Myometrial activity after local application of prostaglandin E2 for cervical ripening and term labor induction Lena Granstrom, MD,' Gunvor Ekman, MD: and Ulf Ulmsten, MDb Danderyd and Uppala, Sweden Twelve pregnant women at term with unfavorable cervices (s5 points according to Bishop score) were given prostaglandin E2 for cervical priming and labor induction. Prostaglandin E2 was given in the following manner: 0.5 mg in gel strictly intracervically (n = 4), extraamniotically (n = 4), or prostaglandin E2 (4 mg) in gel vaginally (n = 4). The myometrial activity was registered over a period of 30 minutes before and at least 3 hours after gel application by means of an extraamniotic microtransducer catheter. After both extraamniotic and vaginal gel application, myometrial activity was significantly increased compared with intracervical application. All the women had favorable cervical states 6 hours after treatment and were delivered vaginally within 24 hours. All infants were delivered in good condition with 1-minute Apgar scores > 7. From these results we conclude that proper intracervical prostaglandin E2 gel application. in contrast to extraamniotic or vaginal application, induces cervical ripening without significant myometrial activity. Because careful intracervical application appears to avoid or minimize the risks of myometrial hyperstimulation. thiS technique should be considered particularly in women with unfavorable cervices and delicate fetuses. (AM J OBSTET GVNECOl 1990;162:691-4.)
Key words: Cervical priming, PGE", myometrial contractions, labor induction
Several studies have confirmed that local application of prostaglandins is an effective method for ripening of the cervix at term ."" However, unwanted myometrial contractions or hyperstimulation have been reported as side effects. 2. 6. 7 It is therefore important to study and quantify the risk for possible side effects that may jeopardize a delicate fetus. The purpose of this investigation was to evaluate both the risk of induction of unwanted myomerial contractions after local application of prostaglandin E2 (PGE,) gel and to identify a gel technique that minimizes this side effect.
Material and methods Twelve pregnant women at term with unfavorable cervices (Bishop score:55 points) participated in the study. They were allocated into three g-roups. Group A consisted of four women (Bishop sC()J'e:55 points) who were treated with PGE 2 (0.5 mg) in gel that was applied strictly within the cervical canal. 1 , Group B included four women, also with unfavorable From the Departments of Obs/etncs and Gynecology. Karolmska 111stl/utet. Dallderyd Hospilal. Datulayd: and Uppsala Unwemty Hosp!lal. Uppsala.' Supp01'ted b,v the Swedt;/t M edica l Rell'flrch CounCil (grants no 6856, 7479). Magnus Bergwall. Tore N1l.mn. and Allmanna BB FoundatIOns. Received jor pubilcation } ulle 15. 1989; reVISed September 21. 1989; accepted October 24. 1989. Repnnt requests: Lena Granstrom. MD. Department of Ob,tetncs and Gynecology. Karohnska Institutet. Danderyd Hospltal. S-182 88 Dandervd. Sweden. 611 117686 '
cervical states (Bishop score :55 points). These women were treated with PGE 2 (0.5 mg) in gel deliberately applied extraamniotically.' The last group of women (group C) consisting of four pregnant women at term who had unfavorable cervical states (Bishop score:55 points). They were given PGE. (4 mg) in gel applied in the posterior fornix of the vagina." The indications for induction of cervical priming and induction of labor were medical, such as preecla mpsia, suspected postmaturity, or fetal growth retardation. All women were primiparous with intact membranes and no spontaneous uterine contractions according to tocogra phic recordings. Ultrasonographic scans had been performed twice during the pregnancy to estimate correct gestational age and to exclude abnormalities, such as placenta previa, multiple pregnancy, or breech presentation. Relevant data of the patients are given in Table 1. Amniotomy was not done until labor was well established and the cervix dilated ~4 cm. Gel preparation. The PGE" gel (Cervi prost, Organon OSS, The Netherlands) originates from a cross-link starch powder industria lly mixed with PGE, in ethanol solution and lyophilized." Immediately before application. 2.0 ml of saline solution (extraamniotic or intracervical) or 3.0 ml saline solution (intravaginal) was added to the PGE" powder. A highly viscous, stickly gel was thus achieved within 30 seconds. The gel was applied through a plastic catheter 12 cm long as described previously. 1 691
