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Misoprostol for midtrimester termination of pregnancy in women with 1 or more prior cesarean deliveries
International Journal of Gynecology and Obstetrics 120 (2013) 85–87
Contents lists available at SciVerse ScienceDirect
International Journal of Gynecology and Obstetrics journal homepage: www.elsevier.com/locate/ijgo
CLINICAL ARTICLE
Misoprostol for midtrimester termination of pregnancy in women with 1 or more prior cesarean deliveries Ümran Küçükgöz Güleç a,⁎, Ibrahim F. Urunsak a, Esra Eser b, Ahmet B. Guzel a, Fatma T. Ozgunen a, Ismail C. Evruke a, Selim Buyukkurt a a b
Department of Obstetrics and Gynecology, Faculty of Medicine, Cukurova University, Adana, Turkey Department of Obstetrics and Gynecology, Bozyazı Government Hospital, Bozyazı, Turkey
a r t i c l e
i n f o
Article history: Received 16 June 2012 Received in revised form 17 August 2012 Accepted 8 October 2012 Keywords: Midtrimester Misoprostol Scarred uterus Termination of pregnancy Uterine rupture
a b s t r a c t Objective: To evaluate the safety and efficacy of vaginal misoprostol for midtrimester termination of pregnancy (TOP) in women with 1 or more prior cesarean deliveries (CDs). Methods: A retrospective study was conducted with 279 women undergoing TOP with vaginal misoprostol between 14 and 26 weeks of gestation. Of these, 193 had no uterine scars (group 1), 60 had 1 prior CD (group 2), and 26 had 2 or more prior CDs (group 3). The primary outcome was the success rate of TOP. Secondary outcomes were time from induction to abortion, total dose of misoprostol used, and occurrence of uterine rupture. Results: The success rates were 96.4% in group 1, 81.7% in group 2, and 76.9% in group 3 (P = 0.001). Time from induction to abortion, total dose misoprostol, and duration of hospital stay differed significantly among the groups (P = 0.001 for all variables). There were 3 cases (11.5%) of uterine rupture in group 3, for an overall rate of 1.1%. Conclusion: Misoprostol inserted vaginally was effective for midtrimester TOP but the safety of using misoprostol in women with 2 or more prior CDs cannot be confirmed from the present study. Misoprostol should be used carefully, particularly in women with 2 or more prior CDs. © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction The prevalence of women with uterine scars has increased worldwide in the past decades due to the higher rates of cesarean deliveries (CDs). Various procedures have been suggested for termination of pregnancy (TOP) in the midtrimester, and medical abortion has become increasingly considered an alternative to surgical procedures [1]. Although misoprostol, a synthetic analog of prostaglandin E1, is not licensed for medical abortion in many countries, it has been used for this purpose because of its effectiveness, low cost, and stability at room temperature [2]. There has been concern that, depending on the route of administration and the dosage, women undergoing midtrimester TOP with misoprostol were at risk for uterine rupture [2–4]. However, there are insufficient data on the risk of uterine rupture for women with a CD history, especially those with 2 or more prior CDs [5–10]. The present study reports on the authors' experience using misoprostol vaginally for midtrimester TOP in women with a history of CD. 2. Materials and methods A retrospective cohort study of 279 women was carried out between January 1, 2007, and July 31, 2010, at the tertiary Obstetrics ⁎ Corresponding author at: Çukurova Üniversitesi, Tıp Fakültesi, Kadın Hastalıkları ve Doğum AD, 01330 Adana, Türkiye. Tel.: +90 322 3386060 3195; fax: +90 322 3387227. E-mail address: [email protected] (Ü. Küçükgöz Güleç).
