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Cervical preparation with laminaria tents improves induction-to-delivery interval in second- and third-trimester medical termination of pregnancy
Contraception 80 (2009) 101 – 104
Original research article
Cervical preparation with laminaria tents improves induction-to-delivery interval in second- and third-trimester medical termination of pregnancy Chafika Mazounia , Nadège Vejuxa , Jean-Pierre Menarda , Aurore Brunob , Léon Boublia , Claude d'Ercolea , Florence Bretellea,c,⁎ a
Department of Obstetrics and Gynecology, Marseille Public Hospital System (APHM), 13385 Marseille, France b Marseille Midwife School, 13014 Marseille, France c Unit 1, CNRS UMR 6236, Université de la Méditerranée, 13005 Marseille, France Received 1 October 2008; revised 22 January 2009; accepted 26 January 2009
Abstract Background: The purpose of our study was to determine whether cervical preparation with laminaria tents would improve the procedure of second- and third-trimester medical termination of pregnancy (TOP) in terms of duration of abortion and hospitalization. Study: A retrospective comparative study of two historical periods of women undergoing second- and third-trimester medical TOP at a single tertiary care center from September 2004 to December 2006 was conducted. During Period A, patients received oral mifepristone and vaginal misoprostol, while during Period B, laminaria tents were added. Main outcome measures included initiation-to-delivery (ITD) time, induction-to-delivery interval and hospitalization time. Results: Of 186 eligible women, 174 were enrolled in the study: 91 patients during Period A and 83 patients during Period B. The ITD time was reduced during Period B compared to Period A (43.2±6.2 h and 48.5±13.2 h, respectively; p=.001). Similarly, the induction-to-delivery interval was significantly shorter during Period B (7.5 h) compared to Period A (12.7 h; p=.001). A significant reduction in total hospital stay was observed during Period B (3 days) versus Period A (4 days; pb.001). Conclusion: Cervical preparation with laminaria tents significantly shortens the duration of medical TOP that uses mifepristone–misoprostol without adverse events or serious complications. © 2009 Elsevier Inc. All rights reserved. Keywords: Abortion; Laminaria; Mifepristone; Misoprostol; Termination of pregnancy
1. Introduction Advances in biology and ultrasound technology have allowed an improvement in the antenatal detection of fetal malformation. As a result, indications for termination of pregnancy (TOP) are more frequent and may occur later during the course of pregnancy. However, the achievement of successful TOP might be challenging despite the numerous choices of method for second- and third-trimester TOP [1]. Currently, there is insufficient evidence to assess the effectiveness of mechanical methods (D&E) compared with prostaglandins [2]. However, the need for fetal ⁎ Corresponding author. Department of Obstetrics and Gynecology, Hôpital Nord, 13915 Marseille Cedex 20, France. Tel.: +33 4 91 9 646 72; fax: +33 4 91 96 48 53. E-mail address: [email protected] (F. Bretelle). 0010-7824/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.contraception.2009.01.013
anatomopathologic examination to correlate antenatal findings tends to favor the choice for medical procedures. There are, however, some points that might limit the choice of methods to induce the TOP, such as the unpredictability of the interval-to-delivery time or a longer duration of hospitalization. Some authors have proposed use of laminaria tents alone or in combination with prostaglandins to improve the efficiency of medical procedures. These publications have reported contrasting results [3–5]. However, few have reported experience with the combination of mifepristone and misoprostol, a regimen of choice for second- and third-trimester medical TOP [6–8]. Our objective was to evaluate the impact of laminaria placement for cervical preparation in adjunction with mifepristone and misoprostol on delivery interval, during the second- and third-trimester medical TOP.
