the patient’s request. The cervical dilatation was planned to be evaluated by Hegar at 0800 h, using the same technique of pretreatment measurement. If needed, further dilatation by Hegar was performed. The difficulty of operation was scored from 1 to 4 with score 1 for the more difficult operations. Vital signs including temperature, blood pressure and heart rate, and symptoms such as vomiting, diarrhea, chills and pain were registered at the time of hospitalization and 4 weeks later. The results were analyzed using SPSS software on an IBM-PC microcomputer. Student’s t-test was used for testing statistical significance. Results No statistical difference between the PGE,gel and the control groups regarding the patient’s age, gestational age and the pretreatment cervical dilatation (Hegar 1) was noted. There is a significant statistical difference between the two groups in the cervical dilatation after treatment (Hegar II) and DeltaHegar (A), as shown in Table I. Abortions occurred in 17 (85070)patients of the PGE,-gel group: 16 (80%) complete abortions and one (5%) incomplete abortion. Fetal demise occurred in the remaining three patients (15%) and curettage was performed on all
Prostaglandin E,-gel prior to pregnancy termination Table I. Cervical dilatation, pretreatment (Hegar I), post-treatment gel and placebo gel control groups.
Hegar I Hegar II A Hegar
pre-operative (Hegar II) and Delta-Hegar (A Hegar) in PGE,-
Treated group
Control group
121
mean + S.D.
Range
mean k SD.
Range
3.15 f 0.71 4.4 f 0.73 1.25 -c 0.40
2.0 -5 3.5 -6 0.25-1.5
3.3 f 0.91 11.18 f 1.70 7.88 f 2.0
2- 5 7-13 5-10.5
t-test
P-value
0.54 15.97 14.16
NS” 0.001 0.001
‘NS = not significant.
patients to confirm diagnosis. Further dilatation before curettage was required in only one patient of this group. All the spontaneous abortions occurred in the morning, with a mean induction-abortion interval of 7.5 h (range 6-9.5 h). Thus dilatation was determined before the planned time. In the placebo-gel control group no spontaneous abortion occurred, and all of the patients needed cervical dilatation before curettage. In the treated group, patients complained of pain from 5 to 45 min (mean 17 min) after the application of the drug. All the patients (20) in this group needed analgesia (Pethidin 1 mg/kg). In the placebo group no patients complained of pain. Vomiting in 4 (20%) patients was noted in the treated group. The difficulty of operation scored from ldifficult, to Ceasy, is presented in Table 11. In the treated group the total scoring was 76 with a mean of 3.8. In the control group, the operation was difficult in all patients (20), with a total scoring of 20 and mean score 1 (P < 0.001). Table II.
Major complications such as tear of the cervix or perforation of the uterus were not recorded in the two groups. On examination of the patients 4 weeks later, none of them showed any signs of pelvic inflammatory disease, but one patient in the placebo group complained of irregular bleeding and needed recurettage. Discussion
Various methods of application with different doses of prostaglandins have been reported as being used for ripening of the cervix prior to therapeutic abortion [1,3,6,9,12,15,17,19,20]. The best effect with the fewest side effects was obtained with the local application of PGE, .using viscous gel as a vehicle [17,20,21], in comparison to the administration of the drug intramuscularly [5] or by the oral route [14]. Incidence of systemic side effects using PGE, in gel were found to be dose-related with a high rate of side effects using 3 mg of PGE, [ 151.
Score of difficulty from score 1 (difficult) to score 4 (easy) in both groups. Control group
Treated group
No. of patients
Total score (mean)
No. of patients
Total score (mean)
Score 1 Score 2
20 -
20 -
-
-
Score 3 Score 4
-
-
1 2 17
2 6 68
Total
20
20 (1)
20
76 (3.8) -Clinical and Clinical Research
122
Shalev et al.