and Gynecology Clinic of Cukurova University, Adana, Turkey, after approval by the local ethics committee. The women were all undergoing TOP by vaginal misoprostol administration between 14 and 26 weeks of gestation, with gestational age established by ultrasound. The indications for midtrimester TOP were intrauterine fetal demise, structural and chromosomal abnormalities in the fetus, and maternal medical reasons. The exclusion criteria were multiple gestation or placenta previa; known history of classic CD, in which the uterus is incised vertically; known allergy to misoprostol; known contraindication to misoprostol use, such as asthma, liver or heart disease; use of a conflicting medication; and previous administration of misoprostol for the same TOP by another route. Of the 279 patients, 193 had an unscarred uterus (group 1). Of the remaining patients, 60 (group 2) had undergone 1 whereas 26 (group 3) had undergone 2 or more lower-segment CDs. Following appropriate counseling, all patients were explained the TOP procedure and each signed an informed consent form. Misoprostol tablets (Cytotec; Ali Raif, Istanbul, Turkey) moistened with 3 mL of normal saline solution were placed in the posterior vaginal fornix. A 400-μg dose was followed by 400-μg doses every 4 hours, up to 2400 μg, in group 1; half doses, up to 1200 μg, were administered in groups 2 and 3. A new cycle was started after an interval of 24 hours if abortion had not occurred after the maximum dose had been reached. Pulse, blood pressure, and temperature were monitored during the process and the presence of adverse effects, such as nausea, vomiting, diarrhea, tachycardia, and fever, were recorded. Success was defined as vaginal expulsion of the uterine
0020-7292/$ – see front matter © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijgo.2012.08.013
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Table 1 Demographic and clinical characteristics of the women with and without prior CDs who received misoprostol vaginally for midtrimester TOP.a Characteristic
Group 1 (n = 193)
Group 2 (n = 60)
Group 3 (n = 26)
Total (n = 279)
P valueb
P valuec
Age, y Gravidity Parity Gestational age, wk Time since last CD, y
28.2 ± 6.9 2.4 ± 1.7 1.0 ± 1.4 19.3 ± 4.2 4.8 ± 3.6
30.0 ± 6.1 2.7 ± 1.0 1.3 ± 0.7 20.5 ± 3.6 4.1 ± 3.2
31.8 ± 5.1 3.9 ± 1.5 2.2 ± 0.9 18.4 ± 3.3 4.08 ± 2.2
28.9 ± 6.6 2.6 ± 1.6 1.2 ± 1.3 19.5 ± 4.0 4.4 ± 3.3
0.007 0.001 0.001 0.06 0.54
0.15 0.001 0.001 0.02 0.33
Abbreviations: CD, cesarean delivery; TOP, termination of pregnancy. a Values are given as mean ± SD or number (percentage) unless otherwise indicated. b Comparison among groups 1, 2, and 3. c Comparison between groups 2 and 3.
content within 96 hours. The time from TOP induction to abortion was defined as the time from first misoprostol insertion to complete expulsion. Further evacuation of the uterine cavity was performed if the placenta was incomplete, or if the abortion appeared incomplete and transvaginal ultrasound revealed remnants in the uterine cavity. When further evacuation was needed, the patients received a 1-g dose of cefazolin intravenously during the procedure for antimicrobial prophylaxis. Hemoglobin levels were assessed both before TOP induction and in the fourth hour following abortion. A clinical examination and a transvaginal ultrasound were performed when uterine rupture was suspected. Severe bleeding, uterine rupture, and receiving a blood transfusion were recorded as complications. Comparisons between groups were performed using the t test or one-way analysis of variance. The Kruskal–Wallis and the Mann– Whitney U test were used for non-normally distributed variables. Categoric variables were compared between groups by the χ 2 test. Results were expressed as mean and standard deviation or number and percentage. All P values were 2-tailed and P b 0.05 was considered significant. Statistical analysis was performed using SPSS version 11 (IBM, Armonk, NY, USA).
3. Results Of 279 women enrolled over 3 years, 86 (30.8%) had a history of CD. Of these, 60 had 1 prior CD whereas 22 had 2, 3 had 3, and 1 had 5 prior CDs. Patients' characteristics are shown in Table 1 for the 3 groups. In group 1, which consisted of 193 women with an unscarred uterus, 101 (52.3%) were nulliparous. No difference was found between the groups regarding TOP indications (P = 0.40) or gestational age (P = 0.06). Age (P = 0.007), gravidity (P = 0.001), and parity (P = 0.001) were significantly different among the groups, as was expected because group 2 and 3 consisted of women with prior CDs. Outcomes and complications are listed in Table 2. Although time from TOP induction to abortion, total misoprostol dose, and duration of hospital stay (P = 0.001 for each) differed significantly among the
groups, these variables were not significantly different in groups 2 and 3 (P = 0.66, P = 0.89, and P = 0.91, respectively). The success rate was 96.4% in group 1, 81.7% in group 2, and 76.9% in group 3 (P = 0.001). There were no significant differences among the groups regarding the occurrence of adverse effects of misoprostol (P = 0.79). Uterine rupture occurred in 3 patients in group 3 (11.5% for this group and 1.1% overall). The first case occurred in a 34-year-old woman who had 3 previous CDs and had undergone her last CD 4 years previously, and whose indication for TOP was fetal demise at 24 weeks of gestation. The left lateral wall of the uterus ruptured after the patient had received a total dose of 800 μg of misoprostol over 16 hours. She was given 4 units of blood and fresh-frozen plasma while hysterectomy was performed. The second case occurred in a 30-year-old woman who had undergone her second CD 1 year previously, and whose indication for TOP was congenital anomalies in a 20-week-old fetus. The lower uterine segment ruptured, and was repaired via laparotomy, after she had received a total dose of 1200 μg of misoprostol over 24 hours. A blood transfusion was not required and the patient was discharged as healthy. The third case occurred in a 39-year-old woman who had undergone her second CD 4 years previously, and whose indication for TOP was congenital anomalies in a 16-week-old fetus. The lower uterine segment ruptured in the scar area after she received a total dose of 800 μg of misoprostol over 16 hours. A preoperative blood transfusion was not required and the rupture was repaired via laparotomy.