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C. Mazouni et al. / Contraception 80 (2009) 101–104
2. Materials and methods 2.1. Study design A retrospective study of TOP performed between September 2005 and December 2006 at the Department of Obstetrics and Gynecology, North Hospital, a tertiary care center in Marseille (France), was conducted. The study protocol consisted of two cohorts of patients from two periods of treatment: (a) Period A consisted of all TOP cases admitted between September 2004 and October 2005 and (b) Period B comprised all cases from November 2005 to December 2006. The distinction between the two periods was based on the adjunction of laminaria tents for cervical preparation to the medical treatment in Period B compared to Period A, where no additional cervical preparation was performed. The IRB was approached for the study approval, and because this study is not an interventional study but a retrospective chart review, this type of study does not require IRB approval in accordance with the health public code (article L1121-1). 2.2. Study procedures All indications for TOP were discussed in a weekly multidisciplinary counseling of fetal medicine, and each patient signed a written informed consent. During Period A, the protocol for TOP induction consisted of oral (600 mg) mifepristone administration followed after 36 h by vaginal misoprostol (400 mcg=2×200 mcg) every 3 h for a maximum of 1200 mcg per day. During Period B, the same mifepristone–misoprostol protocol was used but cervical preparation was obtained using 5–8 mm laminaria tent (B. Braun Medical Ltd., Tuttlingen, Germany) placement, 24 h after the administration of oral mifepristone. Concerning the timing of hospital admission in relation to mifepristone, both groups were admitted at the same time interval. Laminaria tents were placed intracervically and packed until no additional tents could be inserted. The laminaria remained in the cervix at the time of misoprostol placement, unless they were expelled or membrane rupture occurred. The diameter of laminaria was adapted to the cervix size beginning with the larger size. The presence or absence of the following adverse event side effects was prospectively recorded in medical charts by the responsible midwife: diarrhea, nausea and hyperthermia (fever higher than 38°C) and hemorrhage defined as blood loss greater than 300 mL. The primary outcome measured was the mifepristone-todelivery time (initiation) compared between the two periods; the delivery was defined as fetal expulsion. Secondary outcomes included (a) induction-to-delivery interval defined as time from first misoprostol dose to fetal expulsion and (b) time to discharge from the hospital.
Labor was defined from the beginning of uterine contractions and cervical modifications to fetal expulsion. Retained placenta was defined as lack of expulsion 30 min after delivery of the fetus and was managed at the discretion of the attending physician and usually consisted of manual removal. 2.3. Statistical analysis Group testing of categorical data is presented as n (%), and groups were compared with Fisher's Exact Test or the chi-square test. Differences in continuous variables were analyzed using the Mann–Whitney U test. Kaplan–Meier survival analysis and Cox proportional hazard modeling were applied to examine the interval from induction to delivery according to laminaria use, while adjusting for confounding factors. Groups were compared using the log rank test. 3. Results 3.1. Patient's characteristics During Period A (i.e., TOP without laminaria placement), 97 patients requested TOP, and during Period B, 89 patients did so. From the initial patients selected, 12 (6 in each group) were excluded from the analysis because of missing data. Therefore, a total of 174 patients were evaluated, 91 during Period A and 83 during Period B. The clinical and demographic data of the groups are shown in Table 1. There was no difference in patient characteristics other than the fact that patients during Period A tended to be older than patients during Period B (p=.03). There was no difference between groups for indications for TOP (p=.88) (details for each group are not shown). Overall, the most frequent indication was fetal abnormalities (59.8%), followed by chromosomal anomalies (31.6%), premature rupture of membranes (5.7%) and miscellaneous indications (2.9%). 3.2. Delivery outcome There was no difference in the number of misoprostol tablets administered between the two groups, with a median