692 Granstrom, Ekman, and Ulmsten
March 1990 Am J Obstet Gynecol
' - -_ _ .._TA_A_CE_A_V'_CA_l_ _...JIITRANSCERYtcAL .. EXTRAAMNIOTlcl .... , _ _ _"_T_A"_""_O_'N_A_l_ _-,
10
15
20
Time (minutes)
10
15
10
20
Tim. (minutes)
15
20
Time (minutes )
Fig. 1. Typical tracing illustrates myometrial activity registered by microtransducer catheter before and 30, 60, and 90 minutes after different gel applications. Table I. Twelve term pregnant women treated with local application of PGE2 for cervical priming, labor induction, or both
Age (yr) Mean Range Gestational age (wk) Mean Range Parity Original cervical score Mean Range
Group C
Group A (0.5 mg intracenncal(v)
Group B (0.5 mg extraamniotlcally)
(4 mg in gel vaginally)
25.5 24-29
28 19-39
25 22-26
41 40-42 0
41 40-42 0
41 40-42 0
3.5 3-4
4 3-5
4 3-5
For strictly intracervical application, the tip of the catheter was introduced close to the inner meatus. The gel (corresponding to a volume of approximately 2.5 ml) was then cautiously applied within the cervical canal while the catheter was slowly withdrawn. For extraamniotic gel application, the tip of the catheter was allowed to pass the internal meatus, after which the gel application was commenced. During vaginal application, the gel was introduced in the posterior fornix of the vagina. Irrespective of the mode of application, the catheter was immediately withdrawn after application. Pressure recording. For proper registration of myometrial activity, a flexible 2 mm thin microtransducer catheter (Geltec, Scotland) was applied extraamniotically via the cervical canal without rupturing the membranes. The recording section at the tip of the catheter was placed 2 to 3 cm above the internal meatus. The registrations started 30 minutes before and lasted for 4 to 5 hours after gel application. The recording technique has been described in detail elsewhere. 9
Results The effects on the myometrium and cervix after the three different gel applications are shown in Fig. 1. Stricly intracervical application of PGE 2 gel induced minimal myometrial activity, whereas significant uterine contractions were recorded almost immediately after extraamniotic application . After intravaginal gel application, regular uterine contractions were registered within 30 to 60 minutes. The myometrial activity calculated in Montevideo units is shown in Fig. 2. The activity after extraamniotic and intravaginal application was considerably more pronounced than after intracervical application. Cervical states improved in all women after gel application. No significant difference in this parameter was found within the three groups of patients at reexamination 5 to 6 hours after start of treatment. Induction-to-delivery time differed in the three groups of patients; the longest interval occurred after intravaginal application (l0 to 15 hours) and the shortest interval was after extraamniotic application (6 to 9
Myometrial activity after PGE 2
Volume 162 Number 3
693
100
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..
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p
Key words: Cervical priming, PGE", myometrial contractions, labor induction
Several studies have confirmed that local application of prostaglandins is an effective method for ripening of the cervix at term ."" However, unwanted myometrial contractions or hyperstimulation have been reported as side effects. 2. 6. 7 It is therefore important to study and quantify the risk for possible side effects that may jeopardize a delicate fetus. The purpose of this investigation was to evaluate both the risk of induction of unwanted myomerial contractions after local application of prostaglandin E2 (PGE,) gel and to identify a gel technique that minimizes this side effect.