4. Discussion Although different routes of administration and different doses of misoprostol have been compared for midtrimester TOP, the effect of misoprostol in women with prior CDs has not been sufficiently examined. Owing to the lack of randomized trials, there are no conclusions about the safety and effectiveness of the administration routes or misoprostol dosage used in these women, or the time allowed between doses. Other studies have noted the lack of knowledge about the optimal dosage of
Table 2 Outcomes of vaginal use of misoprostol for midtrimester TOP.a Outcome
Group 1 (n = 193)
Group 2 (n = 60)
Group 3 (n = 26)
Total (n = 279)
P valueb
P valuec
Time from induction to abortion, h Total misoprostol dose, μg Hemoglobin level, g/dL Before TOP Following TOP Hospital stay, d Adverse effects Success rate Uterine rupture
22.7 ± 24.9 1429.0 ± 1178.0
42.6 ± 41.5 1044.1 ± 1130.7
98.7 ± 294.6 955.7 ± 790.3
33.4 ± 70.9 1302.1 ± 1150.0
0.001 0.001
0.66 0.89
11.7 ± 1.4 11.4 ± 1.2 2.4 ± 1.2 121 (62.7) 186 (96.4) 0
11.2 ± 1.4 10.7 ± 1.7 3.6 ± 2.2 29 (48.3) 49 (81.7) 0
11.5 ± 1.3 10.8 ± 1.1 3.6 ± 2.3 14 (53.8) 20 (76.9) 3 (11.5)
11.6 ± 1.4 11.1 ± 1.4 2.8 ± 1.6 164 (58.7) 255 (91.4) 3 (1.1)
0.06 0.01 0.001 0.14 0.001 0.001
0.72 0.62 0.91 0.79 0.06 0.66
Abbreviations: TOP, termination of pregnancy. a Values are given as mean ± SD or number (percentage) unless otherwise indicated. b Comparison among groups 1, 2, and 3. c Comparison between groups 2 and 3.
Ü. Küçükgöz Güleç et al. / International Journal of Gynecology and Obstetrics 120 (2013) 85–87
misoprostol for midtrimester TOP in women with prior CDs [3,4]. In the present study, half of the routine misoprostol dosage was used in groups 2 and 3, which, in comparison with group 1, resulted in a longer time from induction to abortion and higher total doses of misoprostol. These findings may indicate that low doses of misoprostol may be ineffective for TOP in the midtrimester, and the resulting extended induction to abortion interval results in higher total misoprostol doses. A systematic review concluded that although the use of misoprostol for midtrimester TOP was safe for women with 1 prior CD, it was associated with incidence rates of 0.4% and 0.2%, respectively, for uterine rupture and need for transfusion (the rate for hysterectomy was 0%), and in an another review, the reported risk of uterine rupture was less than 0.3% [3,4]. Dickinson [7] reported no uterine rupture among 78 women with 1 prior CD. In the present study, no uterine ruptures occurred among the 60 women with 1 prior CD even though they all received multiple low doses of misoprostol vaginally. There are insufficient data on the risk of uterine rupture for women with 2 or more CDs [9–12]. Fawzy et al. [9] evaluated the safety and efficacy of vaginal misoprostol for midtrimester TOP in 31 women with 3 or more prior CDs, and concluded that vaginal misoprostol had been safe and acceptably effective. In an evaluation of 21 cases, Daponte et al. [12] also considered that vaginal misoprostol was safe and effective for midtrimester TOP. In the present study, there were 3 (11.5%) cases of uterine rupture in group 3, for a total rate of 1.1%, and the ratio of the rate for women with 2 or more CDs to the rate for the entire study population may be the highest reported so far. Two of the patients who experienced uterine rupture in group 3 had 2 prior CDs and the third one had 3. Misoprostol taken vaginally may, therefore, be unsafe for women with 2 or more prior CDs. The doses used for these patients were lower than the doses used in other studies [3], but a long induction time, a more advanced gestation, and a short time between the last CD and TOP with misoprostol may also have played a role. Studies taking into consideration indications for TOP or gestational age are also limited [13–15]. In the present study, TOP was performed because of fetal demise in 25 women (8.9%). A review considering misoprostol to be an effective option for TOP in cases of fetal demise suggested that the most effective regimen, with the shortest time from induction to abortion, consists of low-dose vaginal administration of misoprostol combined with oxytocin administration [13]. The time since the last CD might influence the possibility of rupture during both labor induction at term and midtrimester TOP. In the present study, the time since the last CD was 4, 1, and 4 years, respectively, for the first, second, and third case. Complications during the third stage of labor, such as hemorrhage and placental retention requiring surgical evacuation, have received little attention despite reported surgical placental evacuation rates of 30% to 40% [16]. The findings of Dickinson and Doherty [16] suggest that an intramuscular injection of oxytocin might be useful after fetal expulsion. In a prospective study of TOP with both mifepristone and misoprostol, in which the rate of surgical evacuation was 30.8%, increasing maternal age, a history of curettage, the interval between mifepristone and misoprostol administration, and a fetal indication for TOP increased the risk of surgical evacuation [17]. Although failure of midtrimester TOP with misoprostol is not uncommon, the best medical method for TOP has not been determined [18].