Table 1 Obstetrical characteristics of the study population
Age, mean (±SD) Nulliparous, n (%) Gestational age (weeks), mean (±SD) Previous cesarean delivery, n (%)
Period A (no laminaria) (n=91)
Period B (with laminaria) (n=83)
p value
31.5 (±6.5) 37 (40.7) 24.2 (±6.1)
29.3 (±5.8) 38 (45.8) 23.3 (±6.3)
.03 .50 .32
11 (12.1)
11 (13.3)
.82
C. Mazouni et al. / Contraception 80 (2009) 101–104 Table 2 Delivery interval characteristics between the two periods of study
Mean (±SD) mifepristone-to-delivery interval (h) Induction to delivery, n (%) b6 h b12 h b24 h Median (±SD) (h) Mean (±SD) (h)
103
Table 3 Adverse events
Period A (no laminaria) (n=91)
Period B (with laminaria) (n=83)
p value
48.5 (±13.2)
43.2 (±6.2)
.001
21 (23.1) 60 (65.9) 83 (91.2) 9 (±8) 12.7 (±13.3)
37 (44.6) 73 (88) 80 (96.4) 6.4 (±4) 7.5 (±6.2)
.003 .001 .16 .01 .001
number of 1.5 doses in both groups (median dose, 600 mcg for Period A vs. 600 mcg for Period B, p=.65). In Period B, a median of 1 laminaria (range, 1–4) was placed in the cervix. The median diameter of laminaria used was 8 mm (range, 5–8 mm). Total median duration of the medical termination procedure, defined as the time from mifepristone administration to delivery, was significantly shorter during Period B compared to Period A (43.2 h vs. 48.5 h, p=.001, Table 2). There was a significant reduction in the median inductionto-delivery interval during Period B (laminaria use) (7.5 h vs. 12.7 h) and an increase in the percentage of abortions at 6
Placental retention Nausea/Diarrhea Fever Hemorrhage
Period A (no laminaria) (n=91)
Period B (with laminaria) (n=83)
p value
12 4 11 6
15 (18.1) 0 (0) 6 (7.2) 2 (2.4)
.37 .05 .28 .19
(13.2) (4.4) (12.1) (6.6)
Values are expressed as n (%).
and 12 h after the induction with misoprostol compared to patients in Period A (Table 2). Also, the median duration of labor was shorter (65 min; range, 10–420) in patients during Period B than in patients during Period A (95 min; range, 5–540, p=.01). The median induction-to-delivery interval was significantly shorter in patients with laminaria preparation than patients without laminaria (pb.001, Fig. 1). The results of Cox proportional hazard modeling to examine the relationship between the duration of the induction-to-delivery interval and laminaria use, while adjusting for parity, gestational age and previous cesarean delivery, demonstrated a highly significant effect of parity (HR=1.43, pb.001), gestational age (HR=0.96, p=.006), previous cesarean delivery (HR=4.98, pb.001) and use of laminaria tents (HR=2.02, pb.001). The postabortion hospital stay was significantly shortened in patients during Period B compared to patients during Period A (median time, 1 day vs. 2 days, respectively, pb.001). Equally, a significant reduction in total hospital stay was observed in patients during Period B (median, 3 days) compared to patients hospitalized during Period A (4 days, pb.001). 3.3. Adverse events and complications As shown in Table 3, adverse events were not different between the two study periods. Two uterine scar disjunctions occurred during Period A and none during Period B (p=.17). 4. Discussion
Fig. 1. Survival curves for induction-to-delivery interval according to the use of laminaria. Spontaneous labor and delivery was entered in the analysis as the event of interest. Patients with laminaria (Period B) had a significantly shorter induction-to-delivery interval than those patients who did not receive laminaria (Period B).
The choice of modalities for initiation of medical TOP, apart from an objective of efficiency, needs to integrate some psychological considerations as well as practical organizational elements. In this regard, the duration of the procedure is a major element for the acceptability of the method by patients. The reduction of hospitalization length and the occupation length in the delivery room is essential with regard to the ward organization and cost-effective considerations. In the present study, we showed a potential benefit of the adjunction of laminaria tents to a mifepristone– misoprostol protocol to reduce the length of medical TOP procedure as well as the postabortion stay.