Although cervical dilatation was obtained using a low dose of PGE, in viscous gel (0.25 mg and 0.75 mg), the abortion rate was still low [7,20,21]. Using a low dose, the rate of uterine perforation [22] and cervical tear due to further dilatation was high [7,21]. In the present study with the application of 1 mg of PGE, in viscous gel, significant dilatation was obtained in the treated group in comparison with the placebo, and, furthermore, complete abortion occurred in a high percentage (80%) of the case in the first group; side effects were minimal. We highly advocate the use of 1 mg intracervical PGE; gel in primigravid patients prior to TOP. In the present study, patients were hospitalized because of the study, but the procedure can be adapted to an out-patient setting with application of the drug in the early morning and termination by afternoon. References Djahanbaknch 0, Bassom TS, Marshall DE, Gardner NH: Single extra-amniotic injection of prostaglandin E, in tylose gel to induce first trimester abortion in young nullipara. Acta Obstet Gynecol Stand 61: 445, 1982. Ekman G, Perssen PH. Ulmsten U, Wingerup L: The impact on labour induction of intracervically applied PGE,-gel, related to gestational age in patients with an unripe cervix. Acta Obstet Gynecol Stand Suppl M3: 173, 1983. Fehrman H, Praetorious B: The cervix-ripening effect of prostaglandin E analogue sulprostone, before vacuum aspiration in first trimester pregnancy. Acta Obstet Gyneco1 Stand Suppl M3: 141,1983. Golditch IM, Glasser MH: The use of laminario-tents for cervical dilatation prior to vacuum aspiration abortion. Am J Obstet Gynecol 119: 481, 1973. Grimes DA, Cates W: Complication from legally-induced abortion: A review. Obstet Gynecol Survey 34: 177, 1979. Heinz1 S, Andor J: Pre-operation administration of prostaglandin to avoid dilatation induced damage in first trimester pregnancy termination. Gynecol Obstet Invest 12: 296, 1981. Iversen T, Skjeldestad FE: Intracervical administration of prostaglandin E, Prior to vacuum aspiration a prospective double-blind randomized study. Int J Gynecol Obstet 23: 95, 1985. Killick SR, Vaughan W, Elstein M: A comparison of prostaglandin E, pessaries and laminaria tents for ripening the cervix before termination of pregnancy. Br J Obstet GynecolY2: 518, 1985. Int JGynecol
Obstet 27
9
10
11
12
13
14
15
16 17
18
19
20
21
22
Lauersen NH, Den T, Iliescu C, Wilson KH, Graves ZR: Cervical ripening prior to dilatation and evacuation: A comparison of methods. Am J Obstet Gynecol 144: 890, 1982. Lin DTY, Melville HAH, Martin T: subsequent gestational morbidity after various types of abortion. Lancet 2: 431, 1972. MacKenzie IZ, Embrey MP: Cervical ripening with intravaginal prostaglandin E gel. Br J Obstet Gynecol 88: 1033, 1981. MacKenzie IZ, Embrey MP: Single extra-amniotic injection of prostaglandins in various gel to induce abortion. Br J Obstet Gynecol83: 505, 1976. MacKenzie IZ, Fry A: Prostaglandin E, pessaries to facilitate first trimester aspiration termination. Br J Obstet Gynecol88: 1033.1981. Moberg PJ, Bygdeman M, Carnsjo LG, Frankman 0, Green K: Pre-abortion treatment with a single vaginal suppository containing Y-deoxo-16, Ii-dimethyline PGE, in late first and early second trimester pregnancies. Acta Obstet Gynecol Stand SupplIl3: 137,1983. Nilson S, Johnell H, Langhoff-Roos J, Nyberg R, Green K: Vaginal administration of 15-methyl-PGE,-methylester prior to vacuum aspiration. cell and postoperative complication. Acta Obstet Gynecol Stand 62: 599, 1983. Richardson, JA, Dixon G: Effects of legal termination of subsequent pregnancy. Br Med J 1: 1303,1976. Some11C, Oland A, Kindahl H, Larsson B: Dilatation of the cervix by oral PGE, before first trimester termination of pregnancy. Acta Obstet Gynecol Stand 63: 625,1984. Stallworthy JA, Moolgacker AS, Walsh JJ: Legal abortion: A critical assessment of its risks. Lancet 2: 1245, 1971. Welch C, Elder MC: Cervical dilatation with 16, 16dimethyl-trans PGE, methyl ester vaginal pessaries before surgical termination of first trimster pregnancies. Br J Obstet Gynecol89: 849, 1982. Wingerup L, Ekman G, Ulmsten U: Local application of prostaglandin E, in gel. A new technique to ripen the cervix during pregnancy. Acta Obstet Gynecol Stand SuppI M3: 131,1983. Wingerup L, Imsten U, Andersson KE: Ripening of the cervix by intracetvical application of PGE,-gel before termination of pregnancy with dilatation and evacuation. ActaObstetGynecolScandSuppl84: 15,197Y. Wright CSW, Campbell S, Beazley J: Second trimester abortion after vaginal termination of pregnancy. Lancet 1: 1278, 1972.
Address for reprints: E. Sbnlev. MD Department of Obstetrics and Gynecology Central Emek Hospital Afuln 18 101 Israel