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Indications for TOP and gestational age may affect induction time and induction efficiency [13–15,19]. Induction time and misoprostol doses are expected to differ in early and later midtrimester terminations, as gestational age and the indication might affect the TOP process and perhaps also the intensity and/or nature of complications. Controlled studies focusing on the risks and effectiveness of misoprostol for TOP should be performed with women who had 2 or more CDs. Until then, the decision to attempt TOP in women in this situation should be made on a case-by-case basis, after consideration of the number of CDs, gestational age, the time from the last CD to the current pregnancy, and the indication for TOP. Monitoring should be done carefully because of the risk of uterine rupture. Conflict of interest The authors have no conflicts of interest. References [1] Lalitkumar S, Bygdeman M, Gemzell-Danielsson K. Mid-trimester induced abortion: a review. Hum Reprod Update 2007;13(1):37-52. [2] Elati A, Weeks AD. The use of misoprostol in obstetrics and gynecology. BJOG 2009;116(Suppl. 1):61-9. [3] Berghella V, Airoldi J, O'Neill AM, Einhorn K, Hoffman M. Misoprostol for second trimester pregnancy termination in women with prior caesarean: a systematic review. BJOG 2009;116(9):1151-7. [4] Dodd JM, Crowther CA. Misoprostol for induction of labour to terminate pregnancy in the second or third trimester for women with a fetal anomaly or after intrauterine fetal death. Cochrane Database Syst Rev 2010(4):CD004901. [5] Goyal V. Uterine rupture in second-trimester misoprostol-induced abortion after cesarean delivery: a systematic review. Obstet Gynecol 2009;113(5):1117-23. [6] Herabutya Y, Chanarachakul B, Punyavachira P. Induction of labor with vaginal misoprostol for second trimester termination of pregnancy in the scarred uterus. Int J Gynecol Obstet 2003;83(3):293-7. [7] Dickinson JE. Misoprostol for second-trimester pregnancy termination in women with a prior cesarean delivery. Obstet Gynecol 2005;105(2):352-6. [8] Daskalakis GJ, Mesogitis SA, Papantoniou NE, Moulopoulos GG, Papapanagiotou AA, Antsaklis AJ. Misoprostol for second trimester pregnancy termination in women with prior caesarean section. BJOG 2005;112(1):97-9. [9] Fawzy M, Abdel-Hady el-S. Midtrimester abortion using vaginal misoprostol for women with three or more prior cesarean deliveries. Int J Gynecol Obstet 2010;110(1):50-2. [10] Alsibiani SA. Misoprostol for pregnancy termination in grand multiparous women with three cesarean deliveries. Int J Gynecol Obstet 2009;106(3):255-6. [11] Shammas AG, Momani MD. Misoprostol for termination of second trimester pregnancy in a scarred uterus. Saudi Med J 2006;27(8):1173-6. [12] Daponte A, Nzewenga G, Dimopoulos KD, Guidozzi F. Pregnancy termination using vaginal misoprostol in women with more than one caesarean section. J Obstet Gynecol 2007;27(6):597-600. [13] Gómez Ponce de León R, Wing DA. Misoprostol for termination of pregnancy with intrauterine fetal demise in the second and third trimester of pregnancy - a systematic review. Contraception 2009;79(4):259-71. [14] Ho PC, Blumenthal PD, Gemzell-Danielsson K, Gómez Ponce de León R, Mittal S, Tang OS. Misoprostol for the termination of pregnancy with a live fetus at 13 to 26 weeks. Int J Gynecol Obstet 2007;99(Suppl. 2):S178-81. [15] Lo TK, Lau WL, Lai FK, Lam H, Tse HY, Leung WC, et al. The effect of gestational age on the outcome of second-trimester termination of pregnancies for foetal abnormalities. Prenat Diagn 2008;28(6):508-11. [16] Dickinson JE, Doherty DA. Optimization of third-stage management after secondtrimester medical pregnancy termination. Am J Obstet Gynecol 2009;201(3):303.e1-7. [17] Mentula M, Heikinheimo O. Risk factors of surgical evacuation following secondtrimester medical termination of pregnancy. Contraception 2012;86(2):141-6. [18] Basu JK, Basu D. The management of failed second-trimester termination of pregnancy. Contraception 2009;80(2):170-3. [19] Borgatta L, Kapp N, Society of Family Planning. Clinical guidelines. Labor induction abortion in the second trimester. Contraception 2011;84(1):4–18.