104
C. Mazouni et al. / Contraception 80 (2009) 101–104
In recent studies, the use of laminaria tents for early abortion procedures has shown interesting advantages in surgical procedures [9,10]. However, in late medical TOP, conflicting results have been published [3,4,11]. This is particularly the case in the data from a recent randomized trial that showed no benefit of laminaria placement in addition to misoprostol [4]. The same conclusion was done by Prairie et al. [11], who did not obtain an impact of adjunction of laminaria to misoprostol compared to the addition of mifepristone to misoprostol. In contrary, Hoffer et al. [3] reported good results from the triple association of mifepristone, laminaria and oral misoprostol. Equally, in our present study, we found a significant reduction of the mean time to induction in the group with laminaria. This gain in abortion time was seen regardless of the time from mifepristone or misoprostol administration. Another aspect of this analysis showed no difference of adverse outcomes such as infection, fever or hemorrhage. However, because of the retrospective design of the study, we could not assess patients' pain and satisfaction. The measure of side effects of laminaria (pain at insertion, cramping, vasovagal response) is lacking in our records since these variables were rarely reported or not recorded. In a previous series, Prairie et al. [11] did not report significant difference in pain score other than pain at time of ripening in the group with laminaria. Finally, we need to acknowledge some biases in our study that limit the impact of our results. First, the absence of randomization might represent a significant limit to the generalization of our results. This lack of randomization might bias the interpretation of postabortion as well as the total duration of hospitalization. However, hospitalization the night following the abortion is a policy of the department defined with the anesthesia team. Thus, what we could conclude from our results is that the potential time-saving advantages of laminaria observed in our series may essentially benefit most in an inpatient setting, whereas outpatient use of laminaria may be inconvenient for both the patient and physician. Another element to be raised is the description in the current literature of several regimens without laminaria use, associated with shorter induction times than our proposed regimen as reported in a recent review [12,13].
5. Conclusion The adjunction of laminaria to the association of mifepristone–misoprostol reduces the duration of TOP without increasing adverse events or serious complications. Its use may offer several advantages such as shorter procedure times and reduced hospitalization stay. References [1] Lohr PA, Hayes JL, Gemzell-Danielsson K. Surgical versus medical methods for second trimester induced abortion. Cochrane Database Syst Rev 2008(1):CD006714. [2] Boulvain M, Kelly A, Lohse C, Stan C, Irion O. Mechanical methods for induction of labour. Cochrane Database Syst Rev 2001(4):CD001233. [3] Hoffer MC, Charlier C, Giacalone PL, Zimbris L, Astruc M, Boulot P. Evaluation of combination RU 486–laminaria tents–misoprostol– peridural anesthesia in second and third trimester induced abortions. J Gynecol Obstet Biol Reprod 1998;27:83–6 [French]. [4] Jain JK, Mishell Jr DR. A comparison of misoprostol with and without laminaria tents for induction of second-trimester abortion. Am J Obstet Gynecol 1996;175:173–7. [5] Ho PC, Tsang SS, Ma HK. Reducing the induction to abortion interval in termination of second trimester pregnancies: a comparison of mifepristone with laminaria tent. Br J Obstet Gynaecol 1995;102: 648–51. [6] Mazouni C, Guidicelli B, Gamerre M, Voiret C, Pellegrin V. Influence of epidural analgesia on labor in mid and late termination of pregnancy: an observational study. Int J Obstet Anesth 2007;16:383–4. [7] Mazouni C, Provensal M, Porcu G, et al. Termination of pregnancy in patients with previous cesarean section. Contraception 2006;73:244–8. [8] Jannet D, Aflak N, Abankwa A, Carbonne B, Marpeau L, Milliez J. Termination of 2nd and 3rd trimester pregnancies with mifepristone and misoprostol. Eur J Obstet Gynecol Reprod Biol 1996;70:159–63. [9] Edelman AB, Buckmaster JG, Goetsch MF, Nichols MD, Jensen JT. Cervical preparation using laminaria with adjunctive buccal misoprostol before second-trimester dilation and evacuation procedures: a randomized clinical trial. Am J Obstet Gynecol 2006;194:425–30. [10] Fox MC, Hayes JL. Society of Family Planning. Cervical preparation for second-trimester surgical abortion prior to 20 weeks of gestation. Contraception 2007;76:486–95. [11] Prairie BA, Lauria MR, Kapp N, Mackenzie T, Baker ER, George KE. Mifepristone versus laminaria: a randomized controlled trial of cervical ripening in midtrimester termination. Contraception 2007;76:383–8. [12] Kapp N, Borgatta L, Stubblefield P, Vragovic O, Moreno N. Mifepristone in second-trimester medical abortion: a randomized controlled trial. Obstet Gynecol 2007;110:13004–10. [13] Lalitkumar S, Bygdeman M, Gemzell-Danielsson K. Mid-trimester induced abortion: a review. Hum Reprod Update 2007;13:37–52.