Material and methods Twelve pregnant women at term with unfavorable cervices (Bishop score:55 points) participated in the study. They were allocated into three g-roups. Group A consisted of four women (Bishop sC()J'e:55 points) who were treated with PGE 2 (0.5 mg) in gel that was applied strictly within the cervical canal. 1 , Group B included four women, also with unfavorable From the Departments of Obs/etncs and Gynecology. Karolmska 111stl/utet. Dallderyd Hospilal. Datulayd: and Uppsala Unwemty Hosp!lal. Uppsala.' Supp01'ted b,v the Swedt;/t M edica l Rell'flrch CounCil (grants no 6856, 7479). Magnus Bergwall. Tore N1l.mn. and Allmanna BB FoundatIOns. Received jor pubilcation } ulle 15. 1989; reVISed September 21. 1989; accepted October 24. 1989. Repnnt requests: Lena Granstrom. MD. Department of Ob,tetncs and Gynecology. Karohnska Institutet. Danderyd Hospltal. S-182 88 Dandervd. Sweden. 611 117686 '
cervical states (Bishop score :55 points). These women were treated with PGE 2 (0.5 mg) in gel deliberately applied extraamniotically.' The last group of women (group C) consisting of four pregnant women at term who had unfavorable cervical states (Bishop score:55 points). They were given PGE. (4 mg) in gel applied in the posterior fornix of the vagina." The indications for induction of cervical priming and induction of labor were medical, such as preecla mpsia, suspected postmaturity, or fetal growth retardation. All women were primiparous with intact membranes and no spontaneous uterine contractions according to tocogra phic recordings. Ultrasonographic scans had been performed twice during the pregnancy to estimate correct gestational age and to exclude abnormalities, such as placenta previa, multiple pregnancy, or breech presentation. Relevant data of the patients are given in Table 1. Amniotomy was not done until labor was well established and the cervix dilated ~4 cm. Gel preparation. The PGE" gel (Cervi prost, Organon OSS, The Netherlands) originates from a cross-link starch powder industria lly mixed with PGE, in ethanol solution and lyophilized." Immediately before application. 2.0 ml of saline solution (extraamniotic or intracervical) or 3.0 ml saline solution (intravaginal) was added to the PGE" powder. A highly viscous, stickly gel was thus achieved within 30 seconds. The gel was applied through a plastic catheter 12 cm long as described previously. 1 691
692 Granstrom, Ekman, and Ulmsten
March 1990 Am J Obstet Gynecol
' - -_ _ .._TA_A_CE_A_V'_CA_l_ _...JIITRANSCERYtcAL .. EXTRAAMNIOTlcl .... , _ _ _"_T_A"_""_O_'N_A_l_ _-,
10
15
20
Time (minutes)
10
15
10
20
Tim. (minutes)
15
20
Time (minutes )
Fig. 1. Typical tracing illustrates myometrial activity registered by microtransducer catheter before and 30, 60, and 90 minutes after different gel applications. Table I. Twelve term pregnant women treated with local application of PGE2 for cervical priming, labor induction, or both
Age (yr) Mean Range Gestational age (wk) Mean Range Parity Original cervical score Mean Range
Group C
Group A (0.5 mg intracenncal(v)
Group B (0.5 mg extraamniotlcally)
(4 mg in gel vaginally)
25.5 24-29
28 19-39
25 22-26
41 40-42 0
41 40-42 0
41 40-42 0
3.5 3-4
4 3-5
4 3-5
For strictly intracervical application, the tip of the catheter was introduced close to the inner meatus. The gel (corresponding to a volume of approximately 2.5 ml) was then cautiously applied within the cervical canal while the catheter was slowly withdrawn. For extraamniotic gel application, the tip of the catheter was allowed to pass the internal meatus, after which the gel application was commenced. During vaginal application, the gel was introduced in the posterior fornix of the vagina. Irrespective of the mode of application, the catheter was immediately withdrawn after application. Pressure recording. For proper registration of myometrial activity, a flexible 2 mm thin microtransducer catheter (Geltec, Scotland) was applied extraamniotically via the cervical canal without rupturing the membranes. The recording section at the tip of the catheter was placed 2 to 3 cm above the internal meatus. The registrations started 30 minutes before and lasted for 4 to 5 hours after gel application. The recording technique has been described in detail elsewhere. 9
Results The effects on the myometrium and cervix after the three different gel applications are shown in Fig. 1. Stricly intracervical application of PGE 2 gel induced minimal myometrial activity, whereas significant uterine contractions were recorded almost immediately after extraamniotic application . After intravaginal gel application, regular uterine contractions were registered within 30 to 60 minutes. The myometrial activity calculated in Montevideo units is shown in Fig. 2. The activity after extraamniotic and intravaginal application was considerably more pronounced than after intracervical application. Cervical states improved in all women after gel application. No significant difference in this parameter was found within the three groups of patients at reexamination 5 to 6 hours after start of treatment. Induction-to-delivery time differed in the three groups of patients; the longest interval occurred after intravaginal application (l0 to 15 hours) and the shortest interval was after extraamniotic application (6 to 9
Myometrial activity after PGE 2
Volume 162 Number 3
693
100
§
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II)
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p