Contents lists available at SciVerse ScienceDirect
International Journal of Gynecology and Obstetrics journal homepage: www.elsevier.com/locate/ijgo
CLINICAL ARTICLE
Misoprostol for midtrimester termination of pregnancy in women with 1 or more prior cesarean deliveries Ümran Küçükgöz Güleç a,⁎, Ibrahim F. Urunsak a, Esra Eser b, Ahmet B. Guzel a, Fatma T. Ozgunen a, Ismail C. Evruke a, Selim Buyukkurt a a b
Department of Obstetrics and Gynecology, Faculty of Medicine, Cukurova University, Adana, Turkey Department of Obstetrics and Gynecology, Bozyazı Government Hospital, Bozyazı, Turkey
a r t i c l e
i n f o
Article history: Received 16 June 2012 Received in revised form 17 August 2012 Accepted 8 October 2012 Keywords: Midtrimester Misoprostol Scarred uterus Termination of pregnancy Uterine rupture
a b s t r a c t Objective: To evaluate the safety and efficacy of vaginal misoprostol for midtrimester termination of pregnancy (TOP) in women with 1 or more prior cesarean deliveries (CDs). Methods: A retrospective study was conducted with 279 women undergoing TOP with vaginal misoprostol between 14 and 26 weeks of gestation. Of these, 193 had no uterine scars (group 1), 60 had 1 prior CD (group 2), and 26 had 2 or more prior CDs (group 3). The primary outcome was the success rate of TOP. Secondary outcomes were time from induction to abortion, total dose of misoprostol used, and occurrence of uterine rupture. Results: The success rates were 96.4% in group 1, 81.7% in group 2, and 76.9% in group 3 (P = 0.001). Time from induction to abortion, total dose misoprostol, and duration of hospital stay differed significantly among the groups (P = 0.001 for all variables). There were 3 cases (11.5%) of uterine rupture in group 3, for an overall rate of 1.1%. Conclusion: Misoprostol inserted vaginally was effective for midtrimester TOP but the safety of using misoprostol in women with 2 or more prior CDs cannot be confirmed from the present study. Misoprostol should be used carefully, particularly in women with 2 or more prior CDs. © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction The prevalence of women with uterine scars has increased worldwide in the past decades due to the higher rates of cesarean deliveries (CDs). Various procedures have been suggested for termination of pregnancy (TOP) in the midtrimester, and medical abortion has become increasingly considered an alternative to surgical procedures [1]. Although misoprostol, a synthetic analog of prostaglandin E1, is not licensed for medical abortion in many countries, it has been used for this purpose because of its effectiveness, low cost, and stability at room temperature [2]. There has been concern that, depending on the route of administration and the dosage, women undergoing midtrimester TOP with misoprostol were at risk for uterine rupture [2–4]. However, there are insufficient data on the risk of uterine rupture for women with a CD history, especially those with 2 or more prior CDs [5–10]. The present study reports on the authors' experience using misoprostol vaginally for midtrimester TOP in women with a history of CD. 2. Materials and methods A retrospective cohort study of 279 women was carried out between January 1, 2007, and July 31, 2010, at the tertiary Obstetrics ⁎ Corresponding author at: Çukurova Üniversitesi, Tıp Fakültesi, Kadın Hastalıkları ve Doğum AD, 01330 Adana, Türkiye. Tel.: +90 322 3386060 3195; fax: +90 322 3387227. E-mail address: [email protected] (Ü. Küçükgöz Güleç).