Original research article
Cervical preparation with laminaria tents improves induction-to-delivery interval in second- and third-trimester medical termination of pregnancy Chafika Mazounia , Nadège Vejuxa , Jean-Pierre Menarda , Aurore Brunob , Léon Boublia , Claude d'Ercolea , Florence Bretellea,c,⁎ a
Department of Obstetrics and Gynecology, Marseille Public Hospital System (APHM), 13385 Marseille, France b Marseille Midwife School, 13014 Marseille, France c Unit 1, CNRS UMR 6236, Université de la Méditerranée, 13005 Marseille, France Received 1 October 2008; revised 22 January 2009; accepted 26 January 2009
Abstract Background: The purpose of our study was to determine whether cervical preparation with laminaria tents would improve the procedure of second- and third-trimester medical termination of pregnancy (TOP) in terms of duration of abortion and hospitalization. Study: A retrospective comparative study of two historical periods of women undergoing second- and third-trimester medical TOP at a single tertiary care center from September 2004 to December 2006 was conducted. During Period A, patients received oral mifepristone and vaginal misoprostol, while during Period B, laminaria tents were added. Main outcome measures included initiation-to-delivery (ITD) time, induction-to-delivery interval and hospitalization time. Results: Of 186 eligible women, 174 were enrolled in the study: 91 patients during Period A and 83 patients during Period B. The ITD time was reduced during Period B compared to Period A (43.2±6.2 h and 48.5±13.2 h, respectively; p=.001). Similarly, the induction-to-delivery interval was significantly shorter during Period B (7.5 h) compared to Period A (12.7 h; p=.001). A significant reduction in total hospital stay was observed during Period B (3 days) versus Period A (4 days; pb.001). Conclusion: Cervical preparation with laminaria tents significantly shortens the duration of medical TOP that uses mifepristone–misoprostol without adverse events or serious complications. © 2009 Elsevier Inc. All rights reserved. Keywords: Abortion; Laminaria; Mifepristone; Misoprostol; Termination of pregnancy
1. Introduction Advances in biology and ultrasound technology have allowed an improvement in the antenatal detection of fetal malformation. As a result, indications for termination of pregnancy (TOP) are more frequent and may occur later during the course of pregnancy. However, the achievement of successful TOP might be challenging despite the numerous choices of method for second- and third-trimester TOP [1]. Currently, there is insufficient evidence to assess the effectiveness of mechanical methods (D&E) compared with prostaglandins [2]. However, the need for fetal ⁎ Corresponding author. Department of Obstetrics and Gynecology, Hôpital Nord, 13915 Marseille Cedex 20, France. Tel.: +33 4 91 9 646 72; fax: +33 4 91 96 48 53. E-mail address: [email protected] (F. Bretelle). 0010-7824/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.contraception.2009.01.013
anatomopathologic examination to correlate antenatal findings tends to favor the choice for medical procedures. There are, however, some points that might limit the choice of methods to induce the TOP, such as the unpredictability of the interval-to-delivery time or a longer duration of hospitalization. Some authors have proposed use of laminaria tents alone or in combination with prostaglandins to improve the efficiency of medical procedures. These publications have reported contrasting results [3–5]. However, few have reported experience with the combination of mifepristone and misoprostol, a regimen of choice for second- and third-trimester medical TOP [6–8]. Our objective was to evaluate the impact of laminaria placement for cervical preparation in adjunction with mifepristone and misoprostol on delivery interval, during the second- and third-trimester medical TOP.