and Gynecology Clinic of Cukurova University, Adana, Turkey, after approval by the local ethics committee. The women were all undergoing TOP by vaginal misoprostol administration between 14 and 26 weeks of gestation, with gestational age established by ultrasound. The indications for midtrimester TOP were intrauterine fetal demise, structural and chromosomal abnormalities in the fetus, and maternal medical reasons. The exclusion criteria were multiple gestation or placenta previa; known history of classic CD, in which the uterus is incised vertically; known allergy to misoprostol; known contraindication to misoprostol use, such as asthma, liver or heart disease; use of a conflicting medication; and previous administration of misoprostol for the same TOP by another route. Of the 279 patients, 193 had an unscarred uterus (group 1). Of the remaining patients, 60 (group 2) had undergone 1 whereas 26 (group 3) had undergone 2 or more lower-segment CDs. Following appropriate counseling, all patients were explained the TOP procedure and each signed an informed consent form. Misoprostol tablets (Cytotec; Ali Raif, Istanbul, Turkey) moistened with 3 mL of normal saline solution were placed in the posterior vaginal fornix. A 400-μg dose was followed by 400-μg doses every 4 hours, up to 2400 μg, in group 1; half doses, up to 1200 μg, were administered in groups 2 and 3. A new cycle was started after an interval of 24 hours if abortion had not occurred after the maximum dose had been reached. Pulse, blood pressure, and temperature were monitored during the process and the presence of adverse effects, such as nausea, vomiting, diarrhea, tachycardia, and fever, were recorded. Success was defined as vaginal expulsion of the uterine
0020-7292/$ – see front matter © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijgo.2012.08.013
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Table 1 Demographic and clinical characteristics of the women with and without prior CDs who received misoprostol vaginally for midtrimester TOP.a Characteristic
Group 1 (n = 193)
Group 2 (n = 60)
Group 3 (n = 26)
Total (n = 279)
P valueb
P valuec
Age, y Gravidity Parity Gestational age, wk Time since last CD, y
28.2 ± 6.9 2.4 ± 1.7 1.0 ± 1.4 19.3 ± 4.2 4.8 ± 3.6
30.0 ± 6.1 2.7 ± 1.0 1.3 ± 0.7 20.5 ± 3.6 4.1 ± 3.2
31.8 ± 5.1 3.9 ± 1.5 2.2 ± 0.9 18.4 ± 3.3 4.08 ± 2.2
28.9 ± 6.6 2.6 ± 1.6 1.2 ± 1.3 19.5 ± 4.0 4.4 ± 3.3
0.007 0.001 0.001 0.06 0.54
0.15 0.001 0.001 0.02 0.33
Abbreviations: CD, cesarean delivery; TOP, termination of pregnancy. a Values are given as mean ± SD or number (percentage) unless otherwise indicated. b Comparison among groups 1, 2, and 3. c Comparison between groups 2 and 3.
content within 96 hours. The time from TOP induction to abortion was defined as the time from first misoprostol insertion to complete expulsion. Further evacuation of the uterine cavity was performed if the placenta was incomplete, or if the abortion appeared incomplete and transvaginal ultrasound revealed remnants in the uterine cavity. When further evacuation was needed, the patients received a 1-g dose of cefazolin intravenously during the procedure for antimicrobial prophylaxis. Hemoglobin levels were assessed both before TOP induction and in the fourth hour following abortion. A clinical examination and a transvaginal ultrasound were performed when uterine rupture was suspected. Severe bleeding, uterine rupture, and receiving a blood transfusion were recorded as complications. Comparisons between groups were performed using the t test or one-way analysis of variance. The Kruskal–Wallis and the Mann– Whitney U test were used for non-normally distributed variables. Categoric variables were compared between groups by the χ 2 test. Results were expressed as mean and standard deviation or number and percentage. All P values were 2-tailed and P b 0.05 was considered significant. Statistical analysis was performed using SPSS version 11 (IBM, Armonk, NY, USA).
3. Results Of 279 women enrolled over 3 years, 86 (30.8%) had a history of CD. Of these, 60 had 1 prior CD whereas 22 had 2, 3 had 3, and 1 had 5 prior CDs. Patients' characteristics are shown in Table 1 for the 3 groups. In group 1, which consisted of 193 women with an unscarred uterus, 101 (52.3%) were nulliparous. No difference was found between the groups regarding TOP indications (P = 0.40) or gestational age (P = 0.06). Age (P = 0.007), gravidity (P = 0.001), and parity (P = 0.001) were significantly different among the groups, as was expected because group 2 and 3 consisted of women with prior CDs. Outcomes and complications are listed in Table 2. Although time from TOP induction to abortion, total misoprostol dose, and duration of hospital stay (P = 0.001 for each) differed significantly among the
groups, these variables were not significantly different in groups 2 and 3 (P = 0.66, P = 0.89, and P = 0.91, respectively). The success rate was 96.4% in group 1, 81.7% in group 2, and 76.9% in group 3 (P = 0.001). There were no significant differences among the groups regarding the occurrence of adverse effects of misoprostol (P = 0.79). Uterine rupture occurred in 3 patients in group 3 (11.5% for this group and 1.1% overall). The first case occurred in a 34-year-old woman who had 3 previous CDs and had undergone her last CD 4 years previously, and whose indication for TOP was fetal demise at 24 weeks of gestation. The left lateral wall of the uterus ruptured after the patient had received a total dose of 800 μg of misoprostol over 16 hours. She was given 4 units of blood and fresh-frozen plasma while hysterectomy was performed. The second case occurred in a 30-year-old woman who had undergone her second CD 1 year previously, and whose indication for TOP was congenital anomalies in a 20-week-old fetus. The lower uterine segment ruptured, and was repaired via laparotomy, after she had received a total dose of 1200 μg of misoprostol over 24 hours. A blood transfusion was not required and the patient was discharged as healthy. The third case occurred in a 39-year-old woman who had undergone her second CD 4 years previously, and whose indication for TOP was congenital anomalies in a 16-week-old fetus. The lower uterine segment ruptured in the scar area after she received a total dose of 800 μg of misoprostol over 16 hours. A preoperative blood transfusion was not required and the rupture was repaired via laparotomy.
4. Discussion Although different routes of administration and different doses of misoprostol have been compared for midtrimester TOP, the effect of misoprostol in women with prior CDs has not been sufficiently examined. Owing to the lack of randomized trials, there are no conclusions about the safety and effectiveness of the administration routes or misoprostol dosage used in these women, or the time allowed between doses. Other studies have noted the lack of knowledge about the optimal dosage of
Table 2 Outcomes of vaginal use of misoprostol for midtrimester TOP.a Outcome
Group 1 (n = 193)
Group 2 (n = 60)
Group 3 (n = 26)
Total (n = 279)
P valueb
P valuec
Time from induction to abortion, h Total misoprostol dose, μg Hemoglobin level, g/dL Before TOP Following TOP Hospital stay, d Adverse effects Success rate Uterine rupture
22.7 ± 24.9 1429.0 ± 1178.0
42.6 ± 41.5 1044.1 ± 1130.7
98.7 ± 294.6 955.7 ± 790.3
33.4 ± 70.9 1302.1 ± 1150.0
0.001 0.001
0.66 0.89
11.7 ± 1.4 11.4 ± 1.2 2.4 ± 1.2 121 (62.7) 186 (96.4) 0
11.2 ± 1.4 10.7 ± 1.7 3.6 ± 2.2 29 (48.3) 49 (81.7) 0
11.5 ± 1.3 10.8 ± 1.1 3.6 ± 2.3 14 (53.8) 20 (76.9) 3 (11.5)
11.6 ± 1.4 11.1 ± 1.4 2.8 ± 1.6 164 (58.7) 255 (91.4) 3 (1.1)
0.06 0.01 0.001 0.14 0.001 0.001
0.72 0.62 0.91 0.79 0.06 0.66
Abbreviations: TOP, termination of pregnancy. a Values are given as mean ± SD or number (percentage) unless otherwise indicated. b Comparison among groups 1, 2, and 3. c Comparison between groups 2 and 3.
Ü. Küçükgöz Güleç et al. / International Journal of Gynecology and Obstetrics 120 (2013) 85–87
misoprostol for midtrimester TOP in women with prior CDs [3,4]. In the present study, half of the routine misoprostol dosage was used in groups 2 and 3, which, in comparison with group 1, resulted in a longer time from induction to abortion and higher total doses of misoprostol. These findings may indicate that low doses of misoprostol may be ineffective for TOP in the midtrimester, and the resulting extended induction to abortion interval results in higher total misoprostol doses. A systematic review concluded that although the use of misoprostol for midtrimester TOP was safe for women with 1 prior CD, it was associated with incidence rates of 0.4% and 0.2%, respectively, for uterine rupture and need for transfusion (the rate for hysterectomy was 0%), and in an another review, the reported risk of uterine rupture was less than 0.3% [3,4]. Dickinson [7] reported no uterine rupture among 78 women with 1 prior CD. In the present study, no uterine ruptures occurred among the 60 women with 1 prior CD even though they all received multiple low doses of misoprostol vaginally. There are insufficient data on the risk of uterine rupture for women with 2 or more CDs [9–12]. Fawzy et al. [9] evaluated the safety and efficacy of vaginal misoprostol for midtrimester TOP in 31 women with 3 or more prior CDs, and concluded that vaginal misoprostol had been safe and acceptably effective. In an evaluation of 21 cases, Daponte et al. [12] also considered that vaginal misoprostol was safe and effective for midtrimester TOP. In the present study, there were 3 (11.5%) cases of uterine rupture in group 3, for a total rate of 1.1%, and the ratio of the rate for women with 2 or more CDs to the rate for the entire study population may be the highest reported so far. Two of the patients who experienced uterine rupture in group 3 had 2 prior CDs and the third one had 3. Misoprostol taken vaginally may, therefore, be unsafe for women with 2 or more prior CDs. The doses used for these patients were lower than the doses used in other studies [3], but a long induction time, a more advanced gestation, and a short time between the last CD and TOP with misoprostol may also have played a role. Studies taking into consideration indications for TOP or gestational age are also limited [13–15]. In the present study, TOP was performed because of fetal demise in 25 women (8.9%). A review considering misoprostol to be an effective option for TOP in cases of fetal demise suggested that the most effective regimen, with the shortest time from induction to abortion, consists of low-dose vaginal administration of misoprostol combined with oxytocin administration [13]. The time since the last CD might influence the possibility of rupture during both labor induction at term and midtrimester TOP. In the present study, the time since the last CD was 4, 1, and 4 years, respectively, for the first, second, and third case. Complications during the third stage of labor, such as hemorrhage and placental retention requiring surgical evacuation, have received little attention despite reported surgical placental evacuation rates of 30% to 40% [16]. The findings of Dickinson and Doherty [16] suggest that an intramuscular injection of oxytocin might be useful after fetal expulsion. In a prospective study of TOP with both mifepristone and misoprostol, in which the rate of surgical evacuation was 30.8%, increasing maternal age, a history of curettage, the interval between mifepristone and misoprostol administration, and a fetal indication for TOP increased the risk of surgical evacuation [17]. Although failure of midtrimester TOP with misoprostol is not uncommon, the best medical method for TOP has not been determined [18].