102
C. Mazouni et al. / Contraception 80 (2009) 101–104
2. Materials and methods 2.1. Study design A retrospective study of TOP performed between September 2005 and December 2006 at the Department of Obstetrics and Gynecology, North Hospital, a tertiary care center in Marseille (France), was conducted. The study protocol consisted of two cohorts of patients from two periods of treatment: (a) Period A consisted of all TOP cases admitted between September 2004 and October 2005 and (b) Period B comprised all cases from November 2005 to December 2006. The distinction between the two periods was based on the adjunction of laminaria tents for cervical preparation to the medical treatment in Period B compared to Period A, where no additional cervical preparation was performed. The IRB was approached for the study approval, and because this study is not an interventional study but a retrospective chart review, this type of study does not require IRB approval in accordance with the health public code (article L1121-1). 2.2. Study procedures All indications for TOP were discussed in a weekly multidisciplinary counseling of fetal medicine, and each patient signed a written informed consent. During Period A, the protocol for TOP induction consisted of oral (600 mg) mifepristone administration followed after 36 h by vaginal misoprostol (400 mcg=2×200 mcg) every 3 h for a maximum of 1200 mcg per day. During Period B, the same mifepristone–misoprostol protocol was used but cervical preparation was obtained using 5–8 mm laminaria tent (B. Braun Medical Ltd., Tuttlingen, Germany) placement, 24 h after the administration of oral mifepristone. Concerning the timing of hospital admission in relation to mifepristone, both groups were admitted at the same time interval. Laminaria tents were placed intracervically and packed until no additional tents could be inserted. The laminaria remained in the cervix at the time of misoprostol placement, unless they were expelled or membrane rupture occurred. The diameter of laminaria was adapted to the cervix size beginning with the larger size. The presence or absence of the following adverse event side effects was prospectively recorded in medical charts by the responsible midwife: diarrhea, nausea and hyperthermia (fever higher than 38°C) and hemorrhage defined as blood loss greater than 300 mL. The primary outcome measured was the mifepristone-todelivery time (initiation) compared between the two periods; the delivery was defined as fetal expulsion. Secondary outcomes included (a) induction-to-delivery interval defined as time from first misoprostol dose to fetal expulsion and (b) time to discharge from the hospital.
Labor was defined from the beginning of uterine contractions and cervical modifications to fetal expulsion. Retained placenta was defined as lack of expulsion 30 min after delivery of the fetus and was managed at the discretion of the attending physician and usually consisted of manual removal. 2.3. Statistical analysis Group testing of categorical data is presented as n (%), and groups were compared with Fisher's Exact Test or the chi-square test. Differences in continuous variables were analyzed using the Mann–Whitney U test. Kaplan–Meier survival analysis and Cox proportional hazard modeling were applied to examine the interval from induction to delivery according to laminaria use, while adjusting for confounding factors. Groups were compared using the log rank test. 3. Results 3.1. Patient's characteristics During Period A (i.e., TOP without laminaria placement), 97 patients requested TOP, and during Period B, 89 patients did so. From the initial patients selected, 12 (6 in each group) were excluded from the analysis because of missing data. Therefore, a total of 174 patients were evaluated, 91 during Period A and 83 during Period B. The clinical and demographic data of the groups are shown in Table 1. There was no difference in patient characteristics other than the fact that patients during Period A tended to be older than patients during Period B (p=.03). There was no difference between groups for indications for TOP (p=.88) (details for each group are not shown). Overall, the most frequent indication was fetal abnormalities (59.8%), followed by chromosomal anomalies (31.6%), premature rupture of membranes (5.7%) and miscellaneous indications (2.9%). 3.2. Delivery outcome There was no difference in the number of misoprostol tablets administered between the two groups, with a median