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Indications for TOP and gestational age may affect induction time and induction efficiency [13–15,19]. Induction time and misoprostol doses are expected to differ in early and later midtrimester terminations, as gestational age and the indication might affect the TOP process and perhaps also the intensity and/or nature of complications. Controlled studies focusing on the risks and effectiveness of misoprostol for TOP should be performed with women who had 2 or more CDs. Until then, the decision to attempt TOP in women in this situation should be made on a case-by-case basis, after consideration of the number of CDs, gestational age, the time from the last CD to the current pregnancy, and the indication for TOP. Monitoring should be done carefully because of the risk of uterine rupture. Conflict of interest The authors have no conflicts of interest. References [1] Lalitkumar S, Bygdeman M, Gemzell-Danielsson K. Mid-trimester induced abortion: a review. Hum Reprod Update 2007;13(1):37-52. [2] Elati A, Weeks AD. The use of misoprostol in obstetrics and gynecology. BJOG 2009;116(Suppl. 1):61-9. [3] Berghella V, Airoldi J, O'Neill AM, Einhorn K, Hoffman M. Misoprostol for second trimester pregnancy termination in women with prior caesarean: a systematic review. BJOG 2009;116(9):1151-7. [4] Dodd JM, Crowther CA. Misoprostol for induction of labour to terminate pregnancy in the second or third trimester for women with a fetal anomaly or after intrauterine fetal death. Cochrane Database Syst Rev 2010(4):CD004901. [5] Goyal V. Uterine rupture in second-trimester misoprostol-induced abortion after cesarean delivery: a systematic review. Obstet Gynecol 2009;113(5):1117-23. [6] Herabutya Y, Chanarachakul B, Punyavachira P. Induction of labor with vaginal misoprostol for second trimester termination of pregnancy in the scarred uterus. Int J Gynecol Obstet 2003;83(3):293-7. [7] Dickinson JE. Misoprostol for second-trimester pregnancy termination in women with a prior cesarean delivery. Obstet Gynecol 2005;105(2):352-6. [8] Daskalakis GJ, Mesogitis SA, Papantoniou NE, Moulopoulos GG, Papapanagiotou AA, Antsaklis AJ. Misoprostol for second trimester pregnancy termination in women with prior caesarean section. BJOG 2005;112(1):97-9. [9] Fawzy M, Abdel-Hady el-S. Midtrimester abortion using vaginal misoprostol for women with three or more prior cesarean deliveries. Int J Gynecol Obstet 2010;110(1):50-2. [10] Alsibiani SA. Misoprostol for pregnancy termination in grand multiparous women with three cesarean deliveries. Int J Gynecol Obstet 2009;106(3):255-6. [11] Shammas AG, Momani MD. Misoprostol for termination of second trimester pregnancy in a scarred uterus. Saudi Med J 2006;27(8):1173-6. [12] Daponte A, Nzewenga G, Dimopoulos KD, Guidozzi F. Pregnancy termination using vaginal misoprostol in women with more than one caesarean section. J Obstet Gynecol 2007;27(6):597-600. [13] Gómez Ponce de León R, Wing DA. Misoprostol for termination of pregnancy with intrauterine fetal demise in the second and third trimester of pregnancy - a systematic review. Contraception 2009;79(4):259-71. [14] Ho PC, Blumenthal PD, Gemzell-Danielsson K, Gómez Ponce de León R, Mittal S, Tang OS. Misoprostol for the termination of pregnancy with a live fetus at 13 to 26 weeks. Int J Gynecol Obstet 2007;99(Suppl. 2):S178-81. [15] Lo TK, Lau WL, Lai FK, Lam H, Tse HY, Leung WC, et al. The effect of gestational age on the outcome of second-trimester termination of pregnancies for foetal abnormalities. Prenat Diagn 2008;28(6):508-11. [16] Dickinson JE, Doherty DA. Optimization of third-stage management after secondtrimester medical pregnancy termination. Am J Obstet Gynecol 2009;201(3):303.e1-7. [17] Mentula M, Heikinheimo O. Risk factors of surgical evacuation following secondtrimester medical termination of pregnancy. Contraception 2012;86(2):141-6. [18] Basu JK, Basu D. The management of failed second-trimester termination of pregnancy. Contraception 2009;80(2):170-3. [19] Borgatta L, Kapp N, Society of Family Planning. Clinical guidelines. Labor induction abortion in the second trimester. Contraception 2011;84(1):4–18.