Table 1 Obstetrical characteristics of the study population
Age, mean (±SD) Nulliparous, n (%) Gestational age (weeks), mean (±SD) Previous cesarean delivery, n (%)
Period A (no laminaria) (n=91)
Period B (with laminaria) (n=83)
p value
31.5 (±6.5) 37 (40.7) 24.2 (±6.1)
29.3 (±5.8) 38 (45.8) 23.3 (±6.3)
.03 .50 .32
11 (12.1)
11 (13.3)
.82
C. Mazouni et al. / Contraception 80 (2009) 101–104 Table 2 Delivery interval characteristics between the two periods of study
Mean (±SD) mifepristone-to-delivery interval (h) Induction to delivery, n (%) b6 h b12 h b24 h Median (±SD) (h) Mean (±SD) (h)
103
Table 3 Adverse events
Period A (no laminaria) (n=91)
Period B (with laminaria) (n=83)
p value
48.5 (±13.2)
43.2 (±6.2)
.001
21 (23.1) 60 (65.9) 83 (91.2) 9 (±8) 12.7 (±13.3)
37 (44.6) 73 (88) 80 (96.4) 6.4 (±4) 7.5 (±6.2)
.003 .001 .16 .01 .001
number of 1.5 doses in both groups (median dose, 600 mcg for Period A vs. 600 mcg for Period B, p=.65). In Period B, a median of 1 laminaria (range, 1–4) was placed in the cervix. The median diameter of laminaria used was 8 mm (range, 5–8 mm). Total median duration of the medical termination procedure, defined as the time from mifepristone administration to delivery, was significantly shorter during Period B compared to Period A (43.2 h vs. 48.5 h, p=.001, Table 2). There was a significant reduction in the median inductionto-delivery interval during Period B (laminaria use) (7.5 h vs. 12.7 h) and an increase in the percentage of abortions at 6
Placental retention Nausea/Diarrhea Fever Hemorrhage
Period A (no laminaria) (n=91)
Period B (with laminaria) (n=83)
p value
12 4 11 6
15 (18.1) 0 (0) 6 (7.2) 2 (2.4)
.37 .05 .28 .19
(13.2) (4.4) (12.1) (6.6)
Values are expressed as n (%).
and 12 h after the induction with misoprostol compared to patients in Period A (Table 2). Also, the median duration of labor was shorter (65 min; range, 10–420) in patients during Period B than in patients during Period A (95 min; range, 5–540, p=.01). The median induction-to-delivery interval was significantly shorter in patients with laminaria preparation than patients without laminaria (pb.001, Fig. 1). The results of Cox proportional hazard modeling to examine the relationship between the duration of the induction-to-delivery interval and laminaria use, while adjusting for parity, gestational age and previous cesarean delivery, demonstrated a highly significant effect of parity (HR=1.43, pb.001), gestational age (HR=0.96, p=.006), previous cesarean delivery (HR=4.98, pb.001) and use of laminaria tents (HR=2.02, pb.001). The postabortion hospital stay was significantly shortened in patients during Period B compared to patients during Period A (median time, 1 day vs. 2 days, respectively, pb.001). Equally, a significant reduction in total hospital stay was observed in patients during Period B (median, 3 days) compared to patients hospitalized during Period A (4 days, pb.001). 3.3. Adverse events and complications As shown in Table 3, adverse events were not different between the two study periods. Two uterine scar disjunctions occurred during Period A and none during Period B (p=.17). 4. Discussion
Fig. 1. Survival curves for induction-to-delivery interval according to the use of laminaria. Spontaneous labor and delivery was entered in the analysis as the event of interest. Patients with laminaria (Period B) had a significantly shorter induction-to-delivery interval than those patients who did not receive laminaria (Period B).
The choice of modalities for initiation of medical TOP, apart from an objective of efficiency, needs to integrate some psychological considerations as well as practical organizational elements. In this regard, the duration of the procedure is a major element for the acceptability of the method by patients. The reduction of hospitalization length and the occupation length in the delivery room is essential with regard to the ward organization and cost-effective considerations. In the present study, we showed a potential benefit of the adjunction of laminaria tents to a mifepristone– misoprostol protocol to reduce the length of medical TOP procedure as well as the postabortion stay.
104
C. Mazouni et al. / Contraception 80 (2009) 101–104
In recent studies, the use of laminaria tents for early abortion procedures has shown interesting advantages in surgical procedures [9,10]. However, in late medical TOP, conflicting results have been published [3,4,11]. This is particularly the case in the data from a recent randomized trial that showed no benefit of laminaria placement in addition to misoprostol [4]. The same conclusion was done by Prairie et al. [11], who did not obtain an impact of adjunction of laminaria to misoprostol compared to the addition of mifepristone to misoprostol. In contrary, Hoffer et al. [3] reported good results from the triple association of mifepristone, laminaria and oral misoprostol. Equally, in our present study, we found a significant reduction of the mean time to induction in the group with laminaria. This gain in abortion time was seen regardless of the time from mifepristone or misoprostol administration. Another aspect of this analysis showed no difference of adverse outcomes such as infection, fever or hemorrhage. However, because of the retrospective design of the study, we could not assess patients' pain and satisfaction. The measure of side effects of laminaria (pain at insertion, cramping, vasovagal response) is lacking in our records since these variables were rarely reported or not recorded. In a previous series, Prairie et al. [11] did not report significant difference in pain score other than pain at time of ripening in the group with laminaria. Finally, we need to acknowledge some biases in our study that limit the impact of our results. First, the absence of randomization might represent a significant limit to the generalization of our results. This lack of randomization might bias the interpretation of postabortion as well as the total duration of hospitalization. However, hospitalization the night following the abortion is a policy of the department defined with the anesthesia team. Thus, what we could conclude from our results is that the potential time-saving advantages of laminaria observed in our series may essentially benefit most in an inpatient setting, whereas outpatient use of laminaria may be inconvenient for both the patient and physician. Another element to be raised is the description in the current literature of several regimens without laminaria use, associated with shorter induction times than our proposed regimen as reported in a recent review [12,13].
5. Conclusion The adjunction of laminaria to the association of mifepristone–misoprostol reduces the duration of TOP without increasing adverse events or serious complications. Its use may offer several advantages such as shorter procedure times and reduced hospitalization stay. References [1] Lohr PA, Hayes JL, Gemzell-Danielsson K. Surgical versus medical methods for second trimester induced abortion. Cochrane Database Syst Rev 2008(1):CD006714. [2] Boulvain M, Kelly A, Lohse C, Stan C, Irion O. Mechanical methods for induction of labour. Cochrane Database Syst Rev 2001(4):CD001233. [3] Hoffer MC, Charlier C, Giacalone PL, Zimbris L, Astruc M, Boulot P. Evaluation of combination RU 486–laminaria tents–misoprostol– peridural anesthesia in second and third trimester induced abortions. J Gynecol Obstet Biol Reprod 1998;27:83–6 [French]. [4] Jain JK, Mishell Jr DR. A comparison of misoprostol with and without laminaria tents for induction of second-trimester abortion. Am J Obstet Gynecol 1996;175:173–7. [5] Ho PC, Tsang SS, Ma HK. Reducing the induction to abortion interval in termination of second trimester pregnancies: a comparison of mifepristone with laminaria tent. Br J Obstet Gynaecol 1995;102: 648–51. [6] Mazouni C, Guidicelli B, Gamerre M, Voiret C, Pellegrin V. Influence of epidural analgesia on labor in mid and late termination of pregnancy: an observational study. Int J Obstet Anesth 2007;16:383–4. [7] Mazouni C, Provensal M, Porcu G, et al. Termination of pregnancy in patients with previous cesarean section. Contraception 2006;73:244–8. [8] Jannet D, Aflak N, Abankwa A, Carbonne B, Marpeau L, Milliez J. Termination of 2nd and 3rd trimester pregnancies with mifepristone and misoprostol. Eur J Obstet Gynecol Reprod Biol 1996;70:159–63. [9] Edelman AB, Buckmaster JG, Goetsch MF, Nichols MD, Jensen JT. Cervical preparation using laminaria with adjunctive buccal misoprostol before second-trimester dilation and evacuation procedures: a randomized clinical trial. Am J Obstet Gynecol 2006;194:425–30. [10] Fox MC, Hayes JL. Society of Family Planning. Cervical preparation for second-trimester surgical abortion prior to 20 weeks of gestation. Contraception 2007;76:486–95. [11] Prairie BA, Lauria MR, Kapp N, Mackenzie T, Baker ER, George KE. Mifepristone versus laminaria: a randomized controlled trial of cervical ripening in midtrimester termination. Contraception 2007;76:383–8. [12] Kapp N, Borgatta L, Stubblefield P, Vragovic O, Moreno N. Mifepristone in second-trimester medical abortion: a randomized controlled trial. Obstet Gynecol 2007;110:13004–10. [13] Lalitkumar S, Bygdeman M, Gemzell-Danielsson K. Mid-trimester induced abortion: a review. Hum Reprod Update 2007;13:37–